I agree that the ARR in SELECT is quite small, and vis-a-vis the cost of this agent, the cost-QALY/ICER type cost-effectiveness analyzes (if they ever get done) likely will not be that compelling. It is also unfortunate that, while the result for the composite primary endpoint was positive, th…
I agree that the ARR in SELECT is quite small, and vis-a-vis the cost of this agent, the cost-QALY/ICER type cost-effectiveness analyzes (if they ever get done) likely will not be that compelling. It is also unfortunate that, while the result for the composite primary endpoint was positive, the hierarchical analysis failed at the first secondary endpoint, so we have no clear info on what drove the benefit (it isn’t CV death, although it appears to show a trend for reduction in non-fatal MI).
However, I am less bearish than you on these results, insofar as it potentially represents a new pathway for secondary prevention that is separate from LDL and “inflammation”. Admittedly, we don’t yet know the mechanism of benefit of GLP-1 RA’s for reducing ASCVD outcomes, but there is hope it goes beyond simple weight loss (which seems to be the only mechanism for its benefit shown in HFpEF).
I agree, at the bedside, a decision would need to be made on whether “residual risk” would be better addressed with ezetimibe (although as another commenter noted, a very small effect that took 7 years to be demonstrated; benefit driven by non-fatal MI and stroke); PCSK-9 inhibitors (also not cheap; the landmark trials showed benefit in composite primary endpoint likely driven by CV revasc events…in Fourier….while Odyssey Outcomes hierarchical secondary endpoints also failed at first outcome); or colchicine, which failed to show a benefit in CLEAR SYNERGY OASIS 9 presented at TCT, in contradistinction to its prior results in trials like Lodoco 2 or COLCOT. For the reasons you stated, I don’t think Semaglutide should be the default add-on agent by any means. However, I think there is enough there to warrant its consideration in an appropriate subset of patients, particularly among the cohort will significantly increased BMI.
Very interesting and thought provoking piece.
I agree that the ARR in SELECT is quite small, and vis-a-vis the cost of this agent, the cost-QALY/ICER type cost-effectiveness analyzes (if they ever get done) likely will not be that compelling. It is also unfortunate that, while the result for the composite primary endpoint was positive, the hierarchical analysis failed at the first secondary endpoint, so we have no clear info on what drove the benefit (it isn’t CV death, although it appears to show a trend for reduction in non-fatal MI).
However, I am less bearish than you on these results, insofar as it potentially represents a new pathway for secondary prevention that is separate from LDL and “inflammation”. Admittedly, we don’t yet know the mechanism of benefit of GLP-1 RA’s for reducing ASCVD outcomes, but there is hope it goes beyond simple weight loss (which seems to be the only mechanism for its benefit shown in HFpEF).
I agree, at the bedside, a decision would need to be made on whether “residual risk” would be better addressed with ezetimibe (although as another commenter noted, a very small effect that took 7 years to be demonstrated; benefit driven by non-fatal MI and stroke); PCSK-9 inhibitors (also not cheap; the landmark trials showed benefit in composite primary endpoint likely driven by CV revasc events…in Fourier….while Odyssey Outcomes hierarchical secondary endpoints also failed at first outcome); or colchicine, which failed to show a benefit in CLEAR SYNERGY OASIS 9 presented at TCT, in contradistinction to its prior results in trials like Lodoco 2 or COLCOT. For the reasons you stated, I don’t think Semaglutide should be the default add-on agent by any means. However, I think there is enough there to warrant its consideration in an appropriate subset of patients, particularly among the cohort will significantly increased BMI.