Statins: Are they safe?

Amid research seeking to quash debate about statin protection and efficacy, there is doubt. Is statin protection as debatable as some reports say, or is the controversy behind this category of medicinal products actually harming more people than the drug itself? We’ll find out.

Statins medicine
The safety and efficacy of statins has been surrounded by controversy for decades.

Cholesterol is important for keeping the body working. However, having high levels of “poor cholesterol,” called low-density lipoprotein (LDL), can cause fatty deposits in the arteries to build up in the blood. Such buildup gradually results in narrowing and hardening of the arteries (a disorder known as atherosclerosis), which leads to a greater risk of heart attack and stroke.

Statins are a widely used drug that helps reduce unhealthy LDL cholesterol levels to minimize the cardiovascular disease risks.

US-approved statin forms include atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, and pitavastatin. They all function in a similar way by blocking the enzyme that produces cholesterol in the liver-HMG-CoA reductase.

Cardiac disease is the primary cause of death in the United States. Nearly 801,000 people died in the world in 2013 from a stroke, heart attack or other cardiovascular diseases.

Landmark studies exploring prevention of cardiovascular disease

Studies by Landmark investigated the use of statins in secondary cardiovascular disease prevention.

The Scandinavian Simvastatin Survival Research (4S) studied 4,444 people who had previously had a high cholesterol and heart attack. Simvastatin was found to reduce total cholesterol by 25 percent and LDL cholesterol by 35 per cent after a follow-up duration of nearly 5.5 years. Was encountered few adverse effects.

In the placebo party, the group taking simvastatin had 256 deaths (12 percent) compared to 182 (8 per cent). Simvastatin effectively reduced the probability of death by about one third. The 4S study concluded that “long-term simvastatin therapy is effective” in people with cardiovascular disease and improved survival.

Heart attack in man
Studies have demonstrated a correlation between reducing LDL cholesterol levels with statins and a decline in cardiovascular risk.

The study of Cholesterol and Recurrent Events (CARE) analyzed 4,159 people with coronary heart disease and mean cholesterol levels to investigate the impact of reducing LDL levels on coronary events occurring.

Reducing the levels of LDL cholesterol from high to low with pravastatin significantly decreased the amount of repeated coronary accidents compared with placebo. Pravastatin lowered hdl cholesterol by 20 percent and LDL cholesterol by 28 per cent during the 5-year follow-up.

Individuals treated with pravastatin were 24% less likely to die from coronary heart disease or non-fatal heart attack, and the risk of stroke decreased by 31%. The CARE study found that pravastatin therapy reduces the risk of cardiovascular disease in people with a history of heart attack.

The research Long-Term Intervention in Ischemic Disease (LIPID) with Pravastatin studied 9,014 people with a history of heart failure and a wide range of cholesterol levels. The researchers aimed at evaluating the impact of pravastatin on cardiovascular disease death.

Pravastatin lowered total cholesterol by 18 percent and LDL cholesterol by 25 percent more than the placebo community during the first 5 years of follow-up. Individuals in the pravastatin category had 24 percent lower risk of death from coronary heart disease or non-fatal heart failure, 29 percent lower risk of heart attack, and 19 percent lower risk of stroke.

The LIPID study concluded that pravastatin is associated with a reduction in coronary heart disease mortality and total death in individuals who had never had a heart attack.

Treatment guidelines to decrease high blood cholesterol

A strong link between reducing LDL cholesterol with statins and decreasing cardiovascular risk has been consistently demonstrated in the trials. What the uproar, then?

While the body of evidence testing statins has grown, so have the drug’s indications. Guidelines published in 2013 by the American Cardiology College (ACC) and the American Heart Association (AHA) indicated that statin therapy can be beneficial to individuals in the following four groups:

  • people with cardiovascular disease
  • people who have high LDL cholesterol levels of 190 milligrams per deciliter or higher
  • people aged 40 to 75 years with diabetes and LDL levels of 70-189 milligrams per deciliter
  • people aged 40 to 75 years without diabetes, but with LDL cholesterol levels of 70-189 milligrams per deciliter and a predicted 10-year risk of cardiovascular disease of 7.5

Experts challenged the recommendations for 2013, claiming that a threshold of 7.5 per cent seemed too small. In 2015 two study teams reviewed this threshold and reported their results in the American Medical Association Journal.

The first study, led by Dr. Udo Hoffmann at Massachusetts General Hospital and Harvard Medical School – both in Boston – found that the 2013 guidelines were more effective in recognizing individuals at higher risk for cardiovascular disease compared with the 2004 guidelines. They predicted that between 41,000 and 63,000 cardiovascular accidents will be avoided over 10 years as compared with previous guidelines by following the 2013 guidelines.

The second paper, carried out by Drs. Ankur Pandya and Thomas A. Gaziano measured the cost-effectiveness of the 10-year threshold for cardiovascular disease at the Harvard T.H. Chan School of Public Health – based in Boston. The researchers concluded that a cost-effectiveness profile was appropriate for the risk level of 7.5 per cent or higher.

Due to the growth of the groups stated to benefit from statins, questions were raised about the pharmaceutical industry and the healthcare professionals who were prescribing. Alarm bells started to ring out that people were being over-medicated and placed at risk of harmful effects.

In addition, these concerns can be sparked by a misconception of clinical trials and how they work. Statins are among the drugs best tested in randomized clinical trials. These were found to decrease the number of strokes and heart attacks, even in people with normal levels of cholesterol, and prolong life.

In addition, statins have been shown to enhance cardiovascular health and reduce an increased risk of heart failure in people, particularly though they have already made improvements in their diet and exercise rates.

