Rofecoxib is a COX-2-selective nonsteroidal anti-inflammatory drug ( NSAID ). It was marketed by Merck & Co. to treat osteoarthritis , rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea . Rofecoxib was approved in the US by the US Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx , Ceoxx , and Ceeoxx . Rofecoxib was available by prescription in both tablets and as an oral suspension.
167-412: Rofecoxib gained widespread use among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time. In September 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Merck withdrew
334-411: A blood test for biomarkers (the cardiac protein troponin ). When there is evidence of an MI, it may be classified as an ST elevation myocardial infarction (STEMI) or Non-ST elevation myocardial infarction (NSTEMI) based on the results of an ECG . The phrase "heart attack" is often used non-specifically to refer to myocardial infarction. An MI is different from—but can cause— cardiac arrest , where
501-475: A coronary artery caused by a rupture of an atherosclerotic plaque is usually the underlying mechanism of an MI. MIs are less commonly caused by coronary artery spasms , which may be due to cocaine , significant emotional stress (often known as Takotsubo syndrome or broken heart syndrome ) and extreme cold, among others. Many tests are helpful to help with diagnosis, including electrocardiograms (ECGs), blood tests and coronary angiography . An ECG, which
668-510: A joint venture owned 68% by GlaxoSmithKline and 32% by Pfizer, with plans to make it a public company . The transaction built on a 2018 transaction where GlaxoSmithKline acquired Novartis ' stake in the GSK-Novartis consumer healthcare joint business. The transaction followed negotiations with other companies including Reckitt Benckiser , Sanofi , Johnson & Johnson , and Procter & Gamble . In September 2019, Pfizer initiated
835-628: A $ 3,435,600 study with the CDC Foundation to research "screen-and-treat" strategies for cryptococcal disease in Botswana . In December 2016, Pfizer acquired AstraZeneca 's small-molecule antibiotics business for $ 1.575 billion. In January 2018, Pfizer announced that it would end its work on research into treatments for Alzheimer's disease and Parkinsonism (a symptom of Parkinson's disease and other conditions). The company said about 300 researchers would lose their jobs. In July 2018,
1002-471: A 71-year-old smoker with heart disease, had a fatal heart attack three weeks after finishing a one-week sample of rofecoxib. On April 21, 2006 the jury awarded the plaintiff $ 7 million compensatory and $ 25 million punitive. The Texas Courts of Appeals in San Antonio later ruled Garza's fatal heart attack probably resulted from pre-existing health conditions unrelated to his taking of Vioxx, thus reversing
1169-405: A Merck memo during the depositions for the first federal Vioxx trial, they realized that these data had been available to the authors months before publication. The editors wrote an editorial accusing the authors of deliberately withholding the data. They released the editorial to the media on December 8, 2005, before giving the authors a chance to respond. NEJM editor Gregory Curfman explained that
1336-474: A benefit of 15 to 45%. Physical activity can reduce the risk of cardiovascular disease, and people at risk are advised to engage in 150 minutes of moderate or 75 minutes of vigorous intensity aerobic exercise a week. Keeping a healthy weight, drinking alcohol within the recommended limits, and quitting smoking reduce the risk of cardiovascular disease. Substituting unsaturated fats such as olive oil and rapeseed oil instead of saturated fats may reduce
1503-558: A cancer medication which was approved for human use by the FDA in January 2006. A related compound, SU11654 ( Toceranib ), was also approved for cancer in dogs , and the ALK inhibitor Crizotinib also grew out of a SUGEN program. In October 2006, the company announced it would acquire PowerMed. On October 15, 2009, Pfizer acquired Wyeth for $ 68 billion in cash and stock, including
1670-428: A common, and sometimes the only symptom, occurring when damage to the heart limits the output of the left ventricle , with breathlessness arising either from low oxygen in the blood or pulmonary edema . Other less common symptoms include weakness, light-headedness , palpitations , and abnormalities in heart rate or blood pressure . These symptoms are likely induced by a massive surge of catecholamines from
1837-606: A complaint to the US Food and Drug Administration (FDA). Ventavia fired her later the same day. The European Medicines Agency (EMA) stated in a response to the European Parliament , that "the deficiencies identified do not jeopardize the quality and integrity of the data from the main Comirnaty trial and have no impact on the benefit-risk assessment or on the conclusions on the safety, effectiveness and quality of
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#17327760857522004-566: A coordinated research strategy for prioritizing and speeding up development of COVID-19 vaccines and pharmaceutical products. Pfizer joined the partnership as an industry "leadership organization", and participated as a collaborator in ACTIV-led clinical trials. CEO Albert Bourla attended the GAVI COVAX AMC 2021 Investment Opportunity Launch Event, otherwise named One World Protected, on April 15, 2021. In Canada, Pfizer endorsed
2171-480: A late consequence of Kawasaki disease . Calcium deposits in the coronary arteries can be detected with CT scans . Calcium seen in coronary arteries can provide predictive information beyond that of classical risk factors. High blood levels of the amino acid homocysteine is associated with premature atherosclerosis; whether elevated homocysteine in the normal range is causal is controversial. In people without evident coronary artery disease , possible causes for
2338-402: A later date. On November 9, 2020, Pfizer announced that BioNTech's COVID-19 vaccine, tested on 43,500 people, was found to be 90% effective at preventing symptomatic COVID-19. The efficacy was updated to 95% a week later. Akiko Iwasaki, an immunologist interviewed by The New York Times , described the efficacy figure as "really a spectacular number." The announcement made Pfizer and BioNTech
2505-400: A mean duration of 9 months. The elevated risk began during the second month on rofecoxib. No significant difference in the mortality from cardiovascular events was seen between the two groups, nor did any significant difference occur in the rate of myocardial infarction between the rofecoxib and naproxen treatment groups in patients without high cardiovascular risk. The difference in overall risk
2672-532: A memorandum concluding that risks for serious cardiovascular (CV) events seem to be as great for nonselective NSAIDs as for COX-2–selective agents such as rofecoxib, according to long-term, controlled clinical trials. Based on data up to 2015, the FDA reasserted the likelihood of an increased risk of serious adverse CV events from COX-2–selective and nonselective NSAIDs, dependent on dose and duration. In November 2017, Massachusetts-based Tremeau Pharmaceuticals announced its plan to return rofecoxib (TRM-201) to market as
2839-431: A myocardial infarction before age 55 years, or a female first-degree relative (mother, sister) less than age 65 increases a person's risk of MI. Genome-wide association studies have found 27 genetic variants that are associated with an increased risk of myocardial infarction. The strongest association of MI has been found with chromosome 9 on the short arm p at locus 21, which contains genes CDKN2A and 2B, although
3006-463: A myocardial infarction increases with older age, low physical activity, and low socioeconomic status . Heart attacks appear to occur more commonly in the morning hours, especially between 6AM and noon. Evidence suggests that heart attacks are at least three times more likely to occur in the morning than in the late evening. Shift work is also associated with a higher risk of MI. One analysis has found an increase in heart attacks immediately following
3173-406: A myocardial infarction. Spasm of coronary arteries, such as Prinzmetal's angina may cause blockage. If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade ; the heart cells in the territory of the blocked coronary artery die ( infarction ), chiefly through necrosis , and do not grow back. A collagen scar forms in their place. When an artery
3340-543: A myocardial infarction. The flow of blood can be imaged, and contrast dyes may be given to improve image. Other scans using radioactive contrast include SPECT CT-scans using thallium , sestamibi ( MIBI scans ) or tetrofosmin ; or a PET scan using Fludeoxyglucose or rubidium-82 . These nuclear medicine scans can visualize the perfusion of heart muscle. SPECT may also be used to determine viability of tissue, and whether areas of ischemia are inducible. Medical societies and professional guidelines recommend that
3507-637: A person localizes the chest pain by clenching one or both fists over their sternum , has classically been thought to be predictive of cardiac chest pain, although a prospective observational study showed it had a poor positive predictive value . Typically, chest pain because of ischemia, be it unstable angina or myocardial infarction, lessens with the use of nitroglycerin , but nitroglycerin may also relieve chest pain arising from non-cardiac causes. Chest pain may be accompanied by sweating , nausea or vomiting, and fainting , and these symptoms may also occur without any pain at all. Dizziness or lightheadedness
