A genotype-guided strategy for oral P2Y₁₂ Inhibitors in primary PCI

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.)

Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularisation in patients with stable angina pectoris: study protocol for the PRO-FIT randomised controlled trial

Background: Currently, in the majority of patients with stable angina pectoris (SAP) treatment consists of optimal medical treatment, potentially followed by coronary angiography and subsequent coronary revascularisation if necessary”. Recent work questioned the effectiveness of these invasive procedures in reducing re-events and improving prognosis. The potential of exercise-based cardiac rehabilitation on clinical outcomes in patients with coronary artery disease is well-known. However, in the modern era, no studies compared the effects of cardiac rehabilitation versus coronary revascularisation in patients with SAP. Methods: In this multicentre randomised controlled trial, 216 patients with stable angina pectoris and residual anginal complaints under optimal medical treatment will be randomised to: 1) usual care (i.e., coronary revascularisation), or 2) a 12-month cardiac rehabilitation (CR) programme. CR consists of a multidisciplinary intervention, including education, exercise training, lifestyle coaching and a dietary intervention with a stepped decline in supervision. The primary outcome will be anginal complaints (Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing. Discussion: In this study, we will examine the hypothesis that multidisciplinary CR is at least equally effective in reducing anginal complaints as the contemporary invasive approach at 12-months follow-up for patients with SAP. If proven successful, this study will have significant impact on the treatment of patients with SAP as multidisciplinary CR is a less invasive and potentially less costly and better sustainable treatment than coronary revascularisations. Trial registration: Netherlands Trial Register, NL9537. Registered 14 June 2021

Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI: A Meta-Analysis of Randomized Controlled Trials

Clinical trials comparing thrombectomy devices with conventional percutaneous coronary interventions (PCI) in patients with acute ST elevation myocardial infarction (STEMI) have produced conflicting results. The objective of our study was to systematically evaluate currently available data comparing thrombectomy followed by PCI with conventional PCI alone in patients with acute STEMI

Impact of failed mechanical reperfusion in patients with acute myocardial infarction treated with primary angioplasty

Percutaneous coronary intervention is not successful in all patients whose acute myocardial infarction is controlled with primary angioplasty, and, after an initial successful procedure, reperfusion is not always sustained due to subacute (stent) thrombosis. In a studied population that had acute myocardial infarction, failed mechanical reperfusion occurred in 108 patients (6.9%). Killip's class > I at admission, a left anterior descending artery as the infarct-related vessel, or a preprocedural Thrombolysis In Myocardial Infarction grade 0 or 1 flow was an independent predictor of failed reperfusion. Outcome after successful early and sustained mechanical reperfusion is excellent. Failure of the initial procedure and reocclusion of the infarct-related vessel are important determinants of adverse outcome. (c) 2005 Elsevier Inc. All rights reserved

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

Item does not contain fulltextAIMS: 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

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 pretreatment, 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) (J Am Coll Cardiol 2010; 55: 2446-55) (C) 2010 by the American College of Cardiology Foundatio

Pre-treatment with clopidogrel and postprocedure troponin elevation after elective percutaneous coronary intervention

Elevated troponin after elective percutaneous coronary intervention (PCl) has been associated with a worse prognosis. Pretreatment with clopidogrel may be beneficial in patients undergoing PCl. Therefore, a prospective observational study was conducted to address the potential role of clopidogrel in reducing troponin release after elective PCl.Troponin T was measured 12 hours after elective PCl in 656 patients without elevated troponin before PCl. To assess the independent association between pre-treatment with clopidogrel and increased troponin, multivariate analyses were performed. Mean age of the 656 patients was 63.5 years (SD 10.2), 194 patients (30%) were female and 114 patients (17.4%) had diabetes. In 217 patients (33%) troponin was increased after PCl. Of the 330 patients who were not pre-treated with dopidogrel, 118 patients (34%) had increased troponin after the PCl compared to 99 patients (30%) of the 326 patients who were treated with clopidogrel longer than 24 hours before the procedure (p=0.14). Stratified analyses showed that patients with older age (p=0.03), previous PCl (p=0.013), angina CCS 4 (p=0.03) and multivessel disease (p=0.04) had a significantly lower risk of troponin increase after pre-treatment with clopidogrel compared to patients without pre-treatment. After adjusting for differences in the other variables, patients who were pre-treated with clopidogrel had a significant lower risk of post-PCl increase of troponin T (odds ratio 0.69, 95% confidence interval 0.49-0.99). Pre-treatment with clopidogrel is associated with a significantly lower incidence of increased troponin after elective PCl. Combined with results of other studies, pre-treatment should be advised in patients waiting for elective PCl

A comparison of dual vs. triple antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndrome: results of the ELISA-2 trial

Aims To compare dual vs. triple antiplatelet pre-treatment in patients with non-ST-elevation acute coronary syndrome (NSTE ACS) who were planned for early catheterization. Methods and results A total of 328 consecutive patients with NSTE ACS were included and were randomized to pre-treatment with dual (n = 166, aspirin, clopidogrel 600 mg) or triple antiplatelet therapy (n = 162, aspirin, clopidogrel 300 mg, and Tirofiban). The primary endpoint was enzymatic infarct size, defined as cumulative LDH release (LDHQ(48)). Initial TIMI flow of the culprit vessel was a prespecified secondary endpoint. Angiography was performed in 98% of patients at a median of 23 h after admission. Enzymatic infarct size (median, 25-75%) was 166 (60-349) IU/L in the triple group compared with 193 (75-466) IU/L in the dual group (P = 0.2). Initial TIMI 3 flow of the culprit vessel was significantly more often observed after triple antiplatelet therapy (67 vs. 47%, P = 0.002). At 30 days follow-up, myocardial infarction (MI) occurred in 46% of patients in the triple antiplatelet group, compared with 57% in the dual antiplatelet group, P = 0.052. No significant difference in bleeding was present. Conclusion This study showed that in patients with NSTE ACS, triple antiplatelet pre-treatment was associated with a non-significant reduction in enzymatic infarct size, a significantly better initial perfusion of the culprit vessel, and a trend towards a better survival without death or MI. Further, large-scale studies should be performed to find whether the beneficial trend in favour of triple antiplatelet pre-treatment can be reproduced