Information for Health Professionals
"Does extended release (ER) niacin/laropiprant prevent vascular events in high-risk patients who are receiving intensive LDL-lowering treatment?"
This information is intended for cardiologists, GPs and other healthcare professionals. If you would like to receive a complete copy of the study protocol please contact us. Other study documents can be downloaded from the link on the left-hand menu-bar.
Large-scale randomized trials have demonstrated that lowering LDL cholesterol by about 1 mmol/L for 4-5 years reduces the risks of coronary events and of strokes by about one quarter. Furthermore, recent trials assessing more intensive versus standard statin regimens suggest further benefit with more intensive lowering of LDL cholesterol. Nevertheless, cardiovascular risk remains elevated even after some years of intensive LDL-lowering treatment. For example, in 2 recent trials, over 10% of CHD patients still suffered a major cardiovascular event during 4-5 years of intensive statin therapy. There is limited scope with current agents for much greater reductions in LDL cholesterol, but manipulating other aspects of lipid metabolism may well produce worthwhile reductions in occlusive vascular disease risk.
HDL cholesterol has long been known to have a strong inverse correlation with CHD risk. But, randomized trial evidence for beneficial effects from raising HDL cholesterol is limited. Most previous trials have been performed using fibrates, which raise HDL cholesterol only modestly, and those studies produced mixed results. One of the most effective HDL-raising agents is niacin, but the only previous large randomized trial of niacin was performed before the introduction of effective LDL-lowering treatments. Moreover, the tolerability of niacin has been limited by flushing and cutaneous side-effects, which appear to be mediated largely by prostaglandin D. Laropiprant (formerly MK-0524) is a selective prostaglandin D receptor antagonist that substantially reduces the frequency and intensity of niacin-induced flushing. Daily oral doses of the combined ER niacin/laropiprant 2g have been well tolerated in early studies.
A streamlined international trial
The present study aims to assess the clinical effects of two tablets of ER niacin/laropiprant 1 g versus matching placebo tablets in 25,000 patients with pre-existing atherosclerotic vascular disease who are all receiving simvastatin 40 mg daily (plus, if indicated, ezetimibe 10 mg daily). Such large-scale recruitment will allow reliable assessment of the effects of raising blood HDL cholesterol on the risk of major vascular events among patients receiving effective LDL-lowering therapy (i.e. LDL cholesterol typically below 2 mmol/L [77 mg/dL]). An international collaboration, with a Central Coordinating Office in Oxford and 3 Regional Coordinating Centres in the UK, China and Scandinavia, will conduct the trial in about 200 hospitals. The study design is 'streamlined': extra work for collaborating doctors and hospitals has been kept to a minimum, and only essential data will be collected directly using computer-based systems.
