Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials.

The coagulation system contributes greatly to the evolution of myocardial infarction (MI). Anticoagulation may reduce the occurrence of MI as monotherapy or with concomitant use of aspirin. Activated factor X antagonists (anti-Xa) and direct thrombin inhibitors have promising results in various indications in non-inferiority trials. However, results regarding their cardiovascular safety are heterogeneous. We systematically evaluated the risk of MI and mortality in patients receiving the new-generation oral anti-Xa agent apixaban. Electronic databases were searched to find prospective, randomized, controlled clinical trials (RCT) that evaluated the clinical impact of apixaban. Efficacy measures included frequency of MI, cardiovascular and overall mortality. Outcome parameters of RCTs were pooled with a random-effects model. Between January 2000 and December 2013, 12 RCTs comprising 54,054 patients were identified. Based on the pooled results, there was no increase in the risk of MI in patients treated with apixaban [odds ratio (OR) 0.90; 95 % confidence interval (CI) 0.77-1.05; p = 0.17] compared to different controls. Cardiovascular and overall mortality with apixaban was comparable to the control groups (OR 0.88; 95 % CI 0.72-1.06; p = 0.18, OR 0.89; 95 % CI 0.77-1.03; p = 0.11, respectively). The pooled risk of major bleeding was lower in the apixaban treated groups (OR 0.84; 95 % CI 0.62-1.12; p = 0.23) however this reached significant level only in subgroup analysis of trials with anticoagulant regimes in the control (OR 0.66; 95 % CI 0.51-0.87; p = 0.003). In a broad spectrum of patients and compared to different controls apixaban treatment was not associated with an increase in MI or mortality.

Adaptation of closed-chest infarction porcine model to adult Pannon minipigs.

The aim of the recent study was to collect data on the genotype characteristics of the Hungarian self-bred Pannon minipigs by adapting a standardized infarct model procedure. Closed chest AMI was induced by balloon occlusion for 90 min in the left anterior descendent coronary artery (LAD) in 24 adult intact female minipigs followed by reperfusion. To assess the left ventricular (LV) function, serial cardiac magnetic resonance imaging (cMRI) was performed prior to the experimental procedure, on day 3 post-AMI (72 ± 12 h), and at 1 month follow-up (Day 30 ± 2 days). Compared to baseline cMRI scans the end-diastolic volume (EDV) was increased on days 3 and 30 On day 3 the left ventricular ejection fraction (LVEF) decreased significantly but there was no statistical difference between the baseline and day 30 measurements. Cardiac output, stroke volume, and end-systolic volume significantly were increased compared to baseline on day 30 A high percentage (54%) of malignant arrhythmias occurred during the AMI procedure, with a 25% mortality rate. The compensatory capacity of the Pannon minipig heart is excellent therefore the use of different cardiac parameters and invasive measurements is advisable in chronic pharmacological experiments to complement cMRI data.

The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies.

OBJECTIVES: Internal organ involvement reduces the life expectancy of SSc patients. Cardiopulmonary manifestations are currently the primary cause of death. We aimed to perform a systematic review and meta-analysis to define more precise effect estimates of different cardiopulmonary manifestations and to verify trends in the mortality of SSc. METHODS: A systematic literature search was performed to identify relevant cohort studies. Reports analyzing the role of the organ manifestations in mortality or analysing survival compared with the control population were included. The outcome parameters were pooled with the random-effect model via generic inverse-variance weighting in conventional and cumulative meta-analysis. RESULTS: Eighteen studies comprising a total of 12, 829 patients qualified. The reported causes of death were as follows: 19.7% cardiac, 16.8% interstitial pulmonary disease, 13.1% pulmonary hypertension and 13.8% renal disease. The risk of death was significantly increased in patients with cardiac involvement [hazard ratio (HR) 3.15], with pulmonary interstitial disease (HR 2.58), with pulmonary hypertension (HR 3.50) and with renal manifestations (HR 2.76). A trend for survival improvement (R2)= 0.4295, P = 0.04) was found, and the difference in survival between the diffuse and limited scleroderma subgroups was diminishing (R2)= 0.4119. P = 0.02). CONCLUSION: Meta-analysis of observational studies indicates a trend for improvement over the last decades in which the life expectancy of SSc patients approaches that of the general population. A decreasing tendency in the survival differences between the limited and diffuse SSc subgroups was also verified. Internal organ involvements have similarly unfavourable predictive impact on survival.

