Can Ezetimibe Improve Statin Outcomes?

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The MD Magazine Peer Exchange “Amassing the Clinical Evidence for Optimized Dyslipidemia Management: Vitamin D, Long-Term Statin Outcomes, and PCSK9 Inhibition” features expert insight and analysis of the latest information on managing hypertension and hyperlipidemia, and in-depth discussion on the use of PCSK9 inhibitors in practice.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at the New York-Presbyterian Hospital in New York City.

The panelists are:

• Christie Ballantyne, MD, Co-director of the Lipid Metabolism and Atherosclerosis Clinic at The Methodist Hospital, Director of the Center for Cardiovascular Disease Prevention at the Methodist DeBakey Heart Center, and the Chief of Cardiology at Baylor College of Medicine
• Keith C. Ferdinand, MD, Immediate Past Chair of the National Forum for Heart Disease and Stroke Prevention, and Professor of Clinical Medicine at the Heart and Vascular Institute at Tulane University School of Medicine
• Jennifer G. Robinson, MD, MPH, Professor in the Departments of Epidemiology & Medicine and Director of the Prevention Intervention Center, Department of Epidemiology at the College of Public Health, University of Iowa
• Karol E. Watson, MD, PhD, Professor of Medicine and Cardiology, Co-director of the UCLA Program in Preventive Cardiology, and Director of the UCLA Barbra Streisand Women’s Heart Health Program

In this segment of the Peer Exchange, the panelists discuss clinical outcomes in patients with acute coronary syndrome treated with statins and other medications and review the implications of the results from the IMPROVE-IT trial.

Jennifer Robinson, MD, MPH, says clinicians and patients have waited a long time for the IMPROVE-IT results. The researchers found that high-risk patients with LDL levels between 50 and 120 (50-100 if they were on statin therapy) who had had an acute coronary syndrome within the previous 10 days who were treated with simvastatin and ezetimibe experienced a reduction in coronary events and an incremental reduction in LDL levels from 70 to 54.

“We were so happy to see that we finally have a non-statin added to a statin that further reduces cardiovascular events in direct relationship to how much it lowers LDL,” Robinson said. The reason for this excitement is because previously there were quite a few failed trials of lipid-lowering agents, fibrates, niacin and other therapies that did not show any additional benefit when added to statins,

Because of that, the IMPROVE-IT results are important because clinicians need more options for statin-treated patients who need additional LDL lowering and have genetically high cholesterol or, if they’re on a statin, they can’t take the full dose and need additional LDL lowering.

Karol Watson, MD, PhD, said another reason the IMPROVE-IT results were striking was because some patients in the comparator arm who were treated only with a statin had a median LDL level of 69, but patients in that group who also received ezetimibe had their LDL levels drop to 54. “So even among patients we think already had really well-controlled LDL, getting it even lower made a big difference,” he said.

“I call that the ‘LDL limbo’ -- how low can you go?” said Peter Salgo, MD. “Is there any data to show that there is a point at which lowering LDL doesn’t help?”

Robinson said data from 28 statin trials suggest there is no lower limit. “The lower you get LDL, the greater the risk reduction. One group looked at data from the IVUS trial, looking actually at the atherosclerosis in the artery itself. Down to a level of 15, there continues to be regression.”