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Effect of HDL-raising drugs on cardiovascular outcomes: a systematic review and meta-regression
Navjot Kaur1, Avaneesh Pandey1, Harish Negi1
1Department of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Insights
Raising high-density lipoprotein cholesterol (HDL-C) with drugs does not improve cardiovascular outcomes in patients with coronary artery disease. This meta-analysis found no benefit from HDL-C-raising therapies beyond optimal low-density lipoprotein (LDL) lowering.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Trials
Background:
- Residual cardiovascular risk persists despite optimal low-density lipoprotein (LDL) lowering in patients with established coronary artery disease.
- Pharmacologic agents designed to increase high-density lipoprotein cholesterol (HDL-C) have been investigated to address this risk, but clinical trial results are conflicting.
Purpose of the Study:
- To evaluate if pharmacologic therapies that raise HDL-C lead to improved cardiovascular outcomes.
- To determine if the observed cardiovascular benefits correlate with the percentage change in HDL-C levels.
Main Methods:
- A systematic search of randomized controlled trials (RCTs) up to August 2013 involving HDL-raising therapies for secondary prevention was conducted.
- Data from 12 RCTs (26,858 patients) were pooled to assess outcomes including all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events.
- Meta-regression analysis explored the correlation between HDL-C level changes and cardiovascular outcomes.
Main Results:
- Pooled analysis of 12 RCTs revealed no significant difference in all-cause mortality or secondary cardiovascular outcomes between HDL-C-raising therapy and control groups.
- Meta-regression analysis showed no correlation between the percentage change in HDL-C levels and the occurrence of adverse cardiovascular outcomes.
- The study included 26,858 patients with follow-up periods ranging from 1 to 6.2 years.
Conclusions:
- Pharmacological manipulation of HDL-C levels does not provide additional cardiovascular benefits for secondary prevention in patients already receiving optimal lipid-lowering therapy.
- Current evidence suggests that increasing HDL-C through drug intervention is not a beneficial strategy for reducing cardiovascular risk.
Background:
Substantial 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.
Objectives:
To 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.
Methods:
Electronic 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.
Results:
A 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.
Conclusion:
Increasing HDL levels via pharmacological manipulation beyond optimal lipid lowering therapy for secondary prevention is not beneficial.
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