Browsing by Author "Stehlik, Josef"

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    Induction therapy in heart transplantation: A systematic review and network meta-analysis for developing evidence-based recommendations
    (2024) Kugathasan, Lakshmi; Rayner, Daniel G.; Wang, Sabrina Mianchen; Rodenas-Alesina, Eduardo; Orchanian-Cheff, Ani; Stehlik, Josef; Gustafsson, Finn; Greig, Douglas; Mcdonald, Michael; Bertolotti, Alejandro Mario; Demas-Clarke, Penny; Kozuszko, Stella; Guyatt, Gordon; Foroutan, Farid; Alba, Ana Carolina
    Introduction: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA). Methods: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework. Results: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab. Conclusion: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients.
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    Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence
    (2024) Foroutan, Farid; Guyatt, Gordon; Stehlik, Josef; Gustafsson, Finn; Greig, Douglas; Mcdonald, Michael; Bertolotti, Alejandro Mario; Kugathasan, Lakshmi; Rayner, Daniel G.; Cuello, Carlos A.; Cook, Amanda; Zlatanoski, Darko; Ram, Sujivan; Demas-Clarke, Penny; Kozuszko, Stella; Alba, Ana Carolina
    BackgroundThe use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx).MethodsWe recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab.ResultsThe panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab.ConclusionThis report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.