Inclisiran Linked to Lower MACE, AMI Rates in High-Risk ASCVD Population

Inclisiran (Leqvio; Novartis) may offer meaningful cardiovascular benefits for patients with atherosclerotic cardiovascular disease (ASCVD) who remain at elevated risk despite treatment with maximally tolerated statins, according to data recently presented at the 2026 American College of Cardiology (ACC.26) Scientific Session.¹

In a propensity-matched analysis using the TriNetX US Collaborative Network, investigators found that inclisiran use was associated with lower rates of 4-point major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), and all-cause hospitalization at 1 year compared with standard therapy alone.

Although statins remain the cornerstone of lipid-lowering therapy for ASCVD, many patients continue to experience residual cardiovascular risk even after achieving intensive LDL cholesterol (LDL-C) reduction. Inclisiran, a small interfering RNA therapy targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), has emerged as a novel option that provides durable LDL-C lowering through twice-yearly maintenance dosing after initial treatment.

While inclisiran has demonstrated efficacy in lowering LDL-C in prior clinical trials, long-term cardiovascular outcomes data in real-world populations have remained limited. To evaluate these outcomes, researchers analyzed data from the TriNetX US Collaborative Network between 2022 and 2024. The study included adults with ASCVD receiving maximum-dose statins who either received inclisiran (n = 1000) or did not receive inclisiran (n = 579,443). Investigators assessed 1-year outcomes, including AMI, stroke, hospitalization, heart failure, revascularization procedures, and 4-point MACE, defined as death, stroke, AMI, or revascularization.

To minimize confounding, investigators performed 1:1 propensity score matching using more than 30 covariates, resulting in 999 matched patients in each cohort. Baseline characteristics were similar between groups, with a mean age of 67.5 years in the inclisiran group and 67.8 years in the non-inclisiran group. Women accounted for 40.4% and 39.4% of the groups, respectively.

The analysis demonstrated a statistically significant reduction in 4-point MACE among patients treated with inclisiran. Event rates were 14.6% in the inclisiran group compared with 22.7% in the non-inclisiran cohort, corresponding to an HR of 0.67 (95% CI, 0.54-0.82; P < .001).

Investigators also observed a significant reduction in AMI rates. Patients receiving inclisiran experienced AMI at a rate of 5.0% compared with 8.5% among patients not treated with the therapy (HR, 0.62; 95% CI, 0.44-0.89; P = .01).

Additionally, all-cause hospitalization rates were significantly lower in the inclisiran cohort, occurring in 20.8% of patients vs 28.8% in the comparator group (HR, 0.73; 95% CI, 0.61-0.88; P < .001).

Other cardiovascular outcomes numerically favored inclisiran but did not achieve statistical significance. Stroke rates were 4.1% in the inclisiran group vs 5.4% in the non-inclisiran cohort, while heart failure occurred in 7.2% vs 8.7% of patients, respectively. Revascularization procedures were reported in 7.5% of inclisiran-treated patients compared with 9.2% of controls.

The findings add to growing interest in PCSK9-targeted therapies as clinicians seek additional strategies to reduce cardiovascular risk beyond statins alone. Previous studies evaluating PCSK9 inhibition have demonstrated substantial LDL-C reductions and improved cardiovascular outcomes, particularly in high-risk secondary prevention populations.² Inclisiran’s dosing schedule may also support adherence compared with more frequently administered lipid-lowering therapies.

The investigators concluded that inclisiran, when used alongside maximally tolerated statins, was associated with reduced MACE, AMI, and hospitalization rates in a large real-world ASCVD cohort.¹ They noted that the results highlight the therapy’s potential to improve cardiovascular outcomes in high-risk patients, although further prospective studies will be important to confirm long-term benefits.

References

1. Okorigba EM, Mondal A, Bhandari B, et al. Cardiovascular outcomes of inclisiran use in patients with clinical atherosclerotic cardiovascular disease (ASCVD) on maximally tolerated statins: a propensity matched analysis. Presented at: ACC.26; March 28-30, 2026; New Orleans, LA.

2. Kao G, Chen C, Zhang Y, et al. Efficacy and safety of PCSK-9 inhibitors in patients with acute coronary syndrome: a systematic review and network meta-analysis. BMC Cardiovasc Disord. 2025;25(1):629. doi:10.1186/s12872-025-05070-3