Mei Wang1,2, Dena Zeraatkar1, Michael Obeda3, Munil Lee4, Cristian Garcia1, Laura Nguyen5, Arnav Agarwal6, Farah Al-Shalabi2, Harsukh Benipal1, Afreen Ahmad7, Momina Abbas8, Kristina Vidug2, Anne Holbrook1,2,9. 1. Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. 2. Clinical Pharmacology & Toxicology, Research Institute, St Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, L8N 4A6, Canada. 3. Department of Family Medicine, Queen's University, 220 Bagot St, Kingston, Ontario, K7L 3G2, Canada. 4. Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada. 5. Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, K1H 8M5, Canada. 6. Department of Medicine, University of Toronto, 27 King's College Circle, Toronto, Ontario, M5S 1A, Canada. 7. Bachelor Health Sciences Program, Faculty of Health Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. 8. Bachelor Arts & Science Program, Faculty of Arts & Science, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. 9. Division of Clinical Pharmacology & Toxicology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada.
Abstract
AIMS: The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. METHODS: MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens. CONCLUSIONS: This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.
AIMS: The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. METHODS: MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens. CONCLUSIONS: This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.
Authors: Eslam Mohammed Rabea; Kirellos Said Abbas; Dina M Awad; Nancy H Elgoweini; Amro Ahmed El-Sakka; Nada H Mahmoud; Basel Abdelazeem Journal: Eur J Clin Pharmacol Date: 2022-02-18 Impact factor: 2.953
Authors: Mei Wang; Michael Paterson; Lehana Thabane; Deborah Siegal; Lawrence Mbuagbaw; Laura Targownik; Anne Holbrook Journal: BMJ Open Date: 2022-06-13 Impact factor: 3.006