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

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 s...

Identifying patients likely to be readmitted after transcatheter aortic valve replacement

“…The modifiable factors among the predictors listed in Box 1 should be medically optimised: anaemia may be corrected with transfusion and iron supplementation, and maximal therapy to control diabetes, AF and kidney, liver and lung diseases should be instituted prior to TAVR. Pharmacologically, prescription of a renin-angiotensin system (RAS) inhibitor has been show in a TVT Registry analysis to decrease 1-year heart failure readmission following TAVR (HR 0.86, 95% CI 0.79 to 0.95), regardless of LVEF (p=0.84 for interaction) or renal function (p=0.42 for interaction)36; the association of RAS inhibition with reduced readmission has also been shown in a prospective observational 10-centre study37 and is the subject of a single-arm prospective clinical trial (RASTAVI, NCT03201185). Because impaired pre-TAVR functional capacity, as typified by slow gait speed, and nutrition, as typified by hypoalbuminaemia, are associated with readmission, preprocedure physical therapy (‘prehab’) and protein supplementation may also reduce readmission; the randomised Protein and Exercise to Reverse Frailty in OldeR Men and women undergoing Transcatheter Aortic Valve Replacement (PERFORM-TAVR) trial (NCT03522454) is currently testing this hypothesis.…”

Perioperative use of renin-angiotensin system inhibitors and outcomes in patients undergoing cardiac surgery

“…The unadjusted survival curves trended to show the survival benefit with RASi ( Fig. 5) but it did not reach significant differences between with and without postoperative RASi groups at 3, 5 and 6 year (9.48% vs. 10.77%, RR 0.88, 95% CI 0.72-1.00; 14.87% vs. 16.90%, RR 0.88, 95% CI 0.75-1.01; 17.67% vs. 19.42%, RR 0.91, 95% CI 0.80-1.02, respectively). The survival curves adjusted with the use of the PSM are shown in Fig.…”

“…The results of this multicenter and cohort study showed that preoperative RASi therapy (vs. no preoperative RASi) was associated with a significant decrease of 30-day mortality but no significant changes in postoperative MACE or long-term survival. Postoperative RASi therapy, i.e., patients with the prescription of discharge RASi, was associated with a significant decrease in longterm mortality, up to 6 years after cardiac surgery (17.09% vs. 19.95%, RR 0.84, 95% CI 0.72-0.96, P = 0.0228), suggesting an association between perioperative RASi and benefits of survival (for both short and long-term survival). As previous studies showed, ACE inhibitors block the conversion of angiotensin-I to angiotensin-II (a potent vasoconstrictor), and block the breakdown of bradykinin (a potent vasodilator).…”

“…In a cohort study (2014), the prescription RASi after surgical aortic valve replacement was found to be associated with improved long-term survival (up to 10 yeas) in patients with severe aortic stenosis (594 matched pairs of treated and untreated patients) 8 . The latest clinical study (2018) showed that among patients who underwent transcatheter aortic valve replacement, receiving a prescription of RASi at hospital discharge compared with no prescription was significantly associated with a lower risk of mortality and heart failure readmission 19 . With regard to those conflicting results as above, large clinical trials have established beyond reasonable doubt the value of ACE inhibitors for patients with risk of CVD 1-4 .…”

“…The reported rates of patient RASi adherence for cardiovascular protection are high, range from 68 to 92% in the literature 35,36 . Finally, both CABG and valve surgery patients were included in this study since RASi have been shown to be beneficial in both groups of patients 1,2,[6][7][8][9][10]12,18,19 . The association we found in this study suggests that perioperative RASi may provide cardiovascular protection with potential long-term benefits for survival.…”