Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec 4;320(21):2231-2241.
doi: 10.1001/jama.2018.18077.

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

Taku Inohara  1   2 , Pratik Manandhar  1 , Andrzej S Kosinski  1 , Roland A Matsouaka  1 , Shun Kohsaka  2 , Robert J Mentz  1 , Vinod H Thourani  3 , John D Carroll  4 , Ajay J Kirtane  5 , Joseph E Bavaria  6 , David J Cohen  7   8 , Todd L Kiefer  1 , Jeffrey G Gaca  1 , Samir R Kapadia  9 , Eric D Peterson  1 , Sreekanth Vemulapalli  1
Affiliations

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

Taku Inohara et al. JAMA. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Inohara reported receiving grants from the JSPS Overseas Research fellowship, Boston Scientific, Miyata Cardiac Research Promotion Foundation, and Pfizer Health Research Foundation. Dr Kohsaka reported receiving grants from Bayer Pharmaceutical Co and Daiichi Sankyo; and personal fees from Bristol-Myers Squibb/Pfizer. Dr Mentz reported receiving grants from the National Institutes of Health, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Madeleine, Medtronic, Merck, Novartis, Otsuka, and ResMed; receiving honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, HeartWare, Janssen, Luitpold Pharmaceuticals, Merck, Novartis, ResMed, and Thoratec/St Jude Medical; and serving on advisory boards for Luitpold Pharmaceuticals and Boehringer Ingelheim. Dr Thourani reported serving on advisory boards for Edwards Lifesciences, Abbott Vascular, Boston Scientific, and Gore Vascular. Dr Carroll reported serving as a local site investigator in transcatheter aortic valve replacement studies sponsored by Edwards Lifesciences and Medtronic. Dr Kirtane reported receiving institutional grant support from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical. Dr Bavaria reported serving as a primary investigator for Edwards Lifesciences and Medtronic and as a subprimary investigator for St Jude Medical and Boston Scientific. Dr Cohen reported receiving grants from Edwards Lifesciences, Medtronic, and Boston Scientific; and consulting fees from Medtronic and Edwards Lifesciences. Dr Peterson reported receiving grants and personal fees from Janssen and Eli Lilly; and personal fees from Boehringer Ingelheim, Bayer, and AstraZeneca. Dr Vemulapalli reported receiving grants from the American College of Cardiology, Abbott Vascular, the Agency for Healthcare Research and Quality, the Patient-Centered Outcomes Research Institute, the Society of Thoracic Surgeons, and Boston Scientific; and serving on advisory boards for Premiere Research, Janssen, Boston Scientific, and Novella. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cohort Creation for Study of Renin-Angiotensin Inhibitor Treatment After TAVR
Additional exclusion criteria were applied to create a quality-of-care analysis cohort (eFigure 4 in the Supplement). TAVR indicates transcatheter aortic valve replacement.
Figure 2.
Figure 2.. Kaplan-Meier Curves and Landmark Analysis for Mortality and Cumulative Incidence Curves for Heart Failure Readmission
The median observation time in panel A was 4.7 months (95% CI, 4.2-5.1 months) for no prescription and 5.0 months (95% CI, 4.5-5.5 months) for prescription of an renin-angiotensin system (RAS) inhibitor; panel B, 2.4 months (95% CI, 2.0-6.8 months) vs 2.6 months (95% CI, 2.1-8.0 months), respectively; panel C, 5.3 months (95% CI, 4.9-5.7 months) vs 5.6 months (95% CI, 5.2-6.1 months); and panel D, 4.8 months (95% CI, 4.2-5.7 months) vs 4.6 months (95% CI, 4.0-6.7 months). The landmark analyses were conducted post hoc. Only patients without events at 1 month were considered in the analysis after the landmark time point (panels C and D). ARD indicates absolute risk difference; HR, hazard ratio.
Figure 3.
Figure 3.. Kaplan-Meier Curves for Mortality by Left Ventricular Ejection Fraction Status
The median observation time in panel A was 4.8 months (95% CI, 4.4-5.3 months) for no prescription and 5.1 months (95% CI, 4.6-5.9 months) for prescription of an renin-angiotensin system (RAS) inhibitor; and panel B, 3.9 months (95% CI, 2.6-5.0 months) vs 4.5 months (95% CI, 3.6-5.3 months), respectively. There was a significant interaction between the prescription of a RAS inhibitor and left ventricular ejection fraction (P = .04 for interaction). ARD indicates absolute risk difference; HR, hazard ratio.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nkomo VT, Gardin JM, Skelton TN, et al. . Burden of valvular heart diseases. Lancet. 2006;368(9540):1005-1011. doi:10.1016/S0140-6736(06)69208-8 - DOI - PubMed
    1. Zaid RR, Barker CM, Little SH, Nagueh SF. Pre- and post-operative diastolic dysfunction in patients with valvular heart disease. J Am Coll Cardiol. 2013;62(21):1922-1930. doi:10.1016/j.jacc.2013.08.1619 - DOI - PubMed
    1. CONSENSUS Trial Study Group Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med. 1987;316(23):1429-1435. doi:10.1056/NEJM198706043162301 - DOI - PubMed
    1. Yusuf S, Pitt B, Davis CE, et al. . Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325(5):293-302. doi:10.1056/NEJM199108013250501 - DOI - PubMed
    1. Pfeffer MA, Swedberg K, Granger CB, et al. . Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall Programme. Lancet. 2003;362(9386):759-766. doi:10.1016/S0140-6736(03)14282-1 - DOI - PubMed

Publication types

MeSH terms

Substances