Statins Reduce Major Coronary, Cerebrovascular, and Revascularization Events in Primary-Prevention Patients

November 28, 2006

November 28, 2006 (Boston, MA) – In the arena of primary prevention, statins reduce the risk of major coronary and cerebrovascular events, as well as the need for revascularization, according to the results of a new meta-analysis. Although the cholesterol-lowering drugs did not reduce the risk of coronary heart disease death or overall mortality, investigators say the results support the current recommendations of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III).

"The reason we did the meta-analysis is primarily because there is some discrepancy in the existing data. There have been a number of trials, involving tens of thousands of patients, but the problem with the trials is with their interpretation," senior investigator Dr Niteesh Choudhry (Harvard Medical School, Boston, MA) told heartwire . "They all differ from each other. The message about statins in secondary prevention is much clearer, but in the primary-prevention literature, while the guidelines make some clear statements about who should get treated, figuring out where those recommendations come from is less clear."

The results of the study, led by Dr Paaladinesh Thavendiranathan (University of Toronto, ON), are published in the November 27, 2006 issue of the Archives of Internal Medicine.

Intermediate-risk patients

Current NCEP ATP III treatment guidelines recommend the use of statins in primary-prevention patients based on their cardiovascular risk profile and LDL-cholesterol levels. For those with average or below-average LDL-cholesterol levels, defined as <160 mg/dL, statin therapy is recommended only for patients with diabetes mellitus and for those with two or more risk factors with a 10-year risk of a first CHD event of at least 10%.

However, the data supporting the benefit of statin therapy in primary prevention are conflicting, Choudhry pointed out. For example, statins significantly reduced the risk of major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) and the West of Scotland Coronary Prevention Study (WOSCOPS) but had no impact on this outcome in the Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER) study and the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).

To clarify the benefit of statins in primary prevention, investigators performed a meta-analysis and included, in addition to the four studies mentioned, the Collaborative Atorvastatin Diabetes Study (CARDS), ALLHAT-LLA, and the diabetic subgroup in the Heart Protection Study (HPS). In each of the seven studies, patients were randomly assigned to receive statin therapy or another form of care and were followed for at least one year. Overall, 42 848 patients were studied in the meta-analysis, and the mean pretreatment LDL-cholesterol level was 147 mg/dL.

Treatment with statin therapy reduced the risk of major coronary events, defined as nonfatal MI and coronary heart disease death, a finding driven by the reduction in nonfatal MI. Statin therapy also reduced the risk of major cerebrovascular events and revascularizations. There were no statistically significant differences between the statin and control groups in the rates of coronary heart disease mortality or all-cause mortality.

Summary of treatment effects of statin therapy


Major coronary events

Major cerebrovascular events

All-cause mortality

CHD mortality

Nonfatal MI


All trials







Overall p







"Our results really support the guidelines," said Choudhry. "They suggest that people who are at higher risk, those at moderately high risk or diabetics, should be treated with lipid-lowering therapy to LDL-cholesterol levels below what would be considered average levels. What is striking about these results, though, and what will require some further thought, is what to do with primary-prevention patients who are considered lower risk, those patients who do not have any risk factors. Our data show that these patients would also benefit from cholesterol lowering below the currently recommended levels."

Choudhry pointed out that there is large heterogeneity in primary-prevention patients, with the lowest-risk patients having no risk factors vs those with diabetes or two or more cardiac risk factors. For the higher-risk primary-prevention patients, those with an absolute 10-year CHD event rate exceeding 20%, statins are likely cost-effective, he said, whereas for those at low risk, the drugs are not. It is this intermediate-risk primary-prevention cohort, those with a 10-year CHD risk between 10% and 20%, that the use of statins is still controversial, he said.

"Treating the highest-risk primary-prevention patients, like diabetics, gives you a pretty big bang for your buck," said Choudhry. "Treating lower-risk primary-prevention patients is of benefit, but whether or not it is worth the cost, given the millions and millions of people this will involve, is a different question."

From a clinical perspective, Choudhry said he would likely prescribe a statin to this intermediate-risk patient, but whether this makes sense on societal level is unclear. Future guidelines, he added, should incorporate risk-stratification models that include cerebrovascular and revascularization events, because statins provide benefit in these outcomes also, he added.

  1. Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy. Arch Intern Med 2006; 166:2307-2313.

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