Drug-induced thrombocytopenia and thrombosis: evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial.
OBJECTIVE
To assess etiology and impact of thrombocytopenia in a large oral glycoprotein (GP) IIb/IIIa inhibitor trial.


BACKGROUND
Heparin is known to cause thrombocytopenia, and in some of these patients thrombosis. GP IIb/IIIa inhibitors are also associated with thrombocytopenia.


METHODS
The Orbofiban in Patients with Unstable Coronary Syndromes (OPUS-TIMI 16) Trial randomized 10,392 patients with ACS to the oral GP IIb/IIIa inhibitor orbofiban or placebo. Patients were followed for a minimum of ten months. Thrombocytopenia was defined prospectively as a platelet count < 80,000.


RESULTS
Thrombocytopenia was rare in the OPUS-TIMI 16 trial (0.68% at Day 30 and 0.80% at 1 year), but more common in patients treated with orbofiban (0.92%) compared with those treated with placebo (0.2%), p < 0.001. Patients who developed thrombocytopenia had higher rates of death (11.6% vs. 1.7%, p < 0.001), recurrent MI (12.1% vs. 2.8%, p < 0.001), intracranial hemorrhage (2.9% vs. 0.0%, p < 0.001), and major or severe bleeding (19.0% vs. 2.0%, p < 0.001) at 30 days (with similar results at one year).


CONCLUSIONS
Thrombocytopenia, though uncommon, was associated with orbofiban use and an increased risk of bleeding, but also death and MI. This study provides further evidence that drugs that lead to thrombocytopenia are, in a significant proportion of patients associated with thrombotic events.
Scirica
Benjamin M
BM
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis st., Boston, MA 02115, USA. bscirica@partners.org
Cannon
Christopher P
CP
Cooper
Richard
R
Aster
Richard H
RH
Brassard
Jacqueline
J
McCabe
Carolyn H
CH
Charlesworth
Andrew
A
Skene
Allan M
AM
Braunwald
Eugene
E
D000368:Aged; D000409:Alanine / Q000009:adverse effects; D000789:Angina, Unstable / Q000188:drug therapy*; D001241:Aspirin / Q000494:pharmacology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011759:Pyrrolidines / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000401:mortality; D013927:Thrombosis / Q000209:etiology* / Q000401:mortality
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011759:Pyrrolidines; C120234:orbofiban; D000409:Alanine; D001241:Aspirin