Secondary Prevention Therapies in Real-World Patients with Myocardial Infarction: Eligibility Based on Randomized Trials Supporting European and American Guidelines.

OBJECTIVE: We aimed to evaluate the applicability of the eligibility criteria of randomized controlled trials (RCTs) cited in guideline recommendations in a real-world cohort of patients receiving secondary prevention after acute myocardial infarction from the EPICOR registries. METHODS: Recommendations provided by American and European guidelines for acute myocardial infarction were classified into general (applying to all patients) and specific (applying to patients with left ventricular dysfunction or heart failure). Randomized controlled trials cited in these recommendations were selected, and their entry criteria were applied to our international cohort of 18,117 patients. RESULTS: There were 91.5% patients eligible for beta blockers (84.6% for general, and 5.9% for specific recommendations), 97.7% eligible for renin-angiotensin system inhibitor (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers [ACEI/ARB]) recommendations (69.9% for general, 27.9% for specific) and 4.1% eligible for mineralocorticoid receptor antagonists (only specific recommendations). The percentages of patients with eligibility criteria who were discharged with a prescription of the recommended therapies were 80%-85% for beta blockers, 70%-75% for ACEI/ARB, and 29% for mineralocorticoid receptor antagonists. There were large regional variations in the percentage of eligible patients and in those receiving the medications (eg, 95% in Northern Europe and 57% in Southeast Asia for beta blockers). CONCLUSION: Most real-world acute myocardial infarction patients are eligible for secondary prevention therapy in both general and specific guideline recommendations, and the percentage of those on beta blockers and ACEI/ARB at hospital discharge is high. There are large regional variations in the proportion of patients receiving recommended therapies. Local targeted interventions are needed for quality improvement.

Impact of standard modifiable cardiovascular risk factors on 2-year all-cause mortality: Insights from an international cohort of 23,489 patients with acute coronary syndrome.

BACKGROUND: Controversial findings have been reported in the literature regarding the impact of the absence of standard modifiable cardiovascular risk factors (SMuRFs) on long-term mortality risk in patients with acute coronary syndrome (ACS). While the prognostic additive value of SMuRFs has been well described, the prognostic role of prior cardiovascular disease (CVD) by sex is less well-known in patients with and without SMuRFs. METHODS: EPICOR and EPICOR Asia are prospective, observational registries conducted between 2010 and 2014, which enrolled ACS patients in 28 countries across Europe, Latin America, and Asia. Association between SMuRFs (diabetes, dyslipidaemia, hypertension, and smoking) and 2-year postdischarge mortality was evaluated using adjusted Cox models stratified by geographical region. RESULTS: Among 23,489 patients, the mean age was 60.9 ± 11.9 years, 24.3% were women, 4,582 (20.1%) presented without SMuRFs, and 16,055 (69.5%) without prior CVD. Patients with SMuRFs had a higher crude 2-year postdischarge mortality (HR 1.86; 95% CI, 1.56-2.22; P < .001), compared to those without SMuRFs. After adjustment for potential confounding, the association between SMuRFs and 2-year mortality risk was substantially attenuated (HR 1.17, 95% CI 0.98-1.41; P = .087), regardless of the type of ACS. The risk conferred by prior CVD was added to the underlying risk of SMuRFs to provide risk-specific phenotypes (eg, women with SMuRFs and with prior CVD were at higher risk of dying than women without SMuRFs and without CVD; HR 1.67, 95% CI 1.34-2.06). CONCLUSIONS: In this large-scale international ACS cohort the absence of SMuRFs was not associated with a lower adjusted 2-year postdischarge mortality risk. Patients with both SMuRFs and prior CVD had a higher mortality irrespective of their sex.

Sex differences in mortality after an acute coronary syndrome increase with lower country wealth and higher income inequality.

