Hi. I am Dr. Jennifer Robinson from the University of Iowa. I am going to talk today about the LAPLACE-2 trial, which was presented as a late-breaking trial at the American College of Cardiology Scientific Session.
LAPLACE-2 is a study sponsored by Amgen evaluating the investigational drug evolocumab. Evolocumab is a monoclonal antibody in the new PCSK9 inhibitor class. The purpose of the LAPLACE-2 study was to look at the efficacy and safety of adding evolocumab to moderate- or high-intensity statin therapy and to compare it with ezetimibe.
This was a large, phase 3 trial with more than 1800 participants who were randomly assigned to receive atorvastatin 80 mg or rosuvastatin 40 mg for high-intensity statin therapy or to atorvastatin 10 mg, rosuvastatin 5 mg, or simvastatin 40 mg for moderate-intensity statin therapy.
The primary finding was that the dose of statin didn't matter. There was an additional 65% reduction in low-density lipoprotein cholesterol (LDL-C) when evolocumab was added to moderate- or high-intensity statin therapy, and that was in comparison with a 20%-25% reduction in LDL-C when ezetimibe was added to moderate- or high-intensity statin therapy.
The other thing that was very interesting about the LAPLACE-2 study is that we reported, for the first time, achieved LDL-C levels. Those who received a moderate-intensity statin started out with a little bit lower LDL-C level than the high-intensity group, but at the end of the day, both groups achieved a fairly similar LDL-C level: 35-40 mg/dL in the high-intensity group compared with 35-45 mg/dL in the moderate-intensity group. We are achieving, for the first time, very low LDL-C levels.
It is exciting to contemplate the added efficacy in terms of reducing heart attack and stroke from achieving very dramatic additional LDL reductions. LAPLACE-2 was only a 12-week study and it did not address that question, but it is basically the model for the design of the ongoing FOURIER trial that is testing whether evolocumab will further reduce heart attack and stroke events in optimally statin-treated patients. That trial is ongoing, and it will be completed in about 2018.
In the meantime, we are all hoping that these PCSK9 inhibitors will be available to treat our patients who need additional LDL lowering -- such as people with genetic hypercholesterolemia whose LDL-C levels are still very high on a high-intensity statin (although many cannot take a high-intensity statin), or people are statin-intolerant and are either not able to tolerate a statin at all or can only tolerate a suboptimal statin dose. It would be very nice to have something to add to further lower their LDL-C levels in the meantime.
Thank you for your attention today.
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Cite this: LAPLACE-2: Is There a Place for Evolocumab in the Age of Statins? - Medscape - Apr 23, 2014.