Effect of HDL-Raising Drugs on Cardiovascular Outcomes: A Systematic Review and Meta-Regression

Abstract

BackgroundSubstantial residual cardiovascular risk remains after optimal LDL lowering in patients of established coronary artery disease. A number of therapeutic agents that raise HDL-C have been tested in clinical trials to cover this risk. However, the results of clinical trials are conflicting.ObjectivesTo determine whether raising HDL-C with pharmacologic therapies translates into beneficial cardiovascular outcomes and to find out if this change was proportional to the percentage change in HDL levels.MethodsElectronic and printed sources were searched up to August, 2013 for randomised controlled trials (RCTs) using at least one of the HDL raising therapies for secondary prevention of adverse cardiovascular events over optimal LDL levels. Data from eligible studies were pooled for the following outcomes: all cause mortality, cardiovascular disease mortality, hospitalization for unstable angina, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Mantel Haensnzel fixed effect model was used preferentially. Meta-regression was done to see the correlation of change in HDL levels and cardiovascular outcomes. Pooled odds ratios with 95% confidence interval (CI) were calculated.ResultsA total of 12 RCTs including 26,858 patients with follow up period ranging from 1 year to 6.2 years were included in the analysis. Pooled analysis showed no significant difference in all-cause mortality between the treatment and control group (Pooled OR 1.07; 95% CI 0.98–1.16, p = 0.15). No significant difference was found between the groups for any of the secondary outcomes. Similarly no correlation was seen between percentage change in HDL and adverse cardiovascular outcomes on meta-regression analysis.ConclusionIncreasing HDL levels via pharmacological manipulation beyond optimal lipid lowering therapy for secondary prevention is not beneficial.

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 1—Full Report

“…212 To date, clinical trials of agents that markedly raise HDL-C, including niacin and cholesteryl ester transfer protein inhibitors, have failed to demonstrate that they reduce all cause mortality, CHD mortality, myocardial infarction, or stroke in statin-treated patients. 210,[213][214][215][216][217] The NLA Expert Panel did not rule out the possibility of a potential ASCVD risk-reduction benefit with raising HDL-C or promoting HDL function, but at this time, HDL-C is not recommended as a target of therapy per se. The HDL-C level is often raised as a consequence of efforts to reduce atherogenic cholesterol through lifestyle and drug therapies.…”

Alcohol and cardiovascular diseases: where do we stand today?

“…Findings suggest that approximately half of the lower CAD risk in drinkers is mediated by higher HDL levels [38,43] and that major HDL subfractions, known as HDL 2 and HDL 3 , are involved [44]. The failure of HDL-raising medications to have a beneficial effect [45] and more sophisticated characterization of HDL subfractions [46] have raised questions about the likelihood of a simplistic interpretation [47]. Nevertheless, the HDL link remains the best established mechanism to explain the beneficial effect of alcohol on CAD.…”

PCSK9 inhibition: A promise fulfilled?

“…However, treatments other than ezetimibe for further management of hyperlipidemia and risk reduction have failed to demonstrate consistent benefi t when added to statin therapy. [15][16][17][18][19] The largest studies were with niacin and fi brates. Unfortunately, most trials demonstrated no overall outcomes benefi t or only benefi ts in subgroup analyses, leaving the door open to other pharmacologic interventions.…”