Hof, A.W.J. van 't

The golden hour of prehospital reperfusion with triple antiplatelet therapy: A sub-analysis from the Ongoing Tirofiban in Myocardial Evaluation 2 (On-TIME 2) trial early initiation of triple antiplatelet therapy (Article)

2010-12-01T00:00:00Z

Background: It is known that the efficacy of thrombolytic therapy in ST-segment elevation myocardial infarction (STEMI) is highly time dependent with the best efficacy when given within the so-called golden hour. This analysis from the On-TIME 2 trial evaluated the efficacy of triple antiplatelet therapy on initial patency and ST-segment resolution (STR) in relation to time from symptom onset to first medical contact. Methods: The On-TIME 2 trial included 1,398 consecutive STEMI patients referred for primary percutaneous coronary intervention (PCI). Patients were randomized to dual (500 mg aspirin and 600 mg clopidogrel) or triple antiplatelet (500 mg aspirin, 600 mg clopidogrel, and tirofiban 25 μg/kg bolus and 0.15 μg/kg per minute maintenance infusion for 18 hours) pretreatment in the ambulance. Primary outcome of this sub-analysis was initial patency of the infarct-related vessel and STR before PCI according to time from symptom onset to first medical contact in quartiles. In addition, the incidence of aborted myocardial infarction, defined as the absence of a rise in creatinine kinase, was assessed. Results: Initial patency, STR before PCI, and the incidence of aborted myocardial infarction gradually increased with shorter time from symptom onset to first medical contact. Initial Thrombolysis in Myocardial Infarction flow was present in 21.2% in the total population and 26.2%, 21.5%, 18.1%, and 18.8% in the time quartiles, respectively (P for trend = .01). The incidence of complete STR pre-angiography was 16.6% in the total population and 23.4%, 18.2%, 14.7%, and 9.9% in the 4 quartiles, respectively (P for trend < .001). This was largely driven by the effect of triple antiplatelet therapy, which further improved initial patency and STR and led to a significantly higher incidence of aborted myocardial infarction (13.2% vs 8.7%, P = .011), especially in the patients with short duration of symptoms. Conclusion: Antiplatelet pretreatment before primary PCI, including a glycoprotein IIb/IIIa blocker, seems to be most effective when given shortly after symptom onset. Further studies should be performed to test this hypothesis.

Effect of Early, Pre-Hospital Initiation of High Bolus Dose Tirofiban in Patients With ST-Segment Elevation Myocardial Infarction on Short- and Long-Term Clinical Outcome (Article)

2010-06-01T00:00:00Z

Objectives: The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). Background: The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. Methods: The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. Results: During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. Conclusions: Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297).

The effect of ITF-1697 on reperfusion in patients undergoing primary angioplasty. Safety and efficacy of a novel tetrapeptide, ITF-1697 (Article)

2004-03-01T00:00:00Z

AIM: ITF-1697 is a C-reactive protein-derived tetrapeptide that, based on pre-clinical studies, is thought to reduce reperfusion injury. We performed a dose-finding study to assess safety, preliminary efficacy and clinical outcome of prolonged i.v. infusion of ITF-1697 in patients with an acute myocardial infarction (AMI) who were eligible for percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a multicentre dose-finding study that was randomised, double blind, and placebo-controlled. Four hundred and two patients were enrolled. Intravenous infusion of four dosages of ITF-1697 (0.1, 0.5, 1.0 or 2.0 microg/kg/min) or placebo was started before PCI and continued for 24 h. After interim analysis of data from 242 patients the study continued with the 0.1 and 1.0 microg/kg/min ITF-1697 regimes. Analysis did not raise any safety concerns. Post-procedure perfusion, assessed by TIMI flow, corrected TIMI frame count, blushgrade and ST-segment resolution, was similar for the placebo, 0.1 and 1.0 microg/kg/min regimes. Furthermore, the results showed no differences between the treatment regimes in enzymatic infarct size or clinical outcome up to 30 days. CONCLUSION: ITF-1697 was well tolerated. However, neither a dose-relation nor improvement of perfusion, clinical outcome or reduction of myocardial damage could be demonstrated with ITF-1697 during and after primary PCI for AMI.

