Safety of Dabigatran As an Anticoagulant: A Systematic Review and Meta-Analysis

Overview

Journal Front Pharmacol

Date 2021 Feb 26

PMID 33633574

Citations 2

Authors

Ya Zhou

Zhihao Yao

Linjie Zhu

Yong Tang

Jie Chen

Jianming Wu

Affiliations

Soon will be listed here.

Abstract

Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor which was developed as an alternative to vitamin K antagonists (VKAs). However, the safety of dabigatran remains controversial so far. In this study, we aimed to compare the risk of bleeding, fatal adverse events, and the all-cause mortality of dabigatran with those of the control group by a systematic review and meta-analysis of randomized controlled trials. We systematically searched PubMed, Web of Science, Cochrane Library, Medline, Embase, Wanfang database, Clinical trial, China National Knowledge Infrastructure Chinese Scientific Journal database (VIP), and Chinese Biological Medicine database (CBM), for clinical trials on conventional treatments compared with dabigatran, published between January 2014 and July 2020. The reported outcomes, including the endpoints of primary safety, were systematically investigated. Seven RCTs ( = 10,743) were included in the present systematic review. Compared to the control groups, dabigatran was not associated with an increased risk of major bleeding (relative risk [RR] 0.86, 95% confidence interval [CI]: 0.61 to 1.21, = 0.06), intracranial hemorrhage (RR 0.89, 95% CI: 0.58 to 1.36, = 0.41), fatal adverse reactions (RR 0.87, 95% CI: 0.65 to 1.17, = 0.66), all-cause mortality (RR 0.88, 95% CI: 0.70 to 1.11, = 0.45, I = 0%), and significantly reduced risk of clinically relevant non-major bleeding (RR 0.96, 95% CI: 0.65 to 1.42, = 0.0007). However, dabigatran is associated with an increased risk of gastrointestinal (GI) bleeding (RR 1.78, 95% CI: 1.02 to 3.13, = 0.05). Dabigatran has a favorable safety profile in terms of major bleeding, intracranial hemorrhage, and life-threatening events, among other safety outcomes. The present study suggested that dabigatran may be a suitable alternative to VKAs as an oral anticoagulant. However, more data are necessary to clarify the incidence of other adverse events and serious adverse reactions.

Citing Articles

Drug Repurposing for Targeting Myeloid-Derived Suppressor-Cell-Generated Immunosuppression in Ovarian Cancer: A Literature Review of Potential Candidates.

Berckmans Y, Hoffert Y, Vankerckhoven A, Dreesen E, Coosemans A Pharmaceutics. 2023; 15(7).

PMID: 37513979 PMC: 10385967. DOI: 10.3390/pharmaceutics15071792.

Mechanistic and Predictive QSAR Analysis of Diverse Molecules to Capture Salient and Hidden Pharmacophores for Anti-Thrombotic Activity.

Zaki M, Al-Hussain S, Masand V, Sabnani M, Samad A Int J Mol Sci. 2021; 22(15).

PMID: 34361118 PMC: 8348508. DOI: 10.3390/ijms22158352.

References

Gombar C, Horvath G, Gality H, Sisak K, Toth K . Comparison of minor bleeding complications using dabigatran or enoxaparin after cemented total hip arthroplasty. Arch Orthop Trauma Surg. 2014; 134(4):449-57. DOI: 10.1007/s00402-014-1933-8. View

Diener H, Sacco R, Easton J, Granger C, Bernstein R, Uchiyama S . Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. N Engl J Med. 2019; 380(20):1906-1917. DOI: 10.1056/NEJMoa1813959. View

Xue P, Ma Z, Liu S . Efficacy and Safety of Ginkgo Leaf Extract and Dipyridamole Injection for Ischemic Stroke: A Systematic Review and Meta Analysis. Front Pharmacol. 2019; 10:1403. PMC: 6904941. DOI: 10.3389/fphar.2019.01403. View

Polzin A, Dannenberg L, Wolff G, Zeus T, Kelm M, Petzold T . Increased risk of myocardial infarction with dabigatran etexilate: Fact or fiction? A critical meta-analysis from integrating randomized controlled trials and real-world studies: Wine or spritzer?. Int J Cardiol. 2018; 270:82. DOI: 10.1016/j.ijcard.2018.07.020. View

