Association between antihypertensive combinations and postoperative mortality and functional decline: a nationwide survey of Japanese adults undergoing major surgeries

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.

Clinical Perspective

What is new?

• This nationwide observational cohort study of Japanese adults undergoing major surgeries from 2018 to 2019 using an administrative claims database showed that all-cause inhospital deaths occurred in 5,777 (1.2%) antihypertensive users and 2,657 (0.7%) nonusers, whereas functional decline was observed in 42,930 (9.2%) antihypertensive users and 22,550 (6.0%) nonusers.

• We found that an increase in the number of antihypertensive classes used, indicative of patients with treatment-resistant hypertension, was associated with a higher risk of mortality and loss of physical function, partly attributed to loop diuretic use for congestion.

What are the clinical implications?

• This study determined combinations of antihypertensive drugs that potentially improve the outcomes of antihypertensive users undergoing major surgeries, with the favorable regimens including RASis independent of the number of antihypertensive classes used.

• After undergoing all major surgery categories except CABG, patients on RASis were at a lower risk of death and functional decline than those who were treated with other antihypertensive classes.