Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The National Cardiogenic Shock Initiative.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) devices increase systemic blood pressure and end organ perfusion while reducing cardiac filling pressures. METHODS AND RESULTS: The National Cardiogenic Shock Initiative (NCT03677180) is a single-arm, multicenter study. The purpose of this study was to assess the feasibility and effectiveness of utilizing early MCS with Impella in patients presenting with AMI-CS. The primary end point was in-hospital mortality. A total of 406 patients were enrolled at 80 sites between 2016 and 2020. Average age was 64±12 years, 24% were female, 17% had a witnessed out-of-hospital cardiac arrest, 27% had in-hospital cardiac arrest, and 9% were under active cardiopulmonary resuscitation during MCS implantation. Patients presented with a mean systolic blood pressure of 77.2±19.2 mm Hg, 85% of patients were on vasopressors or inotropes, mean lactate was 4.8±3.9 mmol/L and cardiac power output was 0.67±0.29 watts. At 24 hours, mean systolic blood pressure improved to 103.9±17.8 mm Hg, lactate to 2.7±2.8 mmol/L, and cardiac power output to 1.0±1.3 watts. Procedural survival, survival to discharge, survival to 30 days, and survival to 1 year were 99%, 71%, 68%, and 53%, respectively. CONCLUSIONS: Early use of MCS in AMI-CS is feasible across varying health care settings and resulted in improvements to early hemodynamics and perfusion. Survival rates to hospital discharge were high. Given the encouraging results from our analysis, randomized clinical trials are warranted to assess the role of utilizing early MCS, using a standardized, multidisciplinary approach.

Sex-Specific Differences in Clinical Outcomes in Patients With Coronary Bifurcation Lesions.

Coronary bifurcation lesions are frequent challenging findings during percutaneous coronary intervention (PCI). Contemporary evidence has explored the potential sex-specific differences in patients undergoing PCI. In the present meta-analysis, we compared clinical outcomes of patients undergoing bifurcation PCI between women and men. Using the random-effects method, we compared the clinical outcomes of patients with a coronary bifurcation lesion following PCI between women and men. The results were reported using relative risk (RR) and 95% confidence interval (CI). Baseline comorbidities and mean age were compared between the 2 studied groups. Four observational studies comprising 30,684 patients (8898 women and 21,786 men) were included in the meta-analysis. Women were significantly older than men with a relatively higher prevalence of baseline comorbidities. After using adjusted data from 2 out of 4 available studies, performing PCI for bifurcation lesions in women was not associated with an increased risk of mortality (RR 1.33, 95% CI, 0.78-2.29), myocardial infarction (RR 1.22, 95% CI, 0.41-3.61), target lesion revascularization (RR 1.06, 95% CI, 0.40-2.81), stent thrombosis (RR 0.99, 95% CI, 0.09-10.52), and stroke (RR 1.19, 95% CI, 0.64-2.22). Women were at higher risk of major bleeding compared to male counterparts (RR 2.23, 95% CI, 1.73-2.89). The present study showed no difference in the risk of adverse clinical outcomes except the risk of bleeding between genders with coronary bifurcation lesions. Future studies with adjustment of age and baseline comorbidities are needed to confirm these findings.

Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

BACKGROUND: Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra. AIM: Aim Our study aims to compare TAVR outcomes in patients with BAV versus tricuspid aortic valves (TAV). METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane trials. Studies were included if they included BAV and TAV patients undergoing TAVR with quantitative data available for at least one of our predefined outcomes. Meta-analysis was performed by the random-effects model using Stata software. RESULTS: Fifty studies of 203,288 patients were included. BAV patients had increased 30-day all-cause mortality (odds ratio [OR] = 1.23 [1.00-1.50], p = 0.05), in-hospital stroke (OR = 1.39 [1.01-1.93], p = 0.05), in-hospital and 30-day PPI (OR = 1.13 [1.00-1.27], p = 0.04; OR = 1.16 [1.04-1.13], p = 0.01) and in-hospital, 30-day and 1-year aortic regurgitation (AR) (OR = 1.48 [1.19-1.83], p < 0.01; OR = 1.79 [1.26-2.52], p < 0.01; OR = 1.64 [1.03-2.60], p = 0.04). Subgroup analysis on new-generation valves showed a reduced 1-year all-cause mortality (OR = 0.86 [CI = 0.75-0.98], p = 0.03), despite higher in-hospital and 30-day PPI (OR = 0.1.21 [1.04-1.41], p = 0.01; OR = 1.17 [1.05-1.31], p = 0.01) and in-hospital AR (OR = 1.62 [1.14-2.31], p = 0.01) in the BAV group. The quality of included studies was moderate-to-high, and only three analyses presented high heterogeneity. CONCLUSION: TAVR is associated with comparable outcomes in patients with BAV and TAV. Careful selection of BAV cases by preprocedural assessment of valve anatomy and burden of calcification, pre- and post-procedural dilation, and implementing newer generations of valves may improve the safety and efficacy of TAVR in BAV patients.

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Implantation in Patients With Small Aortic Annulus: A Meta-Analysis.

Although transcatheter aortic valve implantation (TAVI) is considered a superior option to surgery in patients with small aortic annulus (SAA), it is not clear which type of transcatheter heart valve (THV) has better results in terms of echocardiographic hemodynamics and clinical outcomes. A random-effects meta-analysis was performed comparing balloon-expandable valves (BEVs) and self-expanding valves (SEVs) in patients with SAA who underwent TAVI regarding their impact on hemodynamic and clinical outcomes at short- and midterm follow-up. Relative risk (RR) and mean difference (MD) with 95% confidence interval (95% CI) were measured for the outcomes, as appropriate. Subgroup analyses were performed based on the generation type of devices and study designs. A total of 16 articles comprising 1 randomized trial, 3 propensity-matched studies, and 12 observational studies including 4,341 patients (1,967 in BEV and 2,374 in the SEV group) with SAA were included. The implantation of BEVs correlated with a lower indexed effective orifice area (MD -0.19 [-0.25 to -0.13]) and higher transvalvular mean pressure gradient (MD 3.91, 95% CI 2.96 to 4.87). Compared with SEVs, BEVs had increased risk of prosthesis-patient mismatch (PPM; RR 2.09, 95% CI 1.79 to 2.45) and severe PPM (RR 2.16, 95% CI 1.48 to 3.15). However, BEV had lower moderate and severe paravalvular leak (RR 0.45, 95% CI 0.29 to 0.69), risk of stroke (RR 0.57, 95% CI 0.42 to 0.76), and permanent pacemaker implantation (RR 0.63, 95% CI 0.44 to 0.91). The 1-year all-cause mortality (RR 1.13, 95% CI 0.86 to 1.49) and cardiac-related mortality (RR 1.53, 95% CI 0.24 to 9.81) were not different between the 2 groups. In conclusion, SEVs were associated with larger indexed effective orifice area and lower PPM but higher paravalvular leak. In contrast, patients with SEVs were more likely to develop stroke and required permanent pacemaker implantation. Both THVs did not show difference in terms of early and midterm all-cause and cardiac mortality. Because both types of THVs show similar results regarding mortality data, hemodynamics should be among the factors considered in decision making for patients with SAA who underwent TAVI.

Role of Influenza Vaccination in Cardiovascular Disease: Systematic Review and Meta-Analysis.

