The CARE (Cholesterol and Recurrent Events) trials, involving several American, Canadian and British university hospitals, used pravastatin to lower cholesterol in patients with a previous heart attack (N Engl J Med, 1996; 335: 1001-9). After five years, 5.7 per cent in the control group had died of coronary heart disease compared with only 4.6 per cent in the treatment group. Considering the large number of participants, this result doesn’t seem particularly impressive and, indeed, it wasn’t statistically significant. In fact, the reduction in CHD deaths was offset by the fact that, in those taking pravastatin, a few more had died from other causes.
There were other benefits, however. As in the 4S trial, the number of strokes was smaller in the treatment group 2.8 per cent compared with 3.8 per cent in the controls and there were also fewer nonfatal heart attacks 6.4 per cent versus 8.3 per cent. This effect was most pronounced in women.Both the 4S and CARE trials studied the effect of statins on patients who already had CHD. Is it possible as well to prevent heart disease in healthy individuals whose only ‘abnormality’ is high cholesterol?
This was the question asked by various institutions and hospitals associated with the WOSCOP (West of Scotland Coronary Prevention) trial, from the University of Glasgow in Scotland (N Engl J Med, 1995; 333: 1301-7). This included more than 6000 middle aged men with average cholesterol levels of 272 mg/dL who received either pravastatin or a placebo. Five years later, 1.6 per cent of the men had died from CHD among the controls versus 1.2 per cent in the pravastatin group. This difference was far from being statistically significant but, in the treatment group, fewer had died from either stroke or various non cardiovascular diseases.
If the deaths from any cause are tabulated, 9.4 per cent had died in the control group and 8.6 per cent in the pravastatin group, a difference that was close to being statistically significant. Also, the differences in nonfatal CHD were larger 6.2 per cent versus 4.3 per cent.
Is it possible to prevent heart attacks in healthy individuals with normal cholesterol levels? If so, it would mean that everyone would benefit from taking a statin drug, starting at middle age and continuing for the rest of their lives.
A new statin trial was devised to answer this question AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study) directed by the former president of the American Heart Association and his co-workers from various institutions and hospitals in Texas. Three of the co-workers were employees of Merck, whose drug lovastatin was to be tested.
More than 5000 healthy men and 1000 healthy women with no symptoms of cardiovascular disease were randomly assigned to treatment with the drug or a placebo. After 5.2 years, 2.3 per cent had died in the control group versus 2.4 per cent in the treatment group.
The primary target of the trial was not the total number of deaths, however, but the number of fatal and nonfatal heart attacks, together with the number of cases of severe angina. The difference in these combined ‘events’ 5.5 per cent in the controls versus 3.5 per cent in the lova statin group was statistically significant (JAMA, 1998; 278: 1615-22).