Meta-analysis shows positive effects of nicotinic acid on CV events

A therapeutic strategy including nicotinic acid to raise HDL cholesterol is associated with 25% reduction in cardiovascular events, according to a new report in Atherosclerosis. HDL Forum Editor Professor Philip Barter, Heart Institute, Sydney Australia reviews these findings.

 

Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 2010; doi: 10.1016/j.atherosclerosis.2009.12.023.

 

The meta-analysis included 14 eligible studies that investigated the effects of nicotinic acid on clinical outcomes and/or atherosclerosis progression. In 11 randomized controlled trials involving a total of 6616 patients, treatment with nicotinic acid was associated with 25% relative odds reduction (95% CI 13-35%, p<0.0001) in coronary events. In addition, nicotinic acid treatment was associated with reductions of 26% (95% CI 8-41%, p=0.007) in stroke and 27% (95% CI 15-37%, p<0.0001) in cardiovascular events. Findings for coronary and cardiovascular events remained significant in sensitivity analyses excluding the largest trial (Coronary Drug Project, n=3908) (Table 1).

 

The rate of atherosclerosis progression decreased by 41% (95% CI 25-53%) with nicotinic acid, given either alone or in combination.

 

The authors did note a number of limitations to their analysis. First, they acknowledge limitations in their analysis due to the heterogeneity of the trials. Although the study populations were similar in terms of their cardiovascular risk, there were differences in doses, comparators, and whether nicotinic acid was given alone or in combination. Second, one of the trials, the Coronary Drug Project, accounted for more than 60% of patients. When this trial was excluded in sensitivity analyses, the total number of cardiovascular events was substantially lower (for example, 79/1480 vs. 287/1119 in the CDP for major coronary events). Third, most studies were in the secondary prevention setting. However, only two involved statin-treated patients already at LDL cholesterol goal, reflective of current standards of care. This may limit the wider applicability of the analysis findings.

 

Despite these limitations, the authors concluded that positive findings on clinical outcomes and atherosclerosis strongly suggest the possibility of reducing residual cardiovascular risk by treatment with nicotinic acid, the most potent agent currently available for raising HDL cholesterol.

 

Reducing residual risk by targeting HDL cholesterol with nicotinic acid

 

It is now widely accepted that LDL cholesterol lowering alone fails to eliminate vascular risk. Most recently, this was highlighted by two imaging studies (1,2).  The ARBITER 6‑HALTS trial (1) in high-risk statin-treated patients at LDL cholesterol goal showed that treatment with niacin (nicotinic acid) significantly regressed atherosclerosclerosis, as assessed by carotid intima media thickness, within 14 months. There was, however, no significant change in carotid intima-media thickness in patients treated with ezetimibe, a strategy targeting LDL cholesterol alone.  A second study showed that treatment with modified-release nicotinic acid reduced carotid atherosclerosis (assessed using magnetic resonance imaging) within 12 months vs. placebo in statin-treated patients with low plasma levels of HDL cholesterol and clinical evidence of atherosclerotic disease (2). 

 

Commenting on these findings, Professor Barter said:

‘The results of this meta-analysis, while in mainly secondary prevention patients, provide a really positive message that raising HDL cholesterol with nicotinic acid (niacin) could reduce residual cardiovascular risk. However, we still need outcomes studies to definitively make the case. Two ongoing trials, AIM-HIGH and HPS2-THRIVE, are testing this hypothesis. HPS2-THRIVE (Heart Protection Study 2: Treatment of HDL to Reduce the Incidence of Vascular Events) in 20,000 high-risk patients, is evaluating the effect of niacin combined with laropiprant, which reduces flushing, the main side effect of niacin. As noted by Eric Bruckert and his colleagues, nicotinic acid-associated flushing could have resulted in the use of suboptimal doses and therefore underestimation of the true effect of treatment. Countering flushing with niacin/laropiprant is therefore a more valid test of the concept that raising HDL cholesterol with niacin (nicotinic acid) reduces residual cardiovascular risk.’ 

 

References

1. Taylor AJ, Villines TC, Stanek EJ et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. New Engl J Med. Published on-line November 15, 2009.

DOI 10.1056/NEJMoa0907569.

2. Lee JMS, Robson MD, Yu L-M et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function. J Am Coll Cardiol 2009;54:1787-94.

 


Download Attachment