No More Niacin, Fibrate Combinations With Statins: FDA

The US Food and Drug Administration (FDA) is withdrawing the indication of extended-release niacin and delayed-release fenofibrate when used in combination with a statin following disappointing clinical trials that showed no evidence of benefit.

The drugs affected by the withdrawal include Niaspan and Trilipix, both made by AbbVie, and their generic counterparts. In addition to removing the indication for coadministration with statins, the FDA is withdrawing from the market two niacin-statin combinations, Advicor and Simcor (AbbVie). The two drugs pair extended-release niacin with lovastatin and simvastatin, respectively.  

The FDA announced these changes on Monday, April 18, 2016, in the Federal Register, the daily journal of the US government.

The withdrawn indication for niacin when used with statin therapy, as well wholesale removal of the niacin-statin combination drugs, follows two disappointing clinical trials: AIM-HIGH and HPS2-THRIVE.

In AIM-HIGH, published in the New England Journal of Medicine in 2011, there was no additional clinical benefit when niacin was added to statin therapy in patients with atherosclerotic cardiovascular disease and low LDL cholesterol levels, despite significant improvements in HDL cholesterol and triglyceride levels. In HPS2-THRIVE, the addition of extended-release niacin plus laropiprant (an agent used to prevent niacin-related flushing) to statin therapy also failed to reduce the risk of major vascular events compared with statins alone.

Niaspan was first approved for various indications in 1997. In 2009, the FDA revised the indication so that the drug could be used in combination with simvastatin and lovastatin for the treatment of primary hyperlipidemia and mixed dyslipidemia. The label was amended following AIM-HIGH to state the use of Niaspan failed to reduce cardiovascular mortality and morbidity in a large randomized trial.   

Trilipix, a delayed-release fenofibric acid, was first approved by the FDA in 2008 for several indications, including use in combination with statins to reduce triglycerides and increase HDL cholesterol. In 2010, the ACCORD study failed to show the combination of a statin plus a fibrate reduced the risk of cardiovascular disease in patients with type 2 diabetes at high risk for cardiovascular events when compared with statin therapy alone.

Based on the results of AIM-HIGH, HPS2-THRIVE, and ACCORD, the FDA has concluded the that evidence no longer supports the conclusion that increasing triglycerides and/or HDL cholesterol levels in patients treated with statins reduces the risk of cardiovascular events. “Consistent with this conclusion, FDA has determined that the benefits of niacin [extended-release] tablets and fenofibric acid [delayed-release] capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn,” they write in the Register.

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