Beta-Blocker Therapy Is Associated With Increased 1-Year Survival After Hip Fracture Surgery

A Retrospective Cohort Study

Ahmad Mohammad Ismail, MD; Rebecka Ahl, MB BChir, PhD; Maximilian Peter Forssten, MD; Yang Cao, PhD; Per Wretenberg, MD, PhD; Tomas Borg, MD, PhD; Shahin Mohseni, MD, PhD

Disclosures

Anesth Analg. 2021;133(5):1225-1234. 

In This Article

Abstract and Introduction

Abstract

Background: The high mortality rates seen within the first postoperative year after hip fracture surgery have remained relatively unchanged in many countries for the past 15 years. Recent investigations have shown an association between beta-blocker (BB) therapy and a reduction in risk-adjusted mortality within the first 90 days after hip fracture surgery. We hypothesized that preoperative, and continuous postoperative, BB therapy may also be associated with a decrease in mortality within the first year after hip fracture surgery.

Methods: In this retrospective cohort study, all adults who underwent primary emergency hip fracture surgery in Sweden, between January 1, 2008 and December 31, 2017, were included. Patients with pathological fractures and conservatively managed hip fractures were excluded. Patients who filled a prescription within the year before and after surgery were defined as having ongoing BB therapy. The primary outcome of interest was postoperative mortality within the first year. To reduce the effects of confounding from covariates due to nonrandomization in the current study, the inverse probability of treatment weighting (IPTW) method was used. Subsequently, Cox proportional hazards models were fitted to the weighted cohorts. These analyses were repeated while excluding patients who died within the first 30 days postoperatively. This reduces the effect of early deaths due to surgical and anesthesiologic complications as well as the higher degree of advanced directives present in the study population compared to the general population, which allowed for the evaluation of the long-term association between BB therapy and mortality in isolation. Results are reported as hazard ratios (HR) with 95% confidence intervals (CI). Statistical significance was defined as a 2-sided P value <.05.

Results: A total of 134,915 cases were included in the study. After IPTW, BB therapy was associated with a 42% reduction the risk of mortality within the first postoperative year (adjusted HR = 0.58, 95% CI, 0.57–0.60; P < .001). After excluding patients who died within the first 30 days postoperatively, BB therapy was associated with a 27% reduction in the risk of mortality (adjusted HR = 0.73, 95% CI, 0.71–0.75; P < .001).

Conclusions: A significant reduction in the risk of mortality in the first year following hip fracture surgery was observed in patients with ongoing BB therapy. Further investigations into this finding are warranted.

Introduction

Recent investigations have shown an association between beta-blocker (BB) therapy and a reduction in risk-adjusted 90-day mortality after hip fracture surgery.[1,2] These results are in line with several other studies showing the same positive effect between BB therapy and short-term mortality after major noncardiac surgery or severe traumatic injuries.[3–10] This may be explained by the physiological stress response induced by both the physical and surgical trauma associated with hip fractures. Trauma induces a hyperadrenergic state characterized by the activation of the sympathetic nervous system and the subsequent release of catecholamines.[11,12] This increases the strain on the cardiovascular system and other vital organs, which results in damage and complications, such as arrhythmias or myocardial infarction, where patients with preoperative cardiac conditions are at higher risk for such adverse events.[6] It is therefore postulated that the protective effect is a result of BB therapy inducing a downregulation of the trauma- and surgically induced hyperadrenergic state.[11–14]

The incidence of hip fractures is expected to increase during the coming decades as the global population continues to age.[15–18] Hip fractures primarily occur in a subpopulation that is older and suffers from a high overall disease burden.[1,2,19,20] The postoperative mortality rates within the first year for hip fracture surgery are reported to be as high as 27%, with the most common cause of death being cardiovascular events.[15,20–25] Despite better overall health care, mortality rates in many countries have remained relatively unchanged for the last 15 years in this patient population.[20] Several studies have indicated a protective effect of BBs beyond the immediate postoperative period with better long-term survival after major noncardiac surgery.[4,5,26] However, there is no study investigating the association between ongoing perioperative BB therapy and long-term survival exclusively after hip fracture surgery. The purpose of the current study is to investigate if the association between BB therapy and survival extends beyond the immediate postoperative period after hip fracture surgery. We hypothesized that ongoing preoperative BB therapy, which is continued postoperatively, is associated with a decrease in mortality within the first year after hip fracture surgery.

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