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Updates: The most recent version of this article is available at

Copyrights: Copyright © 2014 by author(s) and International College of Human Nutrition and Functional Medicine



Houston M, Guarneri M, Kahn J. ISIFMC Position Paper on the HPS2-THRIVE Study.

Int J Hum Nutr Funct Med


International Journal of Human Nutrition and Functional Medicine

Photos of Nashville, Tennessee, USA

Position Paper

• Nutritional Science • Cardiology & Cardioprotection

ISIFMC* Position Paper on the HPS2-THRIVE Study

Mark Houston MD MS MSc

, Mimi Guarneri MD, Joel Kahn MD

*International Society of Integrative, Functional and Metabolic Cardiovascular Medicine (ISIFMC)

‡ Corresponding author, contact via website HypertensionIns



In this brief paper, we review data from the study

known as "HPS2-Thrive"


and establish our position in

refutation of this work.

Summary of Data



is a recent study of an investigational

drug (Tredaptive, Merck) containing both extended

release niacin (Niaspan, ERN) and the drug laropiprant,

a selective antagonist of the prostaglandin D2 receptor

subtype 1 (DP1R), which partially blocks the dermal

flushing response to niacin.



randomized 25,673 high-risk patients who could

tolerate niacin to either placebo or extended-release

niacin (ERN) plus laropiprant (ERNL). The study

subjects were all on simvastatin 40 mg/day. The

primary endpoint was the time to first major vascular

event, defined as the composite of non-fatal myocardial

infarction (MI) or coronary death, stroke, or any arterial



The primary composite endpoint of major

vascular events (MVE) was not significantly reduced

(risk ratio 0.96, 95% CI: 0.90-1.03, p=0.3) in the active

arm. “Serious adverse events” were found in 3% more

subjects in the active arm, although most were “minor

hyperglycemic problems.” Myopathy generally was

uncommon (0.34% per year), but was 4-fold higher

overall in the active arm, and 10-fold higher among

Chinese subjects.


The study subjects had excellent baseline

control of serum lipids on statin therapy (simvastatin 40

mg/day) with an average LDL-C of 63 mg/dl, HDL of

44 mg/dl, and triglycerides of 125 mg/dl. In March

2013, the National Lipid Association (NLA) published

their position paper


stating that in HPS2-THRIVE,

“niacin was clinically irrelevant in the average study

subject" and "there was substantial subgroup

heterogeneity" and concluded that the investigators

“tested a drug in patients who, on average, had no

indication to take it." MVE reduction with ERNL was

strongly predicted by baseline LDL-C (heterogeneity

p=0.02), with apparent net benefit if LDL-C was above

58 mg/dl at study entry. Therefore and importantly, this

study population was not likely to have any significant

CVD reduction. Niacin studies, such as the Coronary

Drug Project (CDP)


, have shown significant

reductions in cardiovascular events with niacin

monotherapy in known CHD. For patients in whom

LDL-C or triglycerides are increased, niacin in

combination with statins improves both the lipid profile

and decreases CV events.

Several clinical benefits of ERNL were noted,

including reductions in weight, blood pressure,

lipoprotein(a), a significant reduction in arterial

vascularization procedures (p= 0.03) and significant

reduction in CV risk in the subgroup with the higher

baseline LDL cholesterol level (p=0.02). The adherence

rate was poor at one year and at the completion of the