Justification of 150 mg clopidogrel in patients with high on-clopidogrel platelet reactivity.

BACKGROUND: The GRAVITAS trial showed that 150 mg clopidogrel did not improve outcome in patients with high on-clopidogrel platelet reactivity (HPR) screened by the VerifyNow assay. We aimed to determine the impact of 150 mg clopidogrel in stable angina patients with HPR identified with conventional aggregometry (LTA). MATERIALS AND METHODS: Clopidogrel-naive stable angina patients before ad hoc percutaneous coronary intervention were recruited into a randomized, double-blind, placebo-controlled trial (NCT00638326). Twelve to 24 h after the 600-mg loading dose of clopidogrel, ADP(5µM)-stimulated maximal (AGGmax), late platelet aggregation (AGGlate) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI) were evaluated. Patients with HPR (AGGmax ≥ 34%) were randomly allocated to 75 or 150 mg clopidogrel after 4 weeks. After control platelet function measurements at day 28, 75 mg clopidogrel was administered to all patients until 1 year. RESULTS: The study was prematurely terminated at the stage of 200 enroled patients. Administration of 150 mg clopidogrel significantly reduced platelet aggregation (AGGmax: 45·0 ± 6·8 vs. 33·8 ± 15·1, P < 0·01; AGGlate: 27·1 ± 14·7 vs. 13·8 ± 18·0, P < 0·01) and VASP-PRI (57·5 ± 15·2 vs. 37·2 ± 17·1; P < 0·01), while platelet reactivity remained unchanged in patients with HPR receiving 75 mg clopidogrel. The higher maintenance dose of clopidogrel was associated with a significant reduction in cardiovascular (CV) death and myocardial infarction (MI) (0% vs. 11·4%, P = 0·04) and in CV death, MI or target vessel revascularization (24·6% vs. 3·1%; P = 0·01) during 1 year. CONCLUSIONS: One-month administration of 150 mg maintenance dose of clopidogrel reduces platelet reactivity and might decrease the risk of thrombo-ischaemic complications in stable angina patients with HPR identified by LTA.

Mechanism of coronary flow reserve reduction in systemic sclerosis: insight from intracoronary pressure wire studies.

OBJECTIVE: Functional impairment of coronary microcirculation is thought to be a major pathway in the development of primary cardiac involvement in SSc; however, the underlying mechanism is not fully understood. We aimed to investigate the mechanisms of coronary flow reserve (CFR) reduction in patients with SSc. METHODS: Seventeen SSc patients and 17 gender- and age-matched controls were enrolled. Coronary angiography and determination of coronary flow parameters including index of myocardial resistance (IMR) using intracoronary pressure wire at basal conditions and during vasodilator-induced maximal hyperaemia were performed. Transit times of repeated intracoronary saline injection were measured to evaluate the role of cold exposure. RESULTS: SSc patients with decreased CFR had accelerated basal coronary flow velocity (P < 0.05), and their IMR in hyperaemia (IMR(hyp)) did not differ from either SSc patients with normal CFR or from the controls (P = 0.292 and P = 0.308). The coronary flow velocity of SSc patients correlated with the IMR at baseline (IMR(bas)) (r = 0.56, P = 0.019). Injection of room temperature saline did not provoke changes in coronary transit times. CONCLUSIONS: The lack of decrease in the maximal vasodilatation response indicates that there is no irreversible functional damage at the level of the coronary arterioles. In patients with reduced CFR, the decreased basal IMR and higher velocity reflect compensatory vasodilatory mechanisms probably triggered by ischaemic signals deriving from abnormal myocardial microcirculation.

Successful endovascular treatment of simultaneous acute ischaemic stroke and hyperacute ST-elevation myocardial infarction: the first case report of a single-operator cardio-cerebral intervention.