INTRODUCTION AND OBJECTIVES: Although several factors associated with sex differences in the management and outcomes after acute coronary syndrome (ACS) have been reported, little is known about the influence of socioeconomic factors on sex disparities. Our aim was to evaluate the influence of country wealth and income inequality on national sex differences in mortality after ACS. METHODS: Sex differences in 2-year postdischarge mortality were evaluated in 23 489 ACS patients from the EPICOR and EPICOR Asia registries. Adjusted Cox regression models by country-based terciles of gross national income per capita and income inequality were used. RESULTS: Women (24.3%) were older than men (65.5 vs 59.4 years, P <.001), had more comorbidities, were less often revascularized (63.6% vs 75.6%, P <.001) and received fewer guideline recommended therapies at discharge. Compared with men, a higher percentage of women died during follow-up (6.4% vs 4.9%, P <.001). The association between sex and mortality changed direction from hazard ratio (HR) 1.32 (95%CI, 1.17-1.49) in the univariate assessment to HR 0.76 (95%CI, 0.67-0.87) after adjustment for confounders. These differences were more evident with increasing country wealth (HRlow-incomecountries = 0.85; 95%CI, 0.72-1.00; HRmid-incomecountries = 0.66; 95%CI, 0.50-0.87; HRhigh-incomecountries = 0.60; 95%CI, 0.40-0.90; trend test P = .115) and with decreasing income inequality (HRlow-inequalityindex = 0.54; 95%CI, 0.36-0.81; HRintermediate-inequalityindex = 0.66; 95%CI, 0.50-0.88; HRhigh-inequalityindex = 0.87; 95%CI, 0.74-1.03; trend test P = .031). CONCLUSIONS: Women with ACS living in high socioeconomic countries showed a lower postdischarge mortality risk compared with men. This risk was attenuated in countries with poorer socioeconomic background, where adjusted mortality rates were similar between women and men.

Long-Term Antithrombotic Therapy and Clinical Outcomes in Patients with Acute Coronary Syndrome and Renal Impairment: Insights from EPICOR and EPICOR Asia.

BACKGROUND: Information is lacking on long-term management of patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2). OBJECTIVES: Our objectives were to describe antithrombotic management patterns and outcomes in patients with ACS with varying renal function from the EPICOR (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients; NCT01171404) and EPICOR Asia (NCT01361386) studies. METHODS: EPICOR and EPICOR Asia were prospective observational studies of patients who survived hospitalization for ACS and were enrolled at discharge in 28 countries across Europe, Latin America, and Asia. The studies were conducted from 2010 to 2013 and from 2011 to 2014, respectively. This analysis evaluated patient characteristics and oral antithrombotic management patterns and outcomes up to 2 years post-discharge according to admission eGFR: ≥ 90, 60-89, 30-59, or < 30 mL/min/1.73 m2. RESULTS: Among 22,380 patients with available data, eGFR < 60 mL/min/1.73 m2 was observed in 16.7%. Patients with poorer renal function were older, were at greater cardiovascular risk, and had more prior cardiovascular disease and bleeding. Patients with CKD underwent fewer cardiovascular interventions and had more in-hospital cardiovascular and bleeding events. Dual antiplatelet therapy was less likely at discharge in patients with eGFR < 30 (82.3%) than in those with ≥ 90 (91.3%) mL/min/1.73 m2 and declined more sharply during follow-up in patients with low eGFR (p < 0.0001). An adjusted proportional hazards model showed that patients with lower eGFR levels had a higher risk of cardiovascular events and bleeding. CONCLUSIONS: The presence of CKD in patients with ACS was associated with less aggressive cardiovascular management and an increased risk of cardiovascular events.

Long-term antithrombotic management patterns in Asian patients with acute coronary syndrome: 2-year observations from the EPICOR Asia study.

BACKGROUND: Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real-world AMPs up to 2 years post discharge for ACS. HYPOTHESIS: There is wide variability in AMP use for ACS management in Asia. METHODS: EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months. RESULTS: Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow-up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non-randomized study. CONCLUSIONS: Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring.

Two-year outcomes post-discharge in Asian patients with acute coronary syndrome: Findings from the EPICOR Asia study.

