Statins in Primary Prevention in subjects at “low risk” of Cardiovascular Disease, <10% over a 10 year period

By Alexander J. Cusmano MD, Charles Glueck MD
Cholesterol and Metabolism Center, Jewish Hospital Cincinnati OH, 1/26/11

Heart disease remains the largest cause of death in the United States1.  As such, doctors treat at risk patients with the aim to prevent coronary vascular disease (CVD).  By far the mainstay of current medical therapy is 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also referred to as “statin” therapy.  Statins have been found to reduce the risk of coronary vascular events by as much as one third2.  Numerous studies have found benefit of statin therapy to prevent first episodes of coronary events, stroke or need for coronary re-vascularization3.  Recently however, a review of the data from previous trials concluded that there is not enough evidence to recommend statin therapy for preventative purposes4.   This study was a Cochrane review of previous studies, this meta-analysis only looked at events from low risk patient populations.  Low risk patient populations are defined as having < 10% risk of a coronary heart disease (CHD) event during 10 years of follow-up.  The results of the Cochrane review showed a decreased relative risk (RR) of 17% in total mortality, 28% RR reduction in fatal and non fatal coronary heart disease (CHD) events and a 22% RR reduction of fatal and non fatal stroke. 

 

The authors of this study concluded that based on their data 1,000 patients need to be treated for 1 year to prevent 1 death.  They also cautioned that widespread use of statins for primary prevention would increase the amount of adverse effects related to these medications over the long term.  

Based on our research on this topic for the past 40 years, and the published controlled clinical trials,2,3 we believe that the conclusions of the authors are unfounded.  Statins have been on the market for over 30 years and are well tolerated by the vast majority of patients6.  The current estimate of statin use in the United States is 18.6 million patients7.   Taking the Cochrane review’s estimate of 1000 patients being treated for 1 year to prevent 1 death, would result in 18,600 deaths prevented per year.  Of note as well, is the Cochrane estimate is only for fatalities.  A significant reduction of nonfatal heart attacks and strokes, probably up to 5 per 1000  treated  for 1 year to prevent non-fatal events would result in 93,000 patients not having morbid heart attacks or strokes. Altogether ~117,000 lethal and morbid CVD would be prevented per year in the United States, even when treating “low risk” patients with <10% risk of CVD in 10 years.

A separate argument has been made that treating patients at low risk would have a high cost-benefit ratio.  This can be alleviated by the fact that some statins are now generic and cost $10 for a 3-month supply8.  If one assumes that the USA cost per year of statins is $744,000,000, treating 18,600,000 people per year at generic cost of $40/year, prevention of 117,000 lethal and morbid CVD events would cost $6,400/year per event prevented. Compare the cost of treating 18.6 million Americans per year with statins ($774 million) with the 2.3 billion dollars spent by Americans on chewing gum,  and 88 billion dollars on cigarettes.

In conclusion, statins are  efficacious for the primary prevention of CHD and stroke.  Statins are well tolerated, have a favorable side effect profile and have generic versions available.  Despite recent controversy, statins are and should be the mainstay of preventive medical treatment, including subjects at <10% risk of CVD events over a 10 year period.

References:

1. http://www.cdc.gov/nchs/fastats/lcod.htm
2. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.  Lancet. 2002 Jul 6;360(9326):23-33
3. Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)--can C-reactive protein be used to target statin therapy in primary prevention? Am J Cardiol. 2006 Jan 16;97(2A):33A-41A. Epub 2005 Dec 1
4. Statins for the primary prevention of cardiovascular disease.  Cochrane Database Syst Rev. 2011 Jan 19;1:CD004816
5. Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of intensive LDL-cholesterol-lowering therapy: A meta-analysis of data from 170 000 participants in 26 randomised trials.  Lancet 2010; DOI:10.1016/S0140-6736(10)61350-5
6. Safety and Tolerability of Pravastatin in Long-Term Clinical Trials.  Circulation. 2002;105:2341-2346
7. Estimating the Impact of Adding C-Reactive Protein as a Criterion for Lipid Lowering Treatment in the United States.  J Gen Intern Med. 2007 February; 22(2): 197–204
8. Drugstore.com: http://www.drugstore.com/simvastatin/qxdsimvastatin.  Accessed 1-25-11 3:00pm EST