Yasaka M . [Direct oral thrombin inhibitor, "dabigatran"]. Nihon Rinsho. 2013; 71(1):113-8. View

Duan J, Yang L, Li H, Yamamura N, Harada A . Pharmacokinetics and Safety of Dabigatran Etexilate after Single and Multiple Oral Doses in Healthy Chinese Subjects. Eur J Drug Metab Pharmacokinet. 2020; 45(5):601-609. PMC: 7511473. DOI: 10.1007/s13318-020-00626-4. View

Laslett L, Alagona Jr P, Clark 3rd B, Drozda Jr J, Saldivar F, Wilson S . The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol. 2012; 60(25 Suppl):S1-49. DOI: 10.1016/j.jacc.2012.11.002. View

Schulman S, Angeras U, Bergqvist D, Eriksson B, Lassen M, Fisher W . Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2009; 8(1):202-4. DOI: 10.1111/j.1538-7836.2009.03678.x. View

Mega J, Braunwald E, Wiviott S, Bassand J, Bhatt D, Bode C . Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2011; 366(1):9-19. DOI: 10.1056/NEJMoa1112277. View

10.

Wolberg A, Rosendaal F, Weitz J, Jaffer I, Agnelli G, Baglin T . Venous thrombosis. Nat Rev Dis Primers. 2016; 1:15006. DOI: 10.1038/nrdp.2015.6. View

11.

Lin L, Chu H, Murad M, Hong C, Qu Z, Cole S . Empirical Comparison of Publication Bias Tests in Meta-Analysis. J Gen Intern Med. 2018; 33(8):1260-1267. PMC: 6082203. DOI: 10.1007/s11606-018-4425-7. View

12.

Butt J, Fosbol E, Verhamme P, Gerds T, Iversen K, Bundgaard H . Dabigatran and the Risk of Staphylococcus aureus Bacteremia: A Nationwide Cohort Study. Clin Infect Dis. 2020; 73(3):480-486. DOI: 10.1093/cid/ciaa661. View

13.

Liang H, Liang W, Zhao L, Chen D, Zhang J, Zhang Y . Robotic Versus Video-assisted Lobectomy/Segmentectomy for Lung Cancer: A Meta-analysis. Ann Surg. 2017; 268(2):254-259. DOI: 10.1097/SLA.0000000000002346. View

14.

Ozler T, Ulucay C, Onal A, Altintas F . Comparison of switch-therapy modalities (enoxaparin to rivaroxaban/dabigatran) and enoxaparin monotherapy after hip and knee replacement. Acta Orthop Traumatol Turc. 2015; 49(3):255-9. DOI: 10.3944/AOTT.2015.14.0219. View

15.

Sterne J, Egger M, Smith G . Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001; 323(7304):101-5. PMC: 1120714. DOI: 10.1136/bmj.323.7304.101. View

16.

Song Z, Cao H, Wu H, Wei Q, Tang M, Yang S . Current status of rivaroxaban in elderly patients with pulmonary embolism (Review). Exp Ther Med. 2020; 19(4):2817-2825. PMC: 7086161. DOI: 10.3892/etm.2020.8559. View

17.

Holster I, Valkhoff V, Kuipers E, Tjwa E . New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013; 145(1):105-112.e15. DOI: 10.1053/j.gastro.2013.02.041. View

18.

Schulman S, Kearon C, Kakkar A, Mismetti P, Schellong S, Eriksson H . Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361(24):2342-52. DOI: 10.1056/NEJMoa0906598. View

19.

Di Minno M, Ambrosino P, Di Minno A, Tremoli E, Di Minno G . The risk of gastrointestinal bleeding in patients receiving dabigatran etexilate: a systematic review and meta-analysis of the literature. Ann Med. 2017; 49(4):329-342. DOI: 10.1080/07853890.2016.1268710. View

20.

Pepe Ribeiro de Souza C, Bolzachini Santoni N, Gomes de Melo T, de Oliveira Figueiredo M, Darrieux F, Piegas L . Cost-Effectiveness and Cost-Utility Analyses of Dabigatran Compared with Warfarin in Patients with Nonvalvular Atrial Fibrillation and Risk Factors for Stroke and Systemic Embolism within Brazilian Private and Public Health Care Systems Perspectives. Value Health Reg Issues. 2018; 8:36-42. DOI: 10.1016/j.vhri.2015.02.003. View