Vancouver IM LMR

It feels wrong to post a paper that mentions CRP on the Mark Roberts Fan Club teaching blog but here we go

Thanks for joining us for IM Journal Club on the SELECT trial!

Slides

SELECT trial (NEJM)

Summary:

Among 17,604 patients with BMI of 27 or greater and pre-existing CV disease without diabetes, semaglutide 2.4 mg subQ qweekly reduced the risk of a composite of death from CV causes/non-fatal MI/non-fatal stroke by 20% (HR 0.80, 95% CI 0.72-0.90).

Drug safe and mostly tolerated – incidence of adverse events lower in treatment group than placebo, with most signal for GI symptoms and gallbladder disease, without other adverse effects like pancreatitis, AKI, malignancy risk.

Possible mechanism of reduced CV risk in the absence of diabetes may be related to relieving the pro-inflammatory and pro-thrombotic milieu of adipose tissue.

Our collective thoughts:

• The trial shows a 20% relative risk reduction of the cardiac composite outcome, recognizing that the NNT is pretty high ~70
• The drug is expensive
• Based on the subgroup analysis (no P values, can’t fully make treatment decisions around this) – BMI 27-34 saw benefit, but benefit less clear for BMI 35 and above.
• Dr Wong observed that the cumulative incidence curves for the primary composite outcome looked like a HF outcomes curve with separation at 6 months (vs MACE trials where outcome curves generally separate after a longer period of time) – interesting given that only 25% of the population had heart failure.
• The significant CRP drop in the semaglutide group lends possible support to the proposed inflammatory/adiposopathy mechanism of how obesity generates CV risk