[Bleeding complications after treatment with clopidogrel and acetylsalicylic acid after acute coronary syndrome].
BACKGROUND
The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study showed that patients with unstable angina pectoris (UAP) and non-ST-elevation myocardial infarction (NSTEMI) benefit from combined therapy with acetylsalicylic acid (ASA) and clopidogrel. However, only patients entering clinical randomized trials were studied. We sought to assess whether the risk of bleeding increased after the introduction of the CURE criteria in an unselected population of Danish patients with NSTEMI or UAP.


METHODS
The CURE criteria were implemented in the Department of Cardiology, Odense University Hospital, in December 2001. Two consecutive one-year periods were studied: period 1, December 2000-November 2001, and period 2, December 2001-November 2002. Patient charts were reviewed, and major bleeding complications and the primary clinical end point (non-fatal myocardial infarction, stroke or death) was registered. Follow-up took place one year later.


RESULTS
In all, 290 patients were included in period 1 and 189 in period 2. During period 1, there were 12 (4.1%) and during period 2, 21 (11.1%) major bleeding events (odds ratio 3.07; 95% CI 1.42-6.65; p = 0.005). Compared with the patients treated with clopidogrel and ASA in the CURE study, we also found a three times greater risk of major bleeding in period 2. In particular, patients over 70 years of age and patients undergoing bypass surgery were at heightened risk. The incidence of the primary clinical end point was higher in both period 1 and period 2 than in the CURE study.


CONCLUSIONS
Our study demonstrates an increased risk of major bleeding in unselected patients receiving combination therapy with ASA and clopidogrel after UAP or NSTEMI. Major bleeding complications most frequently occur in patients above 70 years of age and following bypass surgery.
Kjaer
Janus
J
Odense Universitetshospital, Kardiologisk Afdeling B.
Larsen
Christian Hastrup
CH
Poulsen
Tina Svenstrup
TS
Møller
Jacob E
JE
Mickley
Hans
H
D000367:Age Factors; D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy*; D001241:Aspirin / Q000009:adverse effects*; D000077144:Clopidogrel; D001026:Coronary Artery Bypass; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin