122-545: Simvastatin , sold under the brand name Zocor among others, is a statin , a type of lipid-lowering medication . It is used along with exercise, diet, and weight loss to decrease elevated lipid levels . It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth. Common side effects include constipation, headaches, and nausea. Serious side effects may include muscle breakdown , liver problems, and increased blood sugar levels. A lower dose may be needed in people with kidney problems . There
244-556: A generic medication , and is on the World Health Organization's List of Essential Medicines . In 2022, it was the nineteenth most commonly prescribed medication in the United States, with more than 26 million prescriptions. The primary uses of simvastatin are to treat dyslipidemia and to prevent atherosclerosis-related complications such as stroke and heart attacks in those who are at high risk. It
366-743: A medical practitioner 's supervision like ibuprofen . In 2014, the FDA added an Ebola treatment being developed by Canadian pharmaceutical company Tekmira to the Fast Track program , but halted the phase 1 trials in July pending the receipt of more information about how the drug works. This was widely viewed as increasingly important in the face of a major outbreak of the disease in West Africa that began in late March 2014 and ended in June 2016. During
488-460: A "FDA Compliant" or "FDA Acceptable". Medical countermeasures (MCMs) are products such as biologics and pharmaceutical drugs that can protect from or treat the health effects of a chemical, biological, radiological, or nuclear (CBRN) attack. MCMs can also be used for prevention and diagnosis of symptoms associated with CBRN attacks or threats. The FDA runs a program called the "FDA Medical Countermeasures Initiative" (MCMi), with programs funded by
610-431: A 10% 10-year risk of heart disease, as calculated by the 2013 ACC/AHA Pooled Cohort algorithm. Risk factors for coronary heart disease included abnormal lipid levels in the blood , diabetes mellitus , high blood pressure , and smoking . They recommended selective use of low-to-moderate doses statins in the same adults who have a calculated 10-year cardiovascular disease event risk of 7.5–10% or greater. In people over
732-751: A 17% reduced risk of stroke after long-term treatment. A greater benefit is observed with high-intensity statin therapy. They have less effect than the fibrates or niacin in reducing triglycerides and raising HDL-cholesterol ("good cholesterol"). No studies have examined the effect of statins on cognition in patients with prior stroke. However, two large studies (HPS and PROSPER) that included people with vascular diseases reported that simvastatin and pravastatin did not impact cognition. Statins have been studied for improving operative outcomes in cardiac and vascular surgery. Mortality and adverse cardiovascular events were reduced in statin groups. Older adults who receive statin therapy at time of discharge from
854-569: A 2012 review found benefits in both women and men. A 2010 review concluded that treatment without history of cardiovascular disease reduces cardiovascular events in men but not women, and provides no mortality benefit in either sex. Two other meta-analyses published that year, one of which used data obtained exclusively from women, found no mortality benefit in primary prevention. The National Institute for Health and Clinical Excellence (NICE) recommends statin treatment for adults with an estimated 10 year risk of developing cardiovascular disease that
976-425: A REMS program called iPLEDGE . Generic drugs are chemical and therapeutic equivalents of name-brand drugs, normally whose patents have expired. Approved generic drugs should have the same dosage, safety, effectiveness, strength, stability, and quality, as well as route of administration. In general, they are less expensive than their name brand counterparts, are manufactured and marketed by rival companies and, in
1098-704: A case. The FDA has a number of field offices across the United States, in addition to international locations in China, India, Europe, the Middle East, and Latin America. As of 2021, the FDA had responsibility for overseeing $ 2.7 trillion in food, medical, and tobacco products. Some 54% of its budget derives from the federal government, and 46% is covered by industry user fees for FDA services. For example, pharmaceutical firms pay fees to expedite drug reviews. According to Forbes, pharmaceutical firms provide 75% of
1220-527: A company may advertise or promote a drug only for the specific indication or medical use for which it was approved by FDA. Also, an advertisement must contain a "fair balance" between the benefits and the risks (side effects) of a drug. The regulation of drug advertising in the U.S. is divided between the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), based on whether
1342-426: A complaint brought against the FDA by Mylan Laboratories Inc. of Pittsburgh . When its application to manufacture generics were subjected to repeated delays by the FDA, Mylan, convinced that it was being discriminated against, soon began its own private investigation of the agency in 1987. Mylan eventually filed suit against two former FDA employees and four drug-manufacturing companies, charging that corruption within
SECTION 10
#17327869810881464-405: A connection. Lovastatin induces the expression of gene atrogin-1 , which is believed to be responsible in promoting muscle fiber damage. Tendon rupture does not appear to occur. The relationship between statin use and risk of developing diabetes remains unclear and the results of reviews are mixed. Higher doses have a greater effect, but the decrease in cardiovascular disease outweighs
1586-432: A long period of time. The studies are progressively longer, gradually adding more individuals as they progress from stage I to stage III, normally over a period of years, and normally involve drug companies, the government and its laboratories, and often medical schools and hospitals and clinics. However, any exceptions to the aforementioned process are subject to strict review and scrutiny and conditions, and are only given if
1708-693: A more potent HMG-CoA reductase inhibitor from a fermentation product of A. terreus , which was designated MK-733 (later to be named simvastatin). In 1994, publication of the results of the Scandinavian Simvastatin Survival Study (4S) provided the first unequivocal evidence that lowering LDL cholesterol via statin treatment reduces cardiovascular events and overall mortality. A total of 4,444 people with coronary heart disease and blood cholesterol levels from 5.5 to 8.0 mmol/L were randomized to simvastatin treatment or placebo and followed for an average of 5 years. Compared to
1830-591: A net effect of less LDL circulating in blood. Statins, by inhibiting the HMG CoA reductase pathway, inhibit downstream synthesis of isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate . Inhibition of protein prenylation for proteins such as RhoA (and subsequent inhibition of Rho-associated protein kinase ) may be involved, at least partially, in the improvement of endothelial function, modulation of immune function, and other pleiotropic cardiovascular benefits of statins, as well as in