Behandeling van patiënten met acute coronaire syndromen in Nederland in 2000/2001; een vergelijking met andere Europese landen en met de richtlijnen (Article)

2004-01-01T00:00:00Z

Doel. Beschrijven of richtlijnen voor de behandeling van acuut coronair syndroom (ACS) in de dagelijkse praktijk worden toegepast, en op welke punten de behandeling verschilt tussen Nederland en de overige lidstaten van de European Society of Cardiology (ESC). Opzet. Prospectief observationeel onderzoek. Methode. In de periode 4 september 2000-15 mei 2001 werden in Nederland in 6 ziekenhuizen, en in 24 andere ESC-lidstaten in 97 ziekenhuizen, patiënten met een bevestigde diagnose van ACS geïncludeerd. Gegevens werden verzameld over de acute behandeling en secundaire preventie bij patiënten met ST-elevatie en over medicamenteuze behandeling, risicostratificatie en secundaire preventie bij patiënten zonder ST-elevatie. De bevindingen werden vergeleken met de aanbevelingen in de richtlijnen van de ESC. Resultaten. In Nederland werden 223 patiënten met ST-elevatie geïncludeerd en 198 zonder, en in de overige Europese landen respectievelijk 4208 en 5169 patiënten. De mediane leeftijd was 64-67 jaar. Het percentage mannen was 64-73. Van de patiënten met ST-elevatie die binnen 12 uur na het ontstaan van de symptomen in het ziekenhuis arriveerden, ontving 35% noch trombolyse, noch primaire percutane coronaire interventie. Zowel in Nederland als in de andere Europese landen onderging de helft van de patiënten met ST-elevatie trombolyse later dan 40 minuten en primaire percutane coronaire interventie later dan 90 minuten, na binnenkomst in het ziekenhuis. Risicoschatting door een troponinebepaling werd in Nederland vaker toegepast. Van de hoogrisicopatiënten zonder ST-elevatie onderging ruim 50% in zowel Nederland als de rest van Europa coronairangiografie. Bijna 70% en 80% van de laag-risicopatiënten zonder ST-elevatie onderging een inspanningstest en/of coronairangiografie. In Nederland werden clopidogrel, glycoproteïne-IIb/IIIa-antagonisten en statinen vaker voorgeschreven en ACE-remmers minder vaak. Conclusie. Richtlijnen voor de behandeling van ACS werden zowel in Nederland als in de rest van Europa matig gevolgd. De behandeling verschilde op diverse punten tussen Nederland en de andere landen.

A Clinical Evaluation of Primary Angioplasty and Stenting in Acute Myocardial Infarction (Doctoral Thesis)

1998-09-02T00:00:00Z

In 1949 the fibrinolytic effect of streptococcal fibrinolysin (streptokinase) was described for the treatment of fibrous, pUl1llent or sanguineous pleural exudations. The effect of this lytic agent in patients with acute myocardial infarction was described by Fletcher in 1958. In the late nineteensevcnties the pathofysiologic mechanism underlying acute myocardial infarction was recognised. In the majority of patients with acute myocardial infarction a completely occluded coronary artery is present at immediate angiography, caused by the formation of a platelet rich thrombus on reptured atherosclerotic plaque. Reperfusion therapy is aimed at removal of this obstructing clot which can be achieved by t1uombolytic agents (given directly into the coronary artery or intravenously) or by mechanical intervention (Percutaneous Transluminal Coronary Angioplasty (PTCA)) or by a combination of these two. Rentrop et aJ. described his experience with intracoronary administration of streptokinase in 1979. In 1983 it was shown in small trials that the intracoronary administration of streptokinase was beneficial compared to placebo treatment and later, larger randomised trials demonstrated convincingly that intravenous fibrinolytic therapy re·establishes coronaty patency, thereby limiting infarct size and preserving left ventricular function resulting in improved survival. In 1982, Meyer reported a case in which he successfully re-opened an infarct related vessel with a guide wire and a balloon after failed thrombolytic therapy. One year later Hartzler was the first to describe his experience with primary coronary angioplasty (mechanical revascularization without antecedent thrombolysis).