AIMS: Approximately half of cases of cardiovascular disease (CVD) worldwide occur in Asia, with acute coronary syndrome (ACS) a leading cause of mortality. Long-term ACS-related outcomes data in Asia are limited. This analysis examined 2-year ACS-related outcomes in patients enrolled in the EPICOR Asia study, and the association between patient characteristics and management on outcomes. METHODS: EPICOR Asia is a multinational, prospective, primary data collection study of real-world management of Asian patients with ACS. Overall, 12,922 eligible adults (hospitalized for ACS within 48 h of symptom onset and who survived to discharge) were enrolled from 219 centers in eight Asian countries. Patients were followed up post-discharge for 2 years and clinical outcomes recorded. RESULTS: Patients were of mean age 60 years and 76% were male. Diagnoses were STEMI (51.2%), NSTEMI (19.9%), and UA (28.9%). During follow-up, 5.2% of patients died; NSTEMI patients had the highest risk profile. Mortality rate (adjusted HR [95% CI]) was similar in NSTEMI (0.97 [0.81-1.17]) and lower in UA (0.52 [0.33-0.82]) vs STEMI. Similar trends (adjusted) were seen for the composite endpoint of death, myocardial infarction, or ischemic stroke, and bleeding rates did not differ significantly. For all three diagnoses, patients who were medically managed had a markedly elevated risk of both death and the composite endpoint. CONCLUSIONS: During 2-year follow-up, adjusted risks of mortality, the composite endpoint, and bleeding rates were similar in NSTEMI and STEMI patients. Outcomes risk was better for invasive management. Long-term management strategies in Asia need to be optimized.

The REMEDEE trial: 5­Year results on a novel combined sirolimus­eluting and endothelial progenitor cells capturing stent

OBJECTIVES: To evaluate the long-term safety and efficacy of the novel combined sirolimus-eluting endothelial progenitor cell capture Combo stent (OrbusNeich, Fort Lauderdale, FL) at 5 years in the REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coated bio-Engineered stEnt) trial. BACKGROUND: Drug-eluting stents have limited restenosis and reintervention but are complicated by late and very late thrombosis and accelerated neoatherosclerosis. Alternative or adjunctive technologies are needed to address these limitations. METHODS: A total of 183 patients with de novo lesions in native coronary arteries were randomized 2:1 to Combo (n = 124) or Taxus Liberté (n = 59). Primary endpoint was 9 month angiographic in-stent late lumen loss and the secondary endpoint was the occurrence of major adverse events (MACE) through 5-year follow-up. RESULTS: Compared with Taxus, after 5 years the Combo stent was associated with similar rates of MACE (18.3% vs. 16.9%, p = .89), cardiac death (0.8% vs. 5.1%, p = .07), myocardial infarction (4.1% vs. 3.4%, p = .81), target lesion (9.4% vs. 10.2%, p = .78), and target vessel revascularization (14.4% vs. 11.9%, p = .73). No cases of definite stent thrombosis were reported in the Combo group. The follow-up rate at 5 years was 97.7%. CONCLUSION: At 5-year follow-up, the Combo stent remained clinically safe and effective with an overall low rate of MACE comparable to Taxus.

Assessment of quality indicators for acute myocardial infarction management in 28 countries and use of composite quality indicators for benchmarking.

BACKGROUND: The European Society of Cardiology established a set of quality indicators for the management of acute myocardial infarction. Our aim was to evaluate their degree of attainment, prognostic value and potential use for centre benchmarking in a large international cohort. METHODS: Quality indicators were extracted from the long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients (EPICOR) (555 hospitals, 20 countries in Europe and Latin America, 2010-2011) and EPICOR Asia (218 hospitals, eight countries, 2011-2012) registries, including non-ST-segment elevation acute myocardial infarction (n=6558) and ST-segment elevation acute myocardial infarction (n=11,559) hospital survivors. The association between implementation rates for each quality indicator and two-year adjusted mortality was evaluated using adjusted Cox models. Composite quality indicators were categorized for benchmarking assessment at different levels. RESULTS: The degree of attainment of the 17 evaluated quality indicators ranged from 13% to 100%. Attainment of most individual quality indicators was associated with two-year survival. A higher compliance with composite quality indicators was associated with lower mortality at centre-, country- and region-level. Moreover, the higher the risk for two-year mortality, the lower the compliance with composite quality indicators. CONCLUSIONS: When EPICOR and EPICOR Asia were conducted, the European Society of Cardiology quality indicators would have been attained to a limited extent, suggesting wide room for improvement in the management of acute myocardial infarction patients. After adjustment for confounding, most quality indicators were associated with reduced two-year mortality and their prognostic value should receive further attention. The two composite quality indicators can be used as a tool for benchmarking either at centre-, country- or world region-level.

