Evaluation of biochemical and economic outcomes in patients treated with PCSK9 inhibitors in a real clinical practice setting

BACKGROUND: PCSK9 inhibitors (PCSK9i) in combination with high-dose statins can reduce LDL-cholesterol (LDL-C) levels by 50-60% over statin monotherapy. This analysis investigated biochemical (LDL-C reduction) and economic outcomes in Italian patients treated with PCSK9i or potentially eligible but untreated. METHODS: Administrative databases of healthcare institutions covering around 5 million residents were used to identify patients with PCSK9i prescriptions or potentially eligible-untreated patients between 2017 and Oct-2022. Outcomes were assessed during follow-up in cohorts balanced for baseline covariates by propensity score matching (PSM). RESULTS: After PSM-balancing, 2649 treated and 2649 potentially eligible-untreated patients were included: mean age 64.4-64.7 years, 70-68% males, 92-93% with hypertension, 24-25% with diabetes, and 87% with previous atherosclerotic/cardiovascular events. During follow-up, PCSK9i-treated patients versus untreated/eligible showed a reduction of LDL-C levels (68.9 +/- 43.9 vs. 100.4 +/- 34.6 mg/dL, P<0.0001), hospitalization rates for heart attack (4.5% vs. 6.8%, P=0.0069), heart failure (4.5% vs. 6.6%, P=0.010), and lower all-cause mortality (3.2% vs. 9.5%, P<0.0001). The multivariate Cox model confirmed that eligible-untreated patients had a more than doubled mortality risk compared to the PCSK9i-treated ones (HR: 2.291, 95%CI: 1.651-3.178, P<0.0001). Although mean annualized total healthcare costs were higher in PCSK9i-treated versus untreated/eligible patients (6745 vs. 4343, P<0.0001), because of the higher drug costs, PCSK9i therapy was associated with reduced expenses for hospitalizations (1113 vs. 1687, P<0.0001) and specialist outpatient services (386 vs. 787, P<0.0001). CONCLUSIONS: The real-world analysis suggests that therapy with PCSK9i resulted in reduced LDL-C levels, lower mortality rates and cost savings for hospitalizations and specialist services.