Influenza vaccination has shown great promise in terms of its cardioprotective effects. The aim of our analysis is to provide evidence regarding the protective effects of influenza vaccination in patients with cardiovascular disease. We conducted a systematic literature search to identify trials assessing the cardiovascular outcomes of influenza vaccination. Summary effects were calculated using a DerSimonian and Laird fixed effects and random effects model as odds ratio with 95% confidence intervals (CIs) for all the clinical endpoints. Fifteen studies with a total of 745,001 patients were included in our analysis. There was lower rates of all-cause mortality [odds ratio (OR) = 0.74, 95% CI 0.64-0.86], cardiovascular death (OR = 0.73, 95% CI 0.59-0.92), and stroke (OR = 0.71, 95% CI 0.57-0.89) in patients who received the influenza vaccine compared to placebo. There was no significant statistical difference in rates of myocardial infarction (OR = 0.91, 95% CI 0.69-1.21) or heart failure hospitalizations (OR = 1.06, 95% CI 0.85-1.31) in the 2 cohorts. In patients with cardiovascular disease, influenza vaccination is associated with lower all-cause mortality, cardiovascular death, and stroke.

Early Coronary Angiography in Patients With Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation: A Systematic Review, Meta-Analysis, and Comparative Analysis of Studies.

Out-of-hospital cardiac arrest has a high mortality rate. Unlike ST-elevation myocardial infarction, the results of performing early coronary angiography (CAG) in non-ST-elevation myocardial infarction patients are controversial. This study aimed to compare early and nonearly CAG in this population, in addition to the identification of differences between randomized controlled trials (RCTs) and observational studies conducted in this regard. A systematic search in PubMed, Embase, and Cochrane library was performed to identify the relevant studies. Random-effect meta-analysis was done to calculate the pooled effect size of early versus nonearly CAG outcomes in all studies in addition to each of the RCT and observational subgroups of the studies. The relative risk ratio (RR), along with its 95% confidence interval (CI), was used as a measure of difference. A total of 16 studies including 5234 cases were included in our analyses. Compared with observational cohorts, RCT studies had patients with higher baseline comorbidities (older age, hypertension, diabetes, and coronary artery disease). Random-effect analysis revealed a lower rate of in-hospital mortality in the early-CAG group (RR, 0.79; 95% CI, 0.65-0.97; P = 0.02); however, RCT studies did not find a statistical difference in this outcome (RR, 1.01; 95% CI, 0.83-1.23; P = 0.91). Moreover, mid-term mortality rates were lower in the early-CAG group (RR, 0.87; 95% CI, 0.78-0.98; P = 0.02), mostly due to observational studies. There was no significant difference between the groups in other efficacy and safety outcomes. Although early CAG was associated with lower in-hospital and mid-term mortality in overall analyses, no such difference was confirmed by the results obtained from RCTs. Current evidence from RCTs may not be representative of real-world patients and should be interpreted within its limitation.

Clinical Impact of Standardized TAVR Technique and Care Pathway: Insights From the Optimize PRO Study.

BACKGROUND: Procedural success and clinical outcomes after transcatheter aortic valve replacement (TAVR) have improved, but residual aortic regurgitation (AR) and new permanent pacemaker implantation (PPI) rates remain variable because of a lack of uniform periprocedural management and implantation. OBJECTIVES: The Optimize PRO study evaluates valve performance and procedural outcomes using an "optimized" TAVR care pathway and the cusp overlap technique (COT) in patients receiving the Evolut PRO/PRO+ (Medtronic) self-expanding valves. METHODS: Optimize PRO, a nonrandomized, prospective, postmarket study conducted in the United States, Canada, Europe, Middle East, and Australia, is enrolling patients with severe symptomatic aortic stenosis and no pre-existing pacemaker. Sites follow a standardized TAVR care pathway, including early discharge and a conduction disturbance management algorithm, and transfemoral deployment using the COT. RESULTS: A total of 400 attempted implants from the United States and Canada comprised the main cohort of this second interim analysis. The mean age was 78.7 ± 6.6 years, and the mean Society of Thoracic Surgeons predictive risk of mortality was 3.0 ± 2.4. The median length of stay was 1 day. There were no instances of moderate or severe AR at discharge. At 30 days, all-cause mortality or stroke was 3.8%, all-cause mortality was 0.8%, disabling stroke was 0.7%, hospital readmission was 10.1%, and cardiovascular rehospitalization was 6.1%. The new PPI rate was 9.8%, 5.8% with 4-step COT compliance. In the multivariable model, right bundle branch block and the depth of the implant increased the risk of PPI, whereas using the 4-step COT lowered 30-day PPI. CONCLUSIONS: The use of the TAVR care pathway and COT resulted in favorable clinical outcomes with no moderate or severe AR and low PPI rates at 30 days while facilitating early discharge and reproducible outcomes across various sites and operators. (Optimize PRO; NCT04091048).