BACKGROUND: The simultaneous management of cardio-cerebral infarctions is an extremely difficult task, as both organs need to receive reperfusion therapy in a limited time to avoid death or permanent disability. The following case is the first published endovascular treatment of synchronous heart and brain infarctions delivered by a single operator with excellent clinical outcome. CASE SUMMARY: A 67-year-old female patient was directly transported to the emergency room of a comprehensive stroke centre with acute onset global aphasia and right hemiplegia. The onset to admission time exceeded the 4.5-h time window of systemic thrombolysis. Head computed tomography (CT) excluded extensive early extensive brain damage, CT angiography documented left middle cerebral artery occlusion and mechanical thrombectomy was indicated. Extensive anterior ST elevation was detected on the transport monitor while waiting for in-hospital transfer. The two simultaneously evolving pathologies were handled in a single endovascular procedure that took less than 60 min by a dual-trained interventional cardiologist/neurointerventional surgeon. The patient recovered without any major cardiac or neurologic sequela. DISCUSSION: Interventional cardiologists, professionally trained through a neurointerventional fellowship programme to perform endovascular stroke interventions according to the latest multi-society position paper, could not only complement stroke teams lacking manpower, but their unique experience could also help the patients suffering from the most devastating forms of cardio-cerebral infarctions.

Diagnostic pitfalls: intramyocardial lymphoma metastasis mimics acute coronary syndrome in a diffuse large B cell lymphoma patient-case report.

BACKGROUND: Cardiac tumors are very uncommon compared to other cardiac diseases. Their clinical symptoms can vary from absent to non-specific. The most common symptoms are arrhythmias, blood flow obstruction due to valvular dysfunction, shortness of breath, systemic embolization, and accumulation of pericardial fluid. Hereby, we describe a very rare case of a diffuse large B cell lymphoma patient who presented with the symptoms and signs of acute coronary syndrome (ACS) but the patient's complaints were caused by his intramyocardial lymphoma metastasis. CASE PRESENTATION: Forty-eight-year-old diffuse large B cell lymphoma patient was admitted to our emergency department with chest pain, effort dyspnea, and fever. The patient had normal blood pressure, blood oxygen saturation, sinus tachycardia, fever, crackles over the left lower lobe, novum incomplete right bundle branch block with Q waves and minor ST alterations, elevated C-reactive protein, high-sensitivity troponin-T, and d-dimer levels. Chest X-ray revealed consolidation on the left side and enlarged heart. Bed side transthoracic echocardiography showed inferior akinesis with pericardial fluid. Coronary angiography showed no occlusion or significant stenosis. Chest computed tomography demonstrated the progression of his lymphoma in the myocardium. He was admitted to the Department of Hematology for immediate chemotherapy and he reached complete metabolic remission, followed by allogeneic hematopoietic stem cell transplantation. Unfortunately, about 9 months later, he developed bone marrow deficiency consequently severe sepsis, septic shock, and multiple organ failure what he did not survive. CONCLUSIONS: Our case demonstrates a very rare manifestation of a heart metastasis. ACS is an unusual symptom of cardiac tumors. But our patient's intramyocardial lymphoma in the right atrium and ventricle externally compressed the right coronary artery and damaged the heart tissue, causing the patient's symptoms which imitated ACS. Fortunately, the quick diagnostics and immediate aggressive chemotherapy provided the patient's remission and suitability to further treatment.

Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis.

BACKGROUND: A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous coronary intervention. We aimed to perform an updated systematic review and meta-analysis on the clinical relevance of HPR to summarize the available evidence and to define more precise effect estimates. METHODS: Relevant observational studies published between January 2003 and February 2010 were searched that presented intent-to-treat analyses on the clinical relevance of HPR measured with an adenosine diphosphate (ADP)-specific platelet function assay. The main outcome measures were cardiovascular (CV) death, definite/probable stent thrombosis (ST), nonfatal myocardial infarction (MI), and a composite end point of reported ischemic events. The outcome parameters were pooled with the random-effect model via generic inverse variance weighting. RESULTS: Twenty studies comprising a total number of 9,187 patients qualified. High on-clopidogrel platelet reactivity appeared to be a strong predictor of MI, ST, and the composite end point of reported ischemic events (odds ratios [95% CI]: 3.00 [2.26-3.99], 4.14 [2.74-6.25], and 4.95 [3.34-7.34], respectively; P < .00001 for all cases). According to the meta-analysis, patients with HPR had a 3.4-fold higher risk for CV death compared with patients with normal ADP reactivity (odds ratio 3.35, 95% CI 2.39-4.70, P < .00001). Although there were large differences in the methodology as well as in the definition of HPR between studies, the predicted risk for CV death, MI, or ST was not heterogeneous (I(2): 0%, 0%, and 12%, respectively; P = not significant for all cases). CONCLUSIONS: High on-clopidogrel platelet reactivity, measured by an ADP-specific platelet function assay, is a strong predictor of CV death, MI, and ST in patients after percutaneous coronary intervention.

