Fibrates Show "Moderate" Reduction in Cardiac Events in Meta-Analysis

May 14, 2010

May 14, 2010 (Sydney, Australia) — Fibrate drugs do have a moderate effect on reducing coronary events, which could be clinically meaningful in high-risk individuals and in those with combined dyslipidemia, a new meta-analysis suggests [1].

The meta-analysis, published online in the Lancet on May 11, 2010, was conducted by a group led by Dr Min Jun (George Institute for International Health, Sydney, Australia).

Reasonable Option for High Triglycerides and Low HDL

Commenting on the study for heartwire , Dr Roger Blumenthal (Johns Hopkins University, Baltimore, MD) said: "I think that fenofibrate is still reasonable to give on top of a statin in a person with an elevated triglyceride level (over 200 mg/dL) and HDL less than 35 mg/dL, based on this analysis and that of ACCORD. However, the potential impact of adding this onto a moderate dose of a statin is probably quite a bit less than many of us previously believed."

In the paper, the authors explain that although fibrates are clearly effective at raising HDL and lowering triglycerides and could also reduce LDL and chylomicron remnants, clinical trials have given conflicting results on cardiovascular end points. They aimed to synthesize the available clinical-trial evidence in a meta-analysis and thereby improve definition of the likely effects of fibrate therapy on major clinical outcomes. They included 18 trials in the analysis, with data on 45 058 participants, including 2870 major cardiovascular events.

Results showed that fibrate therapy produced a 10% relative reduction in major cardiovascular events compared with placebo and a 13% relative reduction in coronary events but had no benefit on stroke, all-cause mortality, cardiovascular mortality, sudden death, or nonvascular mortality.

Fibrates also appeared to reduce the risk of albuminuria progression by 14% and the risk of retinopathy by 37%. They were not associated with a significant increase in serious drug-related adverse events but did appear to cause an increase in serum creatinine concentration.

Relative Risks of Fibrates vs Placebo on Various Events

Outcome Relative risk (95% CI) p
Composite cardiovascular event 0.90 (0.82–1.00) 0.048
Coronary event 0.87 (0.81–0.93) <0.0001
All-cause mortality 1.00 (0.93–1.08) 0.918
Cardiac death 0.93 (0.85–1.02) 0.116
Cardiovascular death 0.97 (0.88–1.07) 0.587
Sudden death 0.89 (0.74–1.06) 0.190
Nonvascular death 1.10 (0.995–1.21) 0.063
Stroke 1.03 (0.91–1.16) 0.687
Coronary revascularization 0.88 (0.78–0.98) 0.025
Heart failure 0.94 (0.65–1.37) 0.759
Progression of albuminuria 0.86 (0.75–0.98) 0.028
Retinopathy (in diabetics) 0.63 (0.49–0.81 <0.0001
Serious drug-related adverse events 1.21 ( 0.91–1.61) 0.19
Increase in serum creatinine concentration 1.99 (1.46–2.70) 0.0001

The authors note that the magnitude of the proportional risk reduction with fibrates shown in this meta-analysis is more modest than that achieved with other vascular preventive therapies, and the clinical relevance of the effect will be debated.

Noting that for high-risk populations, a proportional risk reduction of 10% to 15% would translate into a worthwhile absolute risk reduction and a plausible number needed to treat, they say that the challenge will be to define this group in the clinical setting.

They point out that trials including individuals with high baseline triglyceride concentrations reported significantly greater proportional risk reductions, and the recent ACCORD trial suggested that individuals with both a low HDL-cholesterol concentration and a high triglyceride concentration were the subset for which the greatest proportional risk reduction was achieved, with only 20 such individuals needing treatment for five years to prevent one cardiovascular event.

They say that because this meta-analysis was based on published data, this limits the capacity to fully explore such subgroups and that "substantial potential remains for an overview based on individual participant data to provide further insight." They conclude: "With modern fibrates being safe and well tolerated, these agents seem to have a role in cardiac protection."

This meta-analysis was funded by the National Health and Medical Research Council of Australia. The authors report numerous disclosures, including consulting fees, lecture fees, travel reimbursements and advisory board membership from multiple pharmaceutical companies, which are listed in the paper.