Association of Renin-Angiotensin Inhibitor Treatment With Mortality and Heart Failure Readmission in Patients With Transcatheter Aortic Valve Replacement

Taku Inohara, Pratik Manandhar, Andrzej S Kosinski, Roland A Matsouaka, Shun Kohsaka, Robert J Mentz, Vinod H Thourani, John D Carroll, Ajay J Kirtane, Joseph E Bavaria, David J Cohen, Todd L Kiefer, Jeffrey G Gaca, Samir R Kapadia, Eric D Peterson, Sreekanth Vemulapalli
JAMA: the Journal of the American Medical Association 2018 December 4, 320 (21): 2231-2241

Importance: Data are lacking on the effect of a renin-angiotensin system (RAS) inhibitor prescribed after transcatheter aortic valve replacement (TAVR). Treatment with a RAS inhibitor may reverse left ventricular remodeling and improve function.

Objective: To investigate the association of prescription of a RAS inhibitor and outcomes after TAVR.

Design, Setting, and Participants: Retrospective cohort study of TAVR procedures performed in the United States (using the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry) between July 2014 and January 2016 that were linked to Medicare claims data (final date of follow-up: March 31, 2017). To account for differences in demographics, echocardiographic findings, and in-hospital complications, 1:1 propensity matching was performed.

Exposures: Initial hospital discharge prescription of a RAS inhibitor after TAVR.

Main Outcomes and Measures: Primary outcomes were all-cause death and readmission due to heart failure at 1 year after discharge, which were considered separately. The secondary outcome was health status assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ; score range: 0-100, with a higher score indicating less symptom burden and better quality of life; a small effect size was defined as 5 points) at 1 year.

Results: Among 21 312 patients who underwent TAVR at 417 US sites, 8468 patients (39.7%) were prescribed a RAS inhibitor at hospital discharge. After propensity matching, 15 896 patients were included (mean [SD] age, 82.4 [6.8] years; 48.1% were women; mean [SD] left ventricular ejection fraction [LVEF], 51.9% [11.5%]). Patients with a prescription for a RAS inhibitor vs those with no prescription had lower mortality rates at 1 year (12.5% vs 14.9%, respectively; absolute risk difference [ARD], -2.4% [95% CI, -3.5% to -1.4%]; hazard ratio [HR], 0.82 [95% CI, 0.76 to 0.90]) and lower heart failure readmission rates at 1 year (12.0% vs 13.8%; ARD, -1.8% [95% CI, -2.8% to -0.7%]; HR, 0.86 [95% CI, 0.79 to 0.95]). When stratified by LVEF, having a prescription for a RAS inhibitor vs no prescription was associated with lower 1-year mortality among patients with preserved LVEF (11.1% vs 13.9%, respectively; ARD, -2.81% [95% CI, -3.95% to -1.67%]; HR, 0.78 [95% CI, 0.71 to 0.86]), but not among those with reduced LVEF (18.8% vs 19.5%; ARD, -0.68% [95% CI, -3.52% to 2.20%]; HR, 0.95 [95% CI, 0.81 to 1.12]) (P = .04 for interaction). Of 15 896 matched patients, 4837 (30.4%) were included in the KCCQ score analysis and improvements at 1 year were greater in patients with a prescription for a RAS inhibitor vs those with no prescription (median, 33.3 [interquartile range, 14.2 to 51.0] vs 31.3 [interquartile range, 13.5 to 51.1], respectively; difference in improvement, 2.10 [95% CI, 0.10 to 4.06]; P < .001), but the effect size was not clinically meaningful.

Conclusions and Relevance: Among patients who underwent TAVR, receiving a prescription for a RAS inhibitor at hospital discharge compared with no prescription was significantly associated with a lower risk of mortality and heart failure readmission. However, due to potential selection bias, this finding requires further investigation in randomized trials.

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