Daniel Caldeira1, Maria José Loureiro2, João Costa3, Fausto J Pinto4, Joaquim J Ferreira5. 1. Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal; Cardiology Department, Hospital Garcia de Orta, Almada, Portugal. Electronic address: dgcaldeira@hotmail.com. 2. Cardiology Department, Hospital Garcia de Orta, Almada, Portugal. 3. Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal; Evidence Based Medicine Centre, Faculty of Medicine, University of Lisbon, Portugal; Portuguese Collaborating Centre of the Cochrane Iberoamerican Network, Faculty of Medicine, University of Lisbon, Portugal. 4. Cardiology Department, CCUL, CAML, University of Lisbon, Portugal. 5. Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal.
Abstract
BACKGROUND: Uncertainty exists about the benefit of oral anticoagulation in the treatment of pulmonary arterial hypertension (PAH), which is a lethal disease. We aimed to review and quantify the effect of oral anticoagulants in overall survival of PAH patients. METHODS: We searched for randomized and observational studies that evaluated oral anticoagulants in PAH in the electronic databases MEDLINE, CENTRAL and ISI Web of Knowledge (December 2013). Review articles and references were also screened. We performed a random effects meta-analysis to estimate pooled HRs and 95% confidence intervals. Statistical heterogeneity was evaluated using the I(2) test. RESULTS: No randomized controlled trials were identified. Nine cohort studies (2 prospective and 7 retrospective) of overall moderate quality that enrolled 1730 PAH patients were included. Oral anticoagulation (warfarin) was associated with a 31% mortality risk reduction (HR, 0.69; 95% confidence interval, 0.57-0.82; I(2) = 28%). Subgroup and sensitivity analyses showed similar results and no significant heterogeneity. CONCLUSIONS: There is no randomized evidence to support the use of oral anticoagulation in PAH. Pooled results from cohort studies suggest a survival benefit, but the moderate study quality, the high risk of publication bias, and the methodological limitations inherent in the analysis of observational studies preclude a definite conclusion. There is an urgent need for pragmatic randomized evidence to definitely answer this important clinical question.
BACKGROUND: Uncertainty exists about the benefit of oral anticoagulation in the treatment of pulmonary arterial hypertension (PAH), which is a lethal disease. We aimed to review and quantify the effect of oral anticoagulants in overall survival of PAH patients. METHODS: We searched for randomized and observational studies that evaluated oral anticoagulants in PAH in the electronic databases MEDLINE, CENTRAL and ISI Web of Knowledge (December 2013). Review articles and references were also screened. We performed a random effects meta-analysis to estimate pooled HRs and 95% confidence intervals. Statistical heterogeneity was evaluated using the I(2) test. RESULTS: No randomized controlled trials were identified. Nine cohort studies (2 prospective and 7 retrospective) of overall moderate quality that enrolled 1730 PAH patients were included. Oral anticoagulation (warfarin) was associated with a 31% mortality risk reduction (HR, 0.69; 95% confidence interval, 0.57-0.82; I(2) = 28%). Subgroup and sensitivity analyses showed similar results and no significant heterogeneity. CONCLUSIONS: There is no randomized evidence to support the use of oral anticoagulation in PAH. Pooled results from cohort studies suggest a survival benefit, but the moderate study quality, the high risk of publication bias, and the methodological limitations inherent in the analysis of observational studies preclude a definite conclusion. There is an urgent need for pragmatic randomized evidence to definitely answer this important clinical question.
Authors: Muhammad Shahzeb Khan; Muhammad Shariq Usman; Tariq Jamal Siddiqi; Safi U Khan; M Hassan Murad; Farouk Mookadam; Vincent M Figueredo; Richard A Krasuski; Raymond L Benza; Jonathan D Rich Journal: Circ Cardiovasc Qual Outcomes Date: 2018-09
Authors: Alicia Calderone; Wendy Stevens; David Prior; Harshal Nandurkar; Eli Gabbay; Susanna M Proudman; Trevor Williams; David Celermajer; Joanne Sahhar; Peter K K Wong; Vivek Thakkar; Nathan Dwyer; Jeremy Wrobel; Weng Chin; Danny Liew; Margaret Staples; Rachelle Buchbinder; Mandana Nikpour Journal: BMJ Open Date: 2016-12-08 Impact factor: 2.692