The HPS2-THRIVE study was a large multi-national, placebo-controlled, randomised 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 randomised in 240 clinics in six countries: China, UK, Denmark, Finland, Norway, and Sweden. These patients were followed up for a median of four years in the study clinics while they continued on their randomised 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 ie 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.
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. The long-term follow-up has been funded by core grants to CTSU from the Medical Research Council, British Heart Foundation and Cancer Research UK. Ongoing long-term follow-up work is funded by the HDR UK, and the University of Oxford.
Long-Term Follow-Up
Participants stopped taking study treatment in 2012. In the UK, we will continue to collect information on health outcomes by obtaining routinely collected data via central data registries and NHS Data Custodians (e.g. NHS England, Public Health Scotland, and SAIL and DHCW – in Wales) until 2035. See our Legacy Study Protocol for more information about this long-term follow-up, and our Privacy Notice for information on how we use participant data.
We have several similar studies (THRIVE, REVEAL, HPS, and SEARCH) with common aims. Due to the similarities between the studies and the participant cohorts, where any one study does not have enough data to be able to give a clear answer for a specific research question, we will perform meta-analyses. This means that we will combine data from all the studies and then analyse it to answer a common research question. All research will be in-line with the original study protocols, and will include methodology work.
PATIENT AND PUBLIC INVOLVEMENT AND ENGAGEMENT (PPIE)
If you were a participant in the THRIVE trial and would like to join the Oxford Population Health PPIE group we would love to hear from you. PPIE is very important for learning about the lived experience of our trial participants and providing feedback about new and ongoing research projects. The Oxford Population Health website gives more information on what this group does and how to get in touch.
Documents
HPS2-THRIVE Legacy Study Privacy Notice
HPS2-THRIVE Participant Information leaflet (2008) [PDF]
HPS2-THRIVE Q&A about results (2013)
HPS2-THRIVE Legacy Study Protocol [PDF]
HPS2-THRIVE Main study protocol (2009) [PDF]
HPS2-THRIVE Main data analysis plan (2012)
HPS2-THRIVE Data Analysis Plan for early safety analyses (2012)
Slide Set presented at the European Society of Cardiology (2012)
Our team
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Jane Armitage
Emeritus Professor of Clinical Trials and Epidemiology, and Honorary Consultant in Public Health Medicine
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Richard Haynes
Professor of Renal Medicine and Clinical Trials
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Jemma Hopewell
Professor of Precision Medicine & Epidemiology
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Martin Landray
Professor of Medicine and Epidemiology
