Preventing a first heart attack or stroke with a statin

Summarized by Robert W. Griffith, MD
January 3, 2007

Summary

Taking a statin drug, whether the cholesterol level is raised or not, reduces the overall risk of a heart attack or a stroke, even if there has not been a previous serious cardiovascular or cerebrovascular event.

Introduction

Statin drugs, originally used to lower raised cholesterol levels, are now the most widely-prescirbed medications in the cardiovascular field. The best known are atorvastatin (Lipitor^®), simvastatin (Zocor^®), and rosuvastatin (Crestor^®). The benefits of statin therapy in patients who have already suffered a severe cardiovascular event (coronary artery disease leading to sudden cardiac death, a heart attack, or angina), or a cerebrovascular event (stroke), is undisputed. They have been demonstrated in numerous clinical trials, even in patients who don't have abnormal lipid levels. This is known as secondary prevention.¹

The ability of statins to be useful in primary prevention has, until now, been less clear. A number of different studies have been done, but their interpretations differ from one another. However, an analysis of published studies reported in the Archives of Internal Medicine yields clearer results. Here is a summary of the main findings.

What was done

The researchers began by searching four large databases for published randomized controlled clinical trials of statins published between 1966 and 2005. Out of 1146 identified aricles, 1113 were rejected for various reasons (outcomes not clearly defined as primary prevention, inadequate data, or not actual trial data); review in depth of the remaining 33 led to the identification of 9 additional trials that hadn't been found in the first search.

Afterr detailed review, another 35 articles were eliminated from the meta-analysis; the reasons included: duration less than a year, less than 80% primary prevention patients, absence of a control group, and focus on cholesterol lowering. This left 7 studies for the meta-analysis.

The data were extracted from the studies by two skilled investigators - disagreements were resolved by concensus. The main outcome measures analyzed were major coronary events (non-fatal myocardial infarction or MI, and coronary heart disease death), and major cerebrovascular events (fatal and non-fatal strokes). Also evaluated were death from any cause, cardiovascular deaths, and the need for revascularization (angioplasty or bypass).

The relative risks (RR) were calculated for the outcomes in each study, and then combined.

What was found

The 7 studies randomized almost 43,000 patients (roughly half to statin therapy and half to placebo). The average follow-up period ranged from 3 to 5 years. The average age of the patients ranged from 55 to 75; most of them were men (well over 50% in 4 of 7 studies). Importantly, over 90% of the patients had no evidence of cardiovascular disease (i.e. they were being given the statin in a primary prevention situation). The average baseline low-density lipoprotein (LDL) cholesterol levels in 6 of the 7 studies were below 150 mg/dL; only one of the studies enrolled people with high cholesterol levels. Overall, the average LDL-cholesterol level was 147 mg/dL, well below the accepted definition of 'raised', i.e. 160 mg/dL.

There were 924 major coronary events in the statin patients, and 1219 in the controls. This represents a significant reduction (29%) in the relative risk of a major coronary event with statin therapy. Major cerebrovascular events occurred in 440 statin patients and in 517 control patients, representing a 14% reduction with statins, which was also significant.

Non-fatal heart attacks and revascularization procedures were also significantly lower in statin patients, by 32% and 34%, respectively.

There was also a 23% reduction in coronary heart disease mortality and an 8% reduction in overall mortality, but these differences were not statistically significant, i.e. they could have occurred by chance alone. The risk of cancer was not increased in the statin group.

What does this mean?

In patients without any evidence of cardiovascular disease and average LDL cholesterol levels, statin therapy over an average 4.2-year period decreased the occurrence of major coronary and cerebrovascular events. Statins did not increase the risk of cancer.

The benefits of primary prevention with a statin are significant, although not as great as those for secondary prevention. They are best expressed by the 'numbers needed to treat', a measure of the number of people needing to be treated for 4.3 years to have one person avoid the adverse event. Here are these numbers:

	Primary Prevention	Secondary Prevention
Major coronary events	60	33
Major cerebrovascular events	268	125
Nonfatal heart attacks	61	(not known)
Revascularization procedures	93	37

It's obvious that the cost-effectiveness of using statins for primary prevention will vary with the patient's condition i.e. the existence of cardiovascular or cerebrovascular risk factors. The principal author of this study, Dr Choudhry of Harvard Medical School, says the results suggest that people who are at higher risk, those at moderately high risk, and diabetics should be treated with lipid-lowering therapy to bring their LDL-cholesterol levels to below the average level. The debate is open, however, about whether those with lower risks should be given a statin prophylactically. Time will provide more studies with more numbers, and a better basis for decision.

Source

• Primary prevention of cardiovascular diseases with statin therapy. A meta-analysis of randomized controlled trials. P. Thavendiranathan, A. Bagai, M. Brookhart, NK. Choudhry, Arch Intern Med, 2006, vol. 166, pp. 2307--2313

Footnotes
1. Secondary prevention is lowering the risk of an event (e.g. sudden cardiac death) following survival of an initial event (e.g. a heart attack). Primary prevention is lowering the risk of an initial event (i.e. the heart attack).

Related Links
How to Avoid a Heart Attack, Wherever You Live
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