THE EFFECT OF BIVALIRUDIN IN COMBINATION WITH TICLOPIDINE
ON LABORATORY COAGULATION PARAMETERS AND THE INCIDENCE OF CLINICALLY
SIGNIFICANT BLEEDING IN PATIENTS UNDERGOING PERCUTANEOUS TRANSLUMINAL CORONARY
ANGIOPLASTY (PTCA) AND STENTING. M.J. Abernethy*1, P.E.
Aylward 2, J.I. Weitz 3, C.M. Frampton 4. 1
Wakefield Heart Centre, Wellington, New Zealand; 2 Flinders Medical
Centre, Adelaide, Australia; 3 Hamilton Civic Hospitals Research
Center, Ontario, Canada; 4 Christchurch School of Medicine,
Christchurch, New Zealand. Background: The primary objective of this trial was to compare two
antithrombotic strategies on the markers of coagulation and platelet function,
as measured by activated clotting time (ACT), and plasma levels of soluble
fibrin and P-selectin. Effective
anticoagulant and antiplatelet therapy suppresses both soluble fibrin and
P-selectin respectively. Methods:
This was a randomised trial of thirty patients: 15 patients were
randomized to ticlopidine tablets and bivalirudin as 1 mg/kg bolus followed by
a 4 hour infusion of 2.5 mg/kg/hr; 15 patients were randomised to ticlopidine
tablets and a heparin 10,000IU bolus injection. Results: The bivalirudin bolus plus
infusion produced steady state ACTs of 333 ± 17 seconds, which was similar to
that obtained in other recent studies.
This suggests that the addition of ticlopidine to the combination of
aspirin and bivalirudin did not alter the anticoagulant effect of bivalirudin. Heparin produced an ACT of 282 ± 10 seconds
at 10 minutes post-bolus. Soluble
fibrin, a reliable marker of unopposed thrombin activity, remained suppressed
both in patients treated with heparin and with bivalirudin. This suggests that
ticlopidine did not produce an unexpected effect on bivalirudin's
antithrombotic action. P-selectin, a sensitive marker of platelet activation,
remained suppressed in both the bivalirudin and heparin groups, suggesting that
bivalirudin did not antagonize the antiplatelet activity of ticlopidine and
aspirin. No major haemorrhage or
serious adverse event was observed in either group. Conclusion: These data suggest there was no pharmacodynamic interaction
between ticlopidine and bivalirudin in these PTCA patients.