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#17327760857523674-522: A personal injury case, in Atlantic City , New Jersey. The plaintiff experienced a mild myocardial infarction and claimed that rofecoxib was responsible, after having taken it for two months. Merck argued that there was no evidence that rofecoxib was the cause of Humeston's injury and that there is no scientific evidence linking rofecoxib to cardiac events with short durations of use. The jury ruled that Merck had adequately warned doctors and patients of
3841-569: A placebo. Preapproval phase III clinical trials , like the APPROVe study, showed no increased relative risk of adverse cardiovascular events for the first 18 months of rofecoxib usage (Merck, 2004). Others have pointed out that "study 090", a preapproval trial, showed a three-fold increase in cardiovascular events compared to placebo, a seven-fold increase compared to nabumetone (another NSAID), and an eight-fold increase in heart attacks and strokes combined compared to both control groups. Although this
4008-447: A prescription anti-inflammatory medication that became Pfizer's first product to reach $ 1 billion in revenue. In 1965, John Powers, Jr. became chief executive officer of the company, succeeding John McKeen. As the area surrounding its Brooklyn, NY plant fell into decline in the 1970s and 1980s, the company formed a public-private partnership with New York City that encompassed the construction of low- and middle-income housing,
4175-407: A previous heart attack is also suggestive. The pain associated with MI is usually diffuse, does not change with position, and lasts for more than 20 minutes. It might be described as pressure, tightness, knifelike, tearing, burning sensation (all these are also manifested during other diseases). It could be felt as an unexplained anxiety, and pain might be absent altogether. Levine's sign , in which
4342-428: A recent retrospective study of 113,000 elderly Canadians suggested a borderline statistically significant increased relative risk of heart attacks of 1.24 from Vioxx usage, with a relative risk of 1.73 for higher-dose Vioxx usage. (Levesque, 2005). Another study, using Kaiser Permanente data, found a 1.47 relative risk for low-dose Vioxx usage and 3.58 for high-dose Vioxx usage compared to current use of celecoxib, though
4509-406: A result. These skills were applied to the deep-submergence mass production of penicillin , an antibiotic , during World War II in response to the need to treat injured Allied soldiers. The company also embarked on a global soil collection program related to improving production yields of penicillin which ultimately resulted in 135,000 samples. On June 2, 1942, the company incorporated under
4676-560: A rise in biomarkers, a rise in the ST segment , changes in the shape or flipping of T waves , new Q waves , or a new left bundle branch block can be used to diagnose an AMI. In addition, ST elevation can be used to diagnose an ST segment myocardial infarction (STEMI). A rise must be new in V2 and V3 ≥2 mm (0,2 mV) for males or ≥1.5 mm (0.15 mV) for females or ≥1 mm (0.1 mV) in two other adjacent chest or limb leads . ST elevation
4843-454: A safer alternative. Some commentators have noted that naproxen would have to be three times as effective as aspirin to account for all of the difference, and some outside scientists warned Merck that this claim was implausible before VIGOR was published. No evidence has since emerged for such a large cardioprotective effect of naproxen, although a number of studies have found protective effects similar in size to those of aspirin. The results of
5010-409: A series of leads placed on a person's chest that measure electrical activity associated with contraction of the heart muscle. The taking of an ECG is an important part of the workup of an AMI, and ECGs are often not just taken once but may be repeated over minutes to hours, or in response to changes in signs or symptoms. ECG readouts produce a waveform with different labeled features. In addition to
5177-433: A shortage of calcium citrate . Pfizer imported the compound from Italy for the manufacture of citric acid, and due to the disruption in supply, the company began a search for an alternative. They found this in the form of a fungus capable of fermenting sugar to citric acid. By 1919, the company was able to commercialize production of citric acid from this source. The company developed expertise in fermentation technology as
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5344-406: A significant effect on blood cholesterol and thus recommendations about its consumption may not be needed. Trans fats do appear to increase risk. Acute and prolonged intake of high quantities of alcoholic drinks (3–4 or more daily) increases the risk of a heart attack. Family history of ischemic heart disease or MI, particularly if one has a male first-degree relative (father, brother) who had
5511-488: A similar adverse-effect profile to other NSAIDs. The VIGOR (Vioxx GI Outcomes Research) study, conducted by Bombardier, et al., compared the efficacy and adverse-effect profiles of a supratherapeutic dose of rofecoxib (50 mg/day) vs. a common dose of naproxen (500 mg/BID), had indicated a significant four-fold increased risk of acute myocardial infarction (heart attack) in rofecoxib patients when compared with naproxen patients (0.4% vs 0.1%, relative risk 0.25) over
5678-424: A spokesperson for the drug. The patents for Viagra expired in 2020. In 1991, William C. Steere, Jr. became chief executive officers of the company, succeeding Edmund T. Pratt Jr. In 1991 Pfizer also began marketing Zoloft ( sertraline ), an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class developed nine years earlier by Pfizer chemists Kenneth Koe and Willard Welch. Sertraline
5845-639: A study with the CDC Foundation to investigate the tracking of healthcare-associated infections , scheduled to run through to June 2023. In December 2019, Pfizer awarded the CDC Foundation a further $ 1,948,482 to continue its cryptococcal disease screening and treatment research in nine African countries. In March 2020, Pfizer joined the COVID-19 Therapeutics Accelerator funding vehicle to expedite development of treatments against COVID-19 . The $ 125 million initiative
6012-426: A treatment for hemophilic arthropathy (HA). Tremeau announced that the FDA had granted an orphan designation for TRM-201 (rofecoxib) for the treatment of HA, and that they had received FDA feedback on their development plan. HA is a degenerative joint disease caused by recurrent intra-articular bleeding. It is the largest cause of morbidity in patients with hemophilia and has no currently approved treatment options in
6179-601: Is a known risk factor, particularly high low-density lipoprotein , low high-density lipoprotein , and high triglycerides . Many risk factors for myocardial infarction are potentially modifiable, with the most important being tobacco smoking (including secondhand smoke ). Smoking appears to be the cause of about 36% and obesity the cause of 20% of coronary artery disease . Lack of physical activity has been linked to 7–12% of cases. Less common causes include stress-related causes such as job stress , which accounts for about 3% of cases, and chronic high stress levels. There
6346-454: Is a recording of the heart's electrical activity, may confirm an ST elevation MI ( STEMI ), if ST elevation is present. Commonly used blood tests include troponin and less often creatine kinase MB . Treatment of an MI is time-critical. Aspirin is an appropriate immediate treatment for a suspected MI. Nitroglycerin or opioids may be used to help with chest pain; however, they do not improve overall outcomes. Supplemental oxygen
6513-806: Is also an important modifiable risk. Short-term exposure to air pollution such as carbon monoxide , nitrogen dioxide , and sulfur dioxide (but not ozone ) has been associated with MI and other acute cardiovascular events. For sudden cardiac deaths, every increment of 30 units in Pollutant Standards Index correlated with an 8% increased risk of out-of-hospital cardiac arrest on the day of exposure. Extremes of temperature are also associated. A number of acute and chronic infections including Chlamydophila pneumoniae , influenza , Helicobacter pylori , and Porphyromonas gingivalis among others have been linked to atherosclerosis and myocardial infarction. Myocardial infarction can also occur as
6680-641: Is an American multinational pharmaceutical and biotechnology corporation headquartered at The Spiral in Manhattan, New York City . The company was established in 1849, in New York by two German entrepreneurs, Charles Pfizer (1824–1906) and his cousin Charles F. Erhart (1821–1891). Pfizer develops and produces medicines and vaccines for immunology , oncology , cardiology , endocrinology , and neurology . The company's largest products by sales are
6847-499: Is associated with infarction, and may be preceded by changes indicating ischemia, such as ST depression or inversion of the T waves. Abnormalities can help differentiate the location of an infarct, based on the leads that are affected by changes. Early STEMIs may be preceded by peaked T waves. Other ECG abnormalities relating to complications of acute myocardial infarctions may also be evident, such as atrial or ventricular fibrillation . Noninvasive imaging plays an important role in
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7014-674: Is based, a jury found Merck not liable, even though the plaintiffs had the NEJM editor testify as to his objections to the VIGOR study. On January 30, 2006, a New Jersey state court dismissed a case brought by Edgar Lee Boyd, who blamed Vioxx for gastrointestinal bleeding that he experienced after taking the drug. The judge said that Boyd failed to prove the drug caused his stomach pain and internal bleeding. In January 2006, Garza v. Merck began trial in Rio Grande City, Texas. The plaintiff,
