ABSTRACT: The aim of this subanalysis was to assess the net clinical effect of prehospital administration of tirofiban in ST-elevation myocardial infarction (STEMI) patients with high risk of bleeding.
This is a retrospective subanalysis of the On- TIME 2 trial, a multicenter, controlled randomized trial of the effects of high bolus-dose tirofiban given in the ambulance in STEMI patients. Tirofiban was given on top of aspirin, heparin, and clopidogrel. According to CRUSADE, patients with a moderate to very high baseline risk of bleeding were defined as high risk and patients with a very low or low baseline bleeding risk were defined as low risk. Primary endpoint was net adverse clinical events (NACE) at 30 days (defined as the combined incidence of death, recurrent myocardial infarction, urgent target vessel revascularization, stroke, or non-coronary artery bypass graft [CABG]-related major bleeding).
Of 1309 patients, a high bleeding risk was present in 291 patients (22.2%). In these high-risk bleeding patients, tirofiban significantly improved after percutaneous coronary intervention (PCI) ST-segment resolution. Administration of tirofiban in high-risk bleeding patients showed no difference in 30-day major adverse cardiac events (MACE) (9.4% vs 13.0%; P=.330; relative risk [RR], 0.72; 95% confidence interval [CI], 0.37-1.39). However, pretreatment with tirofiban was associated with a nonsignificant increase in non-CABG related bleeding (8.6% vs 3.6%; P=.082; RR, 2.38; 95% CI, 0.90-6.39). The net clinical effect (30-day NACE) of tirofiban in this group was balanced (11.5% vs 15.2%; P=.365; RR, 0.76; 95% CI, 0.41-1.38).
Prehospital use of tirofiban in STEMI patients with high risk of bleeding improves post-PCI ST-segment resolution, but increases nonsignificantly the risk of non-CABG related bleeding. The net result is a balanced effect on 30-day NACE. Additional studies should clarify how use of bleeding risk scores should modify medical (antiplatelet) therapy.
The Journal of invasive cardiology 03/2012; 24(3):84-9. · 1.84 Impact Factor
ABSTRACT: Glycoprotein IIb/IIIa inhibitors are favourable in ST-elevation myocardial infarction (STEMI) patients, and the additional value of early pre-hospital high bolus dose tirofiban has recently been established. The aim of this study was to determine the impact of age on myocardial reperfusion and clinical outcomes of pre-hospital administration of high bolus dose tirofiban.
This is a pre-specified sub-analysis of the multicentre, double-blind, placebo-controlled, randomised On-TIME 2 trial and it's open label phase. The primary endpoint was mean residual ST segment deviation 1 h after primary PCI and was evaluated in three age groups.
Of the 466 patients in the highest tertile (≥68 years), median age was 74.4 years (IQR 71.3-78.6 years) and 231 (50%) were randomised to tirofiban. Mean residual ST segment deviation 1 h after PCI was significantly lower in elderly patients pre-treated with tirofiban compared to elderly patients without tirofiban pre-treatment (4.2 ± 5.2 mm vs 6.4 ± 7.5 mm, p = 0.001). Furthermore, elderly patients pre-treated with tirofiban had a non-significantly higher rate of 30-day major or minor bleeding compared to elderly patients without tirofiban pre-treatment (14.2% vs 9.0%, p = 0.088). 30-day net adverse clinical events in elderly patients with- or without tirofiban was not significantly different (11.9% vs 15.2%, p = 0.300).
The effect of pre-hospital initiation of high bolus dose tirofiban on myocardial reperfusion, as determined by ST-segment resolution is highest in the elderly patients. However, this was associated with a trend towards more bleeding complications, resulting in a balanced clinical effect after 30-day follow-up. Future studies should evaluate whether the elderly STEMI patient may benefit from highly effective and safer antiplatelet therapy.
Cardiovascular Drugs and Therapy 08/2011; 25(4):323-30. · 3.13 Impact Factor
ABSTRACT: 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.
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.
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.
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.
American heart journal 12/2010; 160(6):1079-84. · 4.65 Impact Factor
ABSTRACT: 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).
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.
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.
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.
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).
Journal of the American College of Cardiology 06/2010; 55(22):2446-55. · 14.16 Impact Factor