Effect of BMI on patients undergoing transcatheter aortic valve implantation: A systematic review and meta-analysis.

BACKGROUND: The relationship of body mass index (BMI) and an "obesity paradox" with cardiovascular risk prediction is controversial. This systematic review and meta-analysis aims to compare the associations of different BMI ranges on transcatheter aortic valve implantation (TAVI) outcomes. METHODS: International databases, including PubMed, the Web of Science, and the Cochrane Library, were systematically searched for observational and randomized controlled trial studies investigating TAVI outcomes in any of the four BMI categories: underweight, normal weight, overweight, and obese with one of the predefined outcomes. Primary outcomes were in-hospital, 30-day, and long-term all-cause mortality. Random-effects meta-analysis was performed to calculate the odds ratio (OR) or standardized mean differences (SMD) with 95% confidence interval (CI) for each paired comparison between two of the BMI categories. RESULTS: A total of 38 studies were included in our analysis, investigating 99,829 patients undergoing TAVI. There was a trend toward higher comorbidities such as hypertension, diabetes, and dyslipidemia in overweight patients and individuals with obesity. Compared with normal-weight, patients with obesity had a lower rate of 30-day mortality (OR 0.42, 95% CI 0.25-0.72, p < 0.01), paravalvular aortic regurgitation (OR 0.63, 95% CI 0.44-0.91, p = 0.01), 1-year mortality (OR 0.48, 95% CI 0.24-0.96, p = 0.04), and long-term mortality (OR 0.69, 95% CI 0.51-0.94, p = 0.02). However, acute kidney injury (OR 1.16, 95% CI 1.04-1.30, p = 0.01) and permanent pacemaker implantation (OR 1.25, 95% CI 1.05-1.50, p = 0.01) odds were higher in patients with obesity. Noteworthy, major vascular complications were significantly higher in underweight patients in comparison with normal weight cases (OR 1.62, 95% CI 1.07-2.46, p = 0.02). In terms of left ventricular ejection fraction (LVEF), patients with obesity had higher post-operative LVEF compared to normal-weight individuals (SMD 0.12, 95% CI 0.02-0.22, p = 0.02). CONCLUSION: Our results suggest the presence of the "obesity paradox" in TAVI outcomes with higher BMI ranges being associated with lower short- and long-term mortality. BMI can be utilized for risk prediction of patients undergoing TAVI.

Comparative Safety and Effectiveness of Loading Doses of P2Y12 Inhibitors in Patients Undergoing Elective PCI: a Network Meta-analysis.

PURPOSE: Effective platelet inhibition prior to elective percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. Newer P2Y12 inhibitors are preferred agents over clopidogrel for patients presenting with the acute coronary syndrome. However, the comparative efficacy and safety of them over clopidogrel in elective PCI is unclear. We performed a network meta-analysis to compare the safety and efficacy of loading strategies of P2Y12 inhibitors in patients undergoing elective PCI. METHODS: We conducted a systematic review of randomized controlled trials (RCT) up to June 2021 to compare the safety and effectiveness of different loading strategies of P2Y12 inhibitors before elective PCI. The endpoints of interest were overall mortality, rates of myocardial infarction (MI), stroke, revascularization, and major bleeding. Random effects model using the frequentist approach was used to perform a network meta-analysis using R software. RESULTS: Five trials with a total of 5194 patients were included in our analysis. For ischemic outcomes, including MI, stroke, and revascularization, prasugrel had the most favorable trend. However, clopidogrel had the highest probability of being most effective for major bleeding and all-cause mortality. None of these trends was statistically significant due to lack of power for each outcome. CONCLUSION: Although prasugrel and ticagrelor are known as more potent antiplatelet agents, their effects in preventing MI and stroke are marginal and do not translate into improved overall mortality and bleeding compared with clopidogrel.