Antithrombotic management and long-term outcomes following percutaneous coronary intervention for acute coronary syndrome in Asia.

BACKGROUND: Cardiovascular diseases account for approximately half of all deaths in Asia. The present analysis aimed to evaluate characteristics, antithrombotic management patterns (AMPs), and outcomes in patients with acute coronary syndrome (ACS) who underwent in-hospital percutaneous coronary intervention (PCI) and survived to hospital discharge, using data from the EPICOR Asia registry (NCT01361386). METHODS: Two-year post-discharge follow-up data were analyzed from 8757 ACS PCI patients from EPICOR Asia (218 centers, eight countries). Major adverse cardiovascular events (MACE; death, non-fatal myocardial infarction [MI], non-fatal ischemic stroke), PCI characteristics, and AMPs were recorded. For MACE, time - to - event was analyzed using Cox regression. RESULTS: Primary PCI was performed in 62.0% of ST-segment elevation MI (STEMI), 38.7% of non-STEMI (NSTEMI), and 24.2% of unstable angina (UA) patients. At 12 months, 88.1% of patients were on dual antiplatelet therapy (DAPT), with no differences by index event. Most (61.5%) still received DAPT at 2 years. Two-year incidences of mortality, composite MACE, and bleeding were 3.6%, 6.2%, and 6.6%, respectively. Risk of death and MACE was increased with STEMI and NSTEMI vs. UA. Patients from East Asia showed lower mortality and more bleeding vs. Southeast Asia/India. CONCLUSIONS: Many patients in EPICOR Asia underwent PCI and received DAPT up to 2 years post-discharge. These real-world findings improve our understanding of AMP impact on outcomes in Asian patients with ACS undergoing PCI.

Prolonged dual antiplatelet therapy in patients with non-ST-segment elevation myocardial infarction: 2-year findings from EPICOR Asia.

BACKGROUND: Patients with non-ST-segment elevation myocardial infarction (NSTEMI) have a generally poor prognosis and antithrombotic management patterns (AMPs) used post-acute coronary syndrome (ACS) remain unclear. Duration of dual antiplatelet therapy (DAPT) and patient characteristics was evaluated in NSTEMI patients enrolled in EPICOR Asia. HYPOTHESIS: Patients stopping DAPT early may benefit from more intensive monitoring. METHODS: EPICOR Asia was a prospective, real-world, primary data collection, cohort study in adults with an ACS, conducted in eight countries/regions in Asia, with 2 year follow-up. Eligible patients were hospitalized within 48 hours of symptom onset and survived to discharge. We describe AMPs and baseline characteristics in NSTEMI patients surviving ≥12 months with DAPT duration ≤12 and > 12 months post-discharge. Clinical outcomes (composite of death, myocardial infarction, and stroke; and bleeding) were also explored. RESULTS: At discharge, 90.8% of patients were on DAPT (including clopidogrel, 99%). At 1- and 2-year follow-up, this was 79.2% and 60.0%. Patients who stopped DAPT ≤12 months post-discharge tended to be older, female, less obese, have prior cardiovascular disease, and have renal dysfunction. While causality cannot be inferred, the incidence of the composite endpoint over the subsequent 12 months was 10.6% and 3.1% with shorter vs longer use of DAPT, and mortality risk over the same period was 8.4% and 1.6%. CONCLUSIONS: Over 90% of NSTEMI patients were discharged on DAPT, with 60% on DAPT at 2 years. Patients stopping DAPT early were more likely to have higher baseline risk and may therefore benefit from more intensive monitoring during long-term follow-up.

The REMEDEE trial: 5-Year results on a novel combined sirolimus-eluting and endothelial progenitor cells capturing stent.

