Antithrombotic Therapy After Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is a treatment option for symptomatic patients with severe aortic stenosis who are candidates for a bioprosthesis across the entire spectrum of risk. However, TAVR carries a risk for thrombotic and bleeding events, underscoring the importance of defining the optimal adjuvant antithrombotic regimen. Antithrombotic considerations are convoluted by the fact that many patients undergoing TAVR are generally elderly and present with multiple comorbidities, including conditions that may require long-term oral anticoagulation (OAC) (eg, atrial fibrillation) and antiplatelet therapy (eg, coronary artery disease). After TAVR among patients without baseline indications for OAC, recent data suggest dual-antiplatelet therapy to be associated with an increased risk for bleeding events, particularly early postprocedure, compared with single-antiplatelet therapy with aspirin. Concerns surrounding the potential for thrombotic complications have raised the hypothesis of adjunctive use of OAC for patients with no baseline indications for anticoagulation. Although effective in modulating thrombus formation at the valve level, the bleeding hazard has shown to be unacceptably high, and the net benefit of combining antiplatelet and OAC therapy is unproven. For patients with indications for the use of long-term OAC, such as those with atrial fibrillation, the adjunctive use of antiplatelet therapy increases bleeding. Whether direct oral anticoagulant agents achieve better outcomes than vitamin K antagonists remains under investigation. Overall, single-antiplatelet therapy and OAC appear to be reasonable strategies in patients without and with indications for concurrent anticoagulation. The aim of the present review is to appraise the current published research and recommendations surrounding the management of antithrombotic therapy after TAVR, with perspectives on evolving paradigms and ongoing trials.

Risk of bleeding after prehospital administration of high dose tirofiban for ST elevation myocardial infarction.

BACKGROUND: In most patients with ST-elevation myocardial infarction (STEMI), antiplatelet drugs are already administrated in the ambulance, before hospital admission. We investigated the safety of prehospital initiation of a high dose of the glycoprotein IIb/IIIa inhibitor tirofiban on top of aspirin, clopidogrel and heparin. METHODS: It concerns a sub-analysis of the On-TIME 2 trial. 1398 patients were enrolled and 1275 patients (91.2%) had clinical follow up. Non CABG-related bleeding was defined according to the TIMI criteria. Logistic regression was used to determine predictors of 30-day bleeding. The independent association between bleeding and mortality (30-day and 1-year) was evaluated using Cox proportional Hazard models. RESULTS: Bleeding (major or minor) was observed in 47 patients (3.7%), with only 13 patients (1%) with major bleeding. The strongest independent determinants of bleeding were age (OR 1.05, 95% CI 1.01-1.08, p=0.011), Killip class >1 at admission (OR 2.5, 95% CI 1.2-5.3, p=0.020) and intra aortic balloon pump (IABP) use (OR 4.2, 95% CI 1.6-11.1, p=0.003). High dose tirofiban was not an independent predictor of bleeding (OR 1.7, 95% CI 0.9-3.2, p=0.116). Bleeding was associated with an increased risk of 30-day mortality (HR 5.5, 95% CI 1.6-7.8, p<0.001) and one-year mortality (HR 3.2, 95% CI 1.4-7.2, p=0.005). CONCLUSION: Prehospital use of high dose tirofiban is safe and associated with a low risk of bleeding. Age, Killip class >1, IABP use, but not high dose tirofiban are independent determinants of bleeding in STEMI patients. Bleeding is independently associated with 30-day and 1-year mortality.

Higher efficacy of pre-hospital tirofiban with longer pre-treatment time to primary PCI: protection for the negative impact of time delay.

AIMS: To evaluate the impact of longer duration of pre-hospital initiated antiplatelet and antithrombotic therapy on outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: In this sub-analysis of the Ongoing Tirofiban in Myocardial Evaluation (On-TIME) 2 trial, we studied, in 1,370 patients, the effect of pre-treatment time (time from administering study medication to time of angiography) on complete ST-segment resolution (STR), initial patency and 30-day mortality. Study medication consisted of high dose tirofiban (HDT) or control (placebo or no HDT) on top of high dose clopidogrel, aspirin and unfractionated heparin. Median pre-treatment time was 55 min (44-70). Longer pre-treatment was associated with longer transportation times, longer in-hospital delay, longer total ischaemic time (all p<0.001) and higher 30-day mortality (3.6% vs. 1.8%, p=0.046). Longer HDT pre-treatment time was independently associated with increased complete STR both before (odds ratio [OR] 1.51, 95%; confidence interval [CI] 0.98-2.32; p=0.06) and after PCI (OR 1.43, 95%; CI 1.02-2.02; p=0.039) and with a significantly improved initial TIMI 2 or 3 flow (51.4% vs. 43.4%, p=0.042) and reduced 30-day mortality (2.1% vs. 5.0%, p=0.047) as compared to longer control pre-treatment. CONCLUSIONS: Longer time delay before primary PCI is associated with increased mortality. Pre-treatment with high dose tirofiban, however, may compensate for this negative effect by improving ST-segment resolution and initial patency and by reducing mortality. Further studies should be performed to confirm that this is an attractive therapy for patients with longer delays to reperfusion.

Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete ST-segment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: correlates of reperfusion before primary PCI.

OBJECTIVE: The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial. METHODS: Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram. RESULTS: Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality. CONCLUSIONS: Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome.

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.

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).