By Morgan Nwanguma
A powerful cholesterol-lowering drug may be reshaping the prevention of heart disease. Researchers have found that evolocumab, a medicine usually prescribed for people who already have cardiovascular disease, can significantly lower the risk of a first heart attack or stroke in high-risk people with diabetes, even before any plaque build-up is detected in the arteries.
Researchers at Mass General Brigham reported that evolocumab significantly reduced the likelihood of a first major cardiovascular event in people with diabetes who were considered high risk but had not yet been diagnosed with atherosclerosis, the build-up of plaque inside artery walls. The findings were presented at the American College of Cardiology Annual Scientific Session & Expo and published simultaneously in JAMA.
“For over a decade, the intensive cholesterol-lowering have been reserved for patients who already have cardiovascular disease,” said corresponding author Nicholas A. Marston, MD, MPH, a cardiologist with the Mass General Brigham Heart and Vascular Institute. “These results demonstrate the benefit of intensive lowering cholesterol earlier and should change how we think about the prevention of heart attacks, strokes, and heart disease in patients without known significant atherosclerosis.”
Why Lowering “Bad Cholesterol” Matters
Heart disease remains the leading cause of death worldwide. One of the most effective ways to reduce that risk is by lowering low-density lipoprotein cholesterol (LDL-C), often known as “bad cholesterol.” Evolocumab belongs to a class of medicines called PCSK9 inhibitors and can reduce LDL-C levels by about 60 percent. It is usually prescribed alongside statins, which remain the standard treatment. People who are considered high risk but do not yet have atherosclerosis, however, are often treated only with statins, or may not receive cholesterol-lowering medication at all.
The findings come from a subgroup analysis of the VESALIUS-CV randomized trial, funded by Amgen. Researchers evaluated 3,655 patients with high-risk diabetes who did not have significant atherosclerosis. High-risk diabetes included people who had lived with the condition for at least 10 years, required daily insulin, or had diabetes-related damage to small blood vessels.
Participants were randomly assigned to receive either evolocumab injections every two weeks or a placebo. Throughout the study, all participants continued their standard cholesterol treatments, including statins and ezetimibe.
Significant reduction in cholesterol levels
Patients who received evolocumab experienced substantially greater reductions in cholesterol. After 48 weeks, median LDL-C levels were about 51 percent lower in the evolocumab group than in the placebo group, falling to 52 mg/dL compared with 111 mg/dL.
Lower risk of a first heart attack or stroke
Over nearly five years of follow-up, patients treated with evolocumab in addition to standard therapy had a 31 percent lower risk of experiencing a first major cardiovascular event. These events included death from coronary heart disease, heart attack, or ischemic stroke.
By the five-year mark, 5 percent of patients in the evolocumab group had experienced a major event, compared with 7.1 percent of those who received placebo.
Safety and next steps
Serious side effects occurred at similar rates in both groups, suggesting that the treatment was generally well tolerated.
Researchers say further studies will be needed to determine whether the same benefits extend to other high-risk groups who have not yet developed established atherosclerosis.
Authors, Disclosures, and Funding
Apart from Marston, other Mass General Brigham contributors are: Erin A. Bohula, Jeong-Gun Park, Sabina A. Murphy, Ron Blankstein, Robert P. Giugliano, and Marc S. Sabatine. The rest include: Ajay K. Bhatia, Gaetano M. De Ferrari, Lawrence A. Leiter, Jose C. Nicolau, Emileigh Walsh, Lyrica Liu, Subodh Verma, Naveed Sattar, Stephen J. Nicholls, Jose Lopez-Sendon, Ioanna Gouni-Berthold, Lale Tokgozoglu, Marcoli Cyrille, and Gabriel Paiva da Silva Lima.
Disclosures: Marston, Bohula, Kuder, Park, Murphy, Giugliano, and Sabatine belong to the TIMI Study Group. The TIMI Study Group reports grant support via Brigham and Women’s Hospital from Amgen and other pharmaceutical companies. Marston, Bohula, De Ferrari, Nicolau, Gouni-Berthold Tokgozoglu, Giugliano, and Sabatine report personal fees from Amgen. Bhatia, Walsh, Liu, Cyrille, and Paiva da Silva Lima are staff members and ‘co-owners’ of Amgen. Blankstein reports study support and consulting fees from Amgen Inc. Giugliano reports honoraria for lectures and CME programs from Amgen. Further author disclosures can be seen in the article.
Financial support came from Amgen Inc.
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