Relation of different measures of low-density lipoprotein cholesterol to risk of coronary artery disease and death in a meta-regression analysis of large-scale trials of statin therapy.
Relation of different measures of low-density lipoprotein cholesterol to risk of coronary artery disease and death in a meta-regression analysis of large-scale trials of statin therapy.
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DOI：
10.1016/j.amjcard.2009.12.051
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发表时间：
2010-05-01
影响因子：
2.8
通讯作者：
Pasternak, Richard C.
中科院分区：
文献类型：
--
作者：
Kizer, Jorge R.;Madias, Christopher;Wilner, Brian;Vaughan, Carl J.;Mushlin, Alvin I.;Trushin, Paula;Gotto, Antonio M., Jr.;Pasternak, Richard C.
Multiple randomized controlled trials (RCTs) have established the efficacy of statins for prevention of cardiovascular disease. The benefits observed are often framed in terms of percent reductions in low-density lipoprotein cholesterol (LDL-C) from baseline or percent reduction between control and treatment groups, even though epidemiological data suggest that absolute inter-group difference in LDL-C (ΔLDLControl-Rx) is the more informative measure. We conducted a systematic review of large-scale trials of statins versus placebo, usual care or active (lower-dose statin) control to calculate updated summary estimates of risk reduction in coronary heart disease (CHD) and all-cause mortality. Meta-regression analysis was used to ascertain the relations of different LDL-C metrics to outcome. In 20 eligible RCTs, there were significant overall reductions for CHD (OR=0.72, 95% CI=0.67–0.78) and mortality (OR=0.89, 95% CI=0.84–0.94), but with substantial variability in trial results. ΔLDLControl-Rx was the strongest determinant of CHD risk reduction, particularly after excluding active-comparator studies, and was independent of baseline LDL-C. By contrast, baseline LDL-C edged ΔLDLControl-Rx as the strongest determinant of mortality, but neither was significant after exclusion of active-comparator studies. Exclusion of 3 RCTs involving distinct populations, however, rendered ΔLDLControl-Rx the predominant determinant of mortality reduction. In conclusion, these findings underscore the primacy of absolute reductions in LDL-C to the design and interpretation of RCTs of lipid-lowering therapies, and to framing treatment recommendations based on the proven coronary benefits of these drugs.
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