7181-517: Is blocked, cells lack oxygen , needed to produce ATP in mitochondria . ATP is required for the maintenance of electrolyte balance, particularly through the Na/K ATPase . This leads to an ischemic cascade of intracellular changes, necrosis and apoptosis of affected cells. Cells in the area with the worst blood supply, just below the inner surface of the heart ( endocardium ), are most susceptible to damage. Ischemia first affects this region,
7348-433: Is common and occurs due to reduction in oxygen and blood to the brain. In females, the most common symptoms of myocardial infarction include shortness of breath, weakness, and fatigue . Females are more likely to have unusual or unexplained tiredness and nausea or vomiting as symptoms. Females having heart attacks are more likely to have palpitations, back pain, labored breath, vomiting, and left arm pain than males, although
7515-445: Is effective in the management of premenstrual acne. On March 11, 2009, Scott S. Reuben , former chief of acute pain at Baystate Medical Center, Springfield, Mass., revealed that data for 21 studies he had authored for the efficacy of the drug (along with others such as celecoxib ) had been fabricated, overstating the analgesic effects of the drugs. No evidence has been found that Reuben colluded with Merck in falsifying his data. Reuben
7682-477: Is not the only cause of myocardial infarction, but it may exacerbate or contribute to other causes. A myocardial infarction may result from a heart with a limited blood supply subject to increased oxygen demands, such as in fever, a fast heart rate , hyperthyroidism , too few red blood cells in the bloodstream , or low blood pressure . Damage or failure of procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafts (CABG) may cause
7849-430: Is one of the most common symptoms of acute myocardial infarction and is often described as a sensation of tightness, pressure, or squeezing. Pain radiates most often to the left arm, but may also radiate to the lower jaw, neck, right arm, back, and upper abdomen . The pain most suggestive of an acute MI, with the highest likelihood ratio , is pain radiating to the right arm and shoulder. Similarly, chest pain similar to
8016-479: Is primarily prescribed for major depressive disorder in adult outpatients as well as obsessive-compulsive disorder , panic disorder , and social anxiety disorder in both adults and children. In 2005, the year before it became a generic drug, sales were over $ 3 billion and over 100 million people had been treated with the drug. The patent for Zoloft expired in the summer of 2006. In 1996, Eisai , in partnership with Pfizer, received approval from
8183-414: Is recommended in those with low oxygen levels or shortness of breath. In a STEMI, treatments attempt to restore blood flow to the heart and include percutaneous coronary intervention (PCI), where the arteries are pushed open and may be stented , or thrombolysis , where the blockage is removed using medications. People who have a non-ST elevation myocardial infarction ( NSTEMI ) are often managed with
8350-412: Is still unable to be distributed to the affected myocardium despite clearing the occlusion—also contributes to myocardial injury. Topical endothelial swelling is one of many factors contributing to this phenomenon. A myocardial infarction, according to current consensus, is defined by elevated cardiac biomarkers with a rising or falling trend and at least one of the following: A myocardial infarction
8517-789: Is the dangerous type of Acute coronary syndrome . Other symptoms may include shortness of breath , nausea , feeling faint , a cold sweat , feeling tired , and decreased level of consciousness . About 30% of people have atypical symptoms. Women more often present without chest pain and instead have neck pain, arm pain or feel tired. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure , an irregular heartbeat , cardiogenic shock or cardiac arrest . Most MIs occur due to coronary artery disease . Risk factors include high blood pressure , smoking , diabetes , lack of exercise , obesity , high blood cholesterol , poor diet, and excessive alcohol intake . The complete blockage of
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#17327760857528684-457: Is usually clinically classified as an ST-elevation MI (STEMI) or a non-ST elevation MI (NSTEMI). These are based on ST elevation , a portion of a heartbeat graphically recorded on an ECG . STEMIs make up about 25–40% of myocardial infarctions. A more explicit classification system, based on international consensus in 2012, also exists. This classifies myocardial infarctions into five types: There are many different biomarkers used to determine
8851-445: Is varying evidence about the importance of saturated fat in the development of myocardial infarctions. Eating polyunsaturated fat instead of saturated fats has been shown in studies to be associated with a decreased risk of myocardial infarction, while other studies find little evidence that reducing dietary saturated fat or increasing polyunsaturated fat intake affects heart attack risk. Dietary cholesterol does not appear to have
9018-636: The Wall Street Journal reported that a late-night email, written by an outside public relations specialist and sent to Journal staffers hours before the Expression of Concern was released, predicted that "the rebuke would divert attention to Merck and induce the media to ignore the New England Journal of Medicine ' s own role in aiding Vioxx sales." "Internal emails show the New England Journal' s expression of concern
9185-529: The Delaware General Corporation Law . Due to price declines for penicillin , Pfizer searched for new antibiotics with greater profit potential. Pfizer discovered oxytetracycline in 1950, and this changed the company from a manufacturer of fine chemicals to a research-based pharmaceutical company. Pfizer developed a drug discovery program focused on in vitro synthesis to augment its research in fermentation technology. In 1959,
9352-669: The FDA . The company began Phase II-III testing on 30,000 people in the last week of July 2020 and was slated to be paid $ 1.95 billion for 100 million doses of the vaccine by the US government. In September 2020, Pfizer and BioNTech announced that they had completed talks with the European Commission to provide an initial 200 million vaccine doses to the EU, with the option to supply another 100 million doses at
9519-526: The Food and Drug Administration approved enzalutamide , developed by Pfizer and Astellas Pharma for patients with castration -resistant prostate cancer . In August 2018, Pfizer signed an agreement with BioNTech to conduct joint research and development activities regarding mRNA -based influenza vaccines . In October 2018, effective January 1, 2019, Albert Bourla was promoted to chief executive officer , succeeding Ian Read , his mentor. In July 2019,
9686-446: The Food and Drug Administration for donepezil under the brand Aricept for treatment of Alzheimer's disease ; Pfizer also received approval for Norvasc ( amlodipine ), an antihypertensive drug of the dihydropyridine calcium channel blocker class. In 1997, the company entered into a co-marketing agreement with Warner–Lambert for Lipitor ( atorvastatin ), a statin for the treatment of hypercholesterolemia . Although atorvastatin
9853-479: The Food and Drug Administration for palbociclib (Ibrance) for treatment of certain types of breast cancer . In March 2015, the company announced it would restart its collaboration with Eli Lilly and Company surrounding the Phase III trial of Tanezumab . In May 2015, Pfizer and a Bar-Ilan University laboratory announced a partnership based on the development of medical DNA nanotechnology . In June 2015,
10020-467: The NEJM , though it had disclosed that information publicly in March 2000, eight months before publication. The authors of the study, including the non-Merck authors, responded by claiming that the three additional heart attacks had occurred after the prespecified cutoff date for data collection, thus were appropriately not included. (Using the prespecified cutoff date also meant that an additional stroke in
10187-538: The Pfizer–BioNTech COVID-19 vaccine ($ 11 billion in 2023 revenues), apixaban ($ 6 billion in 2023 revenues), a pneumococcal conjugate vaccine ($ 6 billion in 2023 revenues), palbociclib ($ 4 billion in 2023 revenues), and tafamidis ($ 3 billion in 2023 revenues). In 2023, 46% of the company's revenues came from the United States, 6% came from Japan, and 48% came from other countries. As of 2024,
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#173277608575210354-661: The elderly , in those with diabetes mellitus and after heart transplantation . In people with diabetes, differences in pain threshold , autonomic neuropathy , and psychological factors have been cited as possible explanations for the lack of symptoms. In heart transplantation, the donor heart is not fully innervated by the nervous system of the recipient. The most prominent risk factors for myocardial infarction are older age, actively smoking , high blood pressure , diabetes mellitus , and total cholesterol and high-density lipoprotein levels. Many risk factors of myocardial infarction are shared with coronary artery disease ,