Protease-Activated Receptor Antagonist for Reducing Cardiovascular Events - A Review on Vorapaxar.

Acute Coronary Syndrome (ACS) is a term that describes pathologies related to myocardial ischemia, and is comprised of unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. Urgent management of ACS is typically necessary to prevent future morbidity and mortality. Current medical recommendations of ACS management involve use of dual antiplatelet therapy, typically with aspirin and clopidogrel. However, newer therapies are being designed and researched to improve outcomes for patients with ACS. Vorapaxar is a novel antiplatelet therapy that inhibits thrombin-mediated platelet aggregation to prevent recurrence of ischemic events. It has been Food and Drug Administration approved for reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease with concomitant use of clopidogrel and/or aspirin, based upon the findings of the TRA 2°P-TIMI 50 trial. However, Vorapaxar was also found to have a significantly increased risk of bleeding, which must be considered when administering this drug. Based upon further subgroup analysis of both the TRA 2°P-TIMI 50 trial and TRACER trial, Vorapaxar was found to be potentially beneficial in patients with peripheral artery disease, coronary artery bypass grafting, and ischemic stroke. There are current trials in progress that are further evaluating the use of Vorapaxar in those conditions, and future research and trials are necessary to fully determine the utility of this drug.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment. METHODS: A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. RESULTS: Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE), improved cardiovascular (CV) mortality, and reduced incidence of myocardial infarction (MI) in the genotype arm, and a similar stroke incidence in the two arms. Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm. CONCLUSION: Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

Next-Day Discharge vs Early Discharge After Transcatheter Aortic Valve Replacement: Systematic Review and Meta-Analysis.

With the growing utilization of transcatheter aortic valve replacement (TAVR) as an alternative option to surgical valve replacement (SAVR) in patients considered to be suboptimal for surgery, there is a need to explore the possibility of next day discharge (NDD) and its potential outcomes. The aim of our study is to compare outcomes and complications following NDD vs the standard early discharge (ED) (less than 3 days). A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. Studies comparing same-day or next-day discharge vs discharge within the next three days were included in our analysis. 6 studies with 2,672 patients were identified. The risk of bleeding and vascular complications was significantly lower in patients with NDD compared to ED (OR 0.10, P < 0.00001 and OR 0.22, P = 0.002 respectively). The incidence of permanent pacemaker (PPM) implants was significantly lower in patients who had NDD compared to ED (OR 0.21, P = 0.0005). The incidence of 30 day mortality, stroke, AKI and readmission rates was not different between the two groups. NDD after TAVR allows for reduction in hospital stay and can mitigate hospital costs without an increased risk of complications. Our analysis shows that complication rate is comparable to ED, NDD is a reasonable option for certain patients with severe aortic stenosis who undergo TAVR. Further studies are needed to elucidate whether higher risk patients who would benefit from an extended inpatient monitoring post TAVR.

Trends and predictors of coronary revascularization in patients with coronary artery anomalies and acute myocardial infarction: a nationwide analysis of 8131 patients.

