Journal
EUROPEAN HEART JOURNAL
Volume 34, Issue 17, Pages 1279-1291Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/eht055
Keywords
ER niacin; laropiprant; HDL-cholesterol; LDL-cholesterol; secondary prevention; cardiovascular disease
Categories
Funding
- Merck
- UK Medical Research Council
- British Heart Foundation
- Cancer Research UK
- BHF Centre of Research Excellence, Oxford [RE/08/004]
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford
- MRC [MC_U137686855, MC_U137686853, MC_EX_G0801669] Funding Source: UKRI
- Medical Research Council [MC_U137686853, MC_EX_G0801669, MC_U137686855] Funding Source: researchfish
- National Institute for Health Research [CDF-2013-06-012] Funding Source: researchfish
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Niacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. Prior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for 1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25 of participants allocated ERN/LRPT vs. 17 allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16/year) vs. 17 (0.04/year): risk ratio 4.4; 95 CI 2.67.5; P 0.0001]; 7 vs. 5 were rhabdomyolysis. Any myopathy (definite or incipient) was more common among participants in China [138 (0.66/year) vs. 27 (0.13/year)] than among those in Europe [17 (0.07/year) vs. 11 (0.04/year)]. Consecutive alanine transaminase 3 upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10/year) ERN/LRPT vs. 30 (0.06/year) placebo allocated participants. The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for 1 month, three-quarters continued to take it for 4 years.
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