10521-480: The health impact assessment of regional and local plans and policies. Most guidelines recommend combining different preventive strategies. A 2015 Cochrane Review found some evidence that such an approach might help with blood pressure , body mass index and waist circumference . However, there was insufficient evidence to show an effect on mortality or actual cardio-vascular events. Statins , drugs that act to lower blood cholesterol, decrease
10688-507: The pain and inflammation in osteoarthritis , acute pain in adults, rheumatoid arthritis , ankylosing spondylitis , painful menstruation , and juvenile rheumatoid arthritis . SUGEN , a company focused on protein kinase inhibitors, had pioneered the use of ATP-mimetic small molecules to block signal transduction . The SUGEN facility was shut down in 2003 by Pfizer, with the loss of more than 300 jobs, and several programs were transferred to Pfizer. These included sunitinib (Sutent),
10855-522: The single nucleotide polymorphisms that are implicated are within a non-coding region. The majority of these variants are in regions that have not been previously implicated in coronary artery disease. The following genes have an association with MI: PCSK9 , SORT1 , MIA3 , WDR12 , MRAS , PHACTR1 , LPA , TCF21 , MTHFDSL , ZC3HC1 , CDKN2A , 2B , ABO , PDGF0 , APOA5 , MNF1ASM283 , COL4A1 , HHIPC1 , SMAD3 , ADAMTS7 , RAS1 , SMG6 , SNF8 , LDLR , SLC5A3 , MRPS6 , KCNE2 . The risk of having
11022-481: The subendocardial region, and tissue begins to die within 15–30 minutes of loss of blood supply. The dead tissue is surrounded by a zone of potentially reversible ischemia that progresses to become a full-thickness transmural infarct. The initial "wave" of infarction can take place over 3–4 hours. These changes are seen on gross pathology and cannot be predicted by the presence or absence of Q waves on an ECG. The position, size and extent of an infarct depends on
11189-551: The sympathetic nervous system , which occurs in response to pain and, where present, low blood pressure . Loss of consciousness can occur in myocardial infarctions due to inadequate blood flow to the brain and cardiogenic shock , and sudden death , frequently due to the development of ventricular fibrillation . When the brain was without oxygen for too long due to a myocardial infarction, coma and persistent vegetative state can occur. Cardiac arrest, and atypical symptoms such as palpitations , occur more frequently in females,
11356-524: The "Martin Report", was published in February 2006. The report found that Merck's senior management acted in good faith, and that the confusion over the clinical safety of Vioxx was due to the sales team's overzealous behavior. The report that was filed gave a timeline of the events surrounding Vioxx and stated that Merck intended to operate honestly throughout the process. Any mistakes that were made regarding
11523-472: The $ 32 million jury award. Myocardial infarction A myocardial infarction ( MI ), commonly known as a heart attack , occurs when blood flow decreases or stops in one of the coronary arteries of the heart , causing infarction (tissue death) to the heart muscle . The most common symptom is retrosternal chest pain or discomfort that classically radiates to the left shoulder, arm, or jaw. The pain may occasionally feel like heartburn . This
11690-430: The APPROVe (Adenomatous Polyp PRevention On Vioxx) study, a three-year trial with the primary aim of evaluating the efficacy of rofecoxib for the prophylaxis of colorectal polyps . Celecoxib had already been approved for this indication, and it was hoped to add this to the indications for rofecoxib, as well. An additional aim of the study was to further evaluate the cardiovascular safety of rofecoxib. The APPROVe study
11857-606: The Coxib and traditional NSAID Trialists (CNT) Collaborators, respectively, demonstrated that the risk of serious CV events was a dose dependent effect of COX-2 selective and nonselective NSAIDs, with the possible exception of naproxen, and high therapeutic doses of nonselective NSAIDs (e.g. ibuprofen 2400 mg/day, diclofenac 150 mg/day) carried similar CV risk when compared to a combined group of therapeutic and supra-therapeutic doses of COX-2 selective NSAIDs (such as rofecoxib). In 2014, Patrono and Baigent, summarizing all of
12024-425: The FDA approved bosutinib (Bosulif) for chronic myelogenous leukemia (CML), a rare type of leukemia and a blood and bone marrow disease that affects primarily older adults. In November 2012, Pfizer received approval from the Food and Drug Administration for Xeljanz, a tofacitinib , for rheumatoid arthritis and ulcerative colitis . The drug had sales of $ 1.77 billion in 2018, and in January 2019, it
12191-751: The FDA for the continued availability of rofecoxib from 2000 until the recall. Merck responded by issuing a rebuttal of the Jüni et al. meta-analysis that noted that Jüni omitted several studies that showed no increased cardiovascular risk. In 2005, Merck spent $ 21 million US to retain John S. Martin Jr. , a former US District Judge for the Southern District of New York, and colleagues at Debevoise & Plimpton LLP , to investigate Vioxx study results and communications conducted by Merck. The report, which Merck called
12358-407: The FDA that supported previous findings of increased risk of heart attack among rofecoxib users (Grassley, 2004). One FDA analyst estimated that, based upon his mathematical model, Vioxx may have caused between 88,000 and 139,000 heart attacks, 30 to 40 percent of which were probably fatal, in the five years the drug was on the market. Senior FDA officials were quick to note, however, that this estimate
12525-535: The Pfizer CEO Albert Bourla confirmed that the trial results of a fourth dose were pending until March 2022. He said that the firm was setting up a collaboration to develop an anti-COVID pill treatment along with a French company, Novasep . He also said the COVID vaccine was "safe and efficient" for children. In May 2022, reports emerged of patients experiencing "rebound" symptoms after completing
12692-428: The United States. Regulatory authorities worldwide now require warnings about cardiovascular risk of COX-2 inhibitors still on the market. For example, in 2005, EU regulators required the following changes to the product information and/or packaging of all COX-2 inhibitors: Since the withdrawal of Vioxx it has come to light that there may be negative cardiovascular effects with not only other COX-2 inhibitiors, but even
12859-426: The United States. In the developed world, the risk of death in those who have had a STEMI is about 10%. Rates of MI for a given age have decreased globally between 1990 and 2010. In 2011, an MI was one of the top five most expensive conditions during inpatient hospitalizations in the US, with a cost of about $ 11.5 billion for 612,000 hospital stays. Myocardial infarction (MI) refers to tissue death ( infarction ) of
13026-424: The United States. Traditional NSAIDs are avoided in this population due to their effects on platelet aggregation and risk of gastrointestinal ulcers, and high potency opioids are the current standard of care in treating HA. Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the synthesis of prostaglandins responsible for protection of the stomach lining, while COX-2 mediates
13193-534: The VIGOR study were submitted to the US FDA in February 2001. In September 2001, the FDA sent a warning letter to the CEO of Merck, stating, "Your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four- to five-fold increase in myocardial infarctions (MIs) compared to patients on the comparator nonsteroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)." This led to
13360-547: The Ventavia Research Group. Ventavia was hired by Pfizer as a research subcontractor. A regional director (whistleblower) who was employed at Ventavia Research Group has told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer's pivotal phase III trial . The regional director, Brook Jackson, emailed
13527-432: The acute diagnostic algorithm; however, it can confirm a clinical suspicion of Chronic Coronary Syndrome when the patient's history, physical examination (including cardiac examination ) ECG, and cardiac biomarkers suggest coronary artery disease. Echocardiography , an ultrasound scan of the heart, is able to visualize the heart, its size, shape, and any abnormal motion of the heart walls as they beat that may indicate
13694-533: The adequacy of Merck's warnings. The first wrongful death trial, Rogers v. Merck , was scheduled in Alabama in the spring of 2005, but was postponed after Merck argued that the plaintiff had falsified evidence of rofecoxib use. On August 19, 2005, a jury in Texas voted 10–2 to hold Merck liable for the death of Robert Ernst, a 59-year-old man who allegedly died of a rofecoxib-induced heart attack. Merck argued that
13861-409: The affected artery, totality of the blockage, duration of the blockage, the presence of collateral blood vessels , oxygen demand, and success of interventional procedures. Tissue death and myocardial scarring alter the normal conduction pathways of the heart and weaken affected areas. The size and location put a person at risk of abnormal heart rhythms (arrhythmias) or heart block , aneurysm of
14028-423: The article was published, at least two of its authors were aware of critical data on an array of adverse cardiovascular events that were not included in the VIGOR article." These additional data included three additional heart attacks, and raised the relative risk of Vioxx from 4.25-fold to 5-fold. All the additional heart attacks occurred in the group at low risk of heart attack (the "aspirin not indicated" group) and
