The Effects of Platelet-Derived Growth Factor Inhibitor(Trapidil) on Intimal Hyperplasia Following Coronary Stenting: Assessed by Intravascular Ultrasound

BACKGROUND AND OBJECTIVES: Platelet-derived growth factor (PDGF) seems to be one of the most powerful factors associated with the proliferative process that occurs after percutaneous transluminal coronary angioplasty (PTCA), and leads to restenosis. Trapidil (Triazolopyrimidine), a potent inhibitor of PDGF, was shown to decrease restenosis after experimental balloon angioplasty. The aim of this study was to assess the effects of trapidil, on intimal hyperplasia, following coronary artery stenting, using volumetric intravascular ultrasound (IVUS) analysis. SUBJECTS AND METHODS: The patients were divided in 2 groups; Group I (n=14, age=53+/-8, male=11) received trapidil (600 mg) for 6 months, aspirin (200 mg) indefinitely and ticlopidine (250 mg) for 4 weeks, Group 2 (n=15, age=55+/-2, male=9) received aspirin (200mg) indefinitely and ticlopidine (500 mg) for 4 weeks, starting at least 3 days before the angioplasty. A serial IVUS study was performed post-stenting, with a 6 month follow up period. Both the stent (SA) and lumen areas (LA) were measured, and the stent (SV), lumen (LV) and intimal hyperplasia volumes (IHV) were calculated using Simpson's rule. RESULTS: The reference (RD), pre minimal luminal (MLD) and post minimal luminal diameters, as measured by quantitative coronary angiographic analysis (QCA), were not different between the two groups. Using serial IVUS measurements, SV and LV were not different between the two groups. Also, the IHV was not different between the two groups (51.9+/-26.1 and 61.3+/-25.3 mm3, respectively, p=NS). CONCLUSION: Trapidil failed to reduce intimal hyperplasia following coronary stenting compared with the controls.

Efeitos da aspirina e do trapidil sobre os eventos cardiovasculares após infarto afgudo do miocárdio / Effects of aspirin and trapidil on cardiovascular events after acute myocardial infarction

A terapêutica com a aspirina proporciona benefícios reais conclusivos na fase aguda do infarto do miocárdio em evoluçäo, porém näo foi demonstrada em qualquer estudo uma evidência objetiva do benefício a partir do uso a longo prazo da aspirina após infarto agudo do miocárdio (IAM). Este estudo multicêntrico, o estudo JAMIS - Japanese Antiplatelets Myocardial Infarction Study, foi realizado a fim de demonstrar se a aspirina ou o trapidil poderia melhorar a evoluçäo clínica em comparaçlo com a ausência de antiplaquetários em pacientes pós-infarto. O estudo foi um ensaio multicêntrico, controlado, randomizado, de mmodalidade aberta de 81 mg/dia de aspirina, 300 mg/dia de trapidil e ausência de antiplaquetários em pacientes portadores de IAM internados no período de um mês após o início dos sintomas. Foram incluídos 723 pacientes em 70 hospitais de 18 prefeituras do japäo; 250 foram alocados por randomizaçäo para tratamento com 81 mg de aspirina (grupo aspirina), 243 para o tratamento com o trapidil (grupo trapidil) e 230 näo receberam agentes antiplaquetários. O período médio de acompanhamento foi de 475 dias. Este estudo demonstrou que o uso a longo prazo da aspirina, na dose de 81 mg/dia, reduziu a incidência de recidiva de IAM em comparaçäo com o grupo que näo recebeu antiplaquetários após IAM e que o trapidil também reduziu a ocorrência de infarto em comparaçäo com o grupo que näo recebeu antiplaquetários, porém a diferença näo foi significante. Foi reduzida a incidência de eventos cardiovasculares incluindo óbito cardiovascular, reinfarto, angina instável näo controlada, necessitando de internaçäo hospitalar, bem como acidente vascular cerebral (AVC) isquêmico näo fatal no grupo que recebeu 300 mg de trapidil ao dia em comparaçäo com o grupo que näo recebeu antiplaquetários. O uso de 81 mg/dia de aspirina praticamente näo proporcionou benefício em comparaçäo com a ausência de terapêutica com antiplaquetários na incidência de eventos cardiovasculares. Em conclusäo, a aspirina em dose baixa efetivamente preveniu a recidiva de IAM em pacientes pós-infarto após trombólise ou angioplastia coronária quando utilizada durante longo prazo. Adicionalmente, o uso a longo prazo do trapidil acarretou uma reduçäo significante na incidência de eventos cardiovasculares.(au)

Anti-aggregatory Effect of Anti-platelet Agents

We investigated a prospective study to compare the effects of single or combined use of three commonly used anti-platelet agents; aspirin, ticlopidine and trapidil, on the platelet aggregation. Total 78 patients admitted to the neurology ward of Yonsei University Hospital with acute ischemic stroke were randomly divided into 7 groups .The blood was drawn from these patients before and a week after the prescription of anti-platelet agents pertinent to each group. Platelet aggregation was measured by using a platelet aggregometer (Chrono-Log Lumi Aggregometer Model 400) after addition o f adenosine diphosphite (ADP), collagen, epinephrine, ant platelet activating factor (PAF) on the platelet rich plasma. The results showed that 1) trapidil most effectively inhibited platelet aggregation by PAF, 2) aspirin and/or ticlopidine were superior to trapidil for the inhibitory effect on platelet aggregation by ADP. Collagen and epinephrine. 3) all three drug combination therapy successfully inhibited platelet aggregation by ADP. Collagen, epinephrine and PAF. Therefore. This in-vitro study suggests that combined use of anti-platelet agents having different mechanisms may provide more effective anti-platelet act;ons in acute ischemic stroke patients.

Clinical Trial on the Antianginal Effect of Trapidil

Antianginal effect of Trapidil was evaluated in 30 patients (18 male and 12 females) with angina rectoris. The results were follows : 1) Antianginal effect of the drug were good in 18 cases (60%) and fair in 8 cases (37%), and there was no effect in 4 cases(13%). 2) Improvement in ECG changes was observed in 29%. 3) There were no significant change in CBC, RUA, LFT, serum electrolyte and lipid study before and after medication. 4) The adverse effects of trapidil were constipation, gastric cramp and dizziness, respectively one case. But they were not required discontinuing the medicetion. On the basis of these results, Trapidol was evaluated to be promising antianginal drug.