Real-world effectiveness of inclisiran in heart failure patients with coronary artery disease across the ejection fraction spectrum

Background

Patients with chronic heart failure (CHF) and concomitant coronary artery disease (CAD) represent a high-risk population for recurrent atherosclerotic cardiovascular events. The efficacy of inclisiran, a small interfering RNA targeting hepatic PCSK9 synthesis, in patients with CHF remains underexplored.

Purpose

To evaluate the lipid-lowering efficacy of inclisiran in patients with CHF and CAD and to compare its effects according to left ventricular ejection fraction (LVEF <50% vs ≥50%).

Methods

We performed a retrospective, single-center analysis of prospectively collected data from 47 consecutive patients with CHF and established CAD treated with inclisiran. All patients had experienced a prior atherosclerotic cardiovascular event and were receiving optimized guideline-directed lipid-lowering therapy before inclisiran initiation. Demographic, biochemical, and lipid parameters were assessed at baseline (prior to the first inclisiran administration) and at 9-month follow-up (at the time of the third inclisiran injection).

Results

Of the 47 included patients, 31 (66%) were male, with a mean age of 70.6 ± 8.1 years. Ischemic etiology of heart failure was present in all patients. At baseline, 40 patients (85%) were receiving high-intensity statin therapy, while 7 patients (15%) were statin-intolerant. After 9 months of inclisiran therapy, there was a significant reduction in total cholesterol (from 4.38 ± 1.14 mmol/L to 3.05 ± 1.14 mmol/L; P < 0.001) and LDL-C (from 2.76 ± 0.97 mmol/L to 1.45 ± 1.10 mmol/L; P < 0.001). A trend toward a reduction in lipoprotein(a) [Lp(a)] was also observed (from 853 ± 625 mg/L to 612 ± 538 mg/L; P = 0.07). Overall, 34 patients (73%) achieved the LDL-C target of <1.4 mmol/L.

When stratified by LVEF (Group A: LVEF <50%, n = 23; Group B: LVEF ≥50%, n = 24), baseline lipid profiles were comparable between groups, including total cholesterol (4.34 ± 1.18 mmol/L vs 4.42 ± 1.09 mmol/L; P = 0.83), LDL-C (2.70 ± 1.00 mmol/L vs 2.79 ± 0.93 mmol/L; P = 0.82), and Lp(a) (710 ± 532 mg/L vs 630 ± 421 mg/L; P = 0.90). Reductions in LDL-C (−1.51 ± 1.28 mmol/L vs −1.72 ± 0.79 mmol/L; P = 0.58) and Lp(a) (−329 ± 536 mg/L vs −383 ± 561 mg/L; P = 0.96) were also comparable between the two groups. Achievement of the ESC/EAS-recommended LDL-C target (<1.4 mmol/L) did not differ significantly between groups (70% vs 79%). Inclisiran was well tolerated, with no treatment-related adverse events or therapy discontinuations.

Conclusions

In this real-world cohort of patients with CHF and CAD, inclisiran was associated with significant improvement in lipid parameters irrespective of left ventricular ejection fraction. These findings support the effectiveness of inclisiran across the heart failure spectrum. Prospective studies are warranted to validate these preliminary observations.