Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis

被引:12
作者
Hourcade-Potelleret, F. [1 ]
Laporte, S. [2 ]
Lehnert, V. [1 ]
Delmar, P. [1 ]
Benghozi, Renee [1 ]
Torriani, U. [1 ]
Koch, R. [1 ]
Mismetti, P. [2 ]
机构
[1] F Hoffmann La Roche Ltd, Basel, Switzerland
[2] Univ Hosp St Etienne, Hosp Nord, St Etienne, France
关键词
CORONARY-HEART-DISEASE; ESTER TRANSFER PROTEIN; RANDOMIZED CONTROLLED-TRIAL; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; LDL CHOLESTEROL; RISK; HDL; ATHEROSCLEROSIS; METAANALYSIS;
D O I
10.1136/heartjnl-2014-306691
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors. Objectives To assess alternative methods to predict clinical response of CETP inhibitors. Methods Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials. Results 51 trials in secondary prevention with a total of 167 311 patients for a follow-up > 1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499* HDL-C change, R-2=0.21) and niacin (p=0.02, log RR=1.07-0.185* HDL-C change, R-2=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077* HDL-C change, R-2=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin. Conclusions Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant.
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页码:847 / 853
页数:7
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