Cardiovascular outcomes during treatment with dabigatran: Comprehensive analysis of individual subject data by treatment

Vascular Health and Risk Management

Volumn 9, Issue 1, 2013, Pages 599-615

  Clemens, Andreas ^a   Fraessdorf, Mandy ^b   Friedman, Jeffrey ^c  

^a TA Cardiovascular   (Germany)

^b BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^c BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

Atrial fibrillation; Cardiovascular events; Dabigatran etexilate; Myocardial infarction; Stroke; Warfarin

Indexed keywords

DABIGATRAN ETEXILATE; ENOXAPARIN; PLACEBO; WARFARIN;

ARTICLE; CARDIOVASCULAR EFFECT; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; COMPARATIVE STUDY; DRUG EFFICACY; DRUG SAFETY; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; META ANALYSIS (TOPIC); OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIMARY PREVENTION; RISK BENEFIT ANALYSIS; SECONDARY PREVENTION; TREATMENT DURATION; TREATMENT OUTCOME; VENOUS THROMBOEMBOLISM;

ATRIAL FIBRILLATION; CARDIOVASCULAR EVENTS; DABIGATRAN ETEXILATE; MYOCARDIAL INFARCTION; STROKE; WARFARIN;

ACUTE CORONARY SYNDROME; ANTITHROMBINS; ATRIAL FIBRILLATION; BENZIMIDAZOLES; CHI-SQUARE DISTRIBUTION; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; ENOXAPARIN; HUMANS; MYOCARDIAL INFARCTION; ODDS RATIO; PYRIDINES; RISK ASSESSMENT; RISK FACTORS; STROKE; TREATMENT OUTCOME; VENOUS THROMBOEMBOLISM; WARFARIN;

EID: 84889788731     PISSN: 11766344     EISSN: 11782048     Source Type: Journal    
DOI: 10.2147/VHRM.S49830     Document Type: Article

References (51)

1. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363(19): 1875-1876.
2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12): 1139-1151.
3. Olsson SB. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet. 2003;362(9397):1691-1698.
4. Albers GW, Diener HC, Frison L, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA. 2005;293(6):690-698.
5. Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903-1912.
6. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586): 493-503.
7. Bousser MG, Bouthier J, Buller HR, et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet. 2008;371(9609):315-321.
8. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360(20): 2066-2078.
9. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-817.
10. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891.
11. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
12. Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012;125(5):669-676.
13. Eriksson BI, Smith JJ, Caprini J, et al. Evaluation of the acute coronary syndrome safety profile of dabigatran etexilate in patients undergoing major orthopedic surgery: findings from four Phase 3 trials. Thromb Res. 2012;130(3):396-402.
14. Correia LC, Lopes AA. Dabigatran and myocardial infarction: meta-illusion? Arch Intern Med. 2012;172(10):823.
15. Lip GY, Lane DA. Does warfarin for stroke thromboprophylaxis protect against MI in atrial fibrillation patients? Am J Med. 2010;123(9):785-789.
16. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012;172(5):397-402.
17. Jacobs JM, Stessman J. Dabigatran: do we have sufficient data?: comment on "Dabigatran association with higher risk of acute coronary events". Arch Intern Med. 2012;172(5):403-404.
18. Wallentin L, Wilcox RG, Weaver WD, et al. Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial. Lancet. 2003;362(9386):789-797.
19. Lip GY, Rasmussen LH, Olsson SB, et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs vitamin K antagonists. Eur Heart J. 2009;30(23):2897-2907.
20. Eriksson BI, Dahl OE, Buller HR, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005;3(1):103-111.
21. Eriksson BI, Dahl OE, Rosencher N, et al. Oral dabigatran etexilate vs subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007;5(11):2178-2185.
22. Eriksson BI, Dahl OE, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370(9591):949-956.
23. Ginsberg JS, Davidson BL, Comp PC, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009;24(1):1-9.
24. Fuji T, Fuijita S, Ujihira T, Sato T. Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with a safety profile comparable to placebo. J Arthroplasty. 2010;25(8): 1267-1274.
25. Eriksson BI, Dahl OE, Huo MH, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost. 2011;105(4):721-729.
26. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007;100(9): 1419-1426.
27. Tomimori H, Yamamura N, Adachi T. Open label, randomized exploratory, dose response study of the pharmacodynamics and safety of BIBR 1148 (110 mg bid and 150 mg bid) for 12 weeks in patients with non-valvualr atrial fibrillation in comparison to warfarin. 2007. Study Number 1160.49. Report number U07-3126. Boehringer Ingelheim Internal Report.
28. Schulman S, Eriksson H, Goldhaber SZ. Dabigatran or warfarin for extended maintenance therapy of venous thromboembolism (abstract O-TH-033). J Thromb Haemost. 2011;9 Suppl 2:731-732.
29. Schulman S, Baanstra D, Eriksson H. Dabigatran versus placebo for extended maintenance therapy of venous thromboembolism (abstract O-MO-037). J Thromb Haemost. 2011;9 Suppl 2:22.
30. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352.
31. Schulman S, Kakkar AK, Schellong S. A randomized trial of dabigatran versus warfarin in the treatment of acute venous thromboembolism (RE-COVER II). ASH Annual Meeting Abstracts. 2011;118:A205.
32. Oldgren J, Budaj A, Granger CB, et al. Dabigatran versus placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32(22): 2781-2789.
33. Eriksson BI, Dahl OE, Ahnfelt L, et al. Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost. 2004;2(9):1573-1580.
34. PETRO-EX Investigators. Safety and efficacy of extended exposure to several doses of a new oral direct thrombin inhibitor dabigatran etexilate in atrial fibrillation. Cerebrovasc Dis. 2006;21 Suppl 4:2.
35. Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med. 2005;143(4):241-250.
36. Roskell NS, Lip GY, Noack H, Clemens A, Plumb JM. Treatments for stroke prevention in atrial fibrillation: a network meta-analysis and indirect comparisons versus dabigatran etexilate. Thromb Haemost. 2010;104(6):1106-1115.
37. Johnson and Johnson. Slides for the September 8, 2011 Meeting of the Cardiovascular and Renal Drugs Advisory Committee, slide No 129 and 153, 2011.
38. Büller HR, Décousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. September 1, 2013 [Epub ahead of print.].
39. Lopes RD, Starr A, Pieper CF, et al. Warfarin use and outcomes in patients with atrial fibrillation complicating acute coronary syndromes. Am J Med. 2010;123(2):134-140.
40. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347(13): 969-974.
41. Andreotti F, Testa L, Biondi-Zoccai GG, Crea F. Aspirin plus warfarin compared with aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25, 307 patients. Eur Heart J. 2006;27(5):519-526.
42. Breithart G, Baumgartner H, Berkowitz SD, et al. Characteristics and outcomes of patients with atrial fibrillation and significant valvular lesions experience from the ROCKET AF trial. J Am Coll Cardiol. 2013;61(Suppl 10):E282.
43. Kadoglou NP, Moustardas P, Katsimpoulas M, et al. The beneficial effects of a direct thrombin inhibitor, dabigatran etexilate, on the development and stability of atherosclerotic lesions in apolipoprotein E-deficient mice: dabigatran etexilate and atherosclerosis. Cardiovasc Drugs Ther. 2012;26(5):367-374.
44. Lee IO, Kratz MT, Schirmer SH, Baumhakel M, Bohm M. The effects of direct thrombin inhibition with dabigatran on plaque formation and endothelial function in apolipoprotein E-deficient mice. J Pharmacol Exp Ther. 2012;343(2):253-257.
45. Preusch M, Wijelath ES, Murray J. Dabigatran etexilate, a new oral thrombin inhibitor, retards the initiation and progression of atherosclerotic lesions and inhibits the expression of oncostatin M in apolipoprotein E-deficient mice. Arterioscl Thromb Vasc Biol. 2010;30:E185.
46. van Ryn J, Dietz T, Kuritsch I. Effect of direct thrombin inhibitor, dabigatran, on arterial thrombosis when given in combination with aspirin (ASA) in a cyclic flow model of anaesthesised pigs (abstract PP_MO-347). J Thromb Haemost. 2009;7 Suppl 2:435.
47. Connolly SJ, Wallentin L, Ezekowitz MD, et al. The Long Term Multi-Center Observational Study of Dabigatran Treatment in Patients with Atrial Fibrillation: (RELY-ABLE) Study. Circulation. June 14, 2013. [Epub ahead of print.]
48. Direct thrombin inhibitors in acute coronary syndromes and during percutaneous coronary intervention: design of a meta-analysis based on individual patient data. Direct Thrombin Inhibitor Trialists' Collaborative Group. Am Heart J. 2001;141(1):E2.
49. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358(21): 2218-2230.
50. Stone GW, Witzenbichler B, Guagliumi G, et al. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet. 2011;377(9784):2193-2204.
51. Diener HC. Stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with non-valvular atrial fibrillation. Pooled analysis from the SPORTIF III and V studies. Cerebrovasc Dis. 2006;21(4):279-293.