Massachusetts General Brigham researchers report that the cholesterol-lowering drug evolocumab can significantly reduce the risk of a first major cardiovascular event in diabetic patients who are considered high-risk but have not yet been diagnosed with atherosclerosis (plaque buildup within the walls of arteries). The findings were presented at the American College of Cardiology’s Annual Scientific Sessions and Expo and published concurrently. Japan Automobile Manufacturers Association.
“For more than a decade, intensive cholesterol-lowering therapy has been limited to patients who already had cardiovascular disease,” said corresponding author Nicholas A. Marston, MD, MPH, a cardiologist at Massachusetts General Brigham Heart and Vascular Institute. “These results demonstrate the benefits of early and intensive lowering of cholesterol and should change the way we think about preventing heart attacks, strokes and heart disease in patients without known significant atherosclerosis.”
Why it’s important to lower “bad cholesterol”
Heart disease continues to be the leading cause of death worldwide. Lowering levels of low-density lipoprotein cholesterol (LDL-C), often referred to as “bad cholesterol,” is one of the most effective ways to lower your risk. Evolocumab belongs to a class of drugs known as PCSK9 inhibitors and can reduce LDL-C levels by about 60%. It is usually used in conjunction with statins, which are the standard treatment. However, people who do not have atherosclerosis but are at high risk are usually treated with statins only, even if they receive medication.
These results are from a subgroup analysis of the Amgen-funded VESALIUS-CV randomized trial. Researchers studied 3,655 patients with high-risk diabetes but no significant atherosclerosis. High-risk diabetes includes people who have had the condition for at least 10 years, require daily insulin, or have diabetes-related small blood vessel damage.
Participants were assigned to receive evolocumab injections or a placebo every two weeks. All participants continued standard cholesterol treatment, including statins and ezetimibe, throughout the study.
Significant reduction in cholesterol levels
Patients treated with evolocumab experienced significant reductions in cholesterol. After 48 weeks, median LDL-C levels were approximately 51% lower in the evolocumab group compared to the placebo group (52 mg/dL vs. 111 mg/dL).
Lower risk of first heart attack or stroke
Over approximately five years of follow-up, patients who received evolocumab in addition to standard therapy had a 31% lower risk of experiencing a first major cardiovascular event. These events include death from coronary heart disease, heart attack, and ischemic stroke.
At five years, 5% of patients in the evolocumab group experienced an event, compared with 7.1% in the placebo group.
Safety and future research
Serious side effects were reported at similar rates in both groups, indicating that the treatment was generally well tolerated.
The researchers note that additional research is needed to determine whether these benefits apply to other high-risk groups who have not yet established atherosclerosis.
Authors, disclosures, and funding
In addition to Marston, Contributors to Mass General Brigham include Erin A. Bohra, Park Jung-geun, Sabina A. Murphy, Ron Blankstein, Robert P. Giuliano, and Mark S. Sabatine. Other authors include Ajay K. Bhatia, Gaetano M. de Ferrari, Lawrence A. Reiter, Jose C. Nicolau, Emily Walsh, Lilika Liu, Subodh Verma, Naveed Sattar, Stephen J. Nichols, Jose López-Cendon, Ioanna Gouni-Bertold, Lale Togozoglu, Marcoli Cyril, and Gabriel. Paiba da Silva Lima.
Disclosure: Marston, Bohula, Kuder, Park, Murphy, Giugliano, and Sabatine are members of the TIMI research group. The TIMI research group reports grant support from Amgen and other pharmaceutical companies through Brigham and Women’s Hospital. Marston, Bohula, De Ferrari, Nicolau, Gouni-Berthold Tokgozoglu, Giugliano, Sabatine report personal fees from Amgen. Bhatia, Walsh, Liu, Cyrille and Paiva da Silva Lima are employees and shareholders of Amgen. Blankstein reports research support and consulting fees from Amgen. Giuliano reports honoraria for lectures and CME programs from Amgen. Additional author disclosure information is provided in the paper.
Funding: Amgen
