AHA 2012: New Class of Drugs Substantially Lowers “Bad” Cholesterol

December 2012

Some of the biggest news to come out of AHA this year was the results from preliminary clinical trials of two new LDL cholesterol-lowering drugs that show a substantial decrease in LDL levels well below the reductions seen with statins or ezetimibe alone.

The new drugs belong to a class called PCSK9 inhibitors, which increase the liver’s ability to clear LDL cholesterol (LDL-C) from the bloodstream by binding to and blocking the protein PCSK9 that interferes with this clearance process.

One of the new drugs, called AMG-145, was given either to patients with high LDL-C who could not take statins because of their side effects or to patients with inherited high cholesterol not controlled by statins or ezetimibe. Substantially more patients who received AMG-145 in combination with ezetimibe (in the first trial) or statins/ezetimibe (in the second trial) met their target LDL-C-lowering goals than those who received ezetimibe or statins/ezetimibe plus a placebo.

In a trial of the second new drug, called RN-316, patients given one of two high doses of the drug plus a high-dose statin saw their LDL-C levels decline by 46 to 56 per cent compared with patients taking a high-dose statin plus a placebo. Few serious side effects were seen in any of the trials.

Are these drugs the future of cholesterol lowering?  Larger trials with longer follow-up are needed to determine whether the observed effects persist over treatment periods longer than the 12 weeks used in the preliminary trials, whether the reductions seen in LDL-C levels lead to a reduction in cardiovascular events, and whether any dangerous side effects of the drugs emerge over time.

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