Comparison of conventional aggregometry with VASP for monitoring P2Y12-specific platelet inhibition.

No consensus exists regarding the optimal estimate of light transmission aggregometry (LTA) to reflect P2Y12 ADP receptor inhibition in patients receiving thienopyridine therapy. Currently, the only completely P2Y12-receptor specific method is the measurement of vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) with flow cytometry. In the current analysis, we aimed to test the superiority of the late platelet aggregation value over other estimates of light transmission aggregometry in determining P2Y12-receptor inhibition by comparing them to VASP-PRI. On-clopidogrel platelet reactivity was measured in 121 clopidogrel-naïve patients who underwent elective coronary stent implantation. Samples for LTA and VASP assessments were drawn at 12-18 hours after a 600-mg loading dose of clopidogrel and 25 days after the intervention. ADP 5 µM-induced maximal aggregation (AGGmax), 6-minute late aggregation (AGGlate), 6-minute disaggregation (disAGG) and area under the aggregation curve (AUC) were compared to VASP-PRI. Categorical agreement with VASP-defined normal and high platelet reactivity (HPR: PRI ≥ 50%) was calculated according to the optimal cutoff values obtained with receiver-operating characteristic (ROC) curves. The evaluation of 242 measurements showed significant, moderate-strength correlations between VASP-PRI and LTA estimates without the superiority of AGGlate over other estimates (AGGmax: ρ = 0.47; AGGlate: ρ = 0.45; disAGG: ρ = -0.44; AUC: ρ = 0.50). Notably, there were considerable intra-individual differences between VASP and LTA testing. LTA estimates were similar in classifying patients to VASP-defined normal or HPR categories (AGGmax: κ = 0.41; AGGlate: κ = 0.45; disAGG: κ = 0.44; AUC: κ = 0.44). When all estimates of LTA were compared in multivariable models, AUC proved to be the independent linear determinant of VASP-PRI and the best predictor of HPR. Estimates of LTA seem equal in determining the degree of P2Y12-receptor inhibition or in predicting VASP-defined HPR without the superiority of AGGlate over others. These results reject a commonly used hypothesis and might contribute to the standardization of the LTA assay.

Low platelet disaggregation predicts poor response to 150 mg clopidogrel in patients with elevated platelet reactivity.

Raising the maintenance dose of clopidogrel to 150 mg enhances platelet inhibition (PI) in patients with elevated platelet reactivity (EPR); however, large differences were observed between individuals in the extent of this benefit. We aimed to find clinical and platelet function variables that might predict the response to 150 mg clopidogrel in patients with EPR. ADP 5 microM-stimulated peak aggregation (Agg(max)), 6-minute late aggregation (Agg(late)) and 6-minute disaggregation (disAgg) were measured with light transmission aggregometry (LTA) in a consecutive cohort of 202 patients admitted for emergent or elective percutaneous coronary intervention (PCI) after receiving a 600-mg loading dose of clopidogrel. PI was assessed 12 to 18 hours after loading dose and 30 days after the intervention. EPR was defined as a Agg(max) value greater than 34%. From the first day of PCI, 85 patients with EPR received 150 mg clopidogrel for 30 days, while others with normal platelet reactivity (NPR) took 75 mg clopidogrel. Baseline clinical and LTA variables were analyzed in multivariable regression models. Administration of 150 mg clopidogrel enhanced PI and decreased the prevalence of EPR at 30 days compared to the peri-interventional period (Agg(max): 46.9 +/- 8.3 vs. 37.3 +/- 11.5; EPR: 100% vs. 62.4%; p < 0.001 in both cases); however, the achieved level of platelet reactivity was higher than patients with NPR (Agg(max): 20.6 +/- 8.1 vs. 25.3 +/- 10.8, p < 0.001). Multivariable logistic regression revealed low platelet disaggregation (odds ratio (OR): 12.49; 95% CI: 2.52-62.00; P = 0.002) and acute coronary syndrome (OR: 4.83; 95% CI: 1.54-15.09; P = 0.008) as independent predictors of EPR. The area under the receiver-operating-characteristic curve was 0.72 +/- 0.06 for disaggregation to predict NPR after 150 mg clopidogrel. The optimal disaggregation cut-off was 16.5% with a sensitivity of 94% and a specificity of 43%. Administering 150 mg maintenance dose of clopidogrel enhanced antiplatelet potency; however, more than half of the patients persisted with EPR. Acute coronary syndrome and low (<16.5%) platelet disaggregation are independent predictors of poor benefit from dose shift.

