Abrupt vessel closure continues to represent the most dangerous hazard of percutaneous transluminal coronary angioplasty. Despite anticoagulation and inhibition of platelet aggregation, abrupt vessel closure complicates coronary angioplasty in 2–8% of cases. Intracoronary stenting and pharmaceutical blockade of the glycoprotein IIb/IIIa receptor reduce the incidence of abrupt vessel closure, but cannot completely resolve the issue. Numerous predictors of abrupt vessel closure have been established including lesion characteristics, and clinical and angiographic predictors. Owing to local activation of the coagulation system and intracoronary thrombus formation, the use of PTCA in treating acute coronary syndromes such as unstable angina or acute myocardial infarction is associated with an excessively high risk of abrupt vessel closure.
Angioplasty induced injury of the coronary artery is followed by the adhesion and aggregation of platelets leading to intracoronary thrombus formation. Apart from the degree of vessel wall injury, activation of the local coagulation system and coronary perfusion determine the extent of intracoronary thrombus formation. However, Danchin and colleagues described a significant reduction of abrupt vessel closure with intravenous dipyridamole in a retrospective analysis. Since oral or intravenous application of dipyridamole is associated with a high level of plasma protein binding which might counteract a sufficient local concentration at the coronary site, intracoronary application of dipyridamole was performed in this investigation.
PATIENTS Over a 14 months period, 1623 coronary interventions were performed. Patients treated with intracoronary stenting or alternative techniques like coronary atherectomy or laser angioplasty were not included in the analysis. Thus, restricting the analysis to pure balloon angioplasty, 1094 interventions (67.4% of all interventions performed during the study period) in 1082 patients were analysed. In a second step, analysis was performed on an intention to treat basis of 1147 interventions including the 53 interventions in which bailout stenting had been performed following randomisation. In 155 interventions PTCA was performed in the setting of acute coronary syndromes, including 51 dilatations for unstable angina (class III, class B and C, according to Braunwald17), and 17 and 104 dilatations for acute myocardial infarction (defined as onset of symptoms within a period of less than 24 hours).
The study protocol was reviewed and accepted by the local ethics committee. All of the patients included in investigation were treated with intracoronary isosorbide dinitrate (0.3–0.6 mg) directly after placement of the guiding catheter, and were then randomised to receive either conventional pretreatment consisting of heparin 15 000 IU and aspirin 500 mg intravenously or an additional intracoronary application of dipyridamole (0.5 mg/kg bodyweight). Treatment with either conventional medication or additional dipyridamole was not blinded. Intracoronary dipyridamole was administered in two boluses, by manual injection over a time period of one minute per bolus.
According to the randomisation intracoronary dipyridamole was administered in 550 interventions (455 interventions in men, 74 dilatations in the setting of acute coronary syndromes); in 544 dilatations conventional pretreatment was performed (444 interventions in men, 81 dilatations.
SECONDARY END POINTS
Following intracoronary administration of dipyridamole there was a notable reduction in the incidence of myocardial infarction following PTCA which, however, failed to reach significance (odds ratio 0.47, 95% CI 0.20 to 1.10). The incidence of bypass grafting and death were also less frequent after dipyridamole pretreatment, but again this failed to reach significance.
Data indicate that intracoronary pretreatment with dipyridamole is associated with a highly significant reduction in the incidence of abrupt vessel closure. This prevention could be observed in patients with stable angina and in those with acute coronary syndromes. The comparatively high incidence of abrupt vessel closure, especially in the conventionally treated group, is explained by the high percentage of interventions for acute coronary syndromes accounting for 36.2% of all occlusions.
However, in the analysis restricted to balloon angioplasty, patients presenting with acute coronary syndromes seemed to gain the greatest benefit from the addition of intracoronary dipyridamole. Secondary end points defined as myocardial infarction, necessity for bypass grafting, and death following PTCA were reduced by intracoronary dipyridamole but this reduction failed to reach significance. Only in the intention to treat analysis did the incidence of myocardial infarction demonstrate a significant reduction.
Intracoronary application of dipyridamole is associated with a highly significant reduction in the incidence of abrupt vessel closure following PTCA. This beneficial effect was observed in patients presenting with stable angina and acute coronary syndromes.
However, in the analysis restricted to PTCA, patients receiving coronary angioplasty in the setting of myocardial infarction or unstable angina seem to gain the greatest benefit from intensifying the antithrombotic medication by intracoronary dipyridamole. In the intention to treat analysis myocardial infarction following PTCA was observed less frequently following intracoronary dipyridamole.