14195-400: The assumption of debt, making Pfizer the largest pharmaceutical company in the world. The acquisition of Wyeth provided Pfizer with a pneumococcal conjugate vaccine , trademarked Prevnar 13 ; this is used for the prevention of invasive pneumococcal infections. The introduction of the original, 7-valent version of the vaccine, developed by Wyeth in February 2000, led to a 75% reduction in
14362-647: The blood thinner heparin , with the additional use of PCI in those at high risk. In people with blockages of multiple coronary arteries and diabetes, coronary artery bypass surgery (CABG) may be recommended rather than angioplasty . After an MI, lifestyle modifications, along with long-term treatment with aspirin, beta blockers and statins , are typically recommended. Worldwide, about 15.9 million myocardial infarctions occurred in 2015. More than 3 million people had an ST elevation MI, and more than 4 million had an NSTEMI. STEMIs occur about twice as often in men as women. About one million people have an MI each year in
14529-548: The celecoxib PRECISION trial, which showed no difference in CV event rates between the COX-2 selective NSAID celecoxib and the non-selective NSAIDs ibuprofen and naproxen. Due to the findings of its own APPROVe study, Merck publicly announced its voluntary withdrawal of the drug from the market worldwide on September 30, 2004. In addition to its own studies, on September 23, 2004, Merck apparently received information about new research by
14696-924: The combination of torcetrapib and Lipitor (82 deaths during the study) was 60% higher than those taking Lipitor alone (52 deaths during the study). Lipitor alone was not implicated in the results, but Pfizer lost nearly $ 1 billion developing the failed drug and its stock price dropped 11% on the day of the announcement. Between 2007 and 2010, Pfizer spent $ 3.3 million on investigations and legal fees and recovered about $ 5.1 million, and had another $ 5 million of pending recoveries from civil lawsuits against makers of counterfeit prescription drugs. Pfizer has hired customs and narcotics experts worldwide to track down fakes and assemble evidence that can be used to pursue civil suits for trademark infringement . In July 2008, Pfizer announced 275 job cuts at its manufacturing facility in Portage, Michigan . Portage
14863-453: The company acquired Innopharma for $ 225 million, plus up to $ 135 million in milestone payments, in a deal that expanded Pfizer's range of generic and injectable drugs. On January 5, 2015, the company announced it would acquire a controlling interest in Redvax, expanding its vaccine portfolio targeting human cytomegalovirus . In February 2015, the company received approval from
15030-415: The company acquired Nimenrix and Mencevax, meningococcal vaccines , from GlaxoSmithKline for around $ 130 million. In September 2015, Pfizer acquired Hospira for $ 17 billion, including the assumption of debt. Hospira was the largest producer of generic injectable pharmaceuticals in the world. On November 23, 2015, Pfizer and Allergan announced a planned $ 160 billion merger, in
15197-490: The company acquired Therachon for up to $ 810 million, expanding its rare disease portfolio through Therachon's recombinant human fibroblast growth factor receptor 3 compound, aimed at treating conditions such as achondroplasia . Also in July, Pfizer acquired Array Biopharma for $ 10.6 billion, boosting its oncology pipeline. In August 2019, Pfizer merged its consumer health business with that of GlaxoSmithKline, into
15364-683: The company established an animal health division with a 700-acre (2.8 km ) farm and research facility in Terre Haute, Indiana . By the 1950s, Pfizer had established offices in Belgium, Brazil, Canada, Cuba, Mexico, Panama, Puerto Rico, and the United Kingdom. In 1960, the company moved its medical research laboratory operations out of New York City to a new facility in Groton, Connecticut. In 1980, Pfizer launched Feldene ( piroxicam ),
15531-520: The company had not evaluated their COVID-19 vaccine for its ability to reduce transmission of the SARS-CoV-2 virus prior to its release to the general public. Dutch MEP Rob Roos described the admission as "scandalous". CEO Albert Bourla was slated to attend, but withdrew. Roos' statements in turn have been described as "misleading". In November 2021, Pfizer launched a new COVID-19 oral antivirus treatment known as Paxlovid . In January 2022,
15698-461: The company made a $ 40 million bid for the assets of BIND Therapeutics, which was in bankruptcy . The same month, the company acquired Bamboo Therapeutics for $ 645 million, expanding its gene therapy offerings. In September 2016, the company acquired cancer drug-maker Medivation for $ 14 billion. In October 2016, the company licensed the anti- CTLA4 monoclonal antibody, ONC-392, from OncoImmune. In November 2016, Pfizer funded
15865-528: The company ranks 69th on the Fortune 500 . Pfizer was founded in 1849 as "Charles Pfizer & Company" by Charles Pfizer and Charles F. Erhart , two cousins who had immigrated to the United States from Ludwigsburg, Germany . The business produced chemical compounds, and was headquartered on Bartlett Street in Williamsburgh, New York where they produced an antiparasitic called santonin . This
16032-399: The company received approval for Lyrica ( pregabalin ), an anticonvulsant and anxiolytic medication used to treat epilepsy , neuropathic pain , fibromyalgia , restless leg syndrome , and generalized anxiety disorder . The United States patent on Lyrica was challenged by generic manufacturers and was upheld in 2014, extending the expiration date to 2018. In July 2006, Jeff Kindler
16199-457: The countries put sovereign assets as collateral for payments. According to TBIJ, these negotiation tactics resulted in a months long delay in Pfizer reaching a vaccine agreement with one country and a complete failure to reach agreements with two other countries, including Argentina and Brazil. In November 2021, TBMJ published an article after obtaining information from a whistleblower from
16366-477: The currently available data in a review article in Circulation, concluded that with the exception of GI toxicity, neither the efficacy nor the major cardiorenal complications of COX-2 selective NSAIDs appear to be influenced by their level of COX-2 selectivity. They concluded that the CV risk associated with NSAIDs was dependent on dose and duration. This conclusion was further reinforced by the 2016 results of
16533-433: The cutoff date was never mentioned in the article, nor did the authors report that the cutoff for cardiovascular adverse events was before that for gastrointestinal adverse events. The different cutoffs increased the reported benefits of Vioxx (reduced stomach problems) relative to the risks (increased heart attacks). Some scientists have accused the NEJM editorial board of making unfounded accusations. Others have applauded
16700-413: The death was due to cardiac arrhythmia , which had not been shown to be associated with rofecoxib use. The jury awarded Carol Ernst, widow of Robert Ernst, $ 253.4 million in damages. This award was capped at no more than US$ 26.1 million because of punitive damages limits under Texas law. Merck appealed and the verdict was overturned in 2008. On November 3, 2005, Merck won the second case Humeston v. Merck ,
16867-405: The diagnosis and characterisation of myocardial infarction. Tests such as chest X-rays can be used to explore and exclude alternate causes of a person's symptoms. Echocardiography may assist in modifying clinical suspicion of ongoing myocardial infarction in patients that can't be ruled out or ruled in following initial ECG and Troponin testing. Myocardial perfusion imaging has no role in
17034-616: The diagnostic accuracy of troponin testing is improving over time. One high-sensitivity cardiac troponin can rule out a heart attack as long as the ECG is normal. Other tests, such as CK-MB or myoglobin , are discouraged. CK-MB is not as specific as troponins for acute myocardial injury, and may be elevated with past cardiac surgery, inflammation or electrical cardioversion; it rises within 4–8 hours and returns to normal within 2–3 days. Copeptin may be useful to rule out MI rapidly when used along with troponin. Electrocardiograms (ECGs) are
17201-405: The drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, allegedly resulting in between 88,000 and 140,000 cases of serious heart disease. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$ 2.5 billion from Vioxx. In 2005, the FDA issued
17368-573: The drug slowed the onset of Alzheimer's disease. Merck has placed great emphasis on these studies on the grounds that they are relatively large (almost 3000 patients) and compared rofecoxib to a placebo rather than to another pain reliever. These studies found an elevated death rate among rofecoxib patients, although the deaths were not generally heart-related. However, they did not find any elevated cardiovascular risk due to rofecoxib. Before 2004, Merck cited these studies as providing evidence, contrary to VIGOR, of rofecoxib's safety. In 2001, Merck commenced
17535-523: The drug to return to the market despite being found to increase heart risk. The vote in Canada was 12-1, and the Canadian panel noted that the cardiovascular risks from rofecoxib seemed to be no worse than those from ibuprofen —though the panel stated that further study was needed for all NSAIDs to fully understand their risk profiles. Notwithstanding these recommendations, Merck has not returned rofecoxib to
17702-567: The drug's risk. The first federal trial on rofecoxib, Plunkett v. Merck , began on November 29, 2005, in Houston . The trial ended on December 12, 2005, when Judge Eldon E. Fallon of U.S. District Court declared a mistrial because of a hung jury with an eight to one majority, favoring the defense. Upon retrial in February 2006 in New Orleans , where the Vioxx multidistrict litigation (MDL)
