108 The Observational HDL Hypothesis: A Useful Therapeutic Target? a Meta Analysis of 117,411 Patients in Randomised Controlled Trials

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Abstract

Background

Epidemiological studies have shown HDL to be a prognostic marker. We undertook a meta-analysis to assess the benefit on cardiovascular outcomes for those patients on pharmacological interventions aimed at increasing HDL. Niacin, fibrates and cholesteryl ester transfer protein inhibitors (CETP-I) were identified as agents that raise HDL levels.

Design

We conducted a meta-analysis of HDL raising therapies and reported the outcomes on the following events; all-cause mortality, coronary heart disease mortality, non-fatal myocardial infarction (MI) and stroke.

Results

39 trials randomised 117,411 patients to HDL raising therapy or control. All interventions raised HDL.

Results

All-cause mortality was not significantly affected by any pharmacological HDL raising intervention. The reported odds ratios for niacin, fibrates, or CETP-I are (OR), 1.03(95% CI 0.92–1.15 p = 0.59), 0.98(0.89–1.08 p = 0.66), and 1.16(0.93–1.44 p = 0.19) respectively.

Results

None of niacin, fibrates, or CETP-I had a significant effect on CHD mortality, OR 0.93(95% CI 0.76–1.12 p = 0.44), 0.92(0.81–1.04 p = 0.19) and, 1.00(0.80–1.24 p = 0.99) respectively. Likewise for stroke no significant effect was seen for niacin, fibrates or CETP-I, OR 0.96(0.75–1.22 p = 0.72), 1.01(0.90–1.13 p = 0.84) and 1.14(0.90–1.45 p = 0.29) respectively.

Results

Niacin trials conducted prior to the era of routine statin therapy showed a significant reduction in non-fatal MI, OR 0.69(0.56–0.85 p = 0.0004), but with background statin there was no significant effect, OR 0.96(0.85–1.09 p = 0.52).

Results

Fibrates behaved similarly.For non-fatal MI, without background statin OR was 0.78(0.71–0.86 p < 0.00001) but with some or all patients on statin OR was 0.83(0.69–1.01 p = 0.07).

Conclusions

No HDL-raising agents reduced all-cause mortality, coronary heart disease mortality, myocardial infarction or stroke in statin treated patients. The observational hypothesis that raising HDL should reduce cardiovascular events appears to be incorrect.

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