Background: Considering the limited information available regarding the impact of antihypertensive classes on mortality and physical function during hospitalization, we aimed to clarify the impact of six antihypertensive classes, namely thiazide/thiazide-like diuretics (TH), calcium receptor blockers (CCBs), renin-angiotensin-aldosterone system inhibitors (RASis), mineral corticoid receptor antagonists, α-blockers, and β-blockers, on outcomes in adult patients undergoing major surgeries. Methods: This study was a subanalysis of a nationwide observational cohort study involving Japanese adults undergoing major surgeries from 2018 to 2019 using an administrative claims database. We recruited 473,327 antihypertensive medication users and 376,583 nonusers aged ≥50 years who underwent six different types of surgeries, including coronary artery bypass grafting (CABG), thoracic lobectomy, orthopedic surgery, hepatopancreatobiliary surgery, gastrointestinal resection, and urological surgery. The risk for overall death or functional decline, defined as a >5-point decrease in the Barthel Index score during hospitalization, was determined using multivariable logistic regression models. Results: All-cause inhospital deaths occurred in 5,777 (1.2%) users and 2,657 (0.7%) nonusers. Functional decline was observed in 42,930 (9.2%) users and 22,550 (6.0%) nonusers. Among single class users, RASi use had a multivariable odds ratio (OR) of 0.77 (95% confidence interval (CI) 0.63-0.93 vs. TH) for the composite of mortality and functional decline. β-Blocker use was associated with an increased risk for functional decline (OR 1.27, 95% CI 1.01-1.60 vs. TH). Among the recipients of the two medication classes, TH/RASi usage was associated with the lowest risk for composite outcome (OR 0.68, 95% CI 0.60-0.77 vs. TH/CCB). Among the recipients of the three or more medication classes, TH/CCB/RASi or TH/CCB/RASi/other displayed the lowest odds for composite outcome (OR 0.72, 95% CI 0.49-0.82 vs. TH/CCB/other; OR 0.63, 95% CI 0.49-0.82 vs. TH/CCB/others). A stratified analysis revealed that RASi users had a lower OR for the composite outcome after major surgery categories except CABG than non-RASi users. Conclusions: RASis were associated with decreased risk of postoperative mortality and functional decline regardless of the number of antihypertensive classes or surgery type. Managing hypertension through multidrug combinations, including RASis, may mitigate mortality and loss of physical function during the perioperative period.

The authors have declared no competing interest.

This study was supported by the Health and Labour Sciences Research Grant (Grant No. Seisaku-Sitei-22AA2003 to KF) of the Japan Ministry of Health, Labour and Welfare.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Our study protocol was approved by the ethics committee of Tokyo Medical and Dental University.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.