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.
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.


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.
Anand
S S
SS
From the Preventive Cardiology and Therapeutics Program, Hamilton Civics Hospital Research Centre, and Division of Cardiology, McMaster University, Hamilton, Canada. anands@fhs.mcmaster.ca
Yusuf
S
S
Pogue
J
J
Weitz
J I
JI
Flather
M
M
D000284:Administration, Oral; D000789:Angina, Unstable / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D001026:Coronary Artery Bypass; D004562:Electrocardiography; D006470:Hemorrhage / Q000139:chemically induced; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D010349:Patient Compliance; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D001241:Aspirin