Resolving All Doubts: HPS
The recent publication of the Heart Protection Study (HPS) should firmly establish the benefit of statin therapy in preventing adverse events in patients at high risk of atheromatous disease. Patients recruited were defined as being at high risk of coronary mortality because of prior coronary disease (secondary prevention), presence of noncoronary atheromatous disease, or diabetes. A total of 20,536 patients were enrolled and followed up for an average of 5.5 years. Patients were randomized to receive simvastatin 40 mg per day or placebo. Simvastatin reduced the coronary mortality by 18% (P = .0005) and this resulted in a highly significant reduction in total mortality (P = .0003). Highly significant reduction was also seen in stroke, major cardiovascular events, and need for coronary and noncoronary revascularization (all P < .0001). There was no increase in nonhaemorrhagic stroke and no effect on noncardiac mortality. Benefit was seen clearly in women, in the elderly, in diabetics, and in patients with prior noncardiac atheromatous disease. This benefit extends to those patients with initially low total and LDL cholesterol levels. In fact, the proportional reduction in adverse events was found to be the same in all categories of lipid levels in the patients studied, even in those with initial LDL cholesterol below 3 mmol/L and total cholesterol below 5 mmol/L. There can now be no doubt of the strategy to take. All patients at high risk of atheromatous disease must be given statin therapy, which will reduce adverse coronary and other vascular events. Baseline cholesterol levels are just one of the many risk factors in atheromatous disease, and decision on therapy should be based on an assessment of overall risk and not just the lipid level.
With the publication of the HPS, it is hard to argue with the conclusion that statin therapy is safe. All these statin trials have now randomized well over 50,000 patients, and statin therapy has been available to clinicians for more than 2 decades. No therapy is free of adverse effects, and the cerivastatin saga highlights the importance of proper patient monitoring and the need for caution with newer formulations and in combining drugs. Nevertheless, the acceptability of the statins contrasts significantly with the poor palatability and high discontinuation rates of niacin and the sequestrant formulations. Although expensive, statin therapy for hyperlipidemia has been shown to be cost effective if the right patient group is targeted.[38,39,40,41] The evidence from the trials is that all patients with atheromatous disease or who are at high risk of future atheromatous disease need statin therapy. Less emphasis should be placed on the actual lipid level, and more consideration must be given to the cardiovascular risk profile of the patient. Underutilization of statin therapy is still prevalent today and is a practice that needs to be discouraged as it is far better to prevent coronary disease than to treat its consequences.
It is interesting to contrast briefly the statin story with the evidence on antioxidant vitamins. The HPS also looked at the value of antioxidant vitamin supplementation in preventing adverse events in this large group of high-risk patients. Patients received supplementation with 600 mg vitamin E, 250 mg vitamin C, and 2 0 mg beta-carotene daily, or matching placebo. Although vitamin supplementation significantly elevated serum vitamin levels, there was no effect on vascular or nonvascular mortality, strokes, major vascular events, and cancer incidence. The disappointing results in the antioxidant vitamin arm of the HPS means we should discourage such therapy that has been proven to carry no benefit. This need for caution with antioxidants is reinforced by a recent angiographic study. A total of 160 patients with coronary artery disease were enrolled in the 3-year double-blind trial and randomly assigned to simvastatin plus niacin, antioxidants, simvastatin-niacin plus antioxidants, or placebo. The average stenosis progressed by 3.9% on placebo, 1.8% on antioxidants, 0.7% on simvastatin-niacin plus antioxidants (P = .004 compared with placebo), and it regressed by 0.4% on simvastatin-niacin alone (P < .0010). Similarly, clinical end point was 24% with placebo, 21% with antioxidants, 14% with simvastatin-niacin plus antioxidants, and only 3% with simvastatin-niacin. The clinical benefit from statin therapy and its ability to induce regression of atherosclerosis is well known. The surprising result is that antioxidants appear to reduce the benefit derived from hypolipidemic therapy. The disappointing effect of vitamin E has been noted in several large studies that have concurrently shown the value of fish-oil, angiotensin-converting enzyme inhibitor, and aspirin in prevention of adverse cardiac events.[46,47,48] Given this poor record of antioxidants in controlled clinical trials, evidence-based clinical practice means that we should advise patients with IHD to avoid vitamin E and other antioxidants.
© 2002 Medscape
Cite this: Protecting the Heart: A Practical Review of the Statin Studies - Medscape - Dec 12, 2002.