OBJECTIVES: To evaluate the long-term safety and efficacy of the novel combined sirolimus-eluting endothelial progenitor cell capture Combo stent (OrbusNeich, Fort Lauderdale, FL) at 5 years in the REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coated bio-Engineered stEnt) trial. BACKGROUND: Drug-eluting stents have limited restenosis and reintervention but are complicated by late and very late thrombosis and accelerated neoatherosclerosis. Alternative or adjunctive technologies are needed to address these limitations. METHODS: A total of 183 patients with de novo lesions in native coronary arteries were randomized 2:1 to Combo (n = 124) or Taxus Liberté (n = 59). Primary endpoint was 9 month angiographic in-stent late lumen loss and the secondary endpoint was the occurrence of major adverse events (MACE) through 5-year follow-up. RESULTS: Compared with Taxus, after 5 years the Combo stent was associated with similar rates of MACE (18.3% vs. 16.9%, p = .89), cardiac death (0.8% vs. 5.1%, p = .07), myocardial infarction (4.1% vs. 3.4%, p = .81), target lesion (9.4% vs. 10.2%, p = .78), and target vessel revascularization (14.4% vs. 11.9%, p = .73). No cases of definite stent thrombosis were reported in the Combo group. The follow-up rate at 5 years was 97.7%. CONCLUSION: At 5-year follow-up, the Combo stent remained clinically safe and effective with an overall low rate of MACE comparable to Taxus.

In-Hospital Coronary Revascularization Rates and Post-Discharge Mortality Risk in Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The relationship between in-hospital coronary revascularization rate (CRR) and post-discharge mortality rates in survivors of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) at a system level is unclear. OBJECTIVES: The purpose of this study was to evaluate CRR and 2-year post-discharge mortality rate (2YMR) in NSTE-ACS. METHODS: CRR and 2YMR were analyzed by hospital rate of CRR (in deciles), by country, and by world region in 11,931 patients with NSTE-ACS who survived to discharge and were enrolled in the EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients) and EPICOR Asia: twin multinational, observational, prospective cohort studies. RESULTS: Significant differences in patient baseline characteristics, medical therapies, CRR, and 2YMR were found. Mean CRR ranged from 0.0% to 96.8% in the first and tenth decile, respectively (p < 0.001); from 12.3% in Romania to 92.4% in Slovenia (p < 0.001); and from 53.9% in South East Asia (SEAsia) to 90.4% in South Korea-Singapore-Hong Kong. 2YMR varied significantly between hospital deciles of CRR (3.6% in tenth decile vs. 9.2% in first decile; p < 0.001), countries (lowest 1.5% in Slovenia, highest 19.4% in Malaysia; p < 0.001), and regions (lowest 3.8% in South Korea-Singapore-Hong Kong, highest 11.7% in SEAsia; p < 0.001). Poisson regression models, adjusted for 15 mortality predictors, showed a significant inverse association between CRR and 2YMR for hospitals (r = -0.90; p < 0.001), countries (r = -0.65; p < 0.001), and regions (r = -0.87; p = 0.005). CONCLUSIONS: Higher CRRs at the hospital, country, and world region levels are strongly associated with higher post-discharge survival, suggesting CRR as a marker of higher system quality.

New Volumetric Analysis Method for Stent Expansion and its Correlation With Final Fractional Flow Reserve and Clinical Outcome: An ILUMIEN I Substudy.

