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Role of Niacin in Cardiovascular Prevention: The Debate Continues

      To the Editor:
      We read with great interest the meta-analysis of niacin published by Garg et al.
      • Garg A.
      • Sharma A.
      • Krishnamoorthy P.
      • et al.
      Role of niacin in current clinical practice: a systematic review.
      The authors concluded that niacin therapy does not lead to significant reductions in mortality or recurrent cardiovascular events among persons with or at risk of atherosclerotic cardiovascular disease.
      In contrast with this conclusion, we have recently published a meta-analysis that included 35,723 subjects in which we demonstrated that niacin significantly reduces cardiovascular events.
      • Siniawski D.
      • Santos-Gallego C.
      • Badimon J.
      • Masson W.
      Niacin is still beneficial. Implications from an updated meta-regression analysis.
      In addition, we also found significant associations between the amount of on-treatment cholesterol and triglyceride differences between the trial arms and the natural log-adjusted odds ratio for any cardiovascular event after performing random-effects, meta-regression analyses. In line with the conclusion of Garg et al,
      • Garg A.
      • Sharma A.
      • Krishnamoorthy P.
      • et al.
      Role of niacin in current clinical practice: a systematic review.
      we also reported the absence of a significant association between the differences in high-density lipoprotein cholesterol and the incidence of cardiovascular events. These findings led us to postulate that niacin benefits seem to be mediated by the reduction in atherogenic particles.
      Of interest, both meta-analyses agreed in the futility of niacin in stroke prevention; however, their clinical conclusions are discordant. How can we explain these different results?
      We did not evaluate all-cause mortality; however, cardiac death was included in 2 combined end points (any cardiovascular event and major coronary events), outcomes that were selected in previous meta-analyses.
      • Lavigne P.M.
      • Karas R.H.
      The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression.
      • Silverman M.
      • Ference B.
      • Im K.
      • et al.
      Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis.
      We consider that Garg et al's
      • Garg A.
      • Sharma A.
      • Krishnamoorthy P.
      • et al.
      Role of niacin in current clinical practice: a systematic review.
      affirmation on the lack of effect of niacin on preventing recurrent cardiovascular events is too dogmatic, considering that the only nonfatal end point evaluated was myocardial infarction.
      In fact, our meta-analysis showed that niacin treatment was associated with a 41% reduction in any revascularization, whereas Garg et al's analysis
      • Garg A.
      • Sharma A.
      • Krishnamoorthy P.
      • et al.
      Role of niacin in current clinical practice: a systematic review.
      reported a nonsignificant 17%. What could be the possible explanation for this striking difference? First, we incorporated data from the individual primary end point events of the AIM-HIGH trial, whereas Garg et al
      • Garg A.
      • Sharma A.
      • Krishnamoorthy P.
      • et al.
      Role of niacin in current clinical practice: a systematic review.
      took the data from the tertiary end points.
      The AIM-HIGH Investigators
      Niacin in patients with low HDL Cholesterol levels receiving intensive statin therapy.
      Second, we included results from the Coronary Drug Project, which showed a 67% reduction in the rate of coronary bypass surgery.
      Coronary Drug Project Research Group
      Clofibrate and niacin in coronary heart disease.
      Therefore, our findings suggest that niacin could still be a cost-effective therapeutic option for cardiovascular prevention, especially among those patients who do not respond adequately to statins with or without the addition of ezetimibe.

      References

        • Garg A.
        • Sharma A.
        • Krishnamoorthy P.
        • et al.
        Role of niacin in current clinical practice: a systematic review.
        Am J Med. 2017; 130: 173-187
        • Siniawski D.
        • Santos-Gallego C.
        • Badimon J.
        • Masson W.
        Niacin is still beneficial. Implications from an updated meta-regression analysis.
        Acta Cardiol. 2016; 71: 463-472
        • Lavigne P.M.
        • Karas R.H.
        The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression.
        J Am Coll Cardiol. 2013; 61: 440-446
        • Silverman M.
        • Ference B.
        • Im K.
        • et al.
        Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis.
        JAMA. 2016; 316: 1289-1297
        • The AIM-HIGH Investigators
        Niacin in patients with low HDL Cholesterol levels receiving intensive statin therapy.
        N Engl J Med. 2011; 365: 2255-2267
        • Coronary Drug Project Research Group
        Clofibrate and niacin in coronary heart disease.
        JAMA. 1975; 231: 360-381

      Linked Article

      • Concerning Niacin in Current Clinical Practice
        The American Journal of MedicineVol. 130Issue 8
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          In their systematic review of the role of niacin in clinical practice, Garg et al1 found that niacin therapy does not reduce all-cause mortality, cardiovascular mortality, or adverse cardiovascular events. Garg et al1 included niacin studies with and without a statin as part of the intervention.
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      • The Reply
        The American Journal of MedicineVol. 130Issue 8
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          We thank for their interest in our manuscript. Our systematic review showed no significant benefit of niacin when compared with placebo or other lipid-modulating agents on mortality or other cardiovascular end points.1 These findings were consistent with the recent randomized controlled trials AIM-HIGH2 and HPS-2 THRIVE,3 reflecting the “statin era.” We suggested that a lack of benefit with niacin in current clinical practice could be due to widespread statin use, as well as uncertain effects of niacin on high-density lipoprotein particles and function.
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