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To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0. 10, between groups). In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction. • The first randomized trial of hydroxychloroquine in patients with a recent myocardial infarction. • Hydroxychloroquine reduced IL-6 levels more than placebo when treatment was continued six months. • Treatment with hydroxychloroquine was safe. • The number of adverse events did not differ between the hydroxychloroquine and placebo groups. • A larger trial is warranted to prove if hydroxychloroquine can reduce cardiovascular endpoints. [ABSTRACT FROM AUTHOR]

Abstract Aims Despite similar efficacy and safety profile in pilot studies, bioresorbable polymer drug-eluting stents (BP-DES) could have potential benefit over latest generation durable polymer (DP)-DES by facilitating vessel healing, therefore reducing inflammation and neoatherosclerosis leading to enhanced clinical safety. Therefore, we sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of everolimus-eluting BP-DES (BP-EES) to second-generation DP-DES. Methods and results We conducted a systematic review and meta-analysis to examine the safety and efficacy of BP-EES in patients treated for coronary artery disease. We searched PubMed, Scopus, and the Cochrane Library through February 2018 for RCTs that included outcome data on BP-EES. We identified four eligible studies, which included a total of 4631 patients. Three studies reported a follow-up of one year and one study of five years. The BP-EES group, included 2315 patients and the DP-DES group included 2316 patients (1143 treated with DP-EES and 1173 treated with zotarolimus eluting DP-DES). Patient's characteristics were comparable between the two groups except for higher prevalence of prior MI in the DP-DES group (25.7 vs 22.5%, respectively, p = 0.001). Procedural characteristics were comparable among groups except for slightly longer lesions in the BP-EES group compared to the DP-DES group (mean 15.1 vs 14.9 mm, p = 0.04). No significant differences were observed for cardiac mortality (p = 0.72), occurrence of MI (p = 0.64), any TLR (p = 0.93), ST (p = 0.85) or major adverse cardiac events (p = 0.43). Conclusion Overall, based on the available data BP-EES had similar one-year outcomes to contemporary DP-DES. Whether these devices could enhance clinical safety remains to be evaluated at longer follow-up. Highlights • To date, no meta-analysis focused on the safety and efficacy of biodegradable polymer everolimus-eluting stents (BP-EES) to second-generation durable polymer drug-eluting stents (DP-DES). • Overall, BP-EES had similar one-year outcomes compared to contemporary DP-DES. • Whether these devices could enhance long-term clinical efficacy remains to be evaluated at longer follow-up. [ABSTRACT FROM AUTHOR]

Background Angioplasty with paclitaxel-coated balloons (PCB) is recommended for treatment of patients with coronary in-stent restenosis (ISR) according to European clinical practice guidelines. Most clinical trials have investigated iopromide-based PCB and there is a paucity of data comparing efficacy against butyryl-tri-hexyl citrate (BTHC)-based PCB. Our aim was to compare the performance of two widely-used PCB in the treatment of coronary ISR. Methods We analysed patients treated with BTHC- or iopromide-PCB for treatment of drug-eluting stent ISR in the setting of 2 consecutive trials with identical inclusion and exclusion criteria. The primary endpoint was diameter stenosis at 6–8 month angiographic surveillance. The secondary endpoint of interest was the composite of death, myocardial infarction (MI) or target-lesion revascularisation (TLR) at 1 year. Multivariate analysis was performed to adjust for differences in baseline characteristics between groups. Results In total, 264 patients were treated with BTHC-PCB ( n = 127) or iopromide-PCB ( n = 137). Baseline patient characteristics were similar for both groups. Post-procedure stenosis was slightly larger with BTHC-PCB (22.3 [SD 8.2]% vs. 18.4 [SD 9.9]%, P = 0.001). At 6–8 month angiography, diameter stenosis was 40.4 [SD 21.9]% vs. 37.4 [SD 21.4]% in the BTHC-PCB and iopromide-PCB groups, respectively ( P = 0.16, P adjusted = 0.32). At 1 year, death, MI or TLR occurred in 29 (23.2%) vs. 32 (23.4%) patients in the BTHC-PCB and iopromide-PCB groups, respectively (HR 1.03 [95% CI 0.62–1.70], P = 0.91, P adjusted = 0.96). Conclusions In patients undergoing intervention for ISR, angioplasty with BTHC-PCB showed similar angiographic and clinical results at 1 year compared with iopromide-PCB. [ABSTRACT FROM AUTHOR]

Aims To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. Methods Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. Results Fifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7–1.17 and OR 0.92, 95% CI 0.69–1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45–0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15–1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46–0.92), all-cause mortality (OR 0.69, 95% CI 0.52–0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28–0.6) and LVEF (OR 1.49, 95% CI 1.09–2.05). Conclusions Administration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events. [ABSTRACT FROM AUTHOR]

Objective Few studies have focused on the effects of an improved door-to-balloon time on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to explore the effect of improving door-to-balloon time on prognosis and to identify major predictors of mortality. Methods From January 2005 to December 2014, 1751 patients experienced STEMI and received primary percutaneous intervention in our hospital. During a 10-year period, the patients were divided into two groups according to the time period. Since mid-2009, shortening door-to-balloon time has been an important concern of health care. As a result of targeted efforts, as of January 2010, door-to-balloon time shortened significantly. In our study, a total 853 patients were in group 1 during January 2005 to December 2009, and a total 898 patients were in group 2 during January 2010 to December 2014. Results The incidence of major adverse cardiac cerebral events (26.7% vs. 23.2%; p = 0.120), the incidence of cardiovascular mortality (9.3% vs. 8.8%; p = 0.741), and the incidence of all-cause mortality (12.6% vs. 12.2%; p = 0.798) were similar between the two groups. The incidence of target vessel revascularization significantly decreased in group 2 (17.8% vs. 12.6%; p = 0.008). However, the incidence of stroke increased in group 2 (1.8% vs. 3.6%; p = 0.034). Conclusion Improving door-to-balloon time could not improve 1-year cardiovascular mortality whether low-risk or high-risk patients. The improvement in the door-balloon time does not improve outcomes studied, probably because it is not accompanied by a reduction in total reperfusion time, which means from onset of symptoms to reperfusion. [ABSTRACT FROM AUTHOR]

Background Adjunctive therapies, given in addition to reperfusion to reduce myocardial infarct size, have been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. The no-reflow phenomenon occurs commonly after the infarct-related coronary artery is opened and predicts poor clinical outcome. We investigated the effects of a single application of delayed (post-reperfusion) therapeutic hypothermia (TH) in a rat model of coronary artery occlusion/reperfusion. Methods Rats were subjected to 60 min of coronary artery occlusion followed by 3 h of reperfusion. Rats were divided into normothermic ( n = 5) and TH ( n = 5) groups. In the TH, hypothermia was initiated at 1 min after coronary artery reperfusion by pumping room-temperature (22 °C) saline into and out of the thoracic cavity for 1 h. This decreased intrathoracic temperature to around 26 °C within 12 min. At 3 h after reperfusion, hearts were excised for infarct size and no-reflow zone measurement. Results Ischemic risk area and infarct size were similar between the 2 groups. No-reflow area (expressed as % of risk area) was significantly reduced in TH group (18.0 ± 4.4%) compared with normothermic group (39.5 ± 2.9%, P = 0.005). When expressed as % of necrotic area, no-reflow area was reduced by more than half in TH group (25.5 ± 6.4%) versus in normothermic group (54.4 ± 5.3%, P = 0.01). Conclusions In this preliminary study, hypothermia initiated after reperfusion following 60 min of coronary artery occlusion had no effect on infarct size yet substantially reduced the extent of no-reflow. [ABSTRACT FROM AUTHOR]

Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart rate reduction, thus enabling longer diastolic perfusion time, and reduced myocardial oxygen consumption without detrimental changes in arterial blood pressure, coronary vasomotion, and ventricular contractility. The current guideline-based clinical use of Ivabradine is reserved for patients with stable angina pectoris who cannot tolerate or whose symptoms are inadequately controlled with beta blockers. In patients with chronic heart failure and reduced ejection fraction, Ivabradine has demonstrated beneficial effects in improving clinical outcomes when added to conventional therapy. However, the role of Ivabradine in acute coronary syndromes has not been established. Based on the results from some relevant preclinical studies and a limited amount of clinical data that were reported recently, the role of Ivabradine in acute ischemic events warrants further investigation. The aim of this review is to provide an overview of the available literature on the potential role of Ivabradine in the clinical context of acute coronary syndromes. [ABSTRACT FROM AUTHOR]

Background Meta-analyses of cardiac rehabilitation trials up to 2010 showed a significant reduction in all-cause mortality but many of these trials were conducted before the modern management of acute coronary syndromes. Methods We undertook a meta-analysis of contemporary randomised controlled trials published in the period 2010 to 2015, including patients with other forms of atherosclerotic cardiovascular disease, to investigate the impact of cardiovascular prevention and rehabilitation on hard outcomes including survival. Results 18 trials randomising 7691 patients to cardiovascular prevention and rehabilitation or usual care were selected. All-cause mortality was not reduced (RR 1.00, 95% CI 0.88 to 1.14), but cardiovascular mortality was by 58% (95% CI 0.21, 0.88). Myocardial infarction was also reduced by 30% (95% CI 0.54, 0.91) and cerebrovascular events by 60% (95% CI 0.22, 0.74). Comprehensive programmes managing six or more risk factors reduced all-cause mortality in a subgroup analysis (RR 0.63, 95% CI 0.43, 0.93) but those managing less did not. In the three programmes that prescribed and monitored cardioprotective medications for blood pressure and lipids all-cause mortality was also reduced (RR 0.35, 95% CI 0.18, 0.70). Conclusions Comprehensive prevention and rehabilitation programmes managing six or more risk factors, and those prescribing and monitoring medications within programmes to lower blood pressure and lipids, continue to reduce all-cause mortality. In addition, these comprehensive programmes not only reduced cardiovascular mortality and myocardial infarction but also, for the first time, cerebrovascular events, and all these outcomes across a broader spectrum of patients with atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Background Diagnosis of acute myocardial infarction (MI) is challenging in pacemaker patients. Little is known about this patient group. Methods Patients with MI enrolled in the Swiss national AMIS Plus registry between January 2005 and December 2015 were analyzed. All patients with either paced ventricular rhythm or sinus rhythm with intrinsic ventricular conduction (IVC) were included in this study. Outcomes using crude data and propensity score matching were compared between patients with pacemaker rhythm and patients with IVC. The primary endpoint was in-hospital death. Results Data from 300 patients with paced rhythm and 27,595 with IVC were analyzed. Patients with pacemaker rhythm were older (78.2 y vs 65.4 y; p < 0.001), had more comorbidities (Charlson Index (CCI) > 1: 54.0% vs 21.1%; p < 0.001) and a higher rate of heart failure upon presentation (Killip class > 2, 11.0% vs 5.9%; p < 0.001) compared to patients with IVC. Door to balloon time in patients undergoing acute PCI is markedly delayed in contrast to patients with IVC (280 min vs 85 min; p < 0.001). Consequently, crude mortality in patients with pacemakers was high (11.3% vs 4.6%; p < 0.001). However, when analyzed with propensity matching for gender, age, CCI > 1 and Killip > 2, mortality was similar (11.2% vs 10.5%; p = 0.70). Conclusion Pacemaker patients with acute MI represent a high-risk group with doubled crude mortality compared to patients without pacemakers, due to higher age and higher Killip class. Diagnosis is difficult and results in delayed treatment. Treatment algorithms for MI with paced rhythm should possibly be adapted to those used for STEMI or new left bundle branch block. Clinical Trials Registration : NCT01305785. [ABSTRACT FROM AUTHOR]

Background Few clinical trials have focused on populations with a history of distant myocardial infarction (MI). The PEGASUS trial assessed the impact of dual antiplatelet therapy in such patients, selected by enrichment criteria of high cardiovascular risk. Whether the PEGASUS population reflects the risk of a broader post-MI population is questionable. We analyzed whether 4-year mortality of a routine-practice population would differ according to the inclusion and exclusion criteria used in PEGASUS. Methods FAST-MI is a nationwide French registry recruiting acute MI patients in November 2005; 2490 patients alive and without recurrent MI at one year were classified into three groups: Group 1 (“PEGASUS-like” population; n = 1395; 56%), Group 2 (population having ≥ 1 exclusion criterion for the trial; n = 677; 27%), and group 3 (population meeting neither the PEGASUS inclusion nor exclusion criteria; n = 418, 17%). Results Group 1 patients were older than Group 3 patients, with higher GRACE scores, more comorbidity, and less STEMI, but were younger than the PEGASUS trial population. Enrichment criteria successfully defined a population at higher risk: 4-year survival 83% in Group 1, 97% in Group 2, and 68% in Group 3 (P < 0.001). Among risk-enrichment criteria, age alone was highly discriminant: in PEGASUS-like patients, survival was 78% in those ≥ 65 versus 94% in those < 65 years. Conclusions Enrichment criteria used in PEGAGUS succeed in defining a population at increased risk in patients with prior MI, age being the most discriminant factor. The trial population, however, was notably younger and more masculine than the corresponding real-life population in France. Clinicaltrials.gov number: NCT00673036 . [ABSTRACT FROM AUTHOR]

Background Several studies in patients with acute myocardial infarction (AMI) without cardiogenic shock (CS) indicate a better survival in smokers, the so called “smoker's paradox”. For CS, this relationship has not been investigated so far in the primary percutaneous coronary intervention (PCI) era. Methods In a predefined substudy of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial and its accompanying registry including patients with CS complicating AMI we investigated differences in outcome of smokers compared to non-smokers. All-cause-mortality at 1 year was used as primary endpoint. Results Of 772 patients with available smoking status 263 patients were smokers (34%). Smokers were more often male (79% vs. 65%; p < 0.001), of younger age (61 [interquartile range IQR 52–70] vs. 73 [IQR 64–79] years; p < 0.001), had less comorbidity including arterial hypertension (62% vs. 71%; p = 0.007) and diabetes mellitus (26% vs. 38%; p < 0.001) and had lower levels of serum creatinine (13% vs. 25%; p < 0.001). There was no significant difference between the 2 groups regarding left ventricular ejection fraction, initial revascularization strategy or use of IABP. Smokers had lower rates of mortality at 12 months in univariable analysis (43% vs. 59%; p < 0.001) but not after adjustment for important confounders using Cox-regression analysis (hazard ratio 0.77, 95% confidence interval 0.59–1.03; p = 0.08). Conclusion Smoking is not predictive of outcome in patients with CS complicating AMI. The observed survival benefit in univariable analysis seems to be explained by the younger age and lower risk profile of smokers. [ABSTRACT FROM AUTHOR]