17869-587: The editorial. Renowned research cardiologist Eric Topol , a prominent Merck critic, accused Merck of "manipulation of data" and said "I think now the scientific misconduct trial is really fully backed up". Phil Fontanarosa, executive editor of the prestigious Journal of the American Medical Association , welcomed the editorial, saying "this is another in the long list of recent examples that have generated real concerns about trust and confidence in industry-sponsored studies". On May 15, 2006,
18036-538: The editors noted that the omission "resulted in the misleading conclusion that there was a difference in the risk of myocardial infarction between the aspirin indicated and aspirin not indicated groups." The relative risk for myocardial infarctions among the aspirin not indicated patients increased from 2.25 to 3 (although it remained statistically insignificant). The editors also noted a statistically significant (two-fold) increase in risk for serious thromboembolic events for this group, an outcome that Merck had not reported in
18203-505: The efficacy and adverse effect profiles of rofecoxib and naproxen . The therapeutic recommended dosages were 12.5, 25, and 50 mg with an approximate bioavailability of 93%. Rofecoxib crossed the placenta and blood–brain barrier, and took 1–3 hours to reach peak plasma concentration with an effective half-life (based on steady-state levels) around 17 hours. The metabolic products are cis-dihydro and trans-dihydro derivatives of rofecoxib which are primarily excreted through urine. Rofecoxib
18370-414: The elderly, those with diabetes, in people who have just had surgery, and in critically ill patients. "Silent" myocardial infarctions can happen without any symptoms at all. These cases can be discovered later on electrocardiograms , using blood enzyme tests, or at autopsy after a person has died. Such silent myocardial infarctions represent between 22 and 64% of all infarctions, and are more common in
18537-404: The first 18 months of the APPROVe study did not show an increased relative risk of adverse cardiovascular events. Moreover, overall and cardiovascular mortality rates were similar between the rofecoxib and placebo populations. In summary, the APPROVe study suggested that long-term use of rofecoxib resulted in nearly twice the risk of suffering a heart attack or stroke compared to patients receiving
18704-563: The first companies to develop and test a working vaccine for COVID-19. Over the following month and a half, regulators in various countries approved Pfizer's vaccine for emergency use. In February 2021, after a year long investigation relying on unnamed officials, Pfizer was accused by The Bureau of Investigative Journalism (TBIJ) of employing "high-level bullying" against at least two Latin American countries during negotiations to acquire COVID-19 vaccines, including requesting that
18871-637: The greatest support is the Mediterranean diet . Vitamins and mineral supplements are of no proven benefit, and neither are plant stanols or sterols . Public health measures may also act at a population level to reduce the risk of myocardial infarction, for example by reducing unhealthy diets (excessive salt, saturated fat, and trans-fat) including food labeling and marketing requirements as well as requirements for catering and restaurants and stimulating physical activity. This may be part of regional cardiovascular disease prevention programs or through
19038-465: The heart is not contracting at all or so poorly that all vital organs cease to function, thus leading to death. It is also distinct from heart failure , in which the pumping action of the heart is impaired. However, an MI may lead to heart failure. Chest pain that may or may not radiate to other parts of the body is the most typical and significant symptom of myocardial infarction. It might be accompanied by other symptoms such as sweating. Chest pain
19205-410: The heart muscle ( myocardium ) caused by ischemia , the lack of oxygen delivery to myocardial tissue. It is a type of acute coronary syndrome , which describes a sudden or short-term change in symptoms related to blood flow to the heart. Unlike the other type of acute coronary syndrome, unstable angina , a myocardial infarction occurs when there is cell death , which can be estimated by measuring by
19372-441: The heart ventricles , inflammation of the heart wall following infarction, and rupture of the heart wall that can have catastrophic consequences. Injury to the myocardium also occurs during re-perfusion. This might manifest as ventricular arrhythmia. The re-perfusion injury is a consequence of the calcium and sodium uptake from the cardiac cells and the release of oxygen radicals during reperfusion. No-reflow phenomenon—when blood
19539-729: The heart, lungs , gastrointestinal tract , aorta , and other muscles, bones and nerves surrounding the chest. In addition to myocardial infarction, other causes include angina , insufficient blood supply ( ischemia ) to the heart muscles without evidence of cell death, gastroesophageal reflux disease ; pulmonary embolism , tumors of the lungs, pneumonia , rib fracture , costochondritis , heart failure and other musculoskeletal injuries. Rarer severe differential diagnoses include aortic dissection , esophageal rupture , tension pneumothorax , and pericardial effusion causing cardiac tamponade . The chest pain in an MI may mimic heartburn . Causes of sudden-onset breathlessness generally involve
19706-402: The incidence and mortality rates of myocardial infarctions. They are often recommended in those at an elevated risk of cardiovascular diseases. Aspirin has been studied extensively in people considered at increased risk of myocardial infarction. Based on numerous studies in different groups (e.g. people with or without diabetes), there does not appear to be a benefit strong enough to outweigh
19873-512: The incidence of invasive pneumococcal infections among children under age 5 in the United States. Pfizer introduced an improved version of the vaccine in 2010, for which it was granted a patent in India in 2017. Prevnar 13 provides coverage of 13 bacterial variants, expanding beyond the original 7-valent version. By 2012, the rate of invasive infections among children under age 5 had been reduced by an additional 50%. In 2010, Ian Read
20040-593: The introduction, in April 2002, of warnings on Vioxx labeling concerning the increased risk of cardiovascular events (heart attack and stroke). Months after the preliminary version of VIGOR was published in the New England Journal of Medicine in November 2000, the journal editors learned that certain data reported to the FDA were not included in the NEJM article. Several years later, when they were shown
20207-554: The largest pharmaceutical deal ever and the third largest corporate merger in history. The proposed transaction contemplated that the merged company maintain Allergan's Republic of Ireland domicile, resulting in the new company being subject to corporation tax at the relatively low rate of 12.5%. The deal was to constitute a reverse merger , whereby Allergan acquired Pfizer, with the new company then changing its name to "Pfizer, plc". On April 6, 2016, Pfizer and Allergan terminated
20374-414: The least COX-2 selective, and rofecoxib (Vioxx), valdecoxib (Bextra), and etoricoxib (Arcoxia), being highly COX-2 selective. At the time of its withdrawal, rofecoxib was the only coxib approved in the United States with clinical evidence of its superior gastrointestinal adverse effect profile over conventional NSAIDs. This was largely based on the VIGOR (Vioxx GI Outcomes Research) study, which compared
20541-666: The lungs or heart – including pulmonary edema , pneumonia, allergic reactions and asthma , and pulmonary embolus, acute respiratory distress syndrome and metabolic acidosis . There are many different causes of fatigue, and myocardial infarction is not a common cause. There is a large crossover between the lifestyle and activity recommendations to prevent a myocardial infarction, and those that may be adopted as secondary prevention after an initial myocardial infarction, because of shared risk factors and an aim to reduce atherosclerosis affecting heart vessels. The influenza vaccine also appear to protect against myocardial infarction with
20708-470: The majority of other NSAIDs. It is only with the recent development of drugs like Vioxx that drug companies have carried out the kind of well executed trials that could establish such effects and these sort of trials have never been carried out in older "trusted" NSAIDs such as ibuprofen , diclofenac and others. The possible exceptions may be aspirin and naproxen due to their anti-platelet aggregation properties. Analyses in 2011 and 2013 by McGettigan and
20875-697: The market. Following the 2005 FDA Advisory Committee, the FDA issued a memo concluding that data from large long-term controlled clinical trials do not clearly demonstrate that COX-2 selective agents (including rofecoxib) have a greater risk of serious cardiovascular events than non-selective NSAIDs. In 2015, the FDA reinforced this conclusion, stating that the available data support a dose and duration dependent class effect of an increased risk of serious adverse cardiovascular events for COX-2 selective and non-selective NSAIDs. By March 2006, there were over 10,000 cases and 190 class actions filed against Merck over adverse cardiovascular events associated with rofecoxib and
