3.6.3.0 Statin and Niacin

The Atherothrom­bo­sis In­ter­ven­tion in Metabol­ic Syn­drome With Low HDL/High Triglyc­erides: Im­pact on Glob­al Health Out­comes (AIM-‍HIGH) trial ran­dom­ized over 3,000 pa­tients (about one-‍third with di­a­betes) with es­tab­lished ASCVD, low LDL choles­terol lev­els (<180 mg/dL [4.7 mmol/‍L]), low HDL choles­terol lev­els (men <40 mg/dL [1.0 mmol/‍L] and women <50 mg/dL [1.3 mmol/‍L]), and triglyc­eride lev­els of 150–400 mg/dL (1.7–4.5 mmol/‍L) to statin ther­a­py plus ex­tend­ed-‍re­lease niacin or place­bo. The trial was halt­ed early due to lack of efficacy on the pri­ma­ry ASCVD out­come (first event of the com­pos­ite of death from CHD, non­fa­tal MI, is­chemic stroke, hos­pi­tal­iza­tion for an ACS, or symp­tom-‍driv­en coro­nary or cere­bral revas­cu­larization) and a pos­si­ble in­crease in is­chemic stroke in those on com­bi­na­tion ther­a­py (104).

The much larg­er Heart Pro­tec­tion Study 2–Treat­ment of HDL to Re­duce the In­ci­dence of Vas­cu­lar Events (HPS2-THRIVE) trial also failed to show a benefit of adding niacin to back­ground statin ther­a­py (105). A total of 25,673 pa­tients with prior vas­cu­lar dis­ease were ran­dom­ized to re­ceive 2 g of ex­tend­ed-‍re­lease niacin and 40 mg of laropiprant (an an­tag­o­nist of the prostaglandin D2 re­cep­tor DP1 that has been shown to im­prove ad­her­ence to niacin ther­a­py) ver­sus a match­ing place­bo daily and fol­lowed for a me­di­an fol­low-‍up pe­ri­od of 3.9 years. There was no significant dif­ference in the rate of coro­nary death, MI, stroke, or coro­nary revas­cu­larization with the ad­di­tion of niacin–laropiprant ver­sus place­bo (13.2% vs. 13.7%; rate ratio 0.96; P = 0.29). Niacin–laropiprant was as­so­ci­at­ed with an in­creased in­ci­dence of new-‍onset di­a­betes (ab­so­lute ex­cess, 1.3 per­cent­age points; P <0.001) and dis­tur­bances in di­a­betes con­trol among those with di­a­betes. In ad­di­tion, there was an in­crease in se­ri­ous ad­verse events as­so­ci­at­ed with the gas­troin­testi­nal sys­tem, mus­cu­loskele­tal sys­tem, skin, and, un­ex­pect­ed­ly, in­fec­tion and bleed­ing.

There­fore, com­bi­na­tion ther­a­py with a statin and niacin is not rec­om­mend­ed given the lack of efficacy on major ASCVD out­comes and in­creased side ef­fects.