Are declines in cardiovascular disease death rates due to statin use?

While a heart-healthy diet, daily physical activity, and maintaining a healthy weight are all components that can help to lower cholesterol and minimize the risk of heart disease and stroke, certain variables – such as genetics – can not be affected. Changes in lifestyle alone are not enough for reducing cholesterol in certain individuals.

The 2013 ACC / AHA recommendations are focused on a broad and reliable collection of evidence demonstrating the efficacy and safety of using statins to lower LDL and minimize the risk of cardiovascular disease.

In addition, subsequent advisory committees that established recommendations – such as the Consensus Recommendations on Cardiovascular Disease Prevention 2014 for the Joint British Societies, the 2014 Veterans Affairs and Defense Department Recommendations on Dyslipidemia Treatment, and the 2016 U.S. Preventive Services Task Force recommendations for cardiovascular disease prevention – both have used equivalent systematic methods to review evidence, resulting in similar recommendations for treatment, thereby further supporting the ACC / AHA guidelines.

Statin use rose from 18 percent to 26 percent between 2003 and 2012. By 2011-2012, statins were used by about 93 per cent of adults taking a lower cholesterol drug. Persons with elevated blood cholesterol levels fell from 18.3 percent to 12.9 percent between 1999 and 2012. Could the decrease in blood cholesterol levels be down to an rise in statin use?

According to a report published in the Journal of the American Medical Association, heart disease deaths dropped by 68 per cent from 1969 to 2013, and stroke deaths were 77 per cent lower.

There may be a link between the increase in statin use and the decline in cardiovascular disease related deaths. However, the gains made may be due to “the cumulative impact of improved prevention, diagnosis, and care,” says Wayne D. Rosamond, Ph.D., professor of epidemiology at Chapel Hill University of North Carolina.

Efforts that can play a role in decreasing death rates include stopping smoking, improving emergency response to heart disease, improving heart therapy and procedures, advancing medical research, legislation to create healthy environments, and growing public understanding of a healthier lifestyle.

Adverse effects of statins

The notion of a “net ASCVD risk-reduction benefit” was key to the ACC / AHA response to the 2013 recommendations – asking whether the probability of avoiding a significant cardiovascular accident or death is greater than the chance that the drug treatment could cause a severe adverse event.

Statins are commonly seen as healthy and well tolerated. For certain cases, however, statins may have adverse effects, as with any drug.

The most frequently recorded symptom is muscle aches which cramps, and may occur in 5 percent of individuals. In this case it could be given a particular statin or lower dose which is best tolerated. Statins also raise the likelihood that a small number of people develop type 2 diabetes.

The U.S. Food and Drug Administration (FDA) is recommending that statins for pregnant women are not recommended.

Recent study by Imperial College London’s National Heart and Lung Institute – in the United Kingdom – shows that individuals will not show an rise in muscle issues if they are unaware they are taking statins.

The study compared adverse effects recorded during randomized controlled trials (where the patient is unaware of the placebo or medication being taken) and retrospective studies (where the patient is aware of the medication being taken). Studies found that individuals who knew they were taking statins were 41 percent more likely to experience muscle issues – a trend called the nocebo effect.

“We know the statins will avoid a significant number of heart attacks and strokes. We know there’s a slight increase in the risk of diabetes and there’s a very small increase in myopathy at high doses, but overall the benefits far outweigh the harms, “says Peter Sever, professor of clinical pharmacology and therapy at Imperial College London. “Wide-ranging reports of high statin sensitivity levels still discourage so many people from taking an affordable, effective and potentially life-saving drug.”

“There are people out there who are dying because they are not taking statins and the numbers are huge – the numbers are tens of thousands if not hundreds of thousands, and they are dying because of a nocebo effect, in my opinion.”

Peter Sever

This research echoes a study published in the European Journal of Preventative Cardiology in 2014 which analyzed the results of 29 trials involving more than 80,000 individuals. The study concluded that statins had limited side effects and there were less adverse symptoms encountered by people taking statins than those taking placebo.

Benefits of statins outweigh concerns about side effects

A 2016 study published in The Lancet states the side effects of taking statins are widely misunderstood, and the medications are safe and reliable. The study concluded that statin advantages outweigh the risks of an adverse reaction.

In 2015, researchers from the Centers for Disease Control and Prevention (CDC) analyzed results from the 2005-2012 National Health and Nutrition Examination Surveys and found that they were not taken by almost half of the people eligible for cholesterol-lowering medicines.

Statins for use in other circumstances have been investigated. Recent work suggests that statins can minimize 15 to 25 percent risk of venous thromboembolism and 12 to 15 percent risk of Alzheimer’s disease.

Mounting evidence appears to reverse the controversy surrounding statins and seeks to convince physicians and patients that the dangers of not taking statins – heart attack or stroke – greatly outweigh the fears regarding the drug-related side effects. Serious side effects are relatively uncommon. Study authors conclude that “significant misrepresentations of the evidence for its health” have undermined the substantial proven benefits of statins.

Evidence suggests that the statins are safe and efficient at population level. When you have a history of heart disease or stroke, you would possibly receive a statin prescribed for cholesterol levels without thought. In those with no known cardiovascular disease, a physician can use a validated risk Heart Disease to determine the 10-year and lifetime risk of heart attack and stroke.

Changes in lifestyle – including avoidance of smoking, eating a balanced diet and engaging in daily physical activity – may help avoid or delay cardiovascular disease.

Until beginning statin therapy, it is necessary to discuss with your doctor the possible benefits, costs, program tracking and other risk factors management.

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