Source: Lancet  |  Posted 9 years ago

Statins protect a far wider range of people at risk of myocardial infarct and stroke than previously thought.

They have been found to offer protection among patients with diabetes, arterial disease, those who have previously had a stroke, women as well as men, and both the young and old (70 plus). Most strikingly, substantial benefits are shown among high-risk patients considered to have levels of total cholesterol below 5 mmol/l (approx. 200 mg/dl), or LDL cholesterol below 3mmol/l (approx. 120mg/dl), as well as those with high cholesterol levels.

A future report by the clinicians will show that simvastatin not only reduces the risk of a first event but also reduces the risk of subsequent events.

These are the landmark findings in the Heart Protection Study (HPS), led by Dr Rory Collins and colleagues from the University of Oxford Medical Research Council Clinical Trial Service Unit, Oxford, England, and in collaboration with clinicians with the British Heart Foundation.

The researchers are in no doubt that their findings show "unequivocally that statins can produce substantial benefit in a very much wider range of high-risk people than had been previously thought. These new findings are relevant to the treatment of some hundreds of millions of people world-wide.

"If now, as a result, an extra 10 million high-risk people were to go onto statin treatment, this would save about 50,000 lives a year - that's a thousand each week. In addition, this would prevent similar numbers of people from suffering non-fatal heart attack or stroke."

Sir Charles George, medical director of the British Heart Foundation, calls for an urgent review of national and international guidelines on statin use by the National Institute of Clinical Excellence in Britain, the National Institutes of Health in the United States, and the European Society of Cardiology and the American Heart Association for an. The clear message from the study is 'Treat risk' not cholesterol level."

The study enrolled 20,536 British adults between the age of 40 to 80 who had coronary disease, other occlusive arterial disease, or diabetes. They were randomly allocated to receive 40 mg simvastatin daily (average compliance: 85 percent) or matching placebo (average non-study statin use: 17 percent) for five years. Analyses are based on the first occurrence of particular events, and comparing all simvastatin-allocated versus all placebo-allocated patients.

All-cause mortality was significantly reduced, with 1,328 death among 10,269 patients (12.9 percent) allocated simvastatin compared with 1,507 deaths among 10,267 patients (14.7 percent) allocated placebo. This amounts to an 18 percent relative reduction in the coronary death rate in patients assigned simvastatin.

In addition, there was a marginally significant reduction in other vascular deaths - 194 in the simvastatin groups (1.9 percent) compared with 230 in the placebo group (2.2 percent. There was a non-significant reduction in non-vascular deaths.

The clinicians also found relative reductions of some 25 percent for non-fatal myocardial infarction or coronary death, for non-fatal or fatal stroke, and for coronary or non-coronary revascularisation.

Simvastatin was well tolerated, and with no major side-effects. Benefits from simvastatin were in addition to those of other cardioprotective treatments, such as aspirin, beta blockers, and ACE inhibitors.

During the first year, the reduction in major vascular events was not significant, but it was highly significant during each separate year. The annual excess risk of myopathy with this regimen was about 0.01 percent. There were no significant adverse effects on cancer incidence, or on hospitalization for any other non-vascular cause.

Clinicians conclude that treatment for five years should prevent about 70-100 people per 1,000 from experiencing at least one of these major vascular events, largely irrespective of age, sex, or presenting cholesterol concentrations. More prolonged treatment should eventually produce even bigger absolute benefits.

In light of their present findings, and findings in their future report, they add, "It seems likely, therefore, that such treatment will be considered worthwhile for many types of high-risk patients who are not currently being treated, particularly since it has been shown to be so well tolerated and safe."