Warfarin After Anterior ST-Elevation Myocardial Infarction

Myocardial Infarction Clinical Trial

Official title:

Warfarin After Anterior ST-Elevation Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00662467
• Other study ID #: 06-281
• Status: Completed
• Phase: N/A
• First received: April 8, 2008
• Last updated: April 18, 2008
• Start date: November 2006
• Est. completion date: January 2008

Study information

• Verified date: April 2008
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

Following severe heart attacks involving the front wall of the heart (anterior myocardial infarction), patients are at risk of developing blood clots in the main pumping chamber that can cause a stroke. In the past, studies have shown that a blood thinner (warfarin) can decrease the risk of stroke and clot formation if administered to patients after an anterior myocardial infarction.

However, in today's current practice, certain heart attack patients are commonly treated with two blood-thinning medications (aspirin and clopidogrel) to prevent recurrent heart attacks.

Thus, a clinical problem is created as physicians are not clear how to treat patients after an anterior myocardial infarction who are at risk of a clot but require aspirin and clopidogrel to keep their blood vessels open. Adding warfarin to the combination of aspirin and clopidogrel will possibly decrease the risk of stroke but increase the risk of bleeding. Currently, there is no good evidence to help guide physicians. As demonstrated by a survey done at the Hamilton Health Sciences, there is a fifty/fifty split between physicians who use dual (aspirin and clopidogrel) versus triple (aspirin, clopidogrel, and warfarin) therapy in the treatment of similar patients as described above.

The purpose of this study is to address the bleeding and stroke complications in patients after a severe anterior myocardial infarction. Half of the eligible patients will receive dual therapy and half will receive triple therapy. We will compare the incidence of stroke, blood clots, and bleeding complications between the two groups at 3 months.

Description:

Rationale:

Left ventricular mural thrombus (LVT) remains a common complication after anterior ST-elevation myocardial infarction (STEMI) with a reported incidence ranging from 12- 17%. Previous studies from the pre-thrombolytic era have shown that warfarin therapy significantly reduces the incidence of LVT and embolic events in patients post anterior STEMI. However, the risk/benefit ratio of warfarin therapy in the setting of early revascularization and dual antiplatelet therapy with aspirin and clopidogrel remains unknown.

Purpose:

To compare the incidence of death, MI, stroke, embolic events, LVT, and bleeding complications at 3 months in patients with an anterior STEMI and ejection fraction less than 40% treated with ASA and clopidogrel alone versus those treated with aspirin, clopidogrel, and warfarin (triple therapy group).

Sample Size:

This is a pilot project to help establish the feasibility of conducting a full scale externally funded study. As such sample size calculations are not applicable. The primary aim of the study is to determine the safety and feasibility of conducting a large-scale trial, and this pilot project in not expected to reveal a statistically significant difference between the 2 groups.

Design/Methodology:

All patients will be randomized to either aspirin and clopidogrel alone or to triple therapy with aspirin, clopidogrel and warfarin. The randomization process will be centralized and computer generated. Patients with a clear indication for oral anticoagulation such as atrial fibrillation, LV thrombus, mechanical heart valve, or DVT/PE will not undergo randomization but will be followed as part of a registry of patients on triple therapy. All patients will remain on the allocated therapy for 3 months at which time outcomes will be determined.

Study interventions:

Patients will be treated with either ASA and clopidogrel alone (dual therapy) or with aspirin, clopidogrel and warfarin (triple therapy) in combination for 3 months. Patients in the triple therapy arm will be bridged with intravenous unfractionated heparin, low molecular weight heparin, or fondaparinux until their INR is therapeutic, and will be followed by the thrombosis service for the duration of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Anterior STEMI

• An ejection fraction less than 40% as per initial LV angiography or echocardiogram

• Randomization possible within hospital admission if anticoagulated with no interruption > 24 hours

• Patient able and willing to give informed consent to participate in this trial

Exclusion Criteria:

• history of intracranial hemorrhage

• history of GI bleed last 6 months

• hemoglobin < 90 g/L

• platelet count < 100 x 10exp9/L

• ischemic stroke last 30 days

• intracranial tumor or aneurysm

• significant pericardial effusion

• severe renal failure (creatinine > 250 mmol/L).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• aspirin + clopidogrel
Dual therapy
• aspirin + clopidogrel + warfarin
Triple therapy

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences-Hamilton General Hopsital	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation

Country where clinical trial is conducted

Canada, 

References & Publications (12)

Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation. 2004 Aug 31;110(9):e82-292. Erratum in: Circulation. 2005 Apr 19;111(15):2013-4. Circulation. 2007 Apr 17;115(15):e411. Circulation. 2010 Jun 15;121(23):e441. — View Citation

Asinger RW, Mikell FL, Elsperger J, Hodges M. Incidence of left-ventricular thrombosis after acute transmural myocardial infarction. Serial evaluation by two-dimensional echocardiography. N Engl J Med. 1981 Aug 6;305(6):297-302. — View Citation

Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005 Nov 5;366(9497):1607-21. — View Citation

Chiarella F, Santoro E, Domenicucci S, Maggioni A, Vecchio C. Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study. Am J Cardiol. 1998 Apr 1;81(7):822-7. — View Citation

Küpper AJ, Verheugt FW, Peels CH, Galema TW, Roos JP. Left ventricular thrombus incidence and behavior studied by serial two-dimensional echocardiography in acute anterior myocardial infarction: left ventricular wall motion, systemic embolism and oral anticoagulation. J Am Coll Cardiol. 1989 Jun;13(7):1514-20. — View Citation

Meltzer RS, Visser CA, Fuster V. Intracardiac thrombi and systemic embolization. Ann Intern Med. 1986 May;104(5):689-98. Review. — View Citation

Nayak D, Aronow WS, Sukhija R, McClung JA, Monsen CE, Belkin RN. Comparison of frequency of left ventricular thrombi in patients with anterior wall versus non-anterior wall acute myocardial infarction treated with antithrombotic and antiplatelet therapy with or without coronary revascularization. Am J Cardiol. 2004 Jun 15;93(12):1529-30. — View Citation

Nihoyannopoulos P, Smith GC, Maseri A, Foale RA. The natural history of left ventricular thrombus in myocardial infarction: a rationale in support of masterly inactivity. J Am Coll Cardiol. 1989 Oct;14(4):903-11. — View Citation

Sabatine MS, Blake GJ, Drazner MH, Morrow DA, Scirica BM, Murphy SA, McCabe CH, Weintraub WS, Gibson CM, Cannon CP. Influence of race on death and ischemic complications in patients with non-ST-elevation acute coronary syndromes despite modern, protocol-guided treatment. Circulation. 2005 Mar 15;111(10):1217-24. — View Citation

Stratton JR, Lighty GW Jr, Pearlman AS, Ritchie JL. Detection of left ventricular thrombus by two-dimensional echocardiography: sensitivity, specificity, and causes of uncertainty. Circulation. 1982 Jul;66(1):156-66. — View Citation

Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol. 1993 Oct;22(4):1004-9. — View Citation

Weinreich DJ, Burke JF, Pauletto FJ. Left ventricular mural thrombi complicating acute myocardial infarction. Long-term follow-up with serial echocardiography. Ann Intern Med. 1984 Jun;100(6):789-94. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined death, MI, embolic event (TIA, stroke, non-cns emboli), Major Bleeding, and LVT (as determined by echocardiography) at 3 months		3 months	No
Secondary	Individual endpoints of LVT at discharge and at 3 months (determined by echocardiography), death, MI, stroke, TIA, non-CNS emboli, and minor bleeding		3 months	No