Preoperative proprotein convertase subtilisin/kexin type 9 inhibitors versus statins and postoperative adverse events in hyperlipidemia: A nationwide, active-comparator cohort study.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors achieve substantial reductions in low-density lipoprotein cholesterol, yet their effectiveness and safety in the perioperative setting have not been fully delineated. The present study evaluated postoperative adverse events among patients treated with preoperative PCSK9 inhibitors versus statins.

METHODS

We conducted a 1:1 propensity score-matched, active-comparator cohort study using the TriNetX research database, including adults with hyperlipidemia who underwent surgery at U.S. medical institutions between July 1, 2015, and June 30, 2025, and who received either PCSK9 inhibitors or statins within 90 days before surgery. The primary outcome was 30-day postoperative major adverse cardiovascular events (MACEs). Secondary outcomes included all-cause mortality, acute kidney injury (AKI), respiratory infections, and other complications.

RESULTS

Among the 35,923 matched pairs, PCSK9 inhibitor use was associated with significantly lower risks of 30-day MACEs [6.4% vs. 9.6%; number needed to treat: 31; relative risk (RR): 0.67, 95% confidence interval (CI): 0.63-0.70], all-cause mortality (RR: 0.45: 95% CI: 0.35-0.58), AKI (RR: 0.45: 95% CI: 0.41-0.49), and respiratory infections (RR: 0.77: 95% CI: 0.71-0.83; all p < 0.0001). These associations remained consistent across postoperative time intervals and therapy duration strata. Furthermore, PCSK9 inhibitor use was associated with reduced risks of delirium (RR: 0.41: 95% CI: 0.28-0.60) and elevated liver enzymes (RR: 0.58: 95% CI: 0.48-0.70).

CONCLUSIONS

Preoperative PCSK9 inhibitor therapy was associated with more favorable perioperative outcomes and a better safety profile compared with statins. Randomized controlled trials are warranted to confirm these results.