HPS2-THRIVE (n=25,673) had found that over a median follow-up of nearly 4 years, there was no significant reduction in the primary end point of major vascular events associated with niacin–laropiprant, and there were also significant and excess adverse events related to gastrointestinal, musculoskeletal, infectious, and bleeding complications, as well as substantial excess adverse events related to loss of glycaemic control among those with diabetes and new-onset diabetes. Of great concern was a 9% increase in the risk of death (number needed to harm, 200) associated with niacin–laropiprant that was of borderline statistical significance (p=0.08)
Further data are provided on adverse events in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, which had examined addition of extended-release niacin versus placebo to statin therapy in 3414 patients with stable atherosclerotic disease and low HDL cholesterol level. No benefit was found in terms of a reduction in cardiovascular risk with niacin, and there were excess adverse events typically associated with niacin use. These new data suggest a significantly higher rate of infections and infestations among patients on niacin than among those receiving placebo, as well as a non-significantly higher rate of serious bleeding.
An editorial concludes that “the consistent findings of a lack of benefit of raising the HDL cholesterol level with the use of niacin when added to effective LDL cholesterol–lowering therapy with statins seriously undermine the hypothesis that HDL cholesterol is a causal risk factor. The failure (to date) of cholesteryl ester transfer protein inhibitors, such as torcetrapib and dalcetrapib, to show any reduction in cardiovascular risk despite the marked increases in the HDL cholesterol level associated with these drugs lends further credence to the notion that HDL cholesterol is unlikely to be causal. Finally, compelling data from a large mendelian randomisation study also argue that the HDL cholesterol level has a role solely as a risk marker and not a risk factor that merits intervention to reduce cardiovascular events. Although higher HDL cholesterol levels are associated with better outcomes, it is time to face the fact that increasing the HDL cholesterol level in isolation seems unlikely to offer the same benefit.”