HPS2-THRIVE
Trial question
What is the effect of extended-release niacin with laropiprant in patients with atherosclerotic vascular disease?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
17.0% female
83.0% male
N = 25673
25673 patients (4444 female, 21229 male).
Inclusion criteria: adult patients with a history of MI, cerebrovascular disease, PAD, or diabetes mellitus with evidence of symptomatic coronary disease.
Key exclusion criteria: clinically significant hepatic, renal, muscle-related, or other disease, receiving concurrent treatment with potentially interacting drugs, or receiving LDL cholesterol-lowering treatment that was more effective than simvastatin at a dose of 40 mg plus ezetimibe at a dose of 10 mg daily.
Interventions
N=12838 niacin-laropiprant (e 2 g of extended-release niacin and 40 mg of laropiprant daily).
N=12835 placebo (matching placebo daily).
Primary outcome
Major vascular event
13.2%
13.7%
13.7 %
10.3 %
6.8 %
3.4 %
0.0 %
Niacin-laropiprant
Placebo
No significant
difference ↔
No significant difference in major vascular event (13.2% vs. 13.7%; RR 0.96, 96% CI 0.9 to 1.03).
Secondary outcomes
No significant difference in major vascular events excluding hemorrhagic stroke (12.4% vs. 13.1%; RR 0.95, 95% CI 0.88 to 1.01).
No significant difference in major vascular events excluding both hemorrhagic stroke and revascularization procedures (7.9% vs. 8.4%; RR 0.95, 95% CI 0.87 to 1.03).
No significant difference in death from any cause (6.2% vs. 5.7%; RR 1.09, 95% CI 0.99 to 1.21).
Safety outcomes
Significant differences in fatal or nonfatal serious adverse events (55.6% vs. 52.7%, p < 0.001), disturbance in diabetes leading to hospitalization (11.1% vs. 7.5%, p < 0.001), proportional increase in diabetes diagnosis (5.7% vs. 4.3%, p < 0.001), excess of gastrointestinal serious adverse events (4.8% vs. 3.8%, p < 0.001), excess of musculoskeletal serious adverse events (3.7% vs. 3.0%, p < 0.001), skin-related serious adverse events (0.7% vs. 0.4%, p = 0.003), excess infections (8.0% vs. 6.6%, p < 0.001), and excess of bleeding events (2.5% vs. 1.9%, p < 0.001).
Conclusion
In adult patients with a history of MI, cerebrovascular disease, PAD, or diabetes mellitus with evidence of symptomatic coronary disease, niacin-laropiprant was not superior to placebo with respect to major vascular event.
Reference
HPS-THRIVE Collaborative Group, Landray MJ, Haynes R et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014 Jul 17;371(3):203-12.
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