Key result
Inclisiran yields ~41% higher rates of LDL-C target attainment than evolocumab in ischaemic HFrEF.
Why the study?
The comparative efficacy of twice-yearly inclisiran versus bi-weekly evolocumab on top of maximally tolerated oral therapy for achieving LDL-C <55 mg/dL in patients with ischaemic HFrEF remained unknown.
Does subcutaneous inclisiran improve the proportion of patients achieving LDL-C <55 mg/dL compared to evolocumab in patients with ischaemic HFrEF on maximal statin and ezetimibe therapy?
RCT (n=112)
Open-label
1:9.3
No
Does subcutaneous inclisiran improve the proportion of patients achieving LDL-C <55 mg/dL compared to evolocumab in patients with ischaemic HFrEF on maximal statin and ezetimibe therapy?
In patients with ischaemic HFrEF on maximal oral lipid-lowering therapy, twice-yearly inclisiran achieved higher rates of reaching the <55 mg/dL LDL-C target and greater absolute LDL-C reduction than bi-weekly evolocumab, with fewer adverse events.
May favor inclisiran over evolocumab for LDL-C targets in ischaemic HFrEF; hypothesis-generating given small open-label design.
Background Achieving LDL-C <55 mg/dL is a therapeutic goal in very high-risk patients with ischaemic heart failure with reduced ejection fraction (HFrEF). While PCSK9 inhibition is effective, the comparative efficacy of twice-yearly Inclisiran (siRNA) versus bi-weekly Evolocumab (monoclonal antibody) on top of maximally tolerated oral therapy remains unknown in this specific population. Purpose To compare the efficacy and safety of Inclisiran versus Evolocumab in achieving LDL-C <55 mg/dL at 5 months in patients with HFrEF of ischaemic origin and chronic non-revascularisable coronary syndromes. Methods This was a single-centre, randomised, open-label trial. 112 patients with chronic HFrEF (LVEF ≤40%) and ischaemic heart disease on stable atorvastatin 80 mg and ezetimibe 10 mg, with LDL-C >70 mg/dL, were randomised 1:9.3 to receive either Inclisiran 284 mg subcutaneously (Days 1, 90, and Month 6; n=12) or Evolocumab 140 mg subcutaneously every 2 weeks (n=100). The primary endpoint was the proportion of patients achieving LDL-C <55 mg/dL at Month 6. Secondary endpoints included absolute LDL-C reduction and treatment-emergent adverse events (TEAEs). Analysis was by intention-to-treat. Results Baseline characteristics were balanced (mean age 68 years, 75% male, mean LVEF 32%, mean LDL-C 128.4 mg/dL). At 5 months, the primary endpoint was achieved by 91.7% (11/12) of patients in the Inclisiran group versus 65.0% (65/100) in the Evolocumab group (Relative Risk: 1.41; 95% CI 1.12–1.78; p=0.02). Mean LDL-C reduction was significantly greater with Inclisiran (-68.2 mg/dL vs. -58.5 mg/dL; p=0.02). The incidence of TEAEs was lower with Inclisiran (18.3% vs. 28.0%; p=0.04), driven mainly by fewer injection-site reactions (10.5% vs. 17.0%). Serious adverse events occurred in 1.2% (Inclisiran) vs. 6.0% (Evolocumab; p=0.04). Conclusion In patients with ischaemic HFrEF on maximal statin/ezetimibe therapy, Inclisiran was significantly more effective than Evolocumab in achieving the stringent LDL-C target of <55 mg/dL at 5 months, with a favourable safety profile and less frequent dosing. These findings support Inclisiran as a potent and convenient lipid-lowering strategy in this high-risk cohortFigura 1
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Sabido et al. (2026) conducted an RCT in Ischaemic heart failure with reduced ejection fraction (HFrEF) and chronic non-revascularisable coronary syndromes (n=112). Inclisiran vs. Evolocumab 140 mg subcutaneously every 2 weeks was evaluated on Proportion of patients achieving LDL-C <55 mg/dL (RR 1.41, 95% CI 1.12-1.78, p=0.02). Inclisiran achieved LDL-C <55 mg/dL more frequently than evolocumab at 5 months in ischaemic HFrEF patients (91.7% vs 65.0%; RR 1.41; 95% CI 1.12-1.78; p=0.02).
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