We all have these patients – men and women with established cardiovascular disease (CVD), or at high risk for CVD (diabetics who smoke, have hypertension and dyslipidemia etc…). Evidence is solid for treating those with established CVD with a statin. The evidence is not quite so clear for use in primary prevention, but most of us treat with statins anyway.
But what do we do for those patients whose HDL’s remain abysmally low despite statin treatment? Low HDL predicts increased CVD risk, and usually correlates with high triglycerides. Two medication strategies to raise HDL and lower triglycerides have a long history in clinical practice, but do they improve patient-oriented outcomes: niacin, and fibrates (gemfibrozil, fenofibrate)? The answer appears to be “no”.
Niacin raises HDL, is inexpensive, is largely free of serious side-effects (but that flushing is very annoying), and is very cheap. The NIH-sponsored AIM-HIGH trial treated patients with known CVD and low HDL (<40 for men and <50 for women) with a statin (target LDL<80). Most also were on aspirin, a beta blocker, and an ACE-inhibitor. After a run-in to ensure that all could tolerate niacin, patients were randomized to 1500-2000 mg of extended-release niacin daily. After 3 years, the trial was stopped early because there was no suggestion of any cardiovascular benefit, but a trend toward more strokes in the niacin-treated patients. With no evidence for niacin’s benefit in contemporary primary prevention either, we should stop using this vitamin/medication.
Older studies with fibrates (Helsinki Heart Study, VA-HIT) in non-statin-treated patients showed some weak evidence for reduction in coronary events, but likely not in overall mortality. Remarkably, despite lack of evidence of benefit in more recent studies of high-risk patients (FIELD, ACCORD), prescriptions for fibrates are increasing dramatically in the US, but not in Canada! Might this have to do with marketing of brand name fenofibrate – a 1.5 billion dollar drug in the US? Fibrates do not work for prevention of CVD (at least in statin-treated patients) and should not be used!
Elevated homocysteine levels correlate with cardiovascular disease. And homocysteine lowering is so easy with folic acid, vitamin B6, and vitamin B12 (JAMA 2008 May 7; 299:2027; JAMA 2006 Dec 13; 296:2720-6)! Once again, simple explanations for the complex atherosclerotic process of CVD fail: homocysteine lowering does not work to prevent CVD or reduce all-cause mortality in patients with vascular disease or in primary prevention. Don’t routinely check homocysteine levels for CVD risk-stratification, and don’t use these vitamins for treatment or prevention.
What’s the best treatment for all patients with low HDL’s and high triglycerides? NOT A PILL. Exercise, weight loss, and avoidance of simple sugars in the diet. Exercise and weight loss definitely improve patient outcomes of all kinds, including cardiovascular disease. For patients with CVD (and for those at >20% 10-year risk [http://www.mdcalc.com/framingham-cardiac-risk-score], also use a statin, and other proven strategies like BP control. Let’s be as aggressive prescribing exercise & weight loss as we are in prescribing statins!
-Jeremy Golding, MD
Filed under: In The News Tagged: | atherosclerosis, cardiovascular disease, cholesterol, coronary artery disease, dyslipidemia, fenofibrate, fibrates, gemfibrozil, HDL, niacin, primary prevention, secondary prevention
