Saturday, May 28, 2011

Cholesterol drug Niaspan disappoints; better to just have a glass of wine?

This week it was announced that a clinical trial on the use of Niaspan (a sustained release formulation of the vitamin niacin) to raise levels of HDL or “good” cholesterol, was suspended because of disappointing results. While it is well-established that higher levels of HDL (high-density lipoprotein) relative to LDL (its low-density counterpart) are associated with reduced risk of heart attack and stroke, the addition of Niaspan to the cholesterol-lowering statin drugs (for example Lipitor) has failed to deliver the same benefit seen in people who naturally have a high HDL/LDL ratio. In this recent trial, there was even a trend to an increased stroke incidence. Sales of Abbott’s Niaspan totaled nearly $1 billion last year, but development of several cholesterol drugs has been suspended recently due to lack of efficacy in preclinical trials.


It seems appropriate then to take a few steps back and see what we know about what does work. Not smoking, along with exercise and a healthy diet are unquestionably the first steps in reducing the risk of cardiovascular disease. But how is a healthy diet defined? Regular consumption of red wine has long been identified as a significant element in a heart-healthy diet, though randomized prospective clinical trials such as those used in drug development are few. Nevertheless, a positive pattern emerges for wine consumption especially with meals.

Wine consumption is known to affect cardiovascular disease risk factors in several ways: First, alcohol in moderate amounts also raises the HDL/LDL ratio, though in light of the Niaspan study the benefit of this effect seems debatable. Alcohol also helps prevent thrombosis, or clotting in the arteries which is the critical event in heart attack. A 2008 prospective clinical trial from the Netherlands pointed to additional benefits from alcohol, observing that the addition of white wine but not grape juice to the diet of postmenopausal women improved insulin sensitivity—a good thing for cardiovascular risk—while raising HDL and lowering LDL along with triglycerides, another bad actor. At a more fundamental level, tissue levels of a substance called adiponectin were increased, providing a possible explanation for less weight gain observed among middle-aged wine drinkers. A similar trial in men, looking a a broader range of alcoholic beverages, found positive effects on blood pressure and various markers of inflammation in the blood after red wine or beer consumption but not whiskey or white wine.

As anti-alcohol activists point out, alcohol also has deleterious effects on blood pressure, but intervention studies find that the threshold for this is at about 4 drinks per day. So alcohol seems to be at least acceptable if not beneficial in moderate amounts, and when combined with the long list of properties associated with the antioxidant polyphenols in wine, it seems clear that a glass or two of wine with dinner should be a central part of a heart-healthy diet.

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