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.