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      Postimplant Phosphodiesterase Type 5 Inhibitors Use Is Associated With Lower Rates of Thrombotic Events After Left Ventricular Assist Device Implantation

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          Abstract

          Background

          Left ventricular assist device ( LVAD) thrombosis is clinically devastating and impacts the cost effectiveness of LVAD therapy for advanced heart failure. Anticoagulation and antiplatelet therapies represent the standard of care to mitigate LVAD thrombosis. Phosphodiesterase type 5 inhibitors ( PDE‐5is) exhibit hemodynamic, antiplatelet, and antithrombotic effects. Using a national registry, we examined the relationship of PDE‐5i use on thrombotic events in patients with continuous‐flow LVADs.

          Methods and Results

          We obtained data from 13 772 patients with continuous flow LVADs participating in a national registry. Patients implanted with primary LVADs from 2012 to 2017 were included in the analysis. The primary end point was a composite of LVAD thrombosis and ischemic stroke. Patients were analyzed according to any use of PDE‐5i after LVAD implantation ( PDE‐5i group) versus no use after LVAD implantation (no PDE‐5i group). The primary end point was significantly lower in the PDE‐5i group compared with the no PDE‐5i group (hazard ratio [HR], 0.84; 95% CI, 0.77–0.91; P<0.001) at 48 months. The components of the primary end point ( LVAD thrombosis: HR, 0.82; 95% CI, 0.74–0.90; P<0.001; and ischemic stroke: HR, 0.85; 95% CI, 0.75–0.97; P=0.019), as well as the secondary end point all‐cause mortality (HR, 0.86; 95% CI, 0.79–0.93; P<0.001) were lower in the PDE‐5i group versus the no PDE‐5i at 48 months post LVAD. The favorable results observed with postimplant PDE‐5i use were consistent with both axial and centrifugal flow devices.

          Conclusions

          The postimplant use of PDE‐5i was associated with fewer thrombotic events and improved survival in LVAD patients. A randomized clinical trial is warranted to confirm these findings.

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          Most cited references33

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          A Fully Magnetically Levitated Left Ventricular Assist Device — Final Report

          In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device.
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            Long-term use of a left ventricular assist device for end-stage heart failure.

            Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.
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              Advanced heart failure treated with continuous-flow left ventricular assist device.

              Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices. In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuous-flow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity. Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P=0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups. Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.) 2009 Massachusetts Medical Society
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                Author and article information

                Contributors
                starlir@ccf.org
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                10 July 2020
                21 July 2020
                : 9
                : 14 ( doiID: 10.1002/jah3.v9.14 )
                : e015897
                Affiliations
                [ 1 ] Kaufman Center for Heart Failure, Heart and Vascular Institute Cleveland Clinic Cleveland OH
                [ 2 ] Independent Biostatistician Athens Greece
                [ 3 ] Department of Cardiology University General Hospital of Larissa Greece
                Author notes
                [*] [* ]Correspondence to: Randall C. Starling, MD, MPH, FACC, FAHA, FESC, FHFSA, Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. E‐mail: starlir@ 123456ccf.org
                Author information
                https://orcid.org/0000-0002-1254-4860
                Article
                JAH35232
                10.1161/JAHA.119.015897
                7660717
                32648508
                bfa3fd3a-28cb-4e62-a298-aff1ce25f280
                © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 14 January 2020
                : 12 May 2020
                Page count
                Figures: 2, Tables: 3, Pages: 9, Words: 6300
                Categories
                Original Research
                Original Research
                Heart Failure
                Custom metadata
                2.0
                21 July 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.8 mode:remove_FC converted:29.08.2020

                Cardiovascular Medicine
                complications,heart failure,pharmacology,sildenafil,mortality/survival
                Cardiovascular Medicine
                complications, heart failure, pharmacology, sildenafil, mortality/survival

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