TCT 2001 Expert Presentations
| Overview of Oral Anti-Platelets | J. E. Tcheng |
TCT 2000 Expert Presentations
Increased Mortality With Oral Platelet Glycoprotein IIb/IIIa Antagonists : A Meta-Analysis of Phase III Multicenter Randomized Trials
Chew DP || Topol EJ
Circulation 2001;103 201-206
http://circ.ahajournals.org/cgi/content/abstract/103/2/201
Click here to view the figure
Four large-scale, placebo-controlled, randomized trials with oral glycoprotein
IIb/IIIa inhibitors were analysed. Stratification by low-dose or high-dose therapy and the use of concurrent aspirin was also
undertaken. In 33 326 patients followed for >30 days, a consistent and statistically significant increase in mortality was observed with oral glycoprotein
IIb/IIIa therapy (OR, 1.37; 95% CI, 1.13 to 1.66; P=0.001). This effect was evident regardless of aspirin coadministration and treatment with either low-dose or high-dose
therapy. Although a reduction in urgent revascularization was observed with oral glycoprotein
IIb/IIIa inhibition, pooled analysis favored an increase in myocardial infarction that did not demonstrate statistical
significance. In conclusion, Although there was a highly significant excess in mortality consistent across 4 trials with 3 different oral glycoprotein
IIb/IIIa inhibitor agents, this was associated with a reduction in the need for urgent revascularization and no increase in myocardial
infarction. These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic
mechanism. Further investigation to elucidate the cause of this increased fatality risk is
warranted.
Late-Breaking Clinical Trial
BRAVO Trial (Blockade of the IIb/IIIa Receptor to Avoid Vascular
Occlusion)
The trial was stopped earlier in Dec 2000 because of an increased mortality with oral
GpIIb/IIIa blocker, lotrafiban than placebo (2.7% vs 2.0%, p=0.022), more major bleeding (4.2% vs 1.3%, p<0.0001), and a greater incidence of serious thrombocytopenia (2.2% versus 0.5%). Eric
Topol, the chief investigator, says " Until we fully understand what is going on, we
shouldn't expose any more patients to these drugs".
See and hear the multimedia presentation at: http://www.theheart.org/index.cfm?doc_id=20641
OPUS-TIMI 16
http://www.theheart.org/documents/page.cfm?from=590001200&doc_id=14562
No benefits with oral GP IIb/IIIa inhibitor orbofiban in patients with acute coronary syndromes
EXCITE Trial - Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization
O'Neill WW et al.
N Engl J Med 2000;342:1316-1324
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=0010793164
The administration of the glycoprotein IIb/IIIa antagonist xemilofiban before percutaneous coronary revascularization and for up to six months thereafter does not significantly reduce the incidence of important clinical end points To see comments at: theheart.org Click here
SYMPHONY II
Sibrafiban (oral GP IIb/IIIa inhibitor) fails.
- See comments at: theheart.org Click here