Lower incidence of CHD, other vascular events observed with absolute reductions in LDD-C

Utilizing statin therapy, researchers have provided further evidence that absolute reductions in LDL-C reduce the incidence of coronary heart disease (CHD) and other major vascular events.

Statin therapy safely lowered the five-year incidence of major coronary events, coronary revascularization, and stroke by about one-fifth per mmol/L reduction in LDL-C. The prospective meta-analysis of data, published in TheLancet, was largely irrespective of the initial lipid profile or other presenting characteristics.

"Full compliance with available statin regimens can reduce LDL cholesterol by at least 1.5 mmol/L in many circumstances, and hence might be expected to reduce the incidence of major vascular events by about one-third," the researchers stated. "Ensuring that patients at high 5-year risk of any type of occlusive major vascular event achieve and maintain a substantial reduction in LDL-C would result in major clinical and public-health benefits."

During a mean of 5 years, there were 8,186 deaths, 14,348 individuals had major vascular events, and 5,103 developed cancer.

At 1 year, the mean LDL-C differences ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09 mmol/L). There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL-C (rate ratio [RR] 0.88, 95% CI 0.84–0.91; P<.0001).

This indicated a 19% reduction in coronary mortality (0.81, 0.76–0.85; P<.0001), and nonsignificant reductions in noncoronary vascular mortality (0.93, 0.83–1.03; P=.2) and non-vascular mortality (0.95, 0.90–1.01; P=.1).

There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74–0.80; P<.0001), in the need for coronary revascularization (0.76, 0.73–0.80; P<.0001), in fatal or non-fatal stroke (0.83, 0.78–0.88; P<.0001), and combining these, of 21% in any such major vascular event (0.79, 0.77–0.81; P<.0001).

The proportional reduction in major vascular events differed significantly (P<.0001) according to the absolute reduction in LDL-C achieved, but not otherwise.

These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one-fifth per mmol/L LDL-C reduction translated into 48 (95% CI, 39–57) fewer participants having major vascular events per 1,000 among those with pre-existing CHD at baseline, compared with 25 (19–31) per 1,000 among participants with no such history.

"The results of this meta-analysis suggest that this strategy may not realize the full potential of such treatment," the authors stated. "First, assessment of baseline risk should be based on any type of occlusive vascular event (rather than on coronary events alone), since lowering LDL cholesterol with a statin lowers the risk not just of coronary events but also of revascularization procedures and of ischaemic strokes.

"Secondly, treatment goals for statin treatment should aim chiefly to achieve substantial absolute reductions in the LDL cholesterol (rather than to achieve particular target levels of LDL-C), since the risk reductions are proportional to the absolute LDL cholesterol reductions."

There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95–1.06; P=.9) or at any particular site.

"Previously, the results of some observational studies and early randomized trials had raised concerns that lowering blood cholesterol concentrations might increase the risks of various nonvascular cause of death and of particular cancers," the researchers stated. "In the present meta-analysis, however, there was no evidence that lowering LDL cholesterol by 1 mmol/L with 5 years of statin therapy increased the risks of any specific non-vascular cause of death or of any specific type of cancer."

SOURCE Baigent C, Keech A, Kearney PM,, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomized trials of statins. Lancet. 2005; 366(9493):1267–1278.