Background Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI. Methods 2225 STEMI patients ≥ 70 years old (mean age 76.8 ± 5.1 years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥ 70 to 79 years old (elderly) and 27.2% were ≥ 80 years old (very-elderly). The primary end-point was 30-day mortality. Results Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24–0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30–0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥ 2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥ 2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the very-elderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥ 2 and history chronic kidney disease. Conclusions Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients. [ABSTRACT FROM AUTHOR]

Background To investigate the age-dependent impact of the superfast door-to-balloon (D2B) times of ≤ 60 min as recommended by the new ESC Guideline for patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) on mid-term survival rates based on a single center registry dataset. Patients and methods This study enrolled consecutive STEMI patients who underwent PPCI from Jan 1, 2009 through Sep 30, 2013. We compared demographics, clinical characteristics and the D2B-survival relationships between patients aged ≥ 65 and < 65. Results The younger group comprised 242 patients (68%) aged < 65 and the elder group consisted of 115 patients (32%) aged ≥ 65. In patients aged < 65, the mortality rate decreased linearly with D2B time shortening (> 90 min vs. 61–90 min vs. ≤ 60 min = 14.9% vs. 13.3% vs. 1.2%, P = 0.001). Contrarily, shortening of D2B time was not associated with reduced mortality rate in patients aged ≥ 65 (> 90 min vs. 61–90 min vs. ≤ 60 min = 23.5% vs. 19% vs. 18.9%, P = 0.99). In younger patients but not the elderly, a D2B time of < 60 min has sufficient power to predict mortality with a sensitivity of 0.83, specificity of 0.74, and Youden index of 0.57. Conclusions Our results show that the new ESC Guideline recommendation of D2B time ≤ 60 min is associated with better survival rates in younger STEMI patients undergoing PPCI. Our findings stress the importance of guideline adherence to minimize reperfusion delay to improve survival in these patients. [ABSTRACT FROM AUTHOR]

Aims Variations in the delivery of evidence based care to high risk patients with Acute Coronary Syndromes (ACS) exist between hospitals. We hypothesised that the relative proportion of admitted high risk patients contributes to variation in care and outcomes. Methods Receipt of evidence based therapies (EBT) according to patient risk was documented in the Australian Co-operative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE). Hospitals were stratified into quartiles (Q) by fraction of high risk patients according to: GRACE Risk Score (GRS), chronic kidney disease (CKD), age, Killip class, and myocardial infarction (MI). For each category, EBT and mortality were compared between hospital groups. Results This study included 8390 ACS patients from 39 hospitals. Patients with GRS > 130, CKD, and > 80 years, were less likely to receive EBT at high proportion hospitals (p < 0.0001 for all). After adjustment, proportion of patients with CKD negatively predicted coronary angiography (CA) (Q4 vs Q1: OR 0.21, 95%CI 0.10–0.45). Adjusted 6 month mortality was greater in CKD and trended greater in > 80 years in hospitals treating the highest proportions of these patients (Q4 vs Q1 OR 3.80, 95%CI 1.85–7.83, and OR 3.10, 95%CI 0.99–9.70 respectively). Conclusion Elderly ACS patients and those with CKD are less likely to receive EBT at hospitals seeing high proportions of these patients. Failure to provide EBT to these high risk populations may contribute to avoidable mortality in these institutions. [ABSTRACT FROM AUTHOR]

Objectives This double blinded, placebo controlled randomized clinical trial studies the effect of exenatide on myocardial infarct size. The glucagon-like peptide-1 receptor agonist exenatide has possible cardioprotective properties during reperfusion after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods 191 patients were randomly assigned to intravenous exenatide or placebo initiated prior to percutaneous coronary intervention using 10 μg/h for 30 min followed by 0.84 μg/h for 72 h. Patients with a previous myocardial infarction, Trombolysis in Myocardial Infarction flow 2 or 3, multi-vessel disease, or diabetes were excluded. Magnetic resonance imaging (MRI) was performed to determine infarct size, area at risk (AAR) (using T2-weighted hyperintensity (T2W) and late enhancement endocardial surface area (ESA)). The primary endpoint was of 4-month final infarct size, corrected for the AAR measured in the acute phase using MRI. Results After exclusion, 91 patients (age 57.4 ± 10.1 years, 76% male) completed the protocol. There were no baseline differences between groups. No difference was found in infarct size corrected for the AAR in the exenatide group compared to the placebo group (37.1 ± 18.8 vs. 39.3 ± 20.1%, p = 0.662). There was also no difference in infarct size (18.8 ± 13.2 vs. 18.8 ± 11.3% of left ventricular mass, p = 0.965). No major adverse cardiac events occurred during the in-hospital phase. Conclusion Exenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Background ST-segment elevation myocardial infarction (STEMI) in patients with concomitant multivessel (MV) coronary artery disease (CAD) is associated with poor outcomes. Percutaneous coronary intervention (PCI) of the culprit-lesion only (CLO) as compared with a MV PCI approach to revascularization remains uncertain. Our objective is to gain a better understanding of the efficacy and safety of CLO as compared with MV PCI in patients with STEMI by conducting an updated meta-analysis. Methods A comprehensive search of PubMed, CENTRAL, EMBASE, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar databases of randomized controlled trials (RCTs) was performed. Results Seven RCTs were included, enrolling a total of 2006 patients. We found that there was a significant reduction in major adverse cardiovascular events (MACE) (OR, 0.62; 95% CI, 0.43–0.90), cardiovascular mortality (OR, 0.46; 95% CI, 0.27–0.80), and repeat revascularization (RRV) (OR, 0.39; 95% CI, 0.30–0.51) favoring MV over the CLO approach for patients undergoing primary PCI. The number needed to treat in order to prevent one CV mortality, RRV, or MACE event is 47, 11, and 16 patients, respectively. No differences were observed between MV vs. CLO PCI for subsequent myocardial infarction (OR, 0.74; 95% CI, 0.40–1.39), all-cause mortality (OR, 0.78; 95% CI, 0.53–1.15), non-cardiovascular mortality (OR, 1.35; 95% CI, 0.74–2.48), all-bleeding events (OR, 0.82; 95% CI, 0.40–1.65), contrast-induced nephropathy (OR, 0.72; 95% CI, 0.33–1.54), and stroke (OR, 1.28; 95% CI, 0.47–3.46). Conclusions MV PCI significantly reduces the rate of MACE, CV mortality, and RRV without significant harm as compared to CLO PCI. [ABSTRACT FROM AUTHOR]