1952-560: A new master plan for this expansion in December 2018, and construction is expected to be completed by 2035, dependent on GSA appropriations. The Office of Regulatory Affairs is considered the agency's "eyes and ears", conducting the vast majority of the FDA's work in the field. Its employees, known as Consumer Safety Officers, or more commonly known simply as investigators, inspect production, warehousing facilities, investigate complaints, illnesses, or outbreaks, and review documentation in
2074-651: A number of Resident Posts, which are FDA remote offices that serve a particular geographic area. ORA also includes the Agency's network of regulatory laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, and radiation-emitting devices. The Office of Criminal Investigations was established in 1991 to investigate criminal cases. To do so, OCI employs approximately 200 Special Agents nationwide who, unlike ORA Investigators, are armed, have badges, and do not focus on technical aspects of
2196-755: A potency similar to rosuvastatin. Food and Drug Administration The United States Food and Drug Administration ( FDA or US FDA ) is a federal agency of the Department of Health and Human Services . The FDA is responsible for protecting and promoting public health through the control and supervision of food safety , tobacco products, caffeine products, dietary supplements , prescription and over-the-counter pharmaceutical drugs (medications), vaccines , biopharmaceuticals , blood transfusions , medical devices , electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products . The FDA's primary focus
2318-453: A prior heart attack, stroke, stable or unstable angina , aortic aneurysm , or other arterial ischemic disease, in the presence of atherosclerosis. They are also advocated for use in people at high risk of developing coronary heart disease. On average, statins can lower LDL cholesterol by 1.8 mmol/L (70 mg/dL), which translates into an estimated 60% decrease in the number of cardiac events (heart attack, sudden cardiac death ) and
2440-498: A role in monitoring safety through influence on ingredients, but they lack legal authority. According to the ACSH, it has reviewed about 1,200 ingredients and has suggested that several hundred be restricted—but there is no standard or systemic method for reviewing chemicals for safety, or a clear definition of what 'safety' even means so that all chemicals get tested on the same basis. However, on December 29, 2022, President Biden signed
2562-523: A satisfied requirement. The FDA does not approve applied coatings used in the food processing industry . There is no review process to approve the composition of nonstick coatings; nor does the FDA inspect or test these materials. Through their governing of processes, however, the FDA does have a set of regulations that cover the formulation, manufacturing, and use of nonstick coatings. Hence, materials like Polytetrafluoroethylene (Teflon) are not and cannot be considered as FDA Approved, but rather, they are
SECTION 20
#17327869810882684-461: A statin. This is known as statin intolerance. A 2021 double-blind multiple crossover randomized controlled trial (RCT) in statin-intolerant patients found that adverse effects, including muscle pain, were similar between atorvastatin and placebo. A smaller double-blind RCT obtained similar results. The results of these studies help explain why statin symptom rates in observational studies are so much higher than in double-blind RCTs and support
2806-440: A substantial amount of research and at least some preliminary human testing has shown that they are believed to be somewhat safe and possibly effective. (See FDA Special Protocol Assessment about Phase III trials.) The FDA's Office of Prescription Drug Promotion (OPDP) has responsibilities that revolve around the review and regulation of prescription drug advertising and promotion. This is achieved through surveillance activities and
2928-472: A warning about the potential for non-serious and reversible cognitive side effects with the medication (memory loss, confusion). In observational studies 10–15% of people who take statins experience muscle problems; in most cases these consist of muscle pain . These rates, which are much higher than those seen in randomized clinical trials have been the topic of extensive debate and discussion. Muscle and other symptoms often cause patients to stop taking
3050-561: A warning to that effect. According to the industry advocacy group, the American Council on Science and Health , though the cosmetic industry is primarily responsible for its own product safety, the FDA can intervene when necessary to protect the public. In general, though, cosmetics do not require pre-market approval or testing. The ACSH says that companies must place a warning note on their products if they have not been tested, and that experts in cosmetic ingredient review also play
3172-401: Is a center of the FDA that regulates food additives and drugs that are given to animals. CVM regulates animal drugs, animal food including pet animal, and animal medical devices. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers. CVM does not regulate vaccines for animals; these are handled by
3294-399: Is a major inhibitor of only lovastatin, simvastatin, and to a lesser degree, atorvastatin) and some other medications (flavonoids (i.e. naringin ) were thought to be responsible). This increases the levels of the statin, increasing the risk of dose-related adverse effects (including myopathy / rhabdomyolysis ). The absolute prohibition of grapefruit juice consumption for users of some statins
3416-651: Is a separate process, and the drug must be approved through an NDA first. A drug that is approved is said to be "safe and effective when used as directed". Very rare, limited exceptions to this multi-step process involving animal testing and controlled clinical trials can be granted out of compassionate use protocols. This was the case during the 2015 Ebola epidemic with the use, by prescription and authorization, of ZMapp and other experimental treatments, and for new drugs that can be used to treat debilitating and/or very rare conditions for which no existing remedies or drugs are satisfactory, or where there has not been an advance in
3538-591: Is an underlying history of cardiovascular disease, it has a significant impact on the effects of statin. This can be used to divide medication usage into broad categories of primary and secondary prevention. For the primary prevention of cardiovascular disease, the United States Preventive Services Task Force (USPSTF) 2016 guidelines recommend statins for those who have at least one risk factor for coronary heart disease , are between 40 and 75 years old, and have at least
3660-422: Is controversial. The U.S. Food and Drug Administration (FDA) notified healthcare professionals of updates to the prescribing information concerning interactions between protease inhibitors and certain statin drugs. Protease inhibitors and statins taken together may increase the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, rhabdomyolysis, can damage
3782-564: Is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C). However, the agency also enforces other laws, notably Section 361 of the Public Health Service Act as well as associated regulations. Much of this regulatory-enforcement work is not directly related to food or drugs but involves other factors like regulating lasers , cellular phones , and condoms . In addition, the FDA takes control of diseases in
Simvastatin - Misplaced Pages Continue
3904-406: Is evidence of harm to the developing baby when taken during pregnancy and it should not be used by those who are breastfeeding . It is in the statin class of medications and works by decreasing the manufacture of cholesterol by the liver. Simvastatin is made from the fungus Aspergillus terreus . It was patented by Merck in 1980, and came into medical use in 1992. Simvastatin is available as
4026-609: Is greater than 10%. Guidelines by the American College of Cardiology and the American Heart Association recommend statin treatment for primary prevention of cardiovascular disease in adults with LDL cholesterol ≥ 190 mg/dL (4.9 mmol/L) or those with diabetes, age 40–75 with LDL-C 70–190 mg/dL (1.8–4.9 mmol/dL); or in those with a 10-year risk of developing heart attack or stroke of 7.5% or more. In this latter group, statin assignment
4148-527: Is lacking as of 2017 . The gene SLCO1B1 ( Solute carrier organic anion transporter family member 1B1 ) codes for an organic anion-transporting polypeptide that is involved in the regulation of the absorption of statins. A common variation in this gene was found in 2008 to significantly increase the risk of myopathy. Records exist of over 250,000 people treated from 1998 to 2001 with the statin drugs atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. The incidence of rhabdomyolysis
4270-745: Is located in the White Oak area of Silver Spring, Maryland . The agency has 223 field offices and 13 laboratories located across the 50 states, the United States Virgin Islands , and Puerto Rico . In 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. FDA headquarters facilities are currently located in Montgomery County and Prince George's County , Maryland. Since 1990,
4392-427: Is on the World Health Organization's List of Essential Medicines with simvastatin being the listed medicine. In 2005, sales were estimated at US$ 18.7 billion in the United States. The best-selling statin is atorvastatin, also known as Lipitor, which in 2003 became the best-selling pharmaceutical in history. The manufacturer Pfizer reported sales of US$ 12.4 billion in 2008. Patient compliance with statin usage
4514-692: Is problematic despite robust evidence of the benefits. Statins are usually used to lower blood cholesterol levels and reduce risk for illnesses related to atherosclerosis, with a varying degree of effect depending on underlying risk factors and history of cardiovascular disease. Clinical practice guidelines generally recommend people start with lifestyle modification through a cholesterol-lowering diet and physical exercise . For those unable to meet their lipid-lowering goals through such methods, statins can be helpful. The medication appears to work equally well regardless of sex, although some sex-related differences in treatment response were described. If there
4636-414: Is recommended to be used as an addition to a low-cholesterol diet. In heart protection studies, simvastatin showed the ability to lower LDL cholesterol by about 1·5 mmol/L, which resulted in substantial reductions in mortality rates. Simvastatin also reduced the numbers of other events like heart attacks, strokes, and revascularizations and MI significantly. The Heart Protection Study evaluated
4758-449: Is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. These include blood and blood products, vaccines, allergenics, cell and tissue-based products, and gene therapy products. New biologics are required to go through a premarket approval process called a Biologics License Application (BLA), similar to that for drugs. The original authority for government regulation of biological products
4880-741: Is the branch of the FDA responsible for the premarket approval of all medical devices , as well as overseeing the manufacturing, performance and safety of these devices. The definition of a medical device is given in the FD&;C Act, and it includes products from the simple toothbrush to complex devices such as implantable neurostimulators . CDRH also oversees the safety performance of non-medical devices that emit certain types of electromagnetic radiation . Examples of CDRH-regulated devices include cellular phones , airport baggage screening equipment , television receivers , microwave ovens , tanning booths , and laser products . CDRH regulatory powers include
5002-702: Is used for a different purpose, or undergoes any substantial change. The most rigorous requirements apply to new molecular entities : drugs that are not based on existing medications. New drugs receive extensive scrutiny before FDA approval in a process called a new drug application (NDA). Under the Presidency of Donald Trump , the agency has worked to make the drug-approval process go faster. Critics, however, argue that FDA standards are not sufficiently rigorous to prevent unsafe or ineffective drugs from getting approval. New drugs are available only by prescription by default. A change to over-the-counter (OTC) status
Simvastatin - Misplaced Pages Continue
5124-451: Is voluntary. While this remains the primary tool of post-market safety surveillance , FDA requirements for post-marketing risk management are increasing. As a condition of approval, a sponsor may be required to conduct additional clinical trials , called Phase IV trials. In some cases, the FDA requires risk management plans called Risk Evaluation and Mitigation Strategies (REMS) for some drugs that require actions to be taken to ensure that
5246-685: The Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), the Center for Biologics Evaluation and Research (CBER) and offices for the Center for Veterinary Medicine (CVM). With the passing of the FDA Reauthorization Act of 2017, the FDA projects a 64% increase in employees to 18,000 over the next 15 years and wants to add approximately 1,600,000 square feet (150,000 square metres) of office and special use space to their existing facilities. The National Capital Planning Commission approved
5368-627: The JUPITER trial showed statins provided benefit in those who had no history of high cholesterol or heart disease, but only in those with elevated high-sensitivity C-reactive protein (hsCRP) levels, an indicator for inflammation. The study has been criticized due to perceived flaws in the study design, although Paul M. Ridker , lead investigator of the JUPITER trial, has responded to these criticisms at length. Click on genes, proteins and metabolites below to link to respective articles. As
5490-512: The LDL receptor or apolipoprotein B genes, both of which are responsible for LDL clearance from the blood. Statins remain a first-line treatment in familial hypercholesterolemia, although other cholesterol-reducing measures may be required. In people with homozygous deficiencies, statins may still prove helpful, albeit at high doses and in combination with other cholesterol-reducing medications. A 2014 meta-analysis found that statins could reduce
5612-593: The Max Planck Institute . This discovery encouraged scientists worldwide to find an effective inhibitor of this enzyme. By 1976, Akira Endo had isolated the first inhibitor, mevastatin , from the fungus Penicillium citrinium while working at Daiichi Sankyo in Japan. In 1979, Hoffman and colleagues isolated lovastatin from a strain of the fungus Aspergillus terreus . While developing and researching lovastatin, Merck scientists synthetically derived
