Ridogrel in the Setting of Percutaneous Transluminal Coronary Angioplasty Carl Timmermans, MD, Matty Vrolix, MD, Johan Vanhaecke, MD, Francis Stammen, MD, Jan Piessens, MD, Els Vercammen, MD, and Hilaire De Geest, MD
The safety of the combination of heparin and ridogre1 therapy and its antiplatelet efficacy was examined in the setting of percutaneous transluminal coronary angioplasty (PTCA). In 32 patients without known ,aspirin intake for 10 days before PTCA, therapy with ridogrel(300-mg intravenous bolus) was begun just before PTCA and continued orally at a dose of 300 mg twice daily until discharge. Heparin was administered as a 10,000 IU bolus dose before PTCA and followed by an intravenous infusion at a rate of 1,000 IU/hour for 24 hours. Bleeding problems at the arterial entry site occurred in 13 patients, which required a blood transfusion in only 2 patients. One patient underwent emergency bypass surgery without specific problems of hemostasis. Ridogrel virtually eliminated thromboxane B2 from the serum (29,990 f 6,555 pg/O.l ml before vs 63 f 7 pg/O.l ml at 2 hours after ridogrel), with a concomitant increase in serum 6keto-prostaglandin Faar (511 f 34 pg/O.l ml before vs 1,190 f 146 pg/O.l ml at 24 hours after ridogrel). There were no acute reocclusions in the ridogrel-treated patients, whereas acute reocclusions occurred in 5.6% of the patients taking the standard aspirin + heparin regimen during the same period. Furthermore, at 6month clinical follow-up patients treated with ridogrel compared favorably with those receiving standard treatment. (Am J Cardiol1991;66:463-466)
From the Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium and the Department of Clinical Research, Janssen Research Foundation, Becrse, Belgium. Manuscript received January 24,199 1; revised manuscript received and accepted April 16, 199 1. Address for reprints: Matty Vrolix, MD, Department of Cardiology, University Hospital Gasthuisberg, Herestraat 49, B 3000 Leuven, Belgium.
arly acute reocclusion,observedin 2 to 11% of patients the first 24 hours after an initially successful percutaneoustransluminal coronary angioplasty (PTCA), remains a major problem.1-4 The triggering mechanism is incompletely understood and probably variable.5-s Endothelial denudation, together with platelet activation and adhesion,is a major stimulant to thrombus formation9 and the development of local spasm.lo>1 l Becauseactual antiplatelet therapy obviously offers no complete solution to the problem, a more potent and selectiveapproach in antiplatelet strategy could be beneficial. Therefore, ridogrel (R68060), a combined thromboxane B2 synthetase inhibitor and thromboxane-prostaglandin endoperoxide receptor blocker, was compared with salicylate therapy in an open-pilot study in patients undergoing PTCA. The aim was threefold: assessmentof the safety of ridogrel in combination with heparin, monitoring of prostanoids and ridogrel concentrations,and collecting observational data on the effect of ridogrel on acute and chronic restenosisrate.
E
METHODS Patients: Of 352 patients referred for PTCA at our institution betweenMarch 20, 1989, and July 24, 1989, 32 were included in this study. Patients were eligible if they reported no intake of antiplatelet drugs for > 10 days before the study and if no contraindications for this therapy were present. Patients gave informed consent and the study protocol was approved by the ethical committee of our institution. Study methods: PTCA was performed from the brachial (n = 17) or femoral (n = 15) approach using a standard technique.l2 Ridogrel treatment was administered as a slow intravenous injection of 300 mg just before the start of the PTCA procedure. Twelve hours later, oral treatment was begun at a dose of 300 mg twice daily until hospital discharge. Heparin was given at the start of the procedure as a lO,OOO-IUintraarterial bolus dosefollowed by an intravenous infusion for 24 hours at a rate of 1,000 W/hour with otherwise unchanged concomitant medication. At discharge, ridogrel was replaced by aspirin and a calcium antagonist. Bleeding eventswere coded as minor if external and no transfusion therapy was needed. All bleeding episodesrequiring blood transfusion were coded as a major THROMBOXANE SYNTHETASE INHIBITOR IN PTCA 463
bleeding complication. Primary PTCA successwas delined as a residual stenosisof 10000
TXB2S 10000
9
9
f 3'hdose 7
9
L
48
600
pg/O.lCC
t**
4oooq
E
:
~OOOOJ
\
l *
r
1400
y/---I
72 hours
4 51hdose
t 71hdose
3
Z-+dose
1 s=d&e B*dose
1 n
18
20
21
20
19
20
11
FIGURE 1. Serum thromboxane B2 (TXB2) (closed symbols) and 6-keto-prostaglandin Fl, levels (open symbols) before and after administration of ridogrel in patients with a thromboxane B2 pre-treatment level of IlO,OOO p&O.1 ml (A.) and >lO,OOO pg/O.l ml (B.). Values are mean f standard error of the mean. Signifkancy versus pretreatment values was tested by a Wilcoxon test. *p
