Hypertriglyceridemia contributes to the atherosclerotic process and maintaining normal serum triglyceride levels have some support to lower the risk of heart attack, stroke and cardiovascular death. Lifestyle changes, including diet, weight loss, exercise, controlling diabetes mellitus and controlling hypothyroidism all can help lower triglyceride levels.

1. HMG-CoA reductase inhibitors:

Many authorities consider “statins” or inhibitors of the HMG-CoA reductase enzyme to be considered first line therapy for hypertriglyceridemia since they have the strongest evidence in primary prevention trials to reduce cardiovascular mortality. High doses of atorvastatin (80 mg) and rosuvastatin (40 mg) can reduce serum triglyceride levels up to 40% in some trials. If unsuccessful, then another agent can be added to achieve goal triglyceride levels (< 150 mg/dL).

2. Fibrates

The drugs fenofibrate and gemfibrozil can reduce serum triglycerides by as much as 50% in some studies. The mechanism of action is complex. Fibrates activate peroxisome proliferator-activated receptor alpha which in turn activates lipoprotein lipase. This increases lipolysis and the elimination of triglycerides from the plasma. Fibrates must be used with caution in patients on HMG-CoA reductase inhibitors due to potential myalgias and rhabdomyolysis. Pravastatin or fluvastatin are the safest to use in combination with fibrates due to their elimination via the CYP3A4 system. While rosuvastatin also uses this system, doses should not exceed 10 mg daily while taking fibrates concomitantly.

3. Nicotinic acid (Niacin)

Niacin can reduce triglycerides by as much as 25%, however the predominant effect is to raise HDL levels. Niacin works by stimulating a G-protein coupled receptor (GPR109A) which inhibits lipolysis in adipose tissue resulting in decreased VLDL (which is used to make LDL) and increase HDL levels. The predominant side-effect is flushing which can be quite severe. Strong data to support the use of niacin is lacking as there has been few studies showing mortality benefit. Specifically, the AIM-HIGH trial was halted in 2011 since there was no cardiovascular benefit and stroke risk was higher in the niacin group. This study specifically evaluated patients with their LDL levels already at goal on statin therapy.

4. Fish oil or omega-3 fatty acids

Fish oil in higher doses (> 3 g daily) can reduce serum triglycerides by about 50%. The mechanism of action is not clearly defined.