Commentary

The MRC/BHF Heart Protection Study (HPS) of cholesterol lowering and antioxidant supplementation in a wide range of high risk persons is the largest randomised trial of CHD prevention to date and should profoundly influence how statins and antioxidants are prescribed. In terms of vascular event prevention, the trial‘s main message was that risk reductions conferred by long term statin therapy depended chiefly on a person‘s overall risk of major vascular events rather than on their initial blood lipid level. Also, such benefit was achieved safely. Remarkably, the number needed to treat (NNT) with the statin for 5 years to prevent the first major vascular event was similar across pretreatment cholesterol levels (NNT range 18 [95% CI 13 to 27] to 19 [CI 14 to 30]) and age categories (NNT range 16 [CI 11 to 26] to 19 [CI 14 to 36]) and in patients with previous CHD only (NNT 18 [CI 13 to 26]) or diabetes only (NNT 21 [14 to 40]). These observations were also consistent with results from previous statin trials (table 2 on opposite page) in which the greatest benefit (smaller NNT per year) occurred among those at greatest risk.¹ With increasing age, however, smaller NNTs per year for CHD events may not necessarily yield greater cumulative benefit.² Preventing a CHD event at 50 rather than 70 years of age may yield much greater potential for cumulative benefit (life years and quality of life gained). Thus, contrary to implications of the HPS and the National Cholesterol Education Program (ATP III) guidelines,³ greater CHD risk reduction may not parallel greater overall benefit in the elderly.

Antioxidant intervention had no effect on CHD outcomes (or the incidence of cancer) but was associated with minor increases in low density lipoprotein cholesterol and triglyceride levels. These negative findings were in accord with several randomised controlled trials, including the large Heart Outcomes Prevention Evaluation Study.⁴ Thus, the unreal expectations aroused by observational studies and the Cambridge Heart Antioxidant Study (CHAOS)⁵ have been put to rest. Observational studies can mislead owing to unidentified confounding factors, and CHAOS was small, was done in the prestatin era, and had incomplete follow up.

In conclusion, given that benefits conferred by statins are mainly determined by premorbid CHD risk rather than the lipid level, identifying persons with “abnormal” lipid profiles and dosage titration to preset target lipid levels become questionable. It may nevertheless be appropriate to monitor lipid levels during treatment to verify that cholesterol has been lowered to the degree expected. Antioxidants cannot be recommended for CHD prevention. Instead, greater efforts should be directed at implementing appropriate, proven preventive measures (use of aspirin, β blockers, angiotensin converting enzyme inhibitors, and statins) in high risk persons.