The safety of the combination of heparin and ridogre1 therapy and its antiplatelet efficacy was examined in the setting of percutaneous transluminal coronary angioplasty (PTCA). In 32 patients without known ,aspirin intake for 10 days before PTCA, therapy with ridogrel(300-mg intravenous bolus) was begun just before PTCA and continued orally at a dose of 300 mg twice daily until discharge. Heparin was administered as a 10,000 IU bolus dose before PTCA and followed by an intravenous infusion at a rate of 1,000 IU/hour for 24 hours. Bleeding problems at the arterial entry site occurred in 13 patients, which required a blood transfusion in only 2 patients. One patient underwent emergency bypass surgery without specific problems of hemostasis. Ridogrel virtually eliminated thromboxane B2 from the serum (29,990 f 6,555 pg/O.l ml before vs 63 f 7 pg/O.l ml at 2 hours after ridogrel), with a concomitant increase in serum 6keto-prostaglandin Faar (511 f 34 pg/O.l ml before vs 1,190 f 146 pg/O.l ml at 24 hours after ridogrel). There were no acute reocclusions in the ridogrel-treated patients, whereas acute reocclusions occurred in 5.6% of the patients taking the standard aspirin + heparin regimen during the same period. Furthermore, at 6month clinical follow-up patients treated with ridogrel compared favorably with those receiving standard treatment. (Am J Cardiol1991;66:463-466)
From the Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium and the Department of Clinical Research, Janssen Research Foundation, Becrse, Belgium. Manuscript received January 24,199 1; revised manuscript received and accepted April 16, 199 1. Address for reprints: Matty Vrolix, MD, Department of Cardiology, University Hospital Gasthuisberg, Herestraat 49, B 3000 Leuven, Belgium.
arly acute reocclusion,observedin 2 to 11% of patients the first 24 hours after an initially successful percutaneoustransluminal coronary angioplasty (PTCA), remains a major problem.1-4 The triggering mechanism is incompletely understood and probably variable.5-s Endothelial denudation, together with platelet activation and adhesion,is a major stimulant to thrombus formation9 and the development of local spasm.lo>1 l Becauseactual antiplatelet therapy obviously offers no complete solution to the problem, a more potent and selectiveapproach in antiplatelet strategy could be beneficial. Therefore, ridogrel (R68060), a combined thromboxane B2 synthetase inhibitor and thromboxane-prostaglandin endoperoxide receptor blocker, was compared with salicylate therapy in an open-pilot study in patients undergoing PTCA. The aim was threefold: assessmentof the safety of ridogrel in combination with heparin, monitoring of prostanoids and ridogrel concentrations,and collecting observational data on the effect of ridogrel on acute and chronic restenosisrate.
E
METHODS Patients: Of 352 patients referred for PTCA at our institution betweenMarch 20, 1989, and July 24, 1989, 32 were included in this study. Patients were eligible if they reported no intake of antiplatelet drugs for > 10 days before the study and if no contraindications for this therapy were present. Patients gave informed consent and the study protocol was approved by the ethical committee of our institution. Study methods: PTCA was performed from the brachial (n = 17) or femoral (n = 15) approach using a standard technique.l2 Ridogrel treatment was administered as a slow intravenous injection of 300 mg just before the start of the PTCA procedure. Twelve hours later, oral treatment was begun at a dose of 300 mg twice daily until hospital discharge. Heparin was given at the start of the procedure as a lO,OOO-IUintraarterial bolus dosefollowed by an intravenous infusion for 24 hours at a rate of 1,000 W/hour with otherwise unchanged concomitant medication. At discharge, ridogrel was replaced by aspirin and a calcium antagonist. Bleeding eventswere coded as minor if external and no transfusion therapy was needed. All bleeding episodesrequiring blood transfusion were coded as a major THROMBOXANE SYNTHETASE INHIBITOR IN PTCA 463
bleeding complication. Primary PTCA successwas delined as a residual stenosisof 10000
TXB2S 10000
9
9
f 3'hdose 7
9
L
48
600
pg/O.lCC
t**
4oooq
E
:
~OOOOJ
\
l *
r
1400
y/---I
72 hours
4 51hdose
t 71hdose
3
Z-+dose
1 s=d&e B*dose
1 n
18
20
21
20
19
20
11
FIGURE 1. Serum thromboxane B2 (TXB2) (closed symbols) and 6-keto-prostaglandin Fl, levels (open symbols) before and after administration of ridogrel in patients with a thromboxane B2 pre-treatment level of IlO,OOO p&O.1 ml (A.) and >lO,OOO pg/O.l ml (B.). Values are mean f standard error of the mean. Signifkancy versus pretreatment values was tested by a Wilcoxon test. *p