Transradial versus transfemoral percutaneous coronary intervention in acute myocardial infarction Systematic overview and meta-analysis.

BACKGROUND: Although transradial percutaneous coronary intervention (TRPCI) is widely applied for percutaneous procedures, its safety in the setting of ST-segment elevation (STEMI) is controversial. Our aim was to assess the safety and efficacy of TRPCI versus transfemoral PCI in the context of treating patients suffering acute myocardial infarction with STEMI. METHODS: Randomized, case-control, and cohort studies comparing access-related complications were analyzed. Our objective was to determine if radial access reduces major bleeding and thereby reduces death and ischemic events compared to femoral access in this setting. A fixed-effects model was used with random effects for sensitivity analysis. RESULTS: Twelve studies involving 3324 patients were identified. Transradial PCI reduced major bleeding compared to transfemoral PCI (P = .0001), and significant reductions were found in the composite of death, myocardial infarction, or stroke (P = .001). Mortality reduction showed a significant toward benefit in the case of TRPCI (2.04% vs 3.06%, OR 0.54 [95% CI 0.33-0.86], P = .01). The fluoroscopic time was longer, and access site crossover was more frequent for TRPCI (P = .001, P < .00001, respectively). CONCLUSIONS: Transradial PCI reduces the risk of periprocedural major bleeding and major adverse events in the STEMI setting.

Pathfinding to an optimal strategy of revascularization in primary coronary intervention in patients with multivessel disease: a network meta-analysis of randomized trials.

OBJECTIVES: In ST-segment elevation myocardial infarction (STEMI), current guidelines discourage treatment of the non-culprit lesions at the time of the primary intervention. Latest trials have challenged this strategy suggesting benefit of early complete revascularization. We performed a Bayesian multiple treatment network meta-analysis of randomized clinical trials (RCTs) in STEMI on culprit-only intervention (CO) versus different timing multivessel revascularization, including immediate (IM), same hospitalization (SH) or later staged (ST). METHODS: Outcome parameters were pooled with a random-effects model. For multiple-treatment meta-analysis, a Bayesian Markov chain Monte Carlo method was used. RESULTS: Eight RCTs involving 2077 patients were identified. ST and IM revascularization was associated with a decrease in major adverse cardiac events (MACEs) compared to culprit-only approach (risk ratio [RR]: 0.43 credible interval [CrI]: 0.22-0.77 and RR: 0.36 CrI: 0.24-0.54, respectively). IM was superior to SH (RR: 0.49 CrI: 0.29-0.80). With regards to myocardial infarction IM was superior to SH (RR: 0.18 CrI: 0.02-0.99). The posterior probability of being the best choice of treatment regarding the frequency of MACEs was 71.2% for IM, 28.5% for ST, 0.3% for SH and 0.05% for culprit-only approach. CONCLUSIONS: Results from RCTs indicate that immediate or staged revascularization of non-culprit lesions reduces major adverse events in patients after primary percutaneous coronary intervention. Differences in MACEs suggest superiority of the immediate or staged intervention; however, further randomized trials are needed to determine the optimal timing of revascularization of the non-culprit lesions.