Background Patients with chronic kidney disease (CKD) experience poor outcomes after acute myocardial infarction. This study investigated how CKD affects clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving PCI. Methods This retrospective study analyzed record-linked data for 314 patients who had received PCI for NSTEMI between January 2008 and September 2010. The 141 patients with advanced CKD were compared with 173 patients who had mild or no CKD. The primary endpoint was long-term mortality. The secondary endpoint was long-term major adverse cardiac events. Results Compared to the control group, the advanced CKD group had older patients, more females, and more patients with diabetes mellitus and hypertension. The advanced CKD group also had a lower left ventricular ejection fraction and more patients with advanced HF and pulmonary edema. The advanced CKD group and the control group did not significantly differ in total in-hospital mortality, cardiac death or temporary hemodialysis post-PCI. The advanced CKD group had a significantly higher rate of long-term events. Finally, multiple stepwise Cox regression analysis showed that old age, advanced CKD and advanced HF were independent predictors of primary endpoint. The best predictors of secondary endpoint were post-PCI Thrombolysis in Myocardial Infarction-3 flow, multiple vessel disease, advanced HF and advanced CKD. Conclusions In NSTEMI patients undergoing PCI, in-hospital mortality does not significantly differ between patients with and without advanced CKD. However, long-term follow up of CKD patients consistently reveals poor outcomes. [ABSTRACT FROM AUTHOR]

Background Previous trials indicated that intensive glucose lowering in treatment of patients with type 2 diabetes mellitus (T2DM) was associated with a higher incidence of mortality. We therefore conducted a meta-analysis to evaluate the benefits and harms of intensive glucose lowering therapy in treatment of T2DM patients on major cardiovascular outcomes. Methods Randomized controlled trials (RCTs) were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. Relative risk (RR) was used to measure the treatment effect by random-effect model. Meta-regression, sensitivity analyses, subgroup analyses, and publication biases were also conducted. Results Thirteen RCTs were included with 58,160 T2DM patients and reported 5719 major cardiovascular events (MACEs), 6569 deaths, 2057 cardiac death cases, 3201 myocardial infarction (MI) cases, 1835 stroke cases, and 1778 congestive heart failure cases. Intensive glucose lowering therapy significantly reduced risk of MACEs (RR: 0.92; 95%CI: 0.85–1.00; P = 0.042), and MI (RR: 0.90; 95%CI: 0.82–0.98; P = 0.020) compared with conventional glucose control therapy. Furthermore, intensive glucose lowering therapy has no significant effect on the incidence of total mortality (RR: 0.98; 95%CI: 0.91–1.07; P = 0.693), cardiac death (RR: 1.00; 95%CI: 0.87–1.04; P = 0.999), stroke (RR: 0.94; 95%CI: 0.84–1.06; P = 0.333), and congestive heart failure (RR: 1.19; 95%CI: 0.96–1.48; P = 0.108). Conclusion T2DM patients who received intensive glucose lowering therapy are associated with a reduced risk of MACEs and MI, whereas it has no significant effect on the risk of total mortality, cardiac death, stroke, and congestive heart failure. These effects might differ when stratified by baseline characteristics in T2DM patients. [ABSTRACT FROM AUTHOR]

Background Patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD) have higher mortality, especially with comorbid chronic total occlusion (CTO). The origin of collateral flow to the CTO segment has not been studied in regard to short-term mortality. This study examined the impact of collateral feeding donor arteries from an infarct-related artery (IRA) or non-IRA to the comorbid CTO segment in regard to STEMI short-term mortality. Methods Data from 760 consecutive STEMI patients who underwent primary percutaneous coronary intervention were obtained retrospectively from medical records. The number of vessels involved and origin of the collateral feeding donor artery were evaluated using angiograms from the primary percutaneous coronary intervention. The study population was divided into patients with: single-vessel disease (SVD) (n = 483), MVD without CTO (n = 208), and MVD with CTO (n = 64). All CTO segments had collateral flow from an IRA (n = 23) or non-IRA (n = 46). All-cause mortality (30-day) was analyzed. Results Compared to SVD and MVD without CTO, MVD with comorbid CTO had a higher mortality (5.4% vs. 15.9% vs. 24.6%, P < 0.0001, respectively). Of patients with CTO, those with collateral flow from the IRA had significantly higher mortality than the non-IRA group (52.2% vs. 10.9%, P < 0.0001). Collateral flow from the IRA was extracted as an independent predictor associated with 30-day all-cause mortality using a multivariate Cox proportional hazards model (hazard ratio 4.71, 95% confidence interval 1.60–14.2, P = 0.0005). Conclusions The origin of the collateral donor artery from the IRA had an impact on short-term mortality in STEMI patients with comorbid CTO lesions. [ABSTRACT FROM AUTHOR]

Background Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply–demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. Methods Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n = 255) or myonecrosis without definite MI (n = 220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. Results Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p = 0.41). At discharge, only 43% of patients received aspirin and statin therapy. Conclusions Type 2 MI and myonecrosis occur frequently in the setting of supply–demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients. [ABSTRACT FROM AUTHOR]

Background Non-culprit percutaneous coronary intervention (PCI) during a ST-segment elevation myocardial infarction (STEMI) remains controversial. We performed a meta-analysis of the published literature comparing a strategy of complete revascularization (CR) with culprit or target vessel revascularization (TVR)-only after STEMI in patients with multi-vessel disease. Methods We searched PubMed/Medline, Cochrane, EMBASE, Web of Science, CINAHL, Scopus and Google-scholar databases from inception to March-2016 for clinical trials comparing CR with TVR during PCI for STEMI. Mantel–Haenszel risk ratio (MH-RR) with 95% confidence intervals (CI) for individual outcomes was calculated using random-effects model. Results A total of 7 randomized trials with 2004 patients were included in the final analysis. Mean follow-up was 25.4 months. Major adverse cardiac events (MACE) (MH-RR: 0.58, 95% CI: 0.43–0.78, P < 0.001), cardiac deaths (MH-RR: 0.42, 95% CI: 0.24–0.74, P = 0.003) and repeat revascularization (MH-RR: 0.36, 95% CI: 0.27–0.48, P < 0.001) were much lower in the CR group when compared to TVR. However, there was no significant difference in the risk of all-cause mortality (0.84, 95% CI: 0.57–1.25, P = 0.394) or recurrent MI (MH-RR: 0.66, 95% CI: 0.34–1.26, P = 0.205) between the two groups. CR appeared to be safe with no significant increase in adverse events including stroke rates (MH-RR: 2.19, 95% CI: 0.59–8.12, P = 0.241), contrast induced nephropathy (MH-RR: 0.73, 95% CI: 0.34–1.57, P = 0.423) or major bleeding episodes (MH-RR: 0.72, 95% CI: 0.34–1.54, P = 0.399). Conclusions CR strategy in STEMI patients with multivessel coronary artery disease is associated with reduction in MACE, cardiac mortality and need for repeat revascularization but with no decrease in the risk of subsequent MI or all-cause mortality. CR was safe however, with no increase in adverse events including stroke, stent thrombosis or contrast nephropathy when compared to TVR. [ABSTRACT FROM AUTHOR]

