The Next Generation: LIPID and AFCAPS/TexCAPS
The LIPID study emphasized the importance of hypolipidemic therapy in the secondary prevention setting. Patients enrolled had a history of myocardial infarction or unstable angina with a very broad range of initial total cholesterol levels varying from 4.0-7.0 mmol/L. A total of 9014 patients were enrolled in this placebo-controlled study and followed up over a mean of 6.1 years. The primary end point was coronary mortality and this was reduced with pravastatin therapy by 24% (95% CI 12% to 35%). Total mortality was reduced by 22% (95% CI 13% to 31%). There was also a significant reduction of major coronary events (coronary death and nonfatal infarction) by 24%, coronary revascularization by 20%, and strokes by 19%. A later paper showed that the stroke reduction was due to a reduction of nonhaemorrhagic strokes, with no effect on haemorrhagic strokes. Although subgroup analysis of LIPID showed the benefit of hypolipidemic therapy to extend over all ranges of total cholesterol levels, there was a suggestion that benefit was most in those with the highest LDL cholesterol. It stands to reason that even in secondary prevention, it is those at highest risk of another coronary event who will benefit most from intervention.
The focus returned to primary prevention, and AFCAPS/TexCAPS was a placebo-controlled, randomized trial to investigate the effects of lovastatin therapy on an average-risk healthy population with normal total cholesterol levels (mean 5.71 +/- 0.54 mmol/L). After an average follow-up of 5.2 years in a total of 5608 men and 997 women, the first major coronary event, defined as myocardial infarction, unstable angina, or sudden death, was highly significantly reduced (RR 0.63, 95% CI 0.50-0.79). A similar marked improvement was seen in risk of myocardial infarction, unstable angina, and coronary revascularization. Although no adverse effect of therapy was seen in comparison with the placebo group, there was no difference in the total mortality of the 2 groups. In fact, there were 80 deaths in the lovastatin group and 77 in the placebo group (RR 1.04, 95% CI 0.76-1.42). What was equally striking was that of the total deaths (157) in both the treatment and placebo groups, more than two thirds (115) were from noncardiovascular causes. This emphasizes the point that in a group of people not at high risk of coronary deaths, therapy to lower cholesterol cannot do very much to lower mortality as the patients are more likely to succumb to noncardiovascular causes. Previous experiences with nonstatin hypocholesterolemic drugs have revealed similar findings of a reduction in cardiac end points without total mortality reduction in primary prevention trials. AFCAPS/TexCAPS thus emphasizes the point that in primary prevention, targeting patients at higher risk will bring a bigger impact at lower cost.[20,21] Furthermore, the safety and efficacy of lovastatin is most welcomed given its lower cost compared with the other patented statins.
The 4S recruited patients from throughout the Scandinavian countries. WOSCOPS enrolled Scottish patients, CARE and AFCAPS/TexCAPS were North American studies, and the patients for LIPID were from Australasia. That patients from various regions throughout the world similarly benefit from statin therapy is reassuring, but not surprising. The Seven Countries Study clearly showed that the relationship of increasing cholesterol levels and increasing coronary heart disease mortality holds true across various regions of the world, although different regions are at different absolute risk of disease. Thus, it is reassuring to find that treatment of hypercholesterolemia is also similarly useful in various parts of the world. The challenge for clinicians is to get the correct message from these various statin trials. The publication of LIPID and AFCAPS/TexCAPS confirms that patients at high risk should receive therapy to reduce adverse cardiovascular events, even if their actual cholesterol levels were not in the elevated range. The shifting of concern from the actual cholesterol level to the risk profile of the patient certainly is logical when one remembers that hypercholesterolemia by itself is asymptomatic, and it is the cardiovascular disease to which the hypercholesterolemic patient is prone that brings morbidity and mortality.
© 2002 Medscape
Cite this: Protecting the Heart: A Practical Review of the Statin Studies - Medscape - Dec 12, 2002.