Bleeding risk is higher when warfarin used alone compared to the associated use of aspirin with clopidogrel

Abstract

Abstract: AIM: To compare the risk of bleeding complication due to the associated use of aspirin with clopidogrel compared to those warfarin used alone based on FDA Spontaneous Reporting System and Adverse Events Reporting System (SRS/AERS) database.METHODS: After excluding duplicated records, reports were divided into three index groups i.e. associated use of aspirin with clopidogrel group, warfarin group and reference group,and define haemorrhages-related adverse events (HRAEs) according to Medical Dictionary for Regulatory Activities. Descriptive statistics, logistic regression and odds ratios were used to estimate the risk and difference of bleeding complications for these three scenarios.RESULTS: frequency of HRAE connected with the associated aspirin/clopidogrel use was 20.80%, and gastrointestinal system HRAEs were the most frequently reported bleeding event (8.23%). The frequency of HRAE connected with the warfarin used alone was 22.30%, and gastrointestinal system HRAEs were the most frequently reported bleeding event (7.81%). The frequency of nervous system HRAEs for different groups has no significant difference (P>0.05). The frequency of HRAEs increased as age increases for both groups.CONCLUSION: The risk of HRAEs with warfarin used alone (20.80%) is higher than the associated aspirin/clopidogrel use (22.30%) in the clinical use based on FDA SRS/AERS (P<0.05). The types of bleeding complications are not similar for both situation.

Key words: Aspirin, Clopidogrel, Warfarin, Adverse event, Pharmacovigilance

CLC Number:

R442.7

YUN Wen-bo¹, JIANG Peng-li¹, WU Jing¹, SUN He^1,2. Bleeding risk is higher when warfarin used alone compared to the associated use of aspirin with clopidogrel[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(11): 1251-1259.

References

[1] Shehab N, Sperling LS, Kegler SR,et al. National estimates of emergency department visits for hemorrhage-related adverse events from clopidogrel plus aspirin and from warfarin[J].Arch Intern Med,2010,170(21): 1926-1933.
[2] Kearon C, Kahn SR, Agnelli G,et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)[J].Chest,2008,133(6): 454S-545S.
[3] Ansell J, Hirsh J, Hylek E,et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)[J].Chest,2008,133(6): 160S-198S.
[4] Fuster V, Ryden LE, Cannom DS,et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines[J].Circulation,2011,123(10): e269-e367.
[5] Lorenzoni R, Lazzerini G, Cocci F,et al. Short-term prevention of thromboembolic complications in patients with atrial fibrillation with aspirin plus clopidogrel: the Clopidogrel-Aspirin Atrial Fibrillation (CLAAF) pilot study[J].Am Heart J,2004,148(1): e6.
[6] 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[J].Lancet,2006,367(9523): 1903-1912.
[7] Connolly SJ, Pogue J, Hart RG,et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation[J].N Engl J Med,2009,360(20): 2066-2078.
[8] Go AS. The ACTIVE pursuit of stroke prevention in patients with atrial fibrillation[J].N Engl J Med,2009,360(20): 2127-2129.
[9] Wysowski DK, Swartz L. Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reporting suspected reactions[J].Arch Intern Med,2005,165(12): 1363-1369.
[10] Ahmad SR. Adverse drug event monitoring at the Food and Drug Administration[J].J Gen Intern Med,2003,18(1): 57-60.
[11] Rodriguez EM, Staffa JA, Graham DJ. The role of databases in drug postmarketing surveillance[J].Pharmacoepidemiol Drug Saf,2001,10(5): 407-410.
[12] Ali AK, Hartzema AG. Assessing the association between omalizumab and arteriothrombotic events through spontaneous adverse event reporting[J].J Asthma Allergy,2012,5: 1-9.
[13] Tamura T, Sakaeda T, Kadoyama K,et al. Aspirin- and clopidogrel-associated bleeding complications: data mining of the public version of the FDA adverse event reporting system, AERS[J].Int J Med Sci,2012,9(6): 441-446.
[14] Van Puijenbroek EP, Egberts AC, Meyboom RH,et al. Signalling possible drug-drug interactions in a spontaneous reporting system: delay of withdrawal bleeding during concomitant use of oral contraceptives and itraconazole[J].Br J Clin Pharmacol,1999,47(6): 689-693.
[15] Zhou W, Pool V, DeStefano F,et al. A potential signal of Bell's palsy after parenteral inactivated influenza vaccines: reports to the Vaccine Adverse Event Reporting System (VAERS)--United States, 1991-2001[J].Pharmacoepidemiol Drug Saf,2004,13(8): 505-510.
[16] van der Heijden PG, van Puijenbroek EP, van Buuren S,et al. On the assessment of adverse drug reactions from spontaneous reporting systems: the influence of under-reporting on odds ratios[J].Stat Med,2002,21(14): 2027-2044.
[17] Zhou W, Pool V, DeStefano F,et al. A potential signal of Bell's palsy after parenteral inactivated influenza vaccines: reports to the Vaccine Adverse Event Reporting System (VAERS)--United States, 1991-2001[J].Pharmacoepidemiol Drug Saf,2004,13(8): 505-510.