Morphine and P2Y12 receptor inhibitors are both recommended in patients with acute myocardial infarction. Morphine may impede gastrointestinal absorption of several oral drugs including P2Y12 platelet receptor inhibitors. The aim of this review was to critically discuss drug–drug interactions between oral P2Y12 receptor inhibitors and morphine according to currently available knowledge based on the findings of experimental, observational and randomized clinical studies. The morphine–clopidogrel pharmacodynamic interaction has been observed in numerous trials and it has been proposed as an explanation for the negative impact of morphine on the clinical outcomes in patients with acute coronary syndromes. An analogous morphine interaction with ticagrelor and prasugrel was found in several observational studies and finally proven in randomized trials in healthy volunteers and acute myocardial infarction patients. Morphine delays and attenuates exposure and antiplatelet action of oral P2Y12 receptor inhibitors in patients with myocardial infarction. Although this interaction may have potentially harmful consequences, routine avoidance of morphine cannot be recommended until clinically powered trials are completed. [ABSTRACT FROM AUTHOR]

Background To investigate the cardiovascular (CV) outcomes of drug-eluting stents (DESs) versus bare-metal stents (BMSs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Methods Data from the Taiwan National Health Insurance Research Database was analyzed between January 1, 2007 and December 31, 2011. A total of 3051 AMI patients in CS were selected as the study cohort. Their clinical outcomes were evaluated by comparing 1017 subjects who used DESs to 2034 matched subjects who used BMSs. Results The risk of the primary composite outcome (i.e., death, myocardial infarction, stroke, and coronary revascularization) was significantly lower in the DES group compared with the BMS group [56.1% vs. 66.2%, hazard ratio (HR), 0.74; 95% CI, 0.67–0.81] with a mean follow-up of 1.35 years. The patients who received DESs had a lower risk of coronary revascularization (HR, 0.78; 95% CI, 0.67–0.91) and death (HR, 0.70; 95% CI, 0.62–0.79) than those who used BMSs. However, the risks of myocardial infarction (HR, 0.89; 95% CI, 0.66–1.18), ischemic stroke (HR, 1.02; 95% CI, 0.67–1.53) and major bleeding (HR, 0.80; 95% CI, 0.56–1.14) were similar between the two groups. Conclusions Among patients with CS complicating AMI, DES implantation significantly reduced the risk of percutaneous coronary revascularization and death compared to BMS implantation. [ABSTRACT FROM AUTHOR]

Background Although ticagrelor has been well-known to improve clinical outcomes in patients with acute myocardial infarction (AMI) without increased bleeding risk, its clinical impacts have not been well established in East Asian patients. Methods Between November 2011 and June 2015, a total of 8010 patients (1377 patients were prescribed ticagrelor and 6633 patients clopidogrel) undergoing successful revascularization were analyzed from Korea Acute Myocardial Infarction Registry—National Institute of Health. The patients who discontinued or occurred in-hospital switching between two antiplatelet agents were excluded. Results After propensity score matching (1377 pairs), no difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months was observed between two groups (4.2% vs. 4.9%, p = 0.499). However, the incidences of in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding were higher in ticagrelor than clopidogrel (2.6% vs. 1.2%, p = 0.008; 3.8% vs. 2.5%, p = 0.051). The in-hospital mortality was higher in patients with than those without TIMI major bleeding (11.3% vs. 0.9%, p < 0.001). In a subgroup analysis, a higher risk for in-hospital TIMI major bleeding with ticagrelor was observed in patients ≥ 75 years or with body weight < 60 kg (odd ratio [OR] = 3.209; 95% confidence interval [CI] = 1.356–7.592) and in those received trans-femoral intervention (OR = 1.996; 95% CI = 1.061–3.754). Conclusions Our study shows that ticagrelor did not reduce ischemic events yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMI. [ABSTRACT FROM AUTHOR]

Background Autologous progenitor cell therapy comprising granulocyte-colony stimulating factor (G-CSF) for mobilization of bone-marrow derived progenitor cells (BMPCs) into peripheral blood and inhibition of dipeptidylpeptidase-IV by sitagliptin for enhanced myocardial recruitment of circulating BMPCs has been shown to improve survival after acute myocardial infarction (MI) in preclinical studies. In the SITAGRAMI trial we found that during short-term follow-up G-CSF plus sitagliptin (GS) failed to show a beneficial effect on cardiac function and clinical events in patients with acute MI that underwent successful PCI. The objective of the present analysis was to assess the impact of GS versus placebo treatment on long-term clinical outcomes of the SITAGRAMI trial patient population. Methods In the randomized, prospective, double-blind, placebo-controlled SITAGRAMI trial, 174 patients with acute MI were assigned to GS or placebo in a 1:1 ratio. The primary outcome for the present long-term analysis was the composite of death, MI or stroke on long-term follow-up. Results The median [IQR] follow-up duration was 4.50 [3.56–5.95] years. The primary outcome occurred in 12.8% of patients assigned to placebo and 9.2% assigned to GS (HR 0.69, 95% CI 0.28–1.69; p = 0.42). The incidence of the combined cardiovascular outcome was 47.7% in the placebo- and 41.4% in the GS-group (HR 0.75, 95% CI 0.48–1.18; p = 0.21). Overall, there was no significant difference in MACCE rates between both treatment groups (p = 0.41). Conclusion These long-term follow-up data indicate that GS therapy does not improve clinical outcomes of patients with acute MI. [ABSTRACT FROM AUTHOR]

Long-awaiting PHILO trial, conducted in 2011–2012 has been submitted and published late in 2015. In contrast to overall PLATO results, but similar to PLATO-US cohort, PHILO revealed numerical inferiority of ticagrelor with regard to death, myocardial infarction, stroke, and bleeding over clopidogrel. Hence, we comprehend the PHILO results in light of the PLATO-US evidence. To assess the PHILO (n = 801) outcomes, applied statistics, and trial conduct, matching them with the PLATO-US (n = 1413) patients. The Asian, predominantly Japanese ticagrelor patients had worsened outcomes even when compared to the negative American cohort with regard to death (OR = 1.44 (PHILO) vs. 1.17 (PLATO-US); myocardial infarction (OR = 1.63 vs. 1.38); and composite primary endpoint (OR = 1.60 vs. 1.27); but not for stroke (OR = 1.51 vs. 1.75). Moreover, in contrast to the trend in PLATO-US (OR = 1.11; CI = 0.84–1.48, p = 0.46), PHILO revealed significant excess of PLATO-defined composite of major and minor bleeding events (OR = 1.83; CI = 1.27–2.63, p = 0.0014). PLATO-defined “net clinical benefit” in PHILO was also significantly (OR = 1.61; CI = 1.11–2.34, p = 0.0145) inferior for ticagrelor. The “number needed to harm” suggests that for every 29 PHILO patients treated for 12 months with ticagrelor instead of clopidogrel, one will suffer an additional major bleeding event. Finally, unexplained premature closure of PHILO just after 200–210 days mean drug exposure, and short 240 days mean follow-up seems deliberate and concerning with regard to unblinding. Aside from some information censoring, early trial closure, and creative statistics, Asian ticagrelor patients did consistently worse in PHILO, than even in the negative PLATO-US cohort. Especially alarming is a significant bleeding inferiority justifying a necessity for a separate outcome-driven low-dose ticagrelor trial in Asian post-PCI patients. This strategy was successfully implemented with the low-dose prasugrel in Japan. Regulatory authorities in Asia may consider conducting an independent review of PHILO dataset to ensure adequate ticagrelor safety. [ABSTRACT FROM AUTHOR]