5734-643: The coronavirus pandemic , FDA granted emergency use authorization for personal protective equipment (PPE), in vitro diagnostic equipment, ventilators and other medical devices. On March 18, 2020, FDA inspectors postponed most foreign facility inspections and all domestic routine surveillance facility inspections. In contrast, the USDA's Food Safety and Inspection Service (FSIS) continued inspections of meatpacking plants, which resulted in 145 FSIS field employees who tested positive for COVID-19, and three who died. The Center for Biologics Evaluation and Research
5856-545: The hormone insulin . One way this is thought to occur is by interfering with cholesterol synthesis which is necessary for the production of certain proteins responsible for glucose uptake into cells such as GLUT1 . Several meta-analyses have found no increased risk of cancer, and some meta-analyses have found a reduced risk. Specifically, statins may reduce the risk of esophageal cancer , colorectal cancer , gastric cancer , hepatocellular carcinoma , and possibly prostate cancer . They appear to have no effect on
5978-421: The nucleus and bind to the sterol response elements. The sterol response elements then facilitate increased transcription of various other proteins, most notably, LDL receptor . The LDL receptor is transported to the liver cell membrane and binds to passing LDL and VLDL particles, mediating their uptake into the liver, where the cholesterol is reprocessed into bile salts and other byproducts. This results in
6100-486: The rate-limiting enzyme of the HMG-CoA reductase pathway , the metabolic pathway responsible for the endogenous production of cholesterol . Statins are more effective than other lipid-regulating drugs at lowering LDL -cholesterol concentration, but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of
6222-606: The '2023 Consolidated Budget Act', which includes the 'Cosmetics Regulatory Modernization Act of 2022 (MoCRA)', which is a stricter regulation that is different from the previous regulations. MoCRA requires compliance with matters such as serious adverse event reporting, safety substantiation, additional labeling, record keeping, and Good Manufacturing Practices (GMP). MoCRA also calls on the FDA to grant Mandatory Recall Authority and establish regulations for GMP rules, flavor allergen labeling rules, and testing methods for cosmetics containing talc. The Center for Veterinary Medicine (CVM)
SECTION 50
#17327869810886344-406: The 1990s, accounted for about a third of all prescriptions written in the United States. For a pharmaceutical company to gain approval to produce a generic drug, the FDA requires scientific evidence that the generic drug is interchangeable with or therapeutically equivalent to the originally approved drug. This is called an Abbreviated New Drug Application (ANDA). 80% of prescription drugs sold in
6466-602: The 2015 Cochrane systematic review, atorvastatin showed greater cholesterol-lowering effect in women than in men compared to rosuvastatin. In children, statins are effective at reducing cholesterol levels in those with familial hypercholesterolemia . Their long term safety is, however, unclear. Some recommend that if lifestyle changes are not enough statins should be started at 8 years old. Statins may be less effective in reducing LDL cholesterol in people with familial hypercholesterolemia, especially those with homozygous deficiencies. These people have defects usually in either
6588-574: The Clinical Pharmacogenetics Implementation Consortium has released guidelines regarding the use of rs4149056 genotype in guiding dosing of simvastatin and updated the guideline in 2014. In March 2012, the U.S. Food and Drug Administration (FDA) updated its guidance for statin users to address reports of memory loss, liver damage, increased blood sugar, development of type 2 diabetes , and muscle injury. The new guidance indicates: On 19 March 2010,
6710-511: The FD&C Act. OCI Special Agents often come from other criminal investigations backgrounds, and frequently work closely with the Federal Bureau of Investigation , Assistant Attorney General , and even Interpol . OCI receives cases from a variety of sources—including ORA, local agencies, and the FBI, and works with ORA Investigators to help develop the technical and science-based aspects of
6832-633: The FDA exercises differ from one category to the next. Furthermore, legislation had granted the FDA a variety of means to address violations of standards for a given substance category. Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), the FDA is responsible for ensuring that manufacturers and distributors of dietary supplements and dietary ingredients meet the current requirements. These manufacturers and distributors are not allowed to advertise their products in an adulterated way, and they are responsible for evaluating
6954-724: The FDA has had employees and facilities on 130 acres (53 hectares) of the White Oak Federal Research Center in the White Oak area of Silver Spring, Maryland . In 2001, the General Services Administration (GSA) began new construction on the campus to consolidate the FDA's 25 existing operations in the Washington metropolitan area , its headquarters in Rockville , and several fragmented office buildings. The first building,
7076-651: The FDA issued another statement regarding simvastatin, saying it increases the risk of muscle injury (myopathy) when taken at high doses or at lower doses in combination with other drugs. The highest dose rate causes muscle damage in 610 of every 10,000 people in contrast to a lower dose, which causes muscle damage in eight of 10,000 people. The FDA warning, released again on 8 June 2011, suggested that high-dose "simvastatin should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury" and that it "should not be started in new patients, including patients already taking lower doses of
7198-713: The FDA released a statement regarding new guidelines to help food and drug manufacturers "implement protections against potential attacks on the U.S. food supply". One of the guidelines includes the Intentional Adulteration (IA) rule, which requires strategies and procedures by the food industry to reduce the risk of compromise in facilities and processes that are significantly vulnerable. The FDA also uses tactics of regulatory shaming, mainly through online publication of non-compliance, warning letters, and "shaming lists." Regulation by shaming harnesses firms' sensitivity to reputational damage. For example, in 2018,
7320-594: The FDA's drug review budget Emergency Use Authorization (EUA) is a mechanism that was created to facilitate the availability and use of medical countermeasures, including vaccines and personal protective equipment, during public health emergencies such as the Zika virus epidemic, the Ebola virus epidemic and the COVID-19 pandemic. The programs for safety regulation vary widely by the type of product, its potential risks, and
7442-881: The Food and Drug Administration is governed by various statutes enacted by the United States Congress and interpreted by the FDA. Pursuant to the Federal Food, Drug, and Cosmetic Act and accompanying legislation, the FDA has authority to oversee the quality of substances sold as food in the United States, and to monitor claims made in the labeling of both the composition and the health benefits of foods. The FDA subdivides substances that it regulates as food into various categories—including foods, food additives , added substances (human-made substances that are not intentionally introduced into food, but nevertheless end up in it), and dietary supplements . Dietary supplements or dietary ingredients include vitamins, minerals, herbs, amino acids , and enzymes . Specific standards
SECTION 60
#17327869810887564-647: The Life Sciences Laboratory, was dedicated and opened with 104 employees in December 2003. As of December 2018, the FDA campus has a population of 10,987 employees housed in approximately 3,800,000 square feet (350,000 square metres) of space, divided into ten offices and four laboratory buildings. The campus houses the Office of the Commissioner (OC), the Office of Regulatory Affairs (ORA),
7686-598: The Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study and the Health Protection Study (HPS) demonstrated that simvastatin and pravastatin did not affect cognition for patients with risk factors for, or a history of, vascular diseases. There are reports of reversible cognitive impairment with statins. The U.S. Food and Drug Administration (FDA) package insert on statins includes
7808-488: The United States are generic brands. In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. Charges of corruption in generic drug approval first emerged in 1988 during the course of an extensive congressional investigation into the FDA. The oversight subcommittee of the United States House Energy and Commerce Committee resulted from
7930-510: The United States, health plans may cover the costs of simvastatin 10 mg, 20 mg, and 40 mg for adults aged 40–75 years based on United States Preventive Services Task Force (USPSTF) recommendations. Zocor had an original patent expiry date in December 2005, but was extended by the United States Patent and Trademark Office (USPTO) to expire in June 2006. Simvastatin was initially marketed by Merck & Co under
8052-586: The age of 70, statins decrease the risk of cardiovascular disease but only in those with a history of heavy cholesterol blockage in their arteries. Most evidence suggests that statins are also effective in preventing heart disease in those with high cholesterol but no history of heart disease. A 2013 Cochrane review found a decrease in risk of death and other poor outcomes without any evidence of harm. For every 138 people treated for 5 years, one fewer dies; for every 49 treated, one fewer has an episode of heart disease. A 2011 review reached similar conclusions, and
8174-784: The agency published an online "black list", in which it named dozens of branded drug companies that are supposedly using unlawful or unethical means to attempt to impede competition from generic drug companies. The FDA frequently works with other federal agencies, including the Department of Agriculture , the Drug Enforcement Administration , Customs and Border Protection , and the Consumer Product Safety Commission . They also often work with local and state government agencies in performing regulatory inspections and enforcement actions. The regulation of food and dietary supplements by
8296-445: The antidepressant nefazodone ; the cardiovascular drug gemfibrozil ; the immunosuppressant ciclosporin , or the endometriosis drug danazol . Reduced maximum doses of simvastatin apply for patients taking certain other drugs, including the cardiovascular drugs verapamil , diltiazem , amiodarone , amlodipine , and ranolazine . All statins act by inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase ,
8418-468: The authority to require certain technical reports from the manufacturers or importers of regulated products, to require that radiation-emitting products meet mandatory safety performance standards, to declare regulated products defective, and to order the recall of defective or noncompliant products. CDRH also conducts limited amounts of direct product testing. Clearance requests are required for medical devices that prove they are "substantially equivalent" to
8540-404: The biosynthesis of cholesterol in the early 1950s. In 1956, mevalonic acid was isolated from a yeast extract by Karl Folkers , Carl Hoffman, and others at Merck, while Huff and his associates confirmed that mevalonic acid was an intermediate in cholesterol biosynthesis. In 1959, the HMG-CoA reductase enzyme (a major contributor of internal cholesterol production) was discovered by researchers at
8662-629: The blood due to liver damage . Over 5 years of treatment statins result in 75 cases of diabetes, 7.5 cases of bleeding stroke , and 5 cases of muscle damage per 10,000 people treated. This could be due to the statins inhibiting the enzyme (HMG-CoA reductase), which is necessary to make cholesterol, but also for other processes, such as CoQ 10 production, which is important for muscle function and sugar regulation. Other possible adverse effects include neuropathy , pancreatic and liver dysfunction, and sexual dysfunction . The rate at which such events occur has been widely debated, in part because
8784-581: The brand Bestatin manufactured by Berlin Pharmaceutical Industry Co Ltd and others. Statin Statins (or HMG-CoA reductase inhibitors ) are a class of medications that lower cholesterol . They are prescribed typically to people who are at high risk of cardiovascular disease . Low-density lipoprotein (LDL) carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via
8906-709: The brand name Zocor but is available generically in most countries following the patent expiry. A combination of simvastatin along with ezetimibe is sold under the brand name Vytorin and is jointly marketed by Merck and Schering-Plough . Brand names include Zocor, Zocor Heart Pro, marketed by the pharmaceutical company Merck & Co., Simlup, Simvotin, Simcard (India), Denan (Germany), Liponorm, Sinvacor, Sivastin (Italy), Lipovas (Japan), Lodales (France), Zocord (Austria and Sweden), Zimstat, Simvahexal (Australia), Lipex (Australia and New Zealand), Simvastatin-Teva, Simvacor, Simvaxon, Simovil (Israel), available in Thailand under
9028-478: The case of medical devices, drugs, biological products, and other items where it may be difficult to conduct a physical examination or take a physical sample of the product. The Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. The districts are based roughly on the geographic divisions of the Federal court system . Each district comprises a main district office and
9150-411: The case of muscle cramps or of deterioration in kidney function . Consumption of grapefruit or grapefruit juice inhibits the metabolism of certain statins, and bitter oranges may have a similar effect. Furanocoumarins in grapefruit juice (i.e. bergamottin and dihydroxybergamottin ) inhibit the cytochrome P450 enzyme CYP3A4 , which is involved in the metabolism of most statins (however, it
9272-511: The contexts varying from household pets to human sperm donated for use in assisted reproduction . The FDA is led by the commissioner of Food and Drugs , appointed by the President with the advice and consent of the Senate . The commissioner reports to the secretary of health and human services . Robert Califf is the current commissioner as of February 17, 2022. The FDA's headquarters
9394-433: The drug chronically. Serious allergic reactions to simvastatin are rare. A type of DNA variant known as a single nucleotide polymorphism (SNP) may help predict individuals prone to developing myopathy when taking simvastatin; a study ultimately including 32,000 patients concluded the carriers of one or two risk alleles of a particular SNP, rs4149056, were at a five-fold or 16-fold increased risk, respectively. In 2012,