21042-646: The merger agreement after the Obama administration and the United States Department of the Treasury introduced new laws intended to limit corporate inversions (the extent to which companies could move their headquarters overseas in order to reduce the amount of taxes they pay). In June 2016, the company acquired Anacor Pharmaceuticals for $ 5.2 billion, expanding its portfolio in both inflammation and immunology drugs areas. In August 2016,
21209-463: The mishandling of clinical trial results and withholding of information were described as the result of oversight, not malicious behavior. The report did conclude that the Merck's marketing team exaggerated the safety of Vioxx and replaced truthful information with sales tactics. Merck was satisfied with the findings of the report it had commissioned, and promised to consider the recommendations. The report
21376-610: The myocardial infarction are coronary spasm or coronary artery dissection . The most common cause of a myocardial infarction is the rupture of an atherosclerotic plaque on an artery supplying heart muscle. Plaques can become unstable, rupture, and additionally promote the formation of a blood clot that blocks the artery; this can occur in minutes. Blockage of an artery can lead to tissue death in tissue being supplied by that artery. Atherosclerotic plaques are often present for decades before they result in symptoms. The gradual buildup of cholesterol and fibrous tissue in plaques in
21543-453: The naproxen population was not reported.) Furthermore, they said that the additional data did not qualitatively change any of the conclusions of the study, and the results of the full analyses were disclosed to the FDA and reflected on the Vioxx warning label. They further noted that all of the data in the "omitted" table were printed in the text of the article. The authors stood by the original article. NEJM stood by its editorial, noting that
21710-434: The now-demolished 295 Washington Avenue) and Erhart (at 280 Washington Avenue) established their main residences in the nearby Clinton Hill district, known for its concentration of Gilded Age wealth. In 1881, Pfizer moved its administrative headquarters to 81 Maiden Lane in Manhattan , presaging the company's expansion to Chicago, Illinois a year later. By 1906 sales exceeded $ 3 million. World War I caused
21877-409: The other approved COX-2 selective NSAIDs available at the time (i.e., celecoxib, and valdecoxib), rofecoxib was associated with an increased risk of serious adverse cardiovascular events compared to placebo. They also noted that the available data did not permit a rank ordering of these drugs with regard to cardiovascular risk. Only Celebrex (generic name is celecoxib) is still available for purchase in
22044-419: The physician confirm a person is at high risk for Chronic Coronary Syndrome before conducting diagnostic non-invasive imaging tests to make a diagnosis, as such tests are unlikely to change management and result in increased costs. Patients who have a normal ECG and who are able to exercise, for example, most likely do not merit routine imaging. There are many causes of chest pain , which can originate from
22211-471: The plaque and act to stabilize it. A stable plaque may have a thick fibrous cap with calcification . If there is ongoing inflammation, the cap may be thin or ulcerate. Exposed to the pressure associated with blood flow, plaques, especially those with a thin lining, may rupture and trigger the formation of a blood clot (thrombus). The cholesterol crystals have been associated with plaque rupture through mechanical injury and inflammation. Atherosclerotic disease
22378-427: The potential for cardiovascular risk in 1999and it was argued that Merck had manipulated their EKG tests one week after the external review board provided their consultation to specifically exclude high risk factors from the trial subjects to avoid finding effect then predated the changes to their trials to almost three months earlier. In 2000 and 2001, Merck conducted several studies of rofecoxib aimed at determining if
22545-487: The presence of cardiac muscle damage. Troponins , measured through a blood test, are considered to be the best, and are preferred because they have greater sensitivity and specificity for measuring injury to the heart muscle than other tests. A rise in troponin occurs within 2–3 hours of injury to the heart muscle, and peaks within 1–2 days. The level of the troponin, as well as a change over time, are useful in measuring and diagnosing or excluding myocardial infarctions, and
22712-512: The primary cause of myocardial infarction, with other risk factors including male sex, low levels of physical activity, a past family history , obesity , and alcohol use . Risk factors for myocardial disease are often included in risk factor stratification scores, such as the Framingham Risk Score . At any given age, men are more at risk than women for the development of cardiovascular disease. High levels of blood cholesterol
22879-476: The quick release was due to the imminent presentation of his deposition testimony, which he feared would be misinterpreted in the media. He had earlier denied any relationship between the timing of the editorial and the trial. Although his testimony was not actually used in the December trial, Curfman had testified well before the publication of the editorial. The editors charged that "more than four months before
23046-516: The refurbishment of apartment buildings for the homeless and the establishment of a charter school . In 1972, Edmund T. Pratt Jr. became chief executive officer of the company, succeeding John Powers, Jr. In 1981, the company received approval for Diflucan ( fluconazole ), the first oral treatment for severe fungal infections including candidiasis , blastomycosis , coccidiodomycosis , cryptococcosis , histoplasmosis , dermatophytosis , and pityriasis versicolor . In 1986, Pfizer acquired
23213-460: The risk of excessive bleeding. Nevertheless, many clinical practice guidelines continue to recommend aspirin for primary prevention, and some researchers feel that those with very high cardiovascular risk but low risk of bleeding should continue to receive aspirin. Pfizer 40°45′01″N 73°58′21″W / 40.75028°N 73.97250°W / 40.75028; -73.97250 Pfizer Inc. ( / ˈ f aɪ z ər / FY -zər )
23380-486: The risk of myocardial infarction, although there is not universal agreement. Dietary modifications are recommended by some national authorities, with recommendations including increasing the intake of wholegrain starch, reducing sugar intake (particularly of refined sugar), consuming five portions of fruit and vegetables daily, consuming two or more portions of fish per week, and consuming 4–5 portions of unsalted nuts , seeds , or legumes per week. The dietary pattern with
23547-477: The smaller number was not statistically significant, and relative risk compared to other populations was not statistically significant. (Graham, 2005). Furthermore, a more recent meta-study of 114 randomized trials with a total of 116,000+ participants, published in JAMA, showed that Vioxx uniquely increased risk of renal (kidney) disease, and heart arrhythmia. In 2005, the FDA issued a memo concluding that along with
23714-399: The start of daylight saving time . Women who use combined oral contraceptive pills have a modestly increased risk of myocardial infarction, especially in the presence of other risk factors. The use of non-steroidal anti inflammatory drugs (NSAIDs), even for as short as a week, increases risk. Endometriosis in women under the age of 40 is an identified risk factor. Air pollution
23881-400: The studies showing these differences had high variability. Females are less likely to report chest pain during a heart attack and more likely to report nausea, jaw pain, neck pain, cough, and fatigue, although these findings are inconsistent across studies. Females with heart attacks also had more indigestion, dizziness , loss of appetite , and loss of consciousness. Shortness of breath is
24048-451: The synthesis of prostaglandins responsible for pain and inflammation. By creating "selective" NSAIDs that inhibit COX-2, but not COX-1, the same pain relief as traditional NSAIDs is offered, but with greatly reduced risk of fatal or debilitating peptic ulcers. Rofecoxib is a selective COX-2 inhibitor , or "coxib". Though the class of coxibs includes several agents, degrees of COX-2 selectivity vary among them, with celecoxib (Celebrex) being
24215-445: The three additional heart attacks, rather than a blank table that contained no statistical information; "the New England Journal says it didn't attempt to have these mistakes corrected." Investigations revealed that Merck had several years worth of information suggesting an elevated risk of cardiac events, and Vice President Edward Scolnick took much of the blame for the suppression of this information. The FDA reviewers were aware of
24382-436: The time, the second-largest pharmaceutical company worldwide. In 2003, Pfizer merged with Pharmacia , and in the process acquired Searle and SUGEN . Searle had developed Flagyl ( metronidazole ), a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa . Searle also developed celecoxib (Celebrex) a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID) used to treat
24549-904: The use of a vaccine passport mobile app developed by CANImmunize in order to record and track status of COVID-19 vaccination. As the scale of the COVID-19 pandemic became apparent, Pfizer partnered with BioNTech to study and develop COVID-19 mRNA vaccine candidates. Unlike many of its competitors, Pfizer took no initial research funds from the United States' Operation Warp Speed vaccine development program, instead choosing to invest roughly $ 2 billion of its own funds. Pfizer CEO Albert Bourla has said that he declined money from Operation Warp Speed to avoid government intervention, stating later that "when you get money from someone that always comes with strings. They want to see how we are going to progress, what type of moves you are going to do. They want reports. And also, I wanted to keep Pfizer out of politics, by