Background Sleep impairment such as insomnia is an established risk factor for the development of cardiovascular disease and acute myocardial infarction (AMI). The aim of the current study was to examine the association between insomnia and all-cause mortality among AMI patients. Methods This prospective cohort study used data on n = 732 patients recruited from September 2006 to May 2011 as part of the Västmanland Myocardial Infarction Study (VaMIS), a prospective cohort study of AMI patients living in Västmanland County, Sweden. Participants were followed up for all-cause mortality until December 9, 2015. The outcome of interest was time-to-death (TTD), with the presence of insomnia being the risk factor of main interest. Data were analyzed using a piecewise Cox regression model with change point for insomnia at two years of follow-up, adjusted for socioeconomic, lifestyle and clinical risk factors. Results In total, n = 175 (23.9%) of the participants suffered from insomnia. During a mean (SD) follow-up time of 6.0 (2.5) years (4392 person–years), a total of n = 231 (31.6%) participants died, n = 77 (44.0%) in the insomnia group and n = 154 (27.6%) in the non-insomnia group (log-rank test p < 0.001). In a multiple adjusted piecewise Cox regression model, insomnia did not imply a higher risk of death during the first two years after AMI (HR 0.849; 95% CI 0.508–1.421; p = 0.534). During the period after the first two years, however, insomnia implied a 1.6 times higher risk of death (HR 1.597; 95% CI 1.090–2.341; p = 0.016). Conclusions Insomnia implies a higher risk of death among AMI patients in the long term. [ABSTRACT FROM AUTHOR]

Background Women with AMI may have worse outcomes than men. However, it is unclear if this is related to differences in treatment, treatment effect or gender specific factors. We sought to determine whether primary percutaneous intervention (PCI) has a differential impact on infarct size, myocardial perfusion and ST segment resolution in men and women with acute myocardial infarction (AMI). Methods A total of 501 AMI patients were prospectively enrolled in the EMERALD study and underwent PCI with or without distal protection. Post hoc gender subset analysis was performed. Results 501 patients (108 women, 393 men) with ST-segment elevation AMI presenting within 6 h underwent primary (or rescue) PCI with stenting and a distal protection device. Women were older, had more hypertension, less prior AMI, smaller BSA, and smaller vessel size, but had similar rates of diabetes (30% versus 20.2%, p = 0.87), LAD infarct, and time-to-reperfusion compared to men. Women more frequently had complete ST-resolution (> 70%) at 30 days (72.8% versus 59.8%, p = 0.02), and smaller infarct size compared to males (12.2 ± 19.6% versus 18.4 ± 18.5%, p = 0.006). At 6 months, TLR (6.9% versus 5.2%) and MACE (11.4% versus 10.3%) were similar for women and men. Conclusions Despite worse comorbidities, women with AMI treated with primary PCI with stenting showed similar early and midterm outcomes compared to men. [ABSTRACT FROM AUTHOR]

Background/aims Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, has been evaluated in TRA2P and TRACER trials. The drug is currently approved for post-myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The FDA ruled that the overall vorapaxar data quality was acceptable, but conducted the sensitivity analyses for potential censoring. This was unusual, intriguing, and directly related to the challenged quality of ticagrelor dataset in PLATO in the previous New Drug Application for an oral antiplatelet agent submitted to the same Agency. Methods Hence, we compared the FDA-confirmed evidence of conduct and data quality in vorapaxar (TRA2P, and TRACER) with those of ticagrelor (PLATO) trials. Results The FDA provides a detailed report on information censoring, and follow-up completeness for 3 trials. TRA2P and TRACER used independent CRO for site monitoring, exhibit no heterogeneity in trial results dependent on geography, and consistent adjudication results with much less censoring than in PLATO. Conclusion The data quality and trial conduct in vorapaxar trials were better than testing ticagrelor in PLATO, however, there is still some room for improvement especially with regard to follow-up completeness, and less information censoring. [ABSTRACT FROM AUTHOR]

Background Low-range troponin elevations without clear coronary manifestations remain a major diagnostic challenge. We sought to determine if troponin velocity could allow for early identification of patients without an obvious cardiac diagnosis and who are at increased risk for cardiac-specific events. Methods & results All patients presenting to South Australian public hospitals between 1 September 2011 and 30 September 2012, with at least two troponin measurements during the first 6 h after ED presentation were included. Diagnoses were classified as ‘coronary’, ‘non-coronary cardiac’, and ‘non-cardiac’ using the International Classification of Diseases 10 codes. The relationship between troponin velocity and cardiac-specific mortality and combined cardiac outcome (death and myocardial infarction) was assessed using Fine and Gray competing risk models in patients with an initial troponin < 52 ng/L. Sensitivity analyses were performed using different initial and maximum troponin cut-off values. In total, 7300 patients were identified. A troponin velocity of 2.5 ng/L/h or greater in the non-cardiac (n = 2793) patient group was significantly associated with an increased risk for 12-month cardiac mortality (sub-hazard ratio [SHR] 2.90, 95% CI 1.33–6.34) and combined cardiac outcome (SHR 2.08, 95% CI 1.01–4.27). This association was consistent for coronary (n = 3835) and non-coronary cardiac (n = 672) patient groups, and remained after sensitivity analyses. Conclusions The significant association observed across all patient groups suggests that troponin velocity could be used for early risk stratification of patients with low-range troponin elevations without clear cardiac symptoms. These results may help guide future clinical trials aimed at assessing the utility of cardiac-targeted interventions in this challenging patient population. [ABSTRACT FROM AUTHOR]

Background The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Methods In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6 months. A 99m Tc-SPECT was performed to evaluate the 6-month infarct size and severity. Results Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p < 0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%–16%] vs. 12% [0%–30%], p = 0.002) and severity (0.55 [0.44–0.64] vs. 0.45 [0.29–0.60], p = 0.002), and LV dilation (− 1 ml/m 2 [from − 7 ml/m 2 to 9 ml/m 2 ] vs. 3 ml/m 2 [from − 2 ml/m 2 to 19 ml/m 2 ], p = 0.04), compared to their counterpart. Conclusions In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6 month infarct size and severity as well as LV dilation. [ABSTRACT FROM AUTHOR]

Background ST-elevated myocardial infarction (STEMI) holds the highest early mortality among patients with acute coronary syndromes. Despite numerous claims of clinical benefits and superiority over clopidogrel, there are no head-to-head outcome randomized clinical trials (RCTs) directly comparing novel antithrombotic agents in STEMI. Moreover, since most regulatory approvals are based on a single RCT's results, their meta-analyses are rare to compare death rates. We analyzed the 30-day mortality in STEMI patients who underwent percutaneous coronary intervention (PCI) and were treated with antithrombotic agents compared to clopidogrel as a reference. Methods and results Altogether, 10 RCT's and 1 retrospective study with a total number of 26,658 STEMI patients were included. Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Therapy with clopidogrel was associated with 2.76% 30-day STEMI mortality which was similar to that of ticagrelor (2.6%; OR = 0.9395 [CI = 0.76 to 1.17; p = 0.58]), and for bivalirudin (2.8%; OR = 1.02 [CI = 0.82 to 1.27; p = 0.86]), but was slightly higher for heparin (3.0%; OR = 1.08 [CI = 0.86 to 1.35; p = 0.52]). There was a trend towards lower mortality after tirofiban (2.1%; OR = 0.77 [CI = 0.52 to 1.13; p = 0.20]), and cangrelor (1.7%; OR = 0.59 [CI = 0.29 to 1.20; p = 0.19]), although the sample size for both agents was woefully small. The only agent which offers a significant 30-day mortality benefit in STEMI was prasugrel with significant lowest 1.75% death rate (OR = 0.63 [CI = 0.46 to 0.86; p = 0.03]). Conclusions Among antithrombotic agents, prasugrel, but not ticagrelor, offers significant 30-day mortality benefit over clopidogrel in PCI-treated STEMI patients justifying short-term use in such a high-risk population. [ABSTRACT FROM AUTHOR]

Background In cardiogenic shock (CS) renal dysfunction is an important parameter of inadequate end-organ perfusion and an independent predictor of adverse outcome. Early detection of renal dysfunction is therefore important, and novel biomarkers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM1) and Cystatin C (CysC) have been suggested. However, in high-risk CS patients their role for assessing renal injury has not yet been investigated in comparison to the most widely used serum creatinine. Methods This predefined substudy included 190 patients of the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II)-trial. Blood samples were collected directly during primary percutaneous coronary intervention, one day and two days after randomization. The primary endpoint for outcome assessment was 1 year mortality. Results Creatinine, NGAL and KIM-1 were significantly higher in non-survivors in comparison to survivors over time in ANOVA (p < 0.001; p = 0.002 and p = 0.04, respectively). In contrast, CysC levels were not associated with the primary endpoint (p = 0.15). Receiver operator characteristics revealed that creatinine at any time point had the best predictive value for 1 year mortality. This was also true when comparing creatinine to different equations for glomerular filtration rate. In multivariable Cox-regression analysis creatinine remained the only significant independent predictor of kidney biomarkers of time to death during the first year. Conclusions Assessment of novel biomarkers such as CysC, NGAL and KIM-1 or calculation of glomerular filtration rate provide no additional prognostic information in patients with CS complicating acute myocardial infarction in comparison to creatinine. [ABSTRACT FROM AUTHOR]

Background Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia. In non-high risk patients, with proven viability in the infarct-area, the VIAMI trial showed benefit of early in-hospital stenting of the infarct-related coronary artery for the composite of death, myocardial infarction (MI), or unstable angina (UA) at 1 year follow-up. In this study we evaluated the long-term outcome (median 8 years) of patients included in the VIAMI-trial. Methods After being stable during the first 48 h of their acute MI, we randomly assigned 216 patients with viability to an invasive (PCI) or a conservative (ischemia-guided) strategy. The primary outcome was the composite endpoint of death from any cause, recurrent myocardial infarction, or unstable angina. The secondary outcome of this study was the need for (repeat) revascularization. Results The combined endpoint of death, recurrent MI and UA was 20.8% in the invasive group and 32.7% in the conservative group (hazard ratio 0.59; 95% CI 0.36-0.99, p = 0.049). No differences were seen in death (8.5% vs. 8.2%, p = 0.80) or MI (7.5% vs. 10.9%, p = 0.48). Only UA showed a significant difference (4.7% vs. 13.6%, p = 0.002). Repeated revascularization was performed in 22.6% of the invasive group and 41.8% of the conservative group (hazard ratio 0.43; 95% CI 0.29-0.74, p < 0.001). Conclusion In patients with acute MI (treated with thrombolysis or without reperfusion therapy) and proven viability in the infarct-area, we demonstrated a long-term benefit of early in-hospital stenting of the infarct-related coronary artery. [ABSTRACT FROM AUTHOR]

Background Myocardial viability tests have been proposed as a key factor in the decision-making process concerning coronary revascularization procedures in patients with left ventricular dysfunction and coronary artery disease (LVD-CAD). Methods We performed a systematic review and meta-analysis of studies that compared medical treatment with revascularization in patients with viable and non-viable myocardium and recorded mortality as outcome. Results Thirty-two non-randomized (4328 patients) and 4 randomized (1079 patients) studies were analyzed. In non-randomized studies, revascularization provided a significant mortality benefit compared with medical treatment (<0.05). Since the heterogeneity was significant (<0.05) a viability subgroup analysis was performed, showing that revascularization provided a significant mortality benefit compared with medical treatment in patients with viable myocardium (<0.05) but not in patients without (=0.34). There was a significant subgroup effect (<0.05) related to the intensity of the effect, but not to the direction. In randomized studies, revascularization did not provide a significant mortality benefit compared with medical treatment in either patients with viable myocardium or those without (=0.21). There was no significant subgroup effect (=0.72). Neither non-randomized nor randomized studies demonstrated any significant difference in outcomes between patients with and without viable myocardium. Conclusions The available data are inconclusive regarding the usefulness of myocardial viability tests for the decision-making process concerning revascularization in LVD-CAD patients. [ABSTRACT FROM AUTHOR]

Background Dipeptidyl peptidase-4 inhibitors (DPP-4is) improve glucose control in patients with type 2 diabetes mellitus (DM); however, only few studies were properly designed to evaluate their cardiovascular (CV) effects. The purpose of this study was to assess the impact of DPP-4i treatment on CV morbidity and mortality. Methods Randomized clinical trials enrolling more than 200 patients, comparing DPP-4 versus placebo or active treatments in patients with DM and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of heart failure (HF) were included in the analysis. Results Ninety-four trials enrolling 85,224 patients (median follow-up = 29 weeks) were included in the analysis. Compared to control, treatment with DPP-4i did not affect all-cause and CV mortality, as well as stroke, in the short and long terms (< and >= 29 weeks, respectively). DPP-4i reduced the risk of MI in the short (RR: 0.584 [95% CI: 0.361 to 0.943]; p = 0.028), but not in the long term. Additionally, long-term treatment with DPP-4 was associated with a 15.8% increased risk of HF (RR: 1.158 [CI: 1.011 to 1.326]; p = 0.034). No heterogeneity among studies or publication bias was detected. Conclusions DPP4is do not affect all cause- and CV-mortality and stroke in diabetic patients; the reduction in MI observed with short-term treatment does not persist in the long term. Long-term use of DPP-4i in diabetic patients is associated with increased risk of HF. [ABSTRACT FROM AUTHOR]

Background: Concerns regarding the use of selected bone marrow stem cells (BMSCs) in the field of cardiac repair after acute ischemic events have been raised. The current meta-analysis aimed to assess the efficacy and safety of selected BMSC transplantation in patients with acute myocardial infarction (AMI) based on published randomized controlled trials (RCTs). Methods: A systematic literature search of PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane library from 1990 to 2014 was conducted. Results from RCTs involving subjects with AMI receiving selected BMSC therapy and followed up for at least 6 months were pooled. Results: Eight trials with a total of 262 participants were included. Data were analyzed using a random effects model. Overall, selected BMSC therapy improved left ventricular ejection fraction (LVEF) by 3.17% (95% confidence interval [CI] 0.57–5.76, P = 0.02), compared with the controls. There were trends toward reduced left ventricular end-systolic volume (LVESV) and fewer major adverse cardiac events (MACEs). Subgroup analysis revealed a significant difference in LVEF in favor of selected BMSC therapy with bone marrow mesenchymal stem cells (BMMSCs) as the cell type. Conclusions: Transplantation of selected BMSCs for patients with AMI is safe and induces a significant increase in LVEF with a limited impact on left ventricular remodeling. [ABSTRACT FROM AUTHOR]