Clinical outcomes in patients treated for coronary in-stent restenosis with drug-eluting balloons: Impact of high platelet reactivity.

BACKGROUND: The impact of high platelet reactivity (HPR) on clinical outcomes after elective percutaneous coronary interventions (PCI) with drug-eluting balloons (DEB) due to in-stent restenosis (ISR) is unknown. OBJECTIVE: We sought to evaluate the prognostic importance of HPR together with conventional risk factors in patients treated with DEB. METHODS: Patients treated with DEB due to ISR were enrolled in a single-centre, prospective registry between October 2009 and March 2015. Only patients with recent myocardial infarction (MI) received prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test >46U with the Multiplate assay and no adjustments were done based on results. The primary endpoint of the study was a composite of cardiovascular mortality, MI, any revascularization or stroke during one-year follow-up. RESULTS: 194 stable angina patients were recruited of whom 90% were treated with clopidogrel. Clinical characteristics and procedural data were available for all patients; while platelet function testing was performed in 152 subjects of whom 32 (21%) had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45; CI: 1.01-5.92; p = 0.03). The difference was primarily driven by a higher risk for revascularization and MI. According to the multivariate analysis, HPR remained a significant, independent predictor of the primary endpoint (HR: 2.88; CI: 1.02-8.14; p = 0.04), while total DEB length and statin treatment were other independent correlates of the primary outcome. CONCLUSION: HPR was found to be an independent predictor of repeat revascularization and MI among elective patients with ISR undergoing PCI with DEB.

Subcutaneous Versus Transvenous Implantable Defibrillator Therapy: A Meta-Analysis of Case-Control Studies.

OBJECTIVES: This study aims to conduct a meta-analysis comparing efficacy and safety outcomes between subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous implantable cardioverter-defibrillator (TV-ICD). BACKGROUND: The S-ICD was developed to minimize complications related to the conventional TV-ICD. Direct comparison of clinical outcomes between the 2 devices has been limited by varying patient characteristics and definitions of complications with no randomized trials completed comparing these systems. METHODS: Studies in the PubMed and Embase databases and secondary referencing sources were systematically reviewed. Studies meeting criteria were included in the meta-analysis. Baseline characteristics and outcome data of the S-ICD and TV-ICD groups were appraised and analyzed. A random-effects model was used to derive odds ratio (OR) with 95% confidence interval (CI). RESULTS: Five studies met inclusion criteria. Baseline characteristics were similar between the S-ICD and TV-ICD groups. Fewer lead complications occurred in the S-ICD group compared to the TV-ICD group (OR: 0.13; 95% CI: 0.05 to 0.38). The infection rate was similar between the S-ICD and TV-ICD groups (OR: 0.75; 95% CI: 0.30 to 1.89). There were no differences in system or device failures between groups (OR: 1.13; 95% CI: 0.43 to 3.02). Overall, inappropriate therapy (T-wave oversensing, supraventricular tachycardia, episodes of inappropriate sensing) was similar between the 2 groups (OR: 0.87; 95% CI: 0.51 to 1.49). However, the nature of inappropriate therapy was different between the S-ICD and TV-ICD groups. Both devices appear to perform equally well with respect to appropriate shocks. CONCLUSIONS: S-ICD reduced lead-related complications but was similar to TV-ICD with regard to non-lead-related complications, including inappropriate therapy. These results support the concept that S-ICD is a safe and effective alternative to TV-ICD in appropriate patients.

Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrel.

OBJECTIVES: This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). BACKGROUND: The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. METHODS: Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. RESULTS: A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p < 0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p < 0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01). CONCLUSIONS: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

Meta-analysis of randomized trials on access site selection for percutaneous coronary intervention in ST-segment elevation myocardial infarction.

