The HPS2-THRIVE study was a large multi-national, placebo-controlled, randomized trial of extended release niacin plus laropiprant 2g daily versus placebo added to effective background LDL-cholesterol lowering with simvastatin 40mg daily plus ezetimibe 10mg daily, if required. Between 2007 and 2010, 25,673 patients at increased risk of vascular disease were randomized in 240 clinics from 6 countries: China (72 hospitals or clinics), UK (89), Denmark (22), Finland (10), Norway (21), and Sweden (31). These patients were followed up for a median of 4 years in the study clinics while they continued on their randomized treatment and background LDL-lowering treatment. Results were presented at the American College of Cardiology meeting in 2013 and published in the New England Journal of Medicine in 2014.
The HPS2-THRIVE study has shown that:
- Allocation to ER niacin/laropiprant reduced LDL-cholesterol by 0.25 mmol/L and increased HDL-cholesterol by 0.16 mmol/L but did not significantly reduce the risk of major vascular events (MVEs i.e. heart attacks, strokes or coronary or non-coronary revascularisation) compared to placebo
- Allocation to ER niacin/laropiprant significantly increased the risk of disturbances in diabetes control and new onset diabetes and serious adverse events associated with the gastrointestinal and musculoskeletal systems, skin and, unexpectedly, both infection and bleeding
- ER Niacin increased the risk of simvastatin-induced myopathy by about 4-fold
- Participants from China are at higher risk of statin-induced myopathy than those from Europe
The results of HPS2-THRIVE led to the withdrawal of ER niacin/laropiprant from the European market and Merck ceased development of the product. Further analyses of the effects of ER niacin/laropiprant on Lp(a) and the impact on quality of life and cost-effectiveness have been submitted for publication and a publication on other aspects of safety is in preparation.
The HPS2-THRIVE trial was funded by a grant to Oxford University from Merck who also provided the background simvastatin and ezetimibe and the packaged ER niacin/laropiprant and matching placebo.
Further information: http://www.ctsu.ox.ac.uk/~thrive/