What is the risk of intensifying platelet inhibition beyond clopidogrel? A systematic review and a critical appraisal of the role of prasugrel.

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate 2 receptor. They have been shown to significantly reduce platelet activity exerting an important role in those clinical settings in which such an effect is beneficial. Ticlopidine was first to be introduced several years ago but it was quickly replaced by clopidogrel as it had a better risk/benefit profile. Recently, prasugrel has been developed and tested in several ex vivo studies and clinical trials showing able to provide a more powerful antiplatelet effect at the expense of a higher risk of bleeding complications. Great debate rose around its recent approval in the US as well as in Europe. This review aims at exploring the development and available clinical data of this third-generation thienopyridine while discussing its practical implementation in routine practice.

Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition.

AIM: Elevation of Troponin after scheduled percutaneous coronary intervention (PCI) is a recognized consequence. We sought to evaluate the prognostic significance and impact of the newly published definition of PCI-related myocardial infarction (MI) according to which any troponin elevation >3 times the upper reference limit identify a peri-procedural MI. METHODS: Search of BioMedCentral, CENTRAL, mRCT and PubMed (updated May 2008). Outcomes of interest were: MACE [the composite of all cause death, MI, repeat target vessel PCI (re-PCI) and coronary artery bypass grafting (CABG)]; single end points were also assessed. RESULTS: Fifteen studies have been included totalling 7578 patients. Troponin elevation occurred in 28.7% of the procedures. The incidence of PCI-related MI according to the new definition was 14.5%. During the hospitalization, any level of raised troponin was associated with an increased risk of MACE [OR 11.29 (3.00-42.48), Number needed to harm (NNH) 5], death [OR 7.16 (1.95-26.27), NNH = 100], MI [OR 30.85 (6.05-157.38), NNH = 4] and re-PCI [OR 4.13 (1.23-13.88), NNH = 50]. Patients with PCI-related MI had an increased risk of death [OR 17.25 (2.71-109.96), NNH = 100] and re-PCI [OR 10.86 (3.2-36.94), NNH = 25]. At follow up of 18 months any troponin elevation was associated with an increased risk of MACE [OR 1.48 (1.12-1.96), NNH = 20], death [OR 2.19 (1.59-3.00), NNH = 50], MI [OR 3.29 (2.71-6.31), NNH = 33] and re-PCI [OR 1.47 (1.06-2.03), NNH = 25]. In patients with PCI-related MI the risk of MACE was further increased: OR 2.25 (1.26-4.00), NNH = 3. An increase of the troponin level below the cut-off was not associated with MACE. CONCLUSION: A diagnosis of MI according to the new guidelines applies to 15% of patients undergoing PCI and these patients are at high risk of further adverse events both during the hospital stay and at 18 months.

Pexelizumab in ischemic heart disease: a systematic review and meta-analysis on 15,196 patients.

OBJECT: Pexelizumab is a humanized monoclonal antibody inhibiting C5 complement. It has been postulated to improve outcomes in patients undergoing coronary artery bypass surgery and urgent reperfusion therapy for ST elevation myocardial infarction. We aimed at evaluating the risk/benefit profile of pexelizumab (bolus + infusion) versus placebo on top of current approaches in the management of patients with ST elevation myocardial infarction or undergoing coronary artery bypass. METHODS: We conducted a search of BioMedCentral, CENTRAL, mRCT, and PubMed without language restrictions (updated October 2007) for randomized controlled trials. Outcomes of interest were the risk of major adverse events (the composite of all-cause death, myocardial infarction, and thromboembolic stroke), the risk of single end points, and heart failure. RESULTS: Seven trials were included (15,196 patients: 7019 patients with ST elevation myocardial infarction and 8177 undergoing coronary bypass surgery). No benefit of adding pexelizumab was found in the overall analysis for major adverse events (OR 0.91 [0.76-1.09]; P = .29], death (OR 0.79 [0.61-1.03], P = .11], myocardial infarction (OR 1.04 [0.89-1.22]; P = .14), stroke (OR 0.95 [0.66-1.38]; P = .8), heart failure (OR1.0 [0.82-1.22]; P = .99), nor in the settings of patients with ST elevation myocardial infarction treated with mechanical or pharmacologic reperfusion therapy. Pexelizumab was associated with a 26% reduction of the risk of death in the setting of coronary artery bypass (OR 0.74 [0.58-0.94]; P = .01). The number needed to treat was 100. CONCLUSION: Our data ruled out the hypothesis of any benefit of adding pexelizumab on top of currently available therapies for ST elevation myocardial infarction. However, pexelizumab reduces the risk of death in patients undergoing coronary artery bypass grafting.

