Long-term inhibition of platelet aggregation

Lancet Volume 356, Number 9231 26 August 2000

Clinical trials of prolonged pharmacological inhibition of platelet aggregation with oral glycoprotein IIb/IIIa receptor antagonists were mentioned in a review by James N George(April 29, p 1531).1 Secondary prevention of recurrent cardiac events and death in patients after acute coronary syndromes with oral glycoprotein IIb/IIIa blockers have been studied in four large clinical trials with 33 367 observations, which we identified while working on a systematic literature review. Results from one clinical trial were published as a journal article.2 Findings from the other studies are available as conference material.3,4

Oral glycoprotein IIb/IIIa blockers alone or in combination with aspirin were compared with aspirin in patients with acute coronary syndromes and in percutaneous coronary interventions, or with a combination of ticlopidine plus aspirin in patients undergoing coronary stenting (table). None of these studies reported any significant additional benefit over aspirin in preventing death, myocardial infarction, reinfarction, or severe recurrent ischaemia. Although the orbofiban in patients with unstable coronary syndromes-TIMI 16 study showed a decrease in recurrent ischaemic events leading to revascularisation in orbofiban groups, it was associated with excess 30-day mortality.


Source

Glycoprotein IIb/IIIa

Clinical outcomes

Adverse events

 

blockers

   

SYMPHONY2

9233 patients within 7 days

Sibrafiban low and

90-day outcomes. No

Significantly higher rate of

of acute coronary syndrome

high doses*

additional benefit over aspirin

bleeding events and

     

transfusions of red cells

2nd SYMPHONY3

6600 patients within 7 days

Sibrafiban low dose

90-days outcomes. No additional

Rate of bleeding events,

of acute coronary syndrome

plus aspirin and

benefit over aspirin. Significantly

in particular major bleeding,

 

sibrafiban high dose

high rate of death in the high-dose

was almost twice higher

   

sibrafiban group

 

OPUS-TIMI 164

10302 patients within 3 days

2 dosage regimens of

The study was stopped prematurely

Significantly increased

of acute coronary syndromes

orbofiban plus aspirin

because of excess 30-day mortality

number of severe or

   

in one of the orbofiban groups.

major bleeding events

   

Similar trend at 10 months

 

EXCITE4

7232 patients undergoing

2 doses of xemilofiban

No significant difference among

Results were not reported

percutaneous coronary

plus aspirin

treatment groups at 30 days and

 

interventions

 

6 months

 

SYMPHONY=sibrafiban versus aspirin to yield maximum protection from ischaemic heart events post-acute coronary syndromes; OPUS=orbofiban in patients with unstable syndromes; EXCITE=evaluation of oral xemilofiban in controlling thrombotic events.

*Ticlopidine was added in the low-dose sibrafiban group during the study because of the higher rate of stent thrombosis in this group.

A significantly higher rate of bleeding events was observed in patients taking oral glycoprotein IIb/IIIa blockers. Most of the reported bleeding events were mucocutaneous, but severe bleeding was also significantly more frequent. The strong antiplatelet effect of these new drugs is not associated with better clinical outcomes.

*Veronika Kolesnik, André Biskop


*Medical Academy for Postgraduate Studies, St Petersburg 193015, Russia; Regional Cardiology Centre of Leningrad Oblast, St Petersburg; and Swedish Council for Technology Assessment in Health Care, Stockholm, Sweden


1 George JN. Platelets. Lancet 2000; 355: 1531-39. [Text]

2 Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial. The SYMPHONY Investigators. Lancet 2000; 355: 337-45. [Text]

3 Newby K. A randomized comparison of sibrafiban, an oral glycoprotein IIb/IIIa receptor antagonist, with and without aspirin versus aspirin after acute coronary syndromes: results of the 2nd SYMPHONY Trial. In: Late-breaking clinical trial results--session II. ACC Scientific Session 2000, March 15, 2000. (http://www. medscape.com/accessed July 7, 2000).

4 Ferguson JJ. Meeting highlights. Highlights of the 48th scientific sessions of the American College of Cardiology conference. Circulation 1999; 100: 570-75. [PubMed]