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Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy

1
Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98158 Messina, Italy
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Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy
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Department of Pharmacy, Palermo Local Health Unit, 90100 Palermo, Italy
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Division of Cardiology, A.O.R.N. “Sant’Anna e San Sebastiano”, 81100 Caserta, Italy
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Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 81100 Naples, Italy
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Department of Clinical and Experimental Medicine, Section of Cardiology, University of Messina, 98158 Messina, Italy
7
Department of Diagnostic Public Health, University of Verona, 37129 Verona, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Félix Carvalho
Pharmaceuticals 2021, 14(4), 290; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040290
Received: 10 February 2021 / Revised: 16 March 2021 / Accepted: 22 March 2021 / Published: 25 March 2021
(This article belongs to the Section Pharmacology)
Patients enrolled into pivotal randomized controlled trials (RCTs) may differ substantially from those treated in a real-world (RW) setting, which may result in a different benefit–risk profile. The aim of the study was to assess the external validity of pivotal RCT findings concerning direct oral anticoagulants (DOACs) for the treatment of nonvalvular atrial fibrillation (NVAF) by comparing patients recruited in RCTs to those treated with DOACs registered in a southern Italian local health unit (LHU) in the years 2013–2017. The Palermo LHU claims database was used to describe the baseline characteristics of incident DOAC users (washout > 1 year) with NVAF compared with those of enrolled patients in DOAC pivotal RCTs. In the RW, DOAC treatment discontinuation was calculated during the follow-up and compared with DOAC treatment discontinuation of enrolled patients in DOAC pivotal RCTs. Rates of effectiveness and safety outcomes during the follow-up were calculated in an unmatched and in a simulated RCT population, by matching individual incidental RW and RCT DOAC users (excluding edoxaban users) on age, sex, and CHADS2 score. Overall, 42,336 and 7092 incident DOAC users with NVAF were identified from pivotal RCTs and from the RW setting, respectively. In RCTs, DOAC use was more common among males (62.6%) compared with an almost equal sex distribution in the RW. RCT patients were younger (mean age ± standard deviation: 70.7 ± 9.2 years) than RW patients (76.0 ± 8.6 years). Compared with RCTs, a higher proportion of RW dabigatran users (30.4% vs. 19.6%) and a lower proportion of RW apixaban (15.9% vs. 25.3%) and rivaroxaban (20.4% vs. 23.7%) users discontinued the treatment during the follow-up (p-value < 0.001). The rate of ischemic stroke was lower in RW high-dose dabigatran users (unmatched/-matched population: 0.40–0.11% per year) than in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) population (0.93% per year). Major bleeding rates were lower in RW users than in RCT users. In conclusion, except for dabigatran, a lower proportion of DOAC discontinuers was observed in the real-world than in pivotal RCT settings. This study provides reassurance to practicing physicians that DOAC use appears to be effective in stroke prevention and is likely safer in RW patients than in RCT enrolled patients. These results may be related to a lower burden of comorbidities despite more advanced age in the RW population compared to the pivotal RCT population. View Full-Text
Keywords: direct oral anticoagulants; nonvalvular atrial fibrillation; external validity; real world direct oral anticoagulants; nonvalvular atrial fibrillation; external validity; real world
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MDPI and ACS Style

Ingrasciotta, Y.; Fontana, A.; Mancuso, A.; Ientile, V.; Sultana, J.; Uomo, I.; Pastorello, M.; Calabrò, P.; Andò, G.; Trifirò, G. Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy. Pharmaceuticals 2021, 14, 290. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040290

AMA Style

Ingrasciotta Y, Fontana A, Mancuso A, Ientile V, Sultana J, Uomo I, Pastorello M, Calabrò P, Andò G, Trifirò G. Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy. Pharmaceuticals. 2021; 14(4):290. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040290

Chicago/Turabian Style

Ingrasciotta, Ylenia, Andrea Fontana, Anna Mancuso, Valentina Ientile, Janet Sultana, Ilaria Uomo, Maurizio Pastorello, Paolo Calabrò, Giuseppe Andò, and Gianluca Trifirò. 2021. "Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy" Pharmaceuticals 14, no. 4: 290. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040290

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