Repeat thrombolysis or conservative therapy vs. rescue percutaneous coronary intervention for failed thrombolysis: systematic review and meta-analysis.

BACKGROUND: Despite proven advantages of primary percutaneous coronary intervention (PCI), thrombolysis remains the first line treatment for ST-elevation myocardial infarction (STEMI) worldwide. Management of patients with failed thrombolysis is still debated, and data from existing randomized controlled trials are conflicting. AIM: To compare the risk/benefit profile of repeat thrombolysis (RT) vs. rescue PCI in patients with failed thrombolysis. METHODS: Search of BioMedCentral, CENTRAL, mRCT and PubMed for randomized controlled trials comparing rescue PCI vs. conservative therapy and/or RT vs. conservative therapy. Outcomes of interest assessed by adjusted indirect meta-analysis: major adverse events (MAE, defined as the composite of overall mortality and re-infarction), stroke, congestive heart failure (CHF), major bleeds (MB), and minor bleeds. Overall mortality and re-infarction have been also analysed individually. RESULTS: Eight trials were included (1318 patients). Follow-up ranged from 'in-hospital' to 6 months. No significant difference was found for the risk of MAE [OR 0.93(0.26-3.35), P = 0.4], overall mortality [OR 1.01(0.52-1.95), P = 0.15], stroke [OR 5.03(0.64-39.1), P = 0.58] and CHF [OR 0.74(0.28-1.96), P = 0.6]. Compared with conservative therapy, rescue PCI was associated with a 70% reduction in the risk of re-infarction [OR 0.32(0.14-0.74), P = 0.008], number needed to treat 17. No difference in terms of MB was found [OR 0.5(0.1-2.5), P = 0.09], while a greater risk of minor bleeds was observed with rescue PCI [OR 2.48(1.08-5.7), P = 0.04], number needed to harm 50. CONCLUSION: Although the observed benefit is modest, these data support the use of PCI after failed thrombolysis.

Results of primary percutaneous coronary intervention in a consecutive group of patients with acute ST elevation myocardial infarction at a tertiary Australian centre.

BACKGROUND: Multicentre randomized controlled trials (RCT) of primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) have consistently shown lower mortality compared with fibrinolysis, if carried out in a timely manner. Although primary PCI is now standard of care in many centres, it remains unknown whether results from RCT of selected patients are generalizable to a 'real-world' Australian setting. The primary goal of this study was to evaluate whether a strategy of routine invasive management for patients with STEMI can achieve 30-day and 12-month mortality rates comparable with multicentre RCT. Secondary goals were to determine 30-day mortality rates in prespecified high-risk subgroups, and symptom-onset- and door-to-balloon-inflation times. METHODS: A retrospective observational study of 189 consecutive patients treated with primary PCI for STEMI in a single Australian centre performing PCI for acute STEMI. RESULTS: All-cause mortality was 6.9% at 30 days, and 10.4% at 12 months. Mortality in patients presenting without cardiogenic shock was low (2.4% at 30 days; 5.0% at 12 months), whereas 12-month mortality in patients with shock was higher, particularly in the elderly (29.4% for patients <75 years; 85.7% for patients > or =75 years, P = 0.01). Symptom-onset-to-balloon-inflation time was < or =4 h in 56% of patients (median 231 min); however, a door-to-balloon time of <90 min was achieved in only 20% (median 133 min). CONCLUSION: Mortality and symptom-onset-to-balloon-inflation times reported in RCT of primary PCI for STEMI are generalizable to 'real-world' Australian practice; however, further efforts to reduce door-to-balloon times are required.