NEJM Clinician: Finding the Right Medicine – Evidence in an Age of Information
- A major clinical trial, the SELECT trial, has revealed a potential increased risk of cardiovascular events - including heart attack, stroke, and cardiovascular death - in individuals with...
- The SELECT trial followed participants for an average of 3.4 years.
- These findings primarily affect individuals with obesity *and* pre-existing cardiovascular disease.
Ozempic and Cardiovascular Risk: New Findings Demand Closer Scrutiny
What Happened? A Closer Look at the SELECT trial
A major clinical trial, the SELECT trial, has revealed a potential increased risk of cardiovascular events – including heart attack, stroke, and cardiovascular death – in individuals with obesity and established cardiovascular disease who were treated with semaglutide (Ozempic) compared to those receiving a placebo. The study, involving over 17,600 participants, initially aimed to determine if semaglutide could reduce the risk of these events, but the results showed a statistically significant, though modest, increase in risk within the treatment group. This finding challenges previous assumptions about the cardiovascular safety of GLP-1 receptor agonists like semaglutide.
Key Findings and Data
The SELECT trial followed participants for an average of 3.4 years. The primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death occured in 6.5% of participants receiving semaglutide versus 5.8% in the placebo group (hazard ratio 1.13, 95% confidence interval 1.01 to 1.26, p=0.02). Importantly, the trial population consisted of adults with a body mass index (BMI) of 27 or higher and established cardiovascular disease, such as prior heart attack or stroke. the study did *not* include individuals with type 2 diabetes, focusing solely on those with obesity and cardiovascular risk.
| Outcome | Semaglutide Group (%) | Placebo Group (%) | Hazard Ratio (95% CI) |
|---|---|---|---|
| MACE (Myocardial Infarction,Stroke,or CV Death) | 6.5 | 5.8 | 1.13 (1.01-1.26) |
| Myocardial Infarction | 3.4 | 2.9 | 1.17 (0.93-1.47) |
| Stroke | 3.7 | 3.1 | 1.19 (0.95-1.49) |
| Cardiovascular Death | 2.2 | 1.8 | 1.22 (0.89-1.67) |
Who is Affected? Understanding the Risk Profile
These findings primarily affect individuals with obesity *and* pre-existing cardiovascular disease. ItS crucial to understand that the SELECT trial did not involve people without cardiovascular risk factors. Thus, the results do not necessarily apply to individuals using semaglutide for weight loss who have a healthy cardiovascular profile. However, the study highlights the need for careful patient selection and monitoring, especially in vulnerable populations. Individuals currently taking semaglutide should consult with their healthcare provider to discuss their individual risk factors and the implications of these findings.
What does This Mean? Implications for Treatment
The SELECT trial results necessitate a reevaluation of the cardiovascular risk-benefit profile of semaglutide in specific patient populations. While semaglutide remains a valuable tool for weight management and has demonstrated benefits in individuals with type 2 diabetes, clinicians must now weigh the potential cardiovascular risks more carefully, especially when prescribing it to patients with established heart disease. Further research is needed to understand the underlying mechanisms driving this increased risk and to identify strategies for mitigating it.