What is the clinical evidence from this study?

Study design: Cohort. Population: dyslipidaemia and coronary artery disease (n=41396). Intervention: PCSK9 inhibitors (alirocumab, evolocumab or inclisiran) vs. statin. Primary outcome: new-onset heart failure (HR 0.566, 95% CI 0.506-0.634, p=<0.0001).

June 12, 2026Open Access

PCSK9 inhibitor therapy and 1-year risk of incident heart failure among adults with dyslipidaemia and coronary artery disease: a propensity-matched cohort study

Q: What are the key findings of this study?

Initiation of a PCSK9 inhibitor was associated with a significantly lower 1-year risk of new-onset heart failure compared to statins (HR 0.566; 95% CI 0.506–0.634; p<0.0001).

Q: What question did this study set out to answer?

To evaluate the impact of PCSK9 inhibitors on the 1-year risk of new-onset heart failure compared to statins in adults with dyslipidaemia and coronary artery disease.

Key Result

Initiation of a PCSK9 inhibitor was associated with a significantly lower 1-year risk of new-onset heart failure compared to statins (HR 0.566; 95% CI 0.506–0.634; p<0.0001).

Key Points

To evaluate the impact of PCSK9 inhibitors on the 1-year risk of new-onset heart failure compared to statins in adults with dyslipidaemia and coronary artery disease.
Conducted a retrospective cohort study using a federated electronic health record network.
Included adults (≥18 years) with dyslipidaemia and coronary artery disease who initiated either PCSK9 inhibitors or statins between 2015-2025.
Utilized one-to-one propensity score matching to balance participant characteristics, then followed for 1 year.
PCSK9i users experienced fewer incidents of new-onset heart failure (466) compared to statin users (844), with HR 0.566 (95% CI 0.506–0.634; p<0.0001).
Three-point major adverse cardiovascular events were lower in the PCSK9i group (483 vs 840; HR 0.594, 95% CI 0.532–0.665; p<0.0001).
All-cause mortality was significantly reduced in users of PCSK9 inhibitors (166 vs 532; HR 0.325, 95% CI 0.273–0.387; p<0.0001).

Study Design

Type

Cohort (n=41,396)

Multicenter

Yes

Structured PICO

Does PCSK9 inhibitor therapy reduce new-onset heart failure in adults with dyslipidaemia and coronary artery disease compared to statin therapy?

Population

41,396 adults (≥18 years) with dyslipidaemia and coronary artery disease (CAD)

Intervention

PCSK9 inhibitor (alirocumab, evolocumab, or inclisiran) newly initiated

Comparator

Statin therapy newly initiated, 1:1 propensity score matched

Outcome

New-onset heart failure at 1 yearhard clinical

In adults with dyslipidaemia and CAD, initiation of a PCSK9 inhibitor is associated with a significantly lower 1-year risk of incident heart failure, MACE, and mortality compared to statins.

Main Result

Effect estimate: HR 0.566 (95% CI 0.506-0.634)

Absolute Event Rate: 2.25% vs 4.08%

p-value: p=<0.0001

Abstract

Abstract Background/Introduction Whether proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) lower the risk of incident heart failure (HF) beyond statins in patients with dyslipidaemia and coronary artery disease (CAD) is unclear. Purpose To compare 1-year risk of new-onset HF between PCSK9i and statin therapy among adults with dyslipidaemia and CAD. Methods We performed a retrospective cohort study on a large federated electronic health record network. Adults (≥18 years) with dyslipidaemia and CAD who newly initiated a PCSK9i (alirocumab, evolocumab or inclisiran) or a statin (ATC C10AA) between 2015–2025 were eligible. One-to-one propensity score matching (caliper 0.1 SD) balanced demographics, comorbidities, laboratory values and concomitant medications. Follow-up began the day after index prescription and continued to 365 days. Primary outcome: new-onset HF. Secondary outcomes: three-point major adverse cardiovascular events (MACE; myocardial infarction, stroke, cardiovascular death) and all-cause mortality. Cox models estimated hazard ratios (HRs) with 95% CIs. Results After matching, 20,698 patients remained in each group. Over 1 year, PCSK9i users had fewer primary events than statin users (466 vs 844), yielding HR 0.566 (95% CI 0.506–0.634; p0.0001). Three-point MACE was also lower (483 vs 840; HR 0.594, 95% CI 0.532–0.665; p0.0001). All-cause mortality was markedly reduced (166 vs 532; HR 0.325, 95% CI 0.273–0.387; p0.0001). Results were robust in sensitivity analyses; a negative control outcome showed no association. Conclusions In adults with dyslipidaemia and CAD, initiation of a PCSK9i was associated with a significantly lower 1-year risk of new-onset HF, alongside reductions in three-point MACE and all-cause mortality versus statins. These real-world findings support a potential secondary-prevention role of PCSK9i for HF risk reduction and warrant prospective confirmation.For image description, please refer to the figure legend and surrounding text.