Summary: In a small prespecified subgroup of the FOURIER trial comprising 197 statin-treated adults with type 1 diabetes and established atherosclerotic cardiovascular disease, evolocumab was associated with a numerically lower rate of the primary cardiovascular endpoint, but the effect was not statistically significant (hazard ratio 0.66, 95% CI 0.32 to 1.38). The reported absolute risk reduction of 7.3% should be read as hypothesis-generating rather than confirmatory, given the very small sample.
PICO Summary
| Element | Detail |
|---|---|
| Population | 197 statin-treated adults with type 1 diabetes and established ASCVD (the 0.7% type 1 diabetes subgroup of the 27,564-participant FOURIER randomised controlled trial; multinational; median follow-up 2.2 years). |
| Intervention | Evolocumab, a PCSK9 inhibitor, added to background statin therapy. Subgroup arm numbers were not separately reported in the abstract. |
| Comparison | Placebo added to background statin therapy. Subgroup arm numbers were not separately reported in the abstract. |
| Outcome | Primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina, or coronary revascularisation) in the type 1 diabetes subgroup: HR 0.66 (95% CI 0.32 to 1.38), not statistically significant as the interval crosses 1.0. Absolute risk reduction 7.3%. The placebo-arm 2.5-year event rate rose stepwise across no diabetes, type 2 diabetes, and type 1 diabetes (11.0% to 15.2% to 20.4%; P < 0.0001). No diabetes and type 2 diabetes HRs were significant (0.87, 95% CI 0.79 to 0.96; and 0.84, 95% CI 0.75 to 0.93). Subgroup-specific LDL-C reductions and adverse-event data were not reported in the abstract. |
Evolocumab in type 1 diabetes (FOURIER)
RCT subgroup · type 1 diabetes + ASCVD · 2.2 yr
Evolocumab showed a numerically lower event rate in the 197-patient type 1 diabetes subgroup (HR 0.66), but the wide CI crosses 1.0, so the result is hypothesis-generating, not confirmatory.
Expert Commentary
This is a prespecified subgroup analysis of an industry-sponsored outcomes trial, not a dedicated trial in type 1 diabetes, and the verdict must reflect that. The headline figures are striking: a 7.3% absolute risk reduction and a placebo-arm event rate that climbs steeply with diabetes type. Yet the type 1 diabetes hazard ratio of 0.66 carries a confidence interval of 0.32 to 1.38 that comfortably includes no effect, so the result is best described as consistent with, but not proof of, benefit. The dominant limitation is power: only 197 of 27,564 participants had type 1 diabetes, an estimate too fragile to anchor practice on its own. Sponsorship by the manufacturer of evolocumab, with several authors employed by the company, further warrants caution, and the apparently large absolute benefit is plausibly inflated by the small denominator and the high baseline risk in this group. Can I use this with my patients? For a statin-treated adult with type 1 diabetes and established atherosclerotic disease whose LDL-C remains above target, this analysis is reassuring rather than decisive, and the case for PCSK9 inhibition still rests mainly on the much larger overall trial and on guideline LDL-C goals. The authors call for dedicated randomised cardiovascular outcomes trials in type 1 diabetes, and that call should be heeded before this subgroup is treated as established efficacy.
References
Kang YM, Giugliano RP, Ran X, et al. Cardiovascular Outcomes and Efficacy of the PCSK9 Inhibitor Evolocumab in Individuals With Type 1 Diabetes: Insights From the FOURIER Trial. Diabetes Care. 2025;48(9):1512-1516. doi:10.2337/dc25-0942