TY - JOUR
T1 - 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
AU - Kizer, Jorge R.
AU - Madias, Christopher
AU - Wilner, Brian
AU - Vaughan, Carl J.
AU - Mushlin, Alvin I.
AU - Trushin, Paula
AU - Gotto, Antonio M.
AU - Pasternak, Richard C.
N1 - Funding Information:
Dr. Kizer was supported in part by Grant K23 HL070854 from the National Heart, Lung, and Blood Institute , Bethesda, Maryland.
PY - 2010/5/1
Y1 - 2010/5/1
N2 - Multiple randomized controlled trials (RCTs) have established the efficacy of statins for the prevention of cardiovascular disease. The benefits observed are often framed in terms of percentage reductions in low-density lipoprotein (LDL) cholesterol from baseline or percentage reductions between control and treatment groups, although epidemiologic data suggest that the absolute intergroup difference in LDL cholesterol (ΔLDLControl-Rx) is the more informative measure. A systematic review of large-scale trials of statins versus placebo, usual care, or active (lower dose statin) control was conducted to calculate updated summary estimates of risk reduction in coronary artery disease and all-cause mortality. Meta-regression analysis was used to ascertain the relations of different LDL cholesterol metrics to outcomes. In 20 eligible RCTs, there were significant overall reductions for coronary artery disease (odds ratio 0.72, 95% confidence interval 0.67 to 0.78) and mortality (odds ratio 0.89, 95% confidence interval 0.84 to 0.94), but with substantial variability in trial results. ΔLDLControl-Rx was the strongest determinant of coronary artery disease risk reduction, particularly after excluding active-comparator studies, and was independent of baseline LDL cholesterol. In contrast, baseline LDL cholesterol edged out ΔLDLControl-Rx as the strongest determinant of mortality, but neither was significant after the exclusion of active-comparator studies. The 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 cholesterol in the design and interpretation of RCTs of lipid-lowering therapies and in framing treatment recommendations on the basis of the proved coronary benefits of these drugs.
AB - Multiple randomized controlled trials (RCTs) have established the efficacy of statins for the prevention of cardiovascular disease. The benefits observed are often framed in terms of percentage reductions in low-density lipoprotein (LDL) cholesterol from baseline or percentage reductions between control and treatment groups, although epidemiologic data suggest that the absolute intergroup difference in LDL cholesterol (ΔLDLControl-Rx) is the more informative measure. A systematic review of large-scale trials of statins versus placebo, usual care, or active (lower dose statin) control was conducted to calculate updated summary estimates of risk reduction in coronary artery disease and all-cause mortality. Meta-regression analysis was used to ascertain the relations of different LDL cholesterol metrics to outcomes. In 20 eligible RCTs, there were significant overall reductions for coronary artery disease (odds ratio 0.72, 95% confidence interval 0.67 to 0.78) and mortality (odds ratio 0.89, 95% confidence interval 0.84 to 0.94), but with substantial variability in trial results. ΔLDLControl-Rx was the strongest determinant of coronary artery disease risk reduction, particularly after excluding active-comparator studies, and was independent of baseline LDL cholesterol. In contrast, baseline LDL cholesterol edged out ΔLDLControl-Rx as the strongest determinant of mortality, but neither was significant after the exclusion of active-comparator studies. The 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 cholesterol in the design and interpretation of RCTs of lipid-lowering therapies and in framing treatment recommendations on the basis of the proved coronary benefits of these drugs.
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U2 - 10.1016/j.amjcard.2009.12.051
DO - 10.1016/j.amjcard.2009.12.051
M3 - Article
C2 - 20403481
AN - SCOPUS:77950935917
SN - 0002-9149
VL - 105
SP - 1289
EP - 1296
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 9
ER -