Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE
Condition: Cardiovascular Disease; Peripheral Arterial Disease; Diabetes Mellitus; Coronary Heart Disease
MeSH terms: Cardiovascular Diseases; Heart Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Diabetes Mellitus
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary aim is to assess the effects of raising HDL cholesterol (the good type) with
      extended release niacin/laropiprant 2g (previously known as MK-0524A) versus matching placebo
      on the risk of heart attack or coronary death, stroke, or the need for arterial bypass
      procedures (revascularisation) in people with a history of circulatory problems. The
      secondary aim is to assess the effects of extended release niacin/laropiprant 2g daily on
      heart attack, coronary death, stroke, and revascularisation separately and to assess the
      effects on mortality both overall and in various categories of causes of death, and of the
      effects on major cardiovascular events in people with a history of different diseases at the
      beginning of the study.
    

Detailed description: 
      Cardiovascular disease is one of the leading causes of morbidity and mortality in the United
      Kingdom (UK), as well as in the developed and the developing world. Finding new and safe
      treatments to reduce the burden of heart disease and strokes is therefore an important
      contribution to public health and in the wider public interest. HPS2-THRIVE aims to find out
      whether by combining niacin (a drug that has been available for 50 years) with a new drug
      laropiprant(which reduces the side-effects of niacin) is beneficial. All participants in
      HPS2-THRIVE will have established cardiovascular disease and therefore be at very high risk
      of recurrent vascular events (myocardial infarction, stroke or the need for arterial
      revascularisation). Two of the most important risk factors for recurrent events in such
      patients are the blood levels of LDL cholesterol with a positive association, and HDL
      cholesterol levels with a negative association.

      HDL cholesterol has long been known to have a strong inverse correlation with coronary heart
      disease (CHD) risk. But, randomized trial evidence for beneficial effects from raising HDL
      cholesterol is limited. One of the most effective HDL-raising agents is niacin but the
      tolerability of niacin has been severely limited by flushing and cutaneous side-effects,
      which appear to be mediated largely by prostaglandin D. Laropiprant is a selective
      prostaglandin D receptor antagonist that substantially reduces the frequency and intensity of
      niacin-induced flushing. Daily oral doses of extended release (ER) niacin plus Laropiprant
      2g(formerly MK-0524A) have been well tolerated in early studies and increase HDL cholesterol
      by 20-25%. The trial will assess whether this increase in HDL cholesterol translates into
      clinical benefit as is expected from the observational evidence. In addition, all
      participants will also be provided with effective LDL-lowering therapy, as either simvastatin
      40mg daily alone or with ezetimibe 10mg daily in a combination tablet.

      The complementary effects on the HDL (good) and LDL (bad) cholesterol produced by extended
      release niacin/laropiprant 2 g daily and simvastatin 40 mg with or without ezetimibe 10 mg
      should provide an excellent treatment option for patients with vascular disease. However, no
      trials so far have demonstrated clearly that raising HDL cholesterol produces the expected
      reduction in cardiovascular risk. If HPS2-THRIVE is able to demonstrate reliably that raising
      HDL cholesterol reduces the risk of further cardiovascular events then this will be relevant
      to hundreds of millions of people worldwide.
    

Intervention name(s): ER niacin/laropiprant; simvastatin; ezetimibe/simvastatin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level; 10 mg ezetimibe plus 40 mg simvastatin in single tablet taken once daily as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Other intervention name(s): Tredaptive; Zocor; Inegy; Vytorin
Intervention MeSH terms: Niacin; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: coronary heart disease; cardiovascular disease; stroke; peripheral arterial disease; diabetes mellitus; cholesterol; HDL cholesterol; simvastatin; ezetimibe; ER niacin; laropiprant