24716-478: The vaccine". Science-Based Medicine emphasized that Ventavia oversaw just three of the 153 clinical sites involved with Pfizer's trial and "a small fraction (~1,000 by the time the whistleblower was fired) of the trial's over ~44,000 subjects." On 10 October 2022, during a session of the European Parliament 's Special Committee on the COVID-19 Pandemic, Pfizer executive Janine Small testified that
24883-529: The wall of the coronary arteries or other arteries, typically over decades, is termed atherosclerosis . Atherosclerosis is characterized by progressive inflammation of the walls of the arteries. Inflammatory cells, particularly macrophages , move into affected arterial walls. Over time, they become laden with cholesterol products, particularly LDL , and become foam cells . A cholesterol core forms as foam cells die. In response to growth factors secreted by macrophages, smooth muscle and other cells move into
25050-417: The way." In May 2020, Pfizer began testing four different COVID-19 vaccine variations using lipid nanoparticle technology provided by Canadian biotechnology company Acuitas Therapeutics . Vaccines were injected into the first human participants in the U.S. in early May. In July 2020, Pfizer and BioNTech announced that two of the partners' four mRNA vaccine candidates had won fast track designation from
25217-516: The worldwide rights to Zithromax ( azithromycin ), a macrolide antibiotic that is recommended by the Infectious Disease Society of America as a first line treatment for certain cases of community-acquired pneumonia, from Pliva . In 1989, Pfizer scientists Peter Dunn and Albert Wood created Viagra ( sildenafil ) for treating high blood pressure and angina , a chest pain associated with coronary artery disease . In 1991, it
25384-563: Was a relatively small study and only the last result was statistically significant, critics have charged that this early finding should have prompted Merck to quickly conduct larger studies of rofecoxib's cardiovascular safety. Merck notes that it had already begun VIGOR at the time Study 090 was completed. Although VIGOR was primarily designed to demonstrate new uses for rofecoxib, it also collected data on adverse cardiovascular outcomes. Several very large observational studies have also found elevated risk of heart attack from rofecoxib. For example,
25551-694: Was also a former paid spokesperson for the drug company Pfizer (which owns the intellectual property rights for marketing celecoxib in the United States). The retracted studies were not submitted to either the FDA or the European Union's regulatory agencies prior to the drug's approval. Drug manufacturer Merck had no comment on the disclosure. In addition to the reduced incidence of gastric ulceration, rofecoxib exhibits no effect on bleeding time or platelet aggregation, even at supratherapeutic doses. Aside from these features, rofecoxib exhibits
25718-633: Was an immediate success, although it was production of citric acid that led to Pfizer's growth in the 1880s. Pfizer continued to buy property in the area (by now the Williamsburg district of the city of Brooklyn, New York and beginning in 1898, the City of Greater New York ) to expand its lab and factory, retaining offices on Flushing Avenue until the 1960s; the Brooklyn plant ultimately closed in 2009. Following their success with citric acid, Pfizer (at
25885-505: Was approved by the FDA to treat osteoarthritis , rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea . When it was marketed, it gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. A 2003 placebo-controlled, small, short-term study in India of 80 women with premenstrual acne vulgaris , were given rofecoxib or placebo for two cycles of 10 days suggest that "rofecoxib
26052-437: Was based solely on a mathematical model, and must be interpreted with caution. On November 5, 2004, the medical journal The Lancet published a meta-analysis of the available studies on the safety of rofecoxib (Jüni et al. , 2004). The authors concluded that, owing to the known cardiovascular risk, rofecoxib should have been withdrawn several years earlier. The Lancet published an editorial which condemned both Merck and
26219-623: Was by the patients at higher risk of heart attack, i.e. those meeting the criteria for low-dose aspirin prophylaxis of secondary cardiovascular events (previous myocardial infarction, angina, cerebrovascular accident , transient ischemic attack , or coronary artery bypass ). Merck's scientists interpreted the finding as a protective effect of naproxen, telling the FDA that the difference in heart attacks "is primarily due to" this protective effect. The Martin Report excused senior management by stating they believed they were victims of Pfizer's alleged manipulation of test results to promote their product as
26386-452: Was criticised in the press as self-serving. Merck insisted that the report was independent and Merck "had no effect at all on the findings and the conclusions". Merck hoped that the report would improve public perception of Merck. In 2005, advisory panels in both the US and Canada encouraged the return of rofecoxib to the market, stating that Rofecoxib's benefits outweighed the risks for some patients. The FDA advisory panel voted 17-15 to allow
26553-748: Was launched by the Bill & Melinda Gates Foundation in partnership with Mastercard and Wellcome Trust , with additional funding announced shortly after from Chan Zuckerberg Initiative , UK Foreign, Commonwealth and Development Office and Madonna . The following month, the Foundation for the National Institutes of Health announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop
26720-434: Was named chief executive officer of the company, replacing Henry McKinnell . On December 3, 2006, Pfizer ceased development of torcetrapib , a drug that increases production of HDL , which reduces LDL thought to be correlated to heart disease. During a Phase III clinical trial involving 15,000 patients, more deaths than expected occurred in the group that took the medicine, and the mortality rate of patients taking
26887-523: Was named chief executive officer of the company. In February 2011, Pfizer announced the closure of its UK research and development facility (formerly also a manufacturing plant) in Sandwich, Kent , which at the time employed 2,400 people. In March 2011, Pfizer acquired King Pharmaceuticals for $ 3.6 billion in cash. King produced emergency injectables such as the EpiPen . On September 4, 2012,
27054-418: Was patented in the United Kingdom as a heart medication. Early trials for the medication showed that it did not work for the treatment of heart disease, but volunteers in the clinical trials had increased erections several days after taking the drug. It was patented in the United States in 1996 and received approval by the Food and Drug Administration in March 1998. In December 1998, Pfizer hired Bob Dole as
27221-602: Was previously the world headquarters of Upjohn Company , which had been acquired as part of Pharmacia. In June 2000, Pfizer acquired Warner-Lambert outright for $ 116 billion. To satisfy conditions imposed by antitrust regulators at the Federal Trade Commission , Pfizer sold off or transferred stakes in several minor products, including RID (a shampoo for treatment of head lice , sold to Bayer ) and Warner-Lambert's antidepressant Celexa (which competes with Zoloft). The acquisition created what was, at
27388-402: Was terminated early when the preliminary data from the study showed an increased relative risk of adverse thrombotic cardiovascular events (including heart attack and stroke), beginning after 18 months of rofecoxib therapy. In patients taking rofecoxib, versus placebo , the relative risk of these events was 1.92 (rofecoxib 1.50 events vs placebo 0.78 events per 100 patient years). The results from
27555-537: Was the fifth statin to be developed, clinical trials showed that atorvastatin caused a more dramatic reduction in low-density lipoprotein pattern C (LDL-C) than the other statin drugs. Upon its patent expiration in 2011, Lipitor was the best-selling drug ever, with approximately $ 125 billion in sales over 14.5 years. In 2001, Henry McKinnell became chief executive officer of the company, replacing William C. Steere, Jr. In 2002, The Bill & Melinda Gates Foundation purchased stock in Pfizer. In 2004,
27722-540: Was the top drug in the United States for direct-to-consumer advertising , passing adalimumab (Humira). On February 1, 2013, Zoetis , the Agriculture Division of Pfizer and later Pfizer Animal Health, became a public company via an initial public offering , raising $ 2.2 billion. Later in 2013, Pfizer completed the corporate spin-off of its remaining stake in Zoetis . In September 2014,
27889-480: Was timed to divert attention from a deposition in which Executive Editor Gregory Curfman made potentially damaging admissions about the journal's handling of the Vioxx study. In the deposition, part of the Vioxx litigation, Dr. Curfman acknowledged that lax editing might have helped the authors make misleading claims in the article." The Journal stated that NEJM ' s "ambiguous" language misled reporters into incorrectly believing that Merck had deleted data regarding
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