9516-469: The drug in question is a prescription drug or an over-the-counter (OTC) drug. The FDA oversees the advertising of prescription drugs, while the FTC regulates the advertising of OTC drugs. The term off-label refers to the practice of prescribing a drug for a different purpose than what the FDA approved. Due to this approval requirement, manufacturers were prohibited from advertising COVID-19 vaccines during
9638-416: The drug is used safely. For example, thalidomide can cause birth defects, but has uses that outweigh the risks if men and women taking the drugs do not conceive a child; a REMS program for thalidomide mandates an auditable process to ensure that people taking the drug take action to avoid pregnancy; many opioid drugs have REMS programs to avoid addiction and diversion of drugs. The drug isotretinoin has
9760-563: The drug." Simvastatin has important interactions with grapefruit juice and other drugs, including some that are commonly used for the treatment of cardiovascular disease. These interactions are clinically important because increasing simvastatin serum levels above those normally provided by the maximum recommended dose increases the risk of muscle damage, including the otherwise rare and potentially fatal side effect of rhabdomyolysis . Consuming large amounts of grapefruit juice increases serum levels of simvastatin by up to three-fold, increasing
9882-696: The early 1990s, the U.S. Securities and Exchange Commission filed securities fraud charges against the Bolar Pharmaceutical Company, a major generic manufacturer based in Long Island, New York. Over-the-counter (OTC) are drugs like aspirin that do not require a doctor's prescription. The FDA has a list of approximately 800 such approved ingredients that are combined in various ways to create more than 100,000 OTC drug products. Many OTC drug ingredients had been previously approved prescription drugs now deemed safe enough for use without
10004-450: The effects of simvastatin in people with risk factors including existing cardiovascular disease, diabetes, or stroke, but having relatively low LDL cholesterol. In this trial, which lasted 5.4 years, overall mortality was reduced by 13% and cardiovascular mortality was reduced by 18%. People receiving simvastatin experienced 38% fewer nonfatal heart attacks and 25% fewer strokes. Statins in general have been proposed as beneficial in reducing
10126-460: The enzyme HMG-CoA reductase , which plays a central role in the production of cholesterol. High cholesterol levels have been associated with cardiovascular disease. There are various forms of statins, some of which include atorvastatin , fluvastatin , lovastatin , pitavastatin , pravastatin , rosuvastatin , and simvastatin . Combination preparations of a statin and another agent, such as ezetimibe/simvastatin , are also available. The class
10248-503: The fact that a number of other drugs that lower LDL have not shown the same cardiovascular risk benefits in studies as statins, and may also account for some of the benefits seen in cancer reduction with statins. In addition, the inhibitory effect on protein prenylation may also be involved in a number of unwanted side effects associated with statins, including muscle pain (myopathy) and elevated blood sugar (diabetes). As noted above, statins exhibit action beyond lipid-lowering activity in
10370-648: The federal agency resulted in racketeering and in violations of antitrust law . "The order in which new generic drugs were approved was set by the FDA employees even before drug manufacturers submitted applications" and, according to Mylan, this illegal procedure was followed to give preferential treatment to certain companies. During the summer of 1989, three FDA officials (Charles Y. Chang, David J. Brancato, Walter Kletch) pleaded guilty to criminal charges of accepting bribes from generic drugs makers, and two companies ( Par Pharmaceutical and its subsidiary Quad Pharmaceuticals) pleaded guilty to giving bribes. Furthermore, it
10492-436: The federal government. It helps support "partner" agencies and organisations prepare for public health emergencies that could require MCMs. The Center for Drug Evaluation and Research uses different requirements for the three main drug product types: new drugs, generic drugs, and over-the-counter drugs. A drug is considered "new" if it is made by a different manufacturer, uses different excipients or inactive ingredients,
10614-490: The guidelines. The European Society of Cardiology and the European Atherosclerosis Society recommend the use of statins for primary prevention, depending on baseline estimated cardiovascular score and LDL thresholds. Statins are effective in decreasing mortality in people with pre-existing cardiovascular disease . Pre-existing disease can have many manifestations. Defining illnesses include
10736-683: The hidden benefits of statin use. The statins are divided into two groups: fermentation -derived and synthetic . Some specific types are listed in the table below. Note that the associated brand names may vary between countries. LDL-lowering potency varies between agents. Cerivastatin is the most potent (withdrawn from the market in August 2001 due to risk of serious rhabdomyolysis), followed by (in order of decreasing potency) rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin. The relative potency of pitavastatin has not yet been fully established, but preliminary studies indicate
10858-436: The hospital after an inpatient stay have been studied. People with cardiac ischemia not previously on statins at the time of admission have a lower risk of major cardiac adverse events and hospital readmission two years post-hospitalization. All statins appear effective regardless of potency or degree of cholesterol reduction. Simvastatin and pravastatin appear to have a reduced incidence of side-effects. According to
10980-597: The incidence of major cardiac events by up to 20% and are not that likely to increase the risk of stroke or kidney failure. Asthma Statins have been identified as having a possible adjunct role in the treatment of asthma through anti-inflammatory pathways. There is low quality evidence for the use of statins in treating asthma, however further research is required to determine the effectiveness and safety of this therapy in those with asthma. The most important adverse side effects are muscle problems, an increased risk of diabetes mellitus , and increased liver enzymes in
11102-703: The infant's lipid metabolism. High doses of simvastatin are also contraindicated with the widely used antihypertensive amlodipine . A lower dose is also recommended in people taking the calcium channel blockers, verapamil and diltiazem , as well as those taking amiodarone . Common side effects (>1% incidence) may include indigestion and eczema. There is evidence to suggest that rare side effects such as joint pain, memory loss, and muscle cramps are more likely to occur in patients who take higher doses of simvastatin. Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving
11224-423: The initial cholesterol concentration. This is a major piece of evidence that statins work in another way than the lowering of cholesterol (called pleiotropic effects). Simvastatin is an effective serum lipid -lowering drug that can decrease low density lipoprotein (LDL) levels by up to 50%. Simvastatin had been shown to interact with lipid-lowering transcription factor PPAR-alpha and that interaction might control
