Ramipril After Transcatheter Aortic Valve Implantation in Patients Without Reduced Ejection Fraction: The RASTAVI Randomized Clinical Trial

Abstract

Background: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation.

Methods and results: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group (P=0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P=0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P=0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis.

Conclusions: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up.

Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.

Keywords: TAVR; renin‐angiotensin; ventricular remodeling.

Figure 1. Flowchart of the study.

LVEF indicates left ventricular ejection fraction; RASi, renin‐angiotensin system inhibitors; and TAVI, transcatheter aortic valve intervention.

Figure 2. Adverse events related to ramipril.

Each box represents 1 patient (red: adverse event leading to treatment withdrawal; green: adverse event leading to temporary or definitive treatment dose reduction).

Figure 3. Kaplan–Meier estimates for the combined end point (A), cardiac mortality (B), and heart failure readmissions (C) in the global study population at 1‐y follow‐up.

HF indicates heart failure.

Figure 4. Summary of the main clinical outcomes of the study.

HR indicates hazard ratio; sHR, subdistribution hazard ratio; and TIA, transient ischemic attack. *Outcomes where sHR was used.

Figure 5. Outcomes according to ramipril dose in the treatment group.

HF indicates heart failure; and sHR, subdistribution hazard ratio.

Figure 6. Outcomes according to ramipril dose in the treatment group.

(A) Left ventricular telediastolic volume and (B) left ventricular telesystolic volume. HF indicates heart failure; and sHR, subdistribution hazard ratio.