You may want to read that title again just to make sure you read it correctly. Clearly, you shouldn’t take my word for this; I know I couldn’t believe it when it first hit me. However, the growing mountain of data shows that statin medications and lowering cholesterol does not reduce a person’s risk of dying from a cardiovascular event but is associated with a whole host of side effects.
Over 20 years ago, a landmark clinical trial appeared in The Lancet that forever changed the course of medicine for patients with coronary heart disease (CHD). The 4S Study employed a cholesterol lowering statin drug and reported a 30% mortality reduction. Other early statin trials reported significant mortality benefits for lowering cholesterol and a multi-billion dollar industry was born.
However, serious concerns have been raised in these studies regarding biased results, premature trial terminations, under reporting adverse events, high numbers of patients lost to follow-up and oversight by the pharmaceutical company sponsor. Heightened awareness within the scientific community regarding problems in clinical trial conduct and analysis – exemplified by the unreported risk of heart attacks in patients taking the pain killers Vioxx and Celebrex and their subsequent removal from the market – led to new regulatory rules for clinical trials in 2005. Interestingly, statin trials conducted after 2005 have failed to demonstrate a consistent mortality benefit.
What they have shown is that statin medication use is riddled with side effects, which has led the United States Food and Drug Administration (FDA) to issue warnings regarding the increased risk of diabetes and decreased cognitive function with statin drug use.
The Cholesterol Hypothethis
Cholesterol is a form of fat that circulates in the blood. It is packaged in many different particles (called lipoproteins) that carry this blood fat throughout the body. Cholesterol has been found to be a component of the atherosclerotic plaque associated with CHD and atherosclerosis. That fact coupled with these early clinical trials on statin medications led to what is often referred to as the cholesterol hypothesis. The cholesterol hypothesis links cholesterol intake and blood levels of cholesterol to cardiovascular disease. Because cholesterol itself is considered a risk factor for atherosclerosis many believe that lowering cholesterol in the blood is the best way to prevent CHD and more specifically, death due to CHD, and these early clinical trials seemed to support that assumption. However, more recent, scientifically valid studies have called the cholesterol hypothesis, and the medications used to address it, into question.
Studies Indicate No Mortality Benefit for Statin Medications
As noted above, early studies (that have since been shown to be flawed or otherwise severely biased) are often used to show a mortality benefit for statin medications. However, more recent analyses do not. A corollary to the cholesterol hypothesis states that patients at the highest risk should derive the greatest benefit from cholesterol lowering. However, statin trials in the elderly, in patients with heart failure and in patients with renal failure have all failed to demonstrate a mortality benefit. A Cochrane meta-analysis of 18 cholesterol lowering trials in patients with peripheral arterial disease also failed to demonstrate a mortality benefit. A separate meta-analysis of 11 statin trials for high-risk primary prevention similarly failed to demonstrate a mortality benefits. A second Cochrane meta-analysis of statin usage after acute coronary syndromes concluded there was no mortality benefit.
So why do you keep hearing that statin medications reduce the risk of heart attacks and strokes? Because some trials show that they do; and this has to be a good thing, right? Not necessarily.
When someone has CHD, what they are most worried about is the risk of dying from CHD, not simply not having another heart attack. And this is where researches skirt the subject – they focus on something the drug may possibly do – reduce the risk of future (minor) heart attacks or strokes, not on what they cannot do, which is reduce your risk of dying from a future heart attack or stroke.
Case in point. The Cholesterol Treatment Trialists (CTT) performed a meta-analysis of 27 statin trials and concluded that statins were clearly beneficial in reducing cardiovascular events. However, when the same 27 trials were assessed for mortality outcomes, no benefit was seen.
So what does all of this mean?
What the available data indicates is that manipulating blood cholesterol may not be all that important for the vast majority of people with or concerned about cardiovascular disease. It means that statin medications may not be of benefit for most people worried about dying from cardiovascular disease and that the use of statin medications over time is associated with many severe side effects.
It also means that we must find and use other more accurate assessments to determine a person’s risk of cardiovascular disease, and once found, how we can best address it in order to reduce the risk of death due to existing cardiovascular disease.
- DuBroff R, de Lorgeril M. Cholesterol confusion and statin controversy. World Cardiol 2015 July 26; 7(7): 404-409.
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389.
- de Lorgeril M. In: Souccar T, editor. Cholesterol and statins. Vergèze, France: Sham science and bad medicine, 2014.
- Miossec M, Miossec P. New regulatory rules for clinical trials in the United States and the European Union: key points and comparisons. Arthritis Rheum 2006; 54: 3735-3740.
- Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G,
Storey RF, Wood D. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32:1769-1818.
- Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC. Lipidlowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev 2007; (4).
- Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, Sattar N. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med 2010; 170: 1024-1031.
- Vale N, Nordmann AJ, Schwartz GG, de Lemos J, Colivicchi F, den Hartog F, Ostadal P, Macin SM, Liem AH, Mills EJ, Bhatnagar N, Bucher HC, Briel M. Statins for acute coronary syndrome. Cochrane
Database Syst Rev 2014; 9: CD006870.
- Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at low
risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380: 581-590.
- Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013; 347:
- Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol 2005; 46: 166-172.