Centrifugal Flow LVADs, Phosphodiesterase-5 Inhibitors, and Risk for Mortality, Stroke

For patients with centrifugal flow left ventricular assist devices (LVADs), postimplant use of phosphodiesterase-5 inhibitors (PDE-5i) decreased risk for mortality and ischemic stroke. These findings were published in JACC: Heart Failure.

Data for this study were sourced from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. Patients (N=7229) who received a primary continuous flow centrifugal LVAD between 2017 and 2020 were assessed for outcomes on the basis of receiving postimplant PDE-5i. The primary endpoint was the composite outcome of pump thrombosis, ischemic stroke, and all-cause mortality.

Patients were aged mean 57.2±13.0 years, 77.1% were men, 28.5% were Black, BMI was 28.8±7.2 kg/m², and time on LVAD was 11.91±8.60 months. Patients who received PDE-5i (30.1%) were younger, more were Black, fewer smoked, more received a Heartware HVAD device, they had higher preimplant international normalized ratio, more pulmonary hypertension, and were more likely to have history of renal disease.

The composite endpoint occurred among 18.9% of the PDE-5i and 21.2% of the no PDE-5i cohorts (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.69-0.86; P <.0001).

Stratified by outcome components, PDE-5i was associated with decreased risk for all-cause mortality (aHR, 0.75; 95% CI, 0.65-0.86; P <.0001) and ischemic stroke (aHR, 0.71; 95% CI, 0.56-0.89; P =.003) but not for pump thrombosis (aHR, 1.01; 95% CI, 0.77-1.32; P =.934).

Stratified by implanted device, PDE-5i was associated with decreased risk for the composite outcome for both Heartware HVAD (aHR, 0.76; 95% CI, 0.66-0.88; P =.0002) and HeartMate 3 (aHR, 0.77; 95% CI, 0.64-0.92; P =.0044) devices. Similar results were observed for all-cause mortality (both P ≤.0098) and ischemic stroke (both P ≤.045).

In subgroup analyses, PDE-5i was favored for younger (<60 years) and older (³60 years) patients (HR range, 0.75-0.78; P ≤.03), men (HR, 0.75; P <.001), White patients (HR, 0.75; P <.001), both types of LVAD (HR range, 0.69-0.80; P ≤.016), all device strategies (HR range, 0.58-0.81; P ≤.021), and any pulmonary hypertension status (HR range, 0.69-0.78; P ≤.031). For women and Black patients, PDE-5i tended to be favored.

This study was limited by not having sufficient data to account for dosage or duration of therapy.

“The adjunctive use of PDE-5is after LVAD might result in incremental improvement with contemporary LVAD technology,” the researchers noted. “A randomized controlled trial is necessary to determine the efficacy and safety with PDE-5i use postimplant of a centrifugal flow LVAD.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Xanthopoulos A, Wolski K, Wang Q, et al. Postimplant phosphodiesterase-5 inhibitor use in centrifugal flow left ventricular assist devices. JACC Heart Fail. 2022;10(2):89-100. doi:10.1016/j.jchf.2021.09.008