Association Between PCSK9 Inhibitor Use and Risk of Incident Heart Failure in Patients With Dyslipidemia.

Aim

To evaluate whether the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) is associated with a reduced 1-year incidence of new-onset heart failure (HF) compared to statins among patients with dyslipidemia.

Methods

We conducted a retrospective cohort study using the TriNetX global health research network. Adults diagnosed with dyslipidemia and initiated on either PCSK9is or statins between 2015 and 2025 were included. One-to-one propensity score matching (PSM) was applied to balance baseline characteristics. The primary outcome was new-onset HF within one year. Cox proportional hazards models were used to estimate hazard ratios (HRs), with E-values calculated to assess unmeasured confounding.

Results

After PSM, 40,098 patients were included in each group. The incidence of new-onset HF was significantly lower in the PCSK9is group (1.8 vs. 2.7 per 100 person-years; HR 0.69, 95% CI 0.63-0.76; P < .001). Subgroup analyses confirmed consistent benefit across age, sex, and comorbidity strata. Secondary outcomes including all-cause mortality, hospitalization, and MACEs were also significantly reduced in the PCSK9is group. A negative control outcome showed no significant association.

Conclusions

Among patients with dyslipidemia, PCSK9i use was associated with a significantly lower 1-year risk of new-onset HF and improved secondary outcomes compared to statin therapy. These findings support a potential preventive role of PCSK9is in HF, warranting further prospective studies to confirm these observations.