11346-555: The issuance of enforcement letters to pharmaceutical manufacturers. Advertising and promotion for over-the-counter drugs is regulated by the Federal Trade Commission . The FDA also implements regulatory oversight through engagement with third-party enforcer-firms. It expects pharmaceutical companies to ensure that third-party suppliers and labs comply with the agency's health and safety guidelines . The drug advertising regulation contains two broad requirements: (1)
11468-422: The kidneys and lead to kidney failure, which can be fatal. Studies have found that the use of statins may protect against getting osteoporosis and fractures or may induce osteoporosis and fractures. A cross-sectional retrospective analysis of the entire Austrian population found that the risk of getting osteoporosis is dependent on the dose used. Statins act by competitively inhibiting HMG-CoA reductase ,
11590-604: The mechanisms described by the lipid hypothesis . As lipid-lowering medications , statins are effective in lowering LDL cholesterol; they are widely used for primary prevention in people at high risk of cardiovascular disease, as well as in secondary prevention for those who have developed cardiovascular disease. Side effects of statins include muscle pain , increased risk of diabetes , and abnormal blood levels of certain liver enzymes . Additionally, they have rare but severe adverse effects, particularly muscle damage, and very rarely rhabdomyolysis . They act by inhibiting
11712-424: The neurotrophic action of the drug. The drug is in the form of an inactive lactone that is hydrolyzed after ingestion to produce the active β-hydroxyacid form. Simvastatin is primarily metabolized by CYP3A4 yielding products which are also active HMG-CoA reductase inhibitors. The development of simvastatin was closely linked with lovastatin . Biochemist Jesse Huff and his colleagues at Merck began researching
11834-1164: The notion that the difference results from the nocebo effect ; that the symptoms are caused by expectations of harm. Media reporting on statins is often negative, and patient leaflets inform patients that rare but potentially serious muscle problems can occur during statin treatment. These create expectations of harm. Nocebo symptoms are real and bothersome and are a major barrier to treatment. Because of this, many people stop taking statins, which have been proven in numerous large-scale RCTs to reduce heart attacks, stroke, and deaths – as long as people continue to take them. Serious muscle problems such as rhabdomyolysis (destruction of muscle cells) and statin-associated autoimmune myopathy occur in less than 0.1% of treated people. Rhabdomyolysis can in turn result in life-threatening kidney injury . The risk of statin-induced rhabdomyolysis increases with older age, use of interacting medications such as fibrates , and hypothyroidism . Coenzyme Q10 (ubiquinone) levels are decreased in statin use; CoQ10 supplements are sometimes used to treat statin-associated myopathy, though evidence of their efficacy
11956-533: The period in which they had only been approved under Emergency Use Authorization . After NDA approval, the sponsor must then review and report to the FDA every single patient adverse drug experience it learns of. They must report unexpected serious and fatal adverse drug events within 15 days, and other events on a quarterly basis. The FDA also receives directly adverse drug event reports through its MedWatch program. These reports are called "spontaneous reports" because reporting by consumers and health professionals
12078-474: The placebo group, those treated with simvastatin experienced a 30% decrease in overall mortality, a 42% reduction in coronary death, a 34% reduction in major coronary events, and a 37% reduction in revascularization procedures. Prior to losing US patent protection, simvastatin was Merck & Co.'s largest-selling drug. Under provisions of the Patient Protection and Affordable Care Act (PPACA) in
12200-422: The predicate devices already on the market. Approved requests are for items that are new or substantially different and need to demonstrate "safety and efficacy", for example they may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed. Cosmetics are regulated by the Center for Food Safety and Applied Nutrition ,
12322-416: The prevention of atherosclerosis through so-called "pleiotropic effects of statins". The pleiotropic effects of statins remain controversial. The ASTEROID trial showed direct ultrasound evidence of atheroma regression during statin therapy. Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research): In 2008,
12444-537: The producer. By inhibiting HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the liver. This is significant because most circulating cholesterol comes from internal manufacture rather than the diet. When the liver can no longer produce cholesterol, levels of cholesterol in the blood will fall. Cholesterol synthesis appears to occur mostly at night, so statins with short half-lives are usually taken at night to maximize their effect. Studies have shown greater LDL and total cholesterol reductions in
12566-588: The progression of Age-related Macular Degeneration (AMD). Multiple observational studies have been conducted to analyse the benefits of statin use in delaying the progression of AMD but have resulted in conflicting outcomes. Given the current available information, simvastatin should not be recommended solely for the treatment of AMD. Simvastatin is contraindicated with pregnancy, breastfeeding, and liver disease. Pregnancy must be avoided while on simvastatin due to potentially severe birth defects. Patients cannot breastfeed while on simvastatin due to potentially disrupting
12688-626: The rate of muscle pain associated with statin use, the rates of rhabdomyolysis are still "reassuringly low" and similar to those seen in clinical trials (about 1–2 per 10,000 person years). Another systematic review from the International Centre for Circulatory Health of the National Heart and Lung Institute in London concluded that only a small fraction of side effects reported by people on statins are actually attributable to
12810-625: The rate-limiting enzyme of the mevalonate pathway . Because statins are similar in structure to HMG-CoA on a molecular level, they will fit into the enzyme's active site and compete with the native substrate (HMG-CoA). This competition reduces the rate by which HMG-CoA reductase is able to produce mevalonate , the next molecule in the cascade that eventually produces cholesterol . A variety of natural statins are produced by Penicillium and Aspergillus fungi as secondary metabolites . These natural statins probably function to inhibit HMG-CoA reductase enzymes in bacteria and fungi that compete with
12932-580: The regulated industries. Rather, OCI agents pursue and develop cases when individuals and companies commit criminal actions, such as fraudulent claims or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI pursues cases involving violations of Title 18 of the United States Code (e.g., conspiracy, false statements, wire fraud, mail fraud), in addition to prohibited acts as defined in Chapter III of