INTRODUCTION: Superior outcomes with transradial (TRPCI) versus transfemoral coronary intervention (TFPCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI) have been suggested by earlier studies. However, this effect was not evident in randomized controlled trials (RCTs), suggesting a possible allocation bias in observational studies. Since important studies with heterogeneous results regarding mortality have been published recently, we aimed to perform an updated review and meta-analysis on the safety and efficacy of TRPCI compared to TFPCI in the setting of STEMI. MATERIAL AND METHODS: Electronic databases were searched for relevant studies from January 1993 to November 2012. Outcome parameters of RCTs were pooled with the DerSimonian-Laird random-effects model. RESULTS: Twelve RCTs involving 5,124 patients were identified. According to the pooled analysis, TRPCI was associated with a significant reduction in major bleeding (odds ratio (OR): 0.52 (95% confidence interval (CI) 0.38-0.71, p < 0.0001)). The risk of mortality and major adverse events was significantly lower after TRPCI (OR = 0.58 (95% CI: 0.43-0.79), p = 0.0005 and OR = 0.67 (95% CI: 0.52-0.86), p = 0.002 respectively). CONCLUSIONS: Robust data from randomized clinical studies indicate that TRPCI reduces both ischemic and bleeding complications in STEMI. These findings support the preferential use of radial access for primary PCI.

Meta-analysis comparing carvedilol versus metoprolol for the prevention of postoperative atrial fibrillation following coronary artery bypass grafting.

A systematic review and meta-analysis was performed to evaluate the effects of carvedilol versus metoprolol on the incidence of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting in randomized controlled trials. Ovid MEDLINE, PubMed, CENTRAL, and Excepta Medica (EMBASE) were searched up to March 2013 for suitable randomized controlled trials. Data were pooled using random-effects model for pairwise analyses. A total of 4 trials with 601 patients were included in this analysis. Pairwise analyses showed that compared with metoprolol, carvedilol significantly reduced the incidence of postoperative atrial fibrillation (odds ratio 0.50, 95% confidence interval 0.32 to 0.80). In conclusion, compared with metoprolol, carvedilol significantly reduces the incidence of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting.

Impact of clopidogrel and potent P2Y 12 -inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.

Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Despite receipt of dual antiplatelet therapy, patients after an acute coronary syndrome (ACS) remain at significant risk for thrombotic events. The role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors is debated in this setting. Our study objective was to evaluate the efficacy and safety of new-generation oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an ACS. METHODS: Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite end point of major ischemic events, while thrombolysis in myocardial infarction-defined major bleeding events were used as a safety end point. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events. RESULTS: For the period January 1, 2000, through December 31, 2011, we identified 7 prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31 286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio, 3.03; 95% CI, 2.20-4.16; P < .001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with new-generation oral anticoagulant agents provided no advantage over placebo (odds ratio, 0.98; 95% CI, 0.90-1.06; P = .57). CONCLUSION: The use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.

Outcomes of patients receiving clopidogrel prior to cardiac surgery.

BACKGROUND: Clinical impact of the concomitant clopidogrel therapy on clinical outcomes in patients undergoing cardiac surgery is unclear. We aimed to pool and systematically analyze outcomes in clopidogrel-treated patients undergoing cardiac operations to achieve greater statistical power and to define precise effect-estimates. METHODS: PubMed and Central databases were searched for relevant studies published between January 2001 and May 2010. The main outcome measures were the rates of red blood cell (RBC) transfusion, reoperation, myocardial infarction and postoperative mortality. The outcome parameters were pooled with the random-effect model via generic-inverse variance-weighting. RESULTS: Twenty studies comprising a total number of 23,668 patients were analyzed. Pooled analysis revealed that the administration of clopidogrel had a higher risk for postoperative mortality (OR: 1.24; 95% CI: 1.03-1.49, p=0.03) that was consistent among studies. The rates of myocardial infarction were similar between groups. Clopidogrel-exposed patients were associated with a significantly higher rate of RBC transfusion (OR: 1.82; 95% CI: 1.40-2.37; p<0.00001) and reoperation (OR: 2.15; 95% CI: 1.38-3.34; p<0.00001), although there was a marked heterogeneity among studies. According to subgroup analysis the mortality and the rates of transfusions were higher in studies in which clopidogrel was not discontinued 5 days prior to surgery, while the higher risk for reoperation was only apparent in studies published before 2006. CONCLUSION: Meta-analysis of observational studies demonstrated that concomitant treatment with clopidogrel before cardiac surgery is associated with a significant risk of bleeding-related complications and with a higher mortality.