Powerful cholesterol drug cuts heart attack risk by 31%

"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 continues to be the leading cause of death worldwide. Reducing levels of low-density lipoprotein cholesterol (LDL-C), often called "bad cholesterol," is one of the most effective ways to lower risk. Evolocumab belongs to a class of drugs known as PCSK9 inhibitors and can cut LDL-C levels by about 60%. It is typically used alongside statins, which are the standard treatment. However, people without atherosclerosis but at high risk are usually treated only with statins, if they receive medication at all.

The results come from a subgroup analysis of the VESALIUS-CV randomized trial, funded by Amgen Inc. Researchers studied 3,655 patients who had high-risk diabetes but no significant atherosclerosis. High-risk diabetes included people who had the condition for at least 10 years, required daily insulin, or had diabetes-related small blood vessel damage.

Participants were assigned to receive either evolocumab injections every two weeks or a placebo. All participants continued standard cholesterol treatments such as statins and ezetimibe during the study.

Significant Drop in Cholesterol Levels

Patients treated with evolocumab experienced much larger reductions in cholesterol. After 48 weeks, median LDL-C levels were about 51% lower in the evolocumab group compared with the placebo group (52 mg/dL versus 111mg/dL).

Lower Risk of First Heart Attack or Stroke

Over a follow-up period of nearly five years, those receiving evolocumab in addition to standard therapy had a 31% lower risk of experiencing their first major cardiovascular event. These events included death from coronary heart disease, heart attack, or ischemic stroke.

At five years, 5% of patients in the evolocumab group had 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.

Researchers note that additional studies will be needed to determine whether these benefits apply to other high-risk groups who do not yet have established atherosclerosis.

Authors, Disclosures, and Funding

In addition to Marston, Mass General Brigham contributors include Erin A. Bohula, Jeong-Gun Park, Sabina A. Murphy, Ron Blankstein, Robert P. Giugliano, and Marc S. Sabatine. Other authors 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 are members of the TIMI Study Group. The TIMI Study Group reports grant support through 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 employees and stockholders of Amgen. Blankstein reports research support and consulting fees from Amgen Inc. Giugliano reports honoraria for lectures and CME programs from Amgen. Additional author disclosures can be found in the paper.

Funding: Amgen Inc.