From the Preventive Cardiology and Therapeutics Program, Hamilton Civics
Hospital Research Centre, and Division of Cardiology, McMaster University,
Hamilton, Canada.
Correspondence to Sonia Anand, McMaster Clinic-2nd Floor, 237 Barton St E, Hamilton, Ontario, L8L 2X2, Canada. E-mail anands{at}fhs.mcmaster.ca
Background—Patients with acute
ischemic syndromes (AIS) suffer high rates of recurrent
ischemic events despite aspirin treatment. Long-term therapy
with oral anticoagulants in addition to aspirin may reduce this risk.
We studied the effects of long-term warfarin at 2 intensities in
patients with AIS without ST elevation in 2 consecutive randomized
controlled studies.
Methods and Results—In phase 1, after the cessation of 3 days of
intravenous antithrombotic therapy, 309 patients were
randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months
that produced a mean international normalized ratio (INR) of 1.5±0.6
or to standard therapy. Eighty-seven percent of patients received
aspirin in both groups. The rates of cardiovascular
(CV) death, new myocardial infarction (MI), and refractory angina at 6
months were 6.5% in the warfarin group and 3.9% in the standard
therapy group (relative risk [RR], 1.66; 95% CI, 0.62 to 4.44;
P=0.31). The rates of death, new MI, and stroke were
6.5% in the warfarin group and 2.6% in the standard therapy group
(RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall
rate of rehospitalization for unstable angina was 21% and did not
differ significantly between the groups. Four patients in the warfarin
group (2.6%) and none in the control group experienced a major bleed
(RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess
of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46;
95% CI, 1.93 to 15.5; P=0.001). In phase 2, the
protocol was modified, and 197 patients were randomized <48 hours from
the onset of symptoms to receive warfarin at an adjusted dose that
produced a mean INR of 2.3±0.6 or standard therapy for 3 months.
Eighty-five percent received aspirin in both groups. The rates of CV
death, new MI, and refractory angina at 3 months were 5.1% in the
warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI,
0.15 to 1.15; P=0.08). The rates of all death, new MI,
and stroke were 5.1% in the warfarin group and 13.1% in the standard
therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05).
Significantly fewer patients were rehospitalized for unstable angina in
the warfarin group than in the control group (7.1% and 17.2%,
respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03).
Two patients in the warfarin group and 1 in the control group
experienced a major bleed, and there was a significant excess of minor
bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI,
1.37 to 4.36; P=0.004).
Conclusions—Long-term treatment with moderate-intensity warfarin
(INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR,
1.5) plus aspirin appears to reduce the rate of recurrent
ischemic events in patients with AIS without ST
elevation.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Long-Term Oral Anticoagulant Therapy in Patients With Unstable Angina or Suspected Non–Q-Wave Myocardial Infarction
Organization to Assess Strategies for Ischemic Syndromes (OASIS) Pilot Study Results
Key Words: warfarin • ischemia • thrombosis • angina
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