Ischaemia−reperfusion (IR) injury is an important cause of myocardial damage during percutaneous coronary intervention (PCI). There are few therapies in widespread clinical use which impact on IR injury and it remains an important and underutilized target for treatment in acute myocardial infarction. This review will examine the translational scientific evidence for ischaemic conditioning and pharmacological agents including conditioning mimetics such as cyclosporine, anti-inflammatory agents, and those which modify myocardial glucose metabolism. We will address the reasons why many trials have failed to demonstrate clinical benefit and emphasize the need to deliver the right therapy to the right patient, at the right time to achieve successful translation of cardioprotection from bench-to-bedside. We critique trial design and offer advice for future translational trials in the field to ensure that effective treatments can be demonstrated clinically to improve patient outcomes during PCI. [ABSTRACT FROM AUTHOR]

Background A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Methods Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. Results In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Conclusion Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. [ABSTRACT FROM AUTHOR]

Background/objectives Over the past decade, the development of novel management strategies has resulted in improved outcomes among patients hospitalized with ST-segment myocardial infarction (STEMI). The aim of the present study was to compare temporal trends in the mortality of smokers versus non-smokers admitted with STEMI in a real world setting between 2000 and 2010. Methods We evaluated time-dependent changes in the clinical characteristics, management strategies, and one year all-cause mortality of STEMI patients who were enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) between 2000 and 2010, categorized as smokers (n = 2399) and non-smokers (n = 3069). We divided the survey periods into early (2000-2004) and late (2006-2010). The primary endpoint of the study was the occurrence of one-year all-cause mortality. Results A total of 4564 STEMI patients were enrolled in the study. Compared with non-smokers, smokers were significantly younger and displayed a significantly lower rate of all-cause mortality at 30 days and 1-year. Both smokers and non-smokers who were enrolled in the late survey period received more evidence-based therapies (primary PCI and guideline-based medications) (p < 0.001 for all). There was a significant reduction in the risk of 1-year all-cause mortality only among non-smokers (HR = 0.664 CI 95% 0.52-0.85, p = 0.0009), whereas smokers who were enrolled in more recent survey periods did not display a significant risk reduction (HR = 1.08 CI 95% 0.77-1.51, p = 0.67). Conclusion Survival following STEMI among smokers has not improved over the past decade despite corresponding changes in management strategies. Future trials should focus on reducing the risk in smokers. [ABSTRACT FROM AUTHOR]

Abstract: Background: The incidence and treatment strategies of acute coronary syndrome (ACS) vary by region. Additionally, the clinical spectrum of ACS is changing and outcomes are improving. Aim: We assessed the incidence, treatment strategies, and outcomes of ACS for a well-defined population within a well-established network of percutaneous coronary intervention (PCI) centers and non-PCI centers. Methods: The CZECH-2 registry included 1221 consecutive patients (mean age: 68±13years; 63.4% males) admitted for suspected ACS to 32 hospitals (including 4 PCI centers) within four Czech counties (total population: 2,370,841 inhabitants) during a 2-month period. Results: The estimated incidence of confirmed ACS was 2149cases/million/year. In 374 (31%) patients, ACS was ruled out during the hospital stay. Coronary angiography (CAG) was performed in 60% of the patients overall and PCI was performed in 59% of the confirmed ACS patients. Killip classifications II–IV on admission were more common in patients with final diagnosis of non ST-elevation myocardial infarction (NSTEMI) than ST-elevation myocardial infarction (STEMI) (37.1% vs. 22.8%; p<0.001). The 30-day mortality rate was 5.7% for the whole study group, 7.3% for STEMI patients, 8.4% for NSTEMI patients, and 1.6% for patients with unstable angina pectoris (UAP), respectively. Conclusions: Almost one-third of the patients admitted for suspected ACS had a different final diagnosis. Among those with confirmed ACS, the use of CAG, PCI, CABG, and effective medications is rational. Outcome in NSTEMI patients was equivalent to those in STEMI patients, mainly due to the high-risk population in this group. [Copyright &y& Elsevier]

Abstract: The ECG studies of the international HERO-2 trial in ST elevation myocardial infarction (STEMI) patients evaluated the prognostic value of ECGs systematically recorded at baseline and at 60-min post-administration of fibrinolytic therapy. Patients were overall managed conservatively with a low percentage undergoing angiography. Many of the analyses were pre-specified. While modern management of STEMI has improved, particularly with the widespread use of primary angioplasty, the HERO-2 database documents the prognostic relationship between ECG findings in STEMI patients managed with fibrinolytic therapy and 30-day mortality. This article describes the history of the HERO-2 ECG sub-studies, discloses new information in the project development and summarizes its findings. The strength of having serial ECG recordings is discussed as is the weakness of lacking angiographic correlation. The paper discusses with take-home points (Table 1) the prognostic implications of bundle branch blocks, QRS duration, Q waves in infarct leads, V1 ST elevation during inferior STEMI, lead aVR ST changes and new ST depression in the infarct leads after fibrinolysis. With the ever increasing emphasis on early (including pre-hospital) therapies for STEMI, a diagnosis based on the 12-lead ECG, the current summary article provides helpful hints to fully extract ECG information, and a vision for future STEMI diagnosis and management. [Copyright &y& Elsevier]

Abstract: Background: There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). Methods: We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. Results: Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio=0.95, 95% CI=0.74–1.21, P =0.67). Target lesion revascularization was also comparable between the groups (hazard ratio=0.89, 95% CI=0.65–1.22, P =0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio=0.52, 95% CI=0.28–0.96, P =0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4years (hazard ratio=0.15, 95% CI=0.03–0.70, P =0.02). Conclusions: In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4years. Rates of stent thrombosis were significantly lower with BP-DES. [Copyright &y& Elsevier]

Abstract: Objective: Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. Methods: We examined information from the FDA complete response review. Results: FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p=0.0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p=0.006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR=1.21, 95% CI: 0.91 to 1.59, p=0.2022), (4) 46% of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p<0.0001), (7) significantly more ticagrelor subjects hospitalized after an index event/hospitalization were not being reported as having a primary event compared to clopidogrel (p=0.002 in favor of ticagrelor), (8) site-reported MI was not significantly reduced with ticagrelor versus clopidogrel, (9) an estimated 23 definite or possible cardiovascular events or deaths on ticagrelor were either not submitted for adjudication, inactivated, deleted or were downgraded to “softer” endpoints (this was not shown in the FDA review for clopidogrel), and (10) four FDA reviewers voted for non-approval of ticagrelor. Discussion: The FDA report highlights what appear to be multiple serious deficiencies in the reporting of the PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality. [Copyright &y& Elsevier]

Abstract: Background: Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro- and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown. Methods: In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Results: Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03–1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06–1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12–1.41;p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76–0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value. Conclusions: Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP. [Copyright &y& Elsevier]