OBJECTIVES: This study sought to compare conventional methodology (CM) with a newly described optical coherence tomography (OCT)-derived volumetric stent expansion analysis in terms of fractional flow reserve (FFR)-derived physiology and device-oriented composite endpoints (DoCE). BACKGROUND: The analysis of coronary stent expansion with intracoronary imaging has used CM that relies on the analysis of selected single cross-sections for several decades. The introduction of OCT with its ability to perform semiautomated volumetric analysis opens opportunities to redefine optimal stent expansion. METHODS: A total of 291 lesions treated with post-stent OCT and FFR were enrolled. The expansion index was calculated by using a novel volumetric algorithm and was defined as: ([actual lumen area / ideal lumen area] × 100) for each frame of the stented segment. The minimum expansion index (MEI) was defined as the minimum value of expansion index along the entire stented segment. MEI and conventional lumen expansion metrics were compared for the ability to predict post-stent low FFR (<0.90) and DoCE at 1 year. RESULTS: There was a stronger correlation between MEI and final FFR, compared with CM and final FFR (r = 0.690; p < 0.001) versus (r = 0.165; p = 0.044). MEI was significantly lower in patients with DoCE than those without DoCE (72.18 ± 8.23% vs. 81.48 ± 11.03%; p < 0.001), although stent expansion by CM was similar between patients with and without DoCE (85.05 ± 22.19% and 83.73 ± 17.52%; p = 0.858), respectively. CONCLUSIONS: OCT analysis of stent expansion with a newly described volumetric method, but not with CM, yielded data that were predictive of both an acute improvement in FFR-derived physiology and DoCE.

Predictors of high-cost hospitalization in the treatment of acute coronary syndrome in Asia: findings from EPICOR Asia.

BACKGROUND: The EPICOR Asia (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) study (NCT01361386) was an observational study of patients hospitalized for acute coronary syndromes (ACS) enrolled in 218 hospitals in eight countries/regions in Asia. This study examined costs, length of stay and the predictors of high costs during an ACS hospitalization. METHODS AND RESULTS: Data for patients hospitalized for an ACS (n = 12,922) were collected on demographics, medical history, event characteristics, socioeconomic and insurance status at discharge. Patients were followed up at 6 weeks' post-hospitalization for an ACS event to assess associated treatment costs from a health sector perspective. Primary outcome was the incurring of costs in the highest quintile by country and index event diagnosis, and identification of associated predictors. Cost data were available for 10,819 patients. Mean length of stay was 10.1 days. The highest-cost countries were China, Singapore, and South Korea. Significant predictors of high-cost care were age, male sex, income, country, prior disease history, hospitalization in 3 months before index event, no dependency before index event, having an invasive procedure, hospital type and length of stay. CONCLUSIONS: Substantial variability exists in healthcare costs for hospitalized ACS patients across Asia. Of concern is the observation that the highest costs were reported in China, given the rapidly increasing numbers of procedures in recent years. TRIAL REGISTRATION: NCT01361386 .

Regional variations in hospital management and post-discharge mortality in patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Therapeutic variability not explained by patient clinical characteristics is a potential source of avoidable morbidity and mortality. We aimed to explore regional variability in the management and mortality of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: 11,931 NSTE-ACS hospital survivors enrolled in two prospective registries: EPICOR [5625 patients, 555 hospitals, 20 countries in Europe (E) and Latin America (LA), September 2010-March 2011] and EPICOR Asia (6306 patients, 218 hospitals, 8 countries, June 2011-May 2012) were compared among eight pre-defined regions: Northern E (NE), Southern E (SE), Eastern E (EE); Latin America (LA); China (CN), India (IN), South-East Asia (SA), and South Korea, Hong Kong and Singapore (KS). Patient characteristics differed between regions: mean age (lowest 59 years, IN; highest 65.9 years, SE), diabetes (21.4% NE; 35.5% IN) and smoking (32% NE; 62% IN). Variations in dual antiplatelet therapy at discharge (lowest 83.1%, IN; highest 97.5%, SA), coronary angiography (53.9% SA; 90.6% KS), percutaneous coronary intervention (35.8% SA; 78.6% KS) and coronary artery bypass graft (0.7% KS; 5.7% NE) were observed. Unadjusted 2-year mortality ranged between 3.8% in KS and 11.7% in SE. Two-year, risk-adjusted mortality rates ranged between 5.1% (95% confidence interval 2.9-7.3%) in KS to 10.5% (8.3-12.7%) in LA. CONCLUSION: Wide regional variations in patient features, hospital care, coronary revascularization and post-discharge mortality are present among patients hospitalized for NSTE-ACS. Focused regional interventions to improve the quality of care for NSTE-ACS patients are still needed.

The OCT-ORION Study: A Randomized Optical Coherence Tomography Study Comparing Resolute Integrity to Biomatrix Drug-Eluting Stent on the Degree of Early Stent Healing and Late Lumