For the first time, investigators report that a weight loss drug led to weight loss without increasing the incidence of heart attacks, strokes and death from heart disease in a population of people who are especially at risk for cardiovascular events. At the 2018 European Society of Cardiology meeting, Brigham and Women’s Hospital investigators from the Thrombolysis in Myocardial Infarction (TIMI) Study Group presented findings from CAMELLIA-TIMI 61, a clinical trial of overweight and obese patients designed to test the cardiovascular safety of lorcaserin, a weight loss drug manufactured by the trial’s sponsor, Eisai Inc. The team’s findings are detailed in a paper published simultaneously in the New England Journal of Medicine.
“The study showed for the first time in a rigorous, randomized way that this weight loss drug helps people lose weight without causing an increase in adverse cardiovascular events in a population at higher risk for heart attacks and strokes,” said lead author Erin Bohula, MD, DPhil, a BWH cardiovascular medicine and critical care specialist and a staff investigator for the Thrombolysis in Myocardial Infarction (TIMI) Study Group at BWH.
Historically, many weight loss agents, have had adverse cardiovascular effects, leading to dangerous conditions such as strokes, heart attacks, pulmonary hypertension and valvular heart disease, and have been withdrawn from the market. Balancing the need for treatments for obesity and the potential risk of such therapies, the FDA has approved weight loss agents like lorcaserin contingent on dedicated follow-up studies to assess the risk of adverse cardiovascular outcomes.
In the Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61 (CAMELLIA-TIMI 61) Trial, 12,000 overweight or obese patients at risk for cardiovascular event were randomly assigned to receive either lorcaserin or a placebo. Patients were followed for a median time of more than three years. The primary safety outcome assessed by the TIMI Study Group was a composite of cardiovascular death, myocardial infarction or stroke (major adverse cardiovascular events or MACE).
The team reports no statistical difference in the proportion of patients with a major adverse cardiovascular event between the group that received lorcaserin (6.1 percent) versus in those that received placebo (6.2 percent) at study completion.
On top of lifestyle counseling, lorcaserin helped patients lower their weight by 4.2 kilograms (9.3 pounds) on average compared to 1.4 kilograms (3 pounds) for placebo at one year. Significantly more patients taking lorcaserin had lost at least 5 percent of their body weight (39 percent of the lorcaserin group versus 17 percent of the placebo group) or at least 10 percent of their body weight (15 percent versus 5 percent of the placebo group) at one year. Differences remained statistically significant through the length of the trial, which had a median follow up of more than three years.
The TIMI Study Group also reported small improvements in several factors generally associated with cardiovascular disease including levels of triglycerides, blood glucose, heart rate and blood pressure.
The most common side effects attributed to drug and leading to drug discontinuation were dizziness, fatigue, headache, nausea, and diarrhea.
“One of our hypotheses was that in the setting of weight loss, you might actually see a cardiovascular benefit. We did not see that. However, the magnitude of impact on cardiovascular risk factors was relatively small,” said Bohula. “For now, after rigorous testing, we can report that this is the first and only weight loss agent to show long-term cardiovascular safety in a high-risk population.”