13054-470: The regulatory powers granted to the agency. For example, the FDA regulates almost every facet of prescription drugs, including testing, manufacturing, labeling, advertising, marketing, efficacy, and safety—yet FDA regulation of cosmetics focuses primarily on labeling and safety. The FDA regulates most products with a set of published standards enforced by a modest number of facility inspections. Inspection observations are documented on Form 483 . In June 2018,
13176-457: The risk decision. Additional factors that could be used were an LDL-C ≥ 160 mg/dL (4.14 mmol/L) or a very high lifetime risk. However, critics such as Steven E. Nissen say that the AHA/ACC guidelines were not properly validated, overestimate the risk by at least 50%, and recommend statins for people who will not benefit, based on populations whose observed risk is lower than predicted by
13298-533: The risk of contrast-induced nephropathy by 53% in people undergoing coronary angiography /percutaneous interventions. The effect was found to be stronger among those with preexisting kidney dysfunction or diabetes mellitus. The risk of cardiovascular disease is similar in people with chronic kidney disease and coronary artery disease and statins are often suggested. There is some evidence that appropriate use of statin medications in people with chronic kidney disease who do not require dialysis may reduce mortality and
13420-441: The risk of lung cancer , kidney cancer , breast cancer , pancreatic cancer , or bladder cancer . Combining any statin with a fibrate or niacin (other categories of lipid-lowering drugs) increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years. Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate combinations, and mandatory in
13542-420: The risk of developing diabetes. Use in postmenopausal women is associated with an increased risk for diabetes. The exact mechanism responsible for the possible increased risk of diabetes mellitus associated with statin use is unclear. However, recent findings have indicated the inhibition of HMGCoAR as a key mechanism. Statins are thought to decrease cells' uptake of glucose from the bloodstream in response to
13664-471: The risk of side effects. The FDA recommends that people taking statins should avoid consuming more than a quart (946 ml) of grapefruit juice per day. Simvastatin also interacts with other drugs, including some used to treat cardiovascular problems. It should not be taken by people who are also taking the antifungal drugs fluconazole , itraconazole , or posaconazole ; the antibiotics erythromycin , clarithromycin , or telithromycin ; HIV protease inhibitors;
13786-662: The risk/benefit ratio of statins in low-risk populations is highly dependent on the rate of adverse events. A Cochrane meta-analysis of statin clinical trials in primary prevention found no evidence of excess adverse events among those treated with statins compared to placebo. Another meta-analysis found a 39% increase in adverse events in statin treated people relative to those receiving placebo, but no increase in serious adverse events. The author of one study argued that adverse events are more common in clinical practice than in randomized clinical trials . A systematic review concluded that while clinical trial meta-analyses underestimate
13908-448: The safety and labeling of their product. The FDA has a "Dietary Supplement Ingredient Advisory List" that includes ingredients that sometimes appear on dietary supplements but need further evaluation. An ingredient is added to this list when it is excluded from use in a dietary supplement, does not appear to be an approved food additive or recognized as safe, and/or is subjected to the requirement for pre-market notification without having
14030-458: The same branch of the FDA that regulates food. Cosmetic products are not, in general, subject to premarket approval by the FDA unless they make "structure or function claims" that make them into drugs (see Cosmeceutical ). However, all color additives must be specifically FDA approved before manufacturers can include them in cosmetic products sold in the U.S. The FDA regulates cosmetics labeling, and cosmetics that have not been safety tested must bear
14152-443: The short-acting simvastatin taken at night rather than the morning, but have shown no difference in the long-acting atorvastatin . In rabbits, liver cells sense the reduced levels of liver cholesterol and seek to compensate by synthesizing LDL receptors to draw cholesterol out of the circulation. This is accomplished via proteases that cleave membrane-bound sterol regulatory element binding proteins , which then migrate to
14274-399: The statin. Multiple systematic reviews and meta-analyses have concluded that the available evidence does not support an association between statin use and cognitive decline. A 2010 meta-review of medical trials involving over 65,000 people concluded that Statins decreased the risk of dementia, Alzheimer's disease, and even improved cognitive impairment in some cases. Additionally, both
14396-512: The target of statins, the HMG-CoA reductase, is highly similar between eukaryota and archaea , statins also act as antibiotics against archaea by inhibiting archaeal mevalonate biosynthesis. This has been shown in vivo and in vitro. Since patients with a constipation phenotype present with higher abundance of methanogenic archaea in the gut, the use of statins for management of irritable bowel syndrome has been proposed and may actually be one of
14518-602: Was 0.44 per 10,000 patients treated with statins other than cerivastatin. However, the risk was over 10-fold greater if cerivastatin was used, or if the standard statins (atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) were combined with a fibrate ( fenofibrate or gemfibrozil ) treatment. Cerivastatin was withdrawn by its manufacturer in 2001. Some researchers have suggested hydrophilic statins, such as fluvastatin, rosuvastatin, and pravastatin, are less toxic than lipophilic statins, such as atorvastatin, lovastatin, and simvastatin, but other studies have not found
14640-533: Was discovered that several manufacturers had falsified data submitted in seeking FDA authorization to market certain generic drugs. Vitarine Pharmaceuticals of New York, which sought approval of a generic version of the drug Dyazide , a medication for high blood pressure, submitted Dyazide, rather than its generic version, for the FDA tests. In April 1989, the FDA investigated 11 manufacturers for irregularities; and later brought that number up to 13. Dozens of drugs were eventually suspended or recalled by manufacturers. In
14762-543: Was established by the 1902 Biologics Control Act , with additional authority established by the 1944 Public Health Service Act . Along with these Acts, the Federal Food, Drug, and Cosmetic Act applies to all biologic products, as well. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health ; this authority was transferred to the FDA in 1972. The Center for Devices and Radiological Health (CDRH)
14884-536: Was not automatic, but was recommended to occur only after a clinician-patient risk discussion with shared decision making where other risk factors and lifestyle are addressed, the potential for benefit from a statin is weighed against the potential for adverse effects or drug interactions and informed patient preference is elicited. Moreover, if a risk decision was uncertain, factors such as family history, coronary calcium score, ankle-brachial index , and an inflammation test ( hs-CRP ≥ 2.0 mg/L) were suggested to inform
#87912