Cardiovascular outcome trial · N Engl J Med 2014
HPS2-THRIVE trial
Effects of extended-release niacin with laropiprant in high-risk patients.
The bottom line
Adding extended-release niacin-laropiprant to statin therapy in patients with vascular disease did not reduce major vascular events and increased serious adverse effects, including new-onset diabetes, infection, and bleeding.
No significant benefitUS status: Not available in US
At a glance
- Medicine
- 2 g of extended-release niacin and 40 mg of laropiprant daily
- Compared with
- matching placebo
- People
- 25,673
- Who took part
- 25,673 adults with vascular disease, on background statin-based LDL cholesterol-lowering therapy
- Design
- randomized, placebo-controlled (with prerandomization run-in phase)
- Follow-up
- median follow-up period of 3.9 years
- Main question
- First major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization)
Main result
13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29
Effect on LDL cholesterol
LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower; HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher
Other results
Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events
Safety
Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P<0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; P<0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; P<0.001), musculoskeletal system (absolute excess, 0.7 percentage points; P<0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; P<0.001) and bleeding (absolute excess, 0.7 percentage points; P<0.001)
In the trial's own words
“Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29).”
Quoted from the abstract of N Engl J Med 2014, checked word for word against PubMed. PubMed 25014686 · Full paper (DOI)
Common questions
What did the HPS2-THRIVE trial find?
Adding extended-release niacin-laropiprant to statin therapy in patients with vascular disease did not reduce major vascular events and increased serious adverse effects, including new-onset diabetes, infection, and bleeding.
Who was in HPS2-THRIVE?
25,673 people. 25,673 adults with vascular disease, on background statin-based LDL cholesterol-lowering therapy.
What was HPS2-THRIVE's main result?
13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29
How much did LDL cholesterol change in HPS2-THRIVE?
LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower; HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher
Related trials
- AIM-HIGH (2011)In statin-treated patients with established cardiovascular disease and already-low LDL, adding extended-release niacin raised HDL and lowered triglycerides but did not reduce cardiovascular events compared with placebo.
- ACCORD Lipid (2010)Adding fenofibrate to simvastatin did not reduce cardiovascular events or death compared with simvastatin alone in high-risk patients with type 2 diabetes, so routine combination therapy is not supported.
- ASCEND (2018)In diabetic patients without known cardiovascular disease, daily 1-g omega-3 fatty acid supplementation did not reduce serious vascular events compared with placebo.
- REDUCE-IT (2019)In statin-treated patients with elevated triglycerides, icosapent ethyl significantly reduced cardiovascular events including cardiovascular death, though at the cost of more atrial fibrillation hospitalizations and a trend toward more serious bleeding.
Get your LDL treated to a goal
Preval Health's protocols follow trials like this one. Licensed clinicians set your goal, prescribe and recheck until you reach it.
Get startedEducation only, not medical advice. Results describe the people in this trial and can differ for you. Talk with your clinician before starting or stopping any medicine. Back to all 106 trials.