OBJECTIVE: Acute myocardial infarction (AMI) is rarely associated with coronary artery anomalies (CAA). This confluence makes it difficult to identify and treat the culprit lesion with percutaneous coronary intervention (PCI). Our objective was to evaluate trends and predictors of revascularization in patients with CAA and AMI using a large national database. METHODS: We included adult patients with CAA presenting as ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) and undergoing coronary angiography from Nationwide Inpatient Sample from 2000 to 2011, using ICD-9 diagnosis code of 746.85 for CAA. Chi-square test for trend was used to compare revascularization rates over time. Multivariate logistic regression was used to identify predictors of revascularization. RESULTS: There were almost 4.7 million subjects with AMI undergoing coronary angiography from 2000 to 2011. Of these, there were 8131 patients with CAA, including 3425 STEMI and 4706 NSTEMI patients. Mean age of the CAA population was 59 years with 63.6% males. Overall PCI rate was 47.8% and coronary artery bypass grafting rate was 8.8%. In STEMI patients with CAA, PCI rate increased from 49.9% in 2000 to 77.8% in 2011 (P < 0.001). In NSTEMI patients with CAA, PCI rate remained unchanged from 33.3% in 2000 to 37.3% in 2011 (P = 0.34). Revascularization trends in AMI patients with CAA mirrored those in AMI patients without CAA. CONCLUSION: Despite the technical challenges associated with PCI in CAA, PCI rates in STEMI patients with CAA continue to increase over time. On the contrary, PCI rates continue to remain low in CAA patients with NSTEMI, reflecting overall contemporary NSTEMI treatment trends.

Evaluation of intracoronary hyperoxemic oxygen therapy in acute anterior myocardial infarction: The IC-HOT study.

BACKGROUND: In the randomized AMIHOT-II trial, supersaturated oxygen [SSO2 ] delivered into the left anterior descending (LAD) artery via an indwelling intracoronary infusion catheter following primary percutaneous coronary intervention (PCI) significantly reduced infarct size in patients with anterior ST-segment elevation myocardial infarction (STEMI) but resulted in a numerically higher incidence of safety events. OBJECTIVES: The IC-HOT study evaluated the safety of SSO2 therapy selectively delivered to the left main coronary artery (LMCA) for 60 minutes after PCI in patients with anterior STEMI. METHODS: SSO2 therapy was administered to the LMCA after stent implantation in 100 patients with anterior STEMI and proximal or mid-LAD occlusion presenting within 6 hours of symptom onset. The primary endpoint was the 30-day composite rate of net adverse clinical events (NACE) (death, reinfarction, clinically driven target vessel revascularization, stent thrombosis, severe heart failure, or TIMI major/minor bleeding) compared against an objective performance goal of 10.7%. Cardiac magnetic resonance imaging was performed at 4 and 30 days to assess infarct size. RESULTS: SSO2 delivery was successful in 98% of patients. NACE at 30 days occurred 7.1% of patients (meeting the primary safety endpoint of the study); there were no deaths, only one stent thrombosis and one case of severe heart failure. Median [interquartile range] infarct size was 24.1% [14.4%, 31.6%] at 4 days and 19.4% [8.8%, 28.9%] at 30 days. CONCLUSION: Following primary PCI in acute anterior STEMI, infusion of SSO2 via the LMCA was feasible and was associated with a favorable early safety profile.

Erythropoietin therapy after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

AIM: To assess safety and efficacy of early erythropoietin (Epo) administration in patients with out-of-hospital cardiac arrest (OHCA). METHODS: A systematic literature search was performed using PubMed, MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases, of all studies published from the inception through October 10, 2016. Inclusion criteria included: (1) Adult humans with OHCA and successful sustained return of spontaneous circulation; and (2) studies including mortality/brain death, acute thrombotic events as their end points. Primary efficacy outcome was "brain death or Cerebral Performance Category (CPC) score of 5". Secondary outcomes were "CPC score 1, and 2-4", "overall thrombotic events" and "acute coronary stent thrombosis". RESULTS: We analyzed a total of 606 participants (n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials. No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5 (OR = 0.77; 95%CI: 0.42-1.39), CPC score 1 (OR = 1.16, 95%CI: 0.82-1.64), and CPC score 2-4 (OR = 0.77, 95%CI: 0.44-1.36). Epo group was associated with increased thrombotic complications (OR = 2.41, 95%CI: 1.26-4.62) and acute coronary stent thrombosis (OR = 8.16, 95%CI: 1.39-47.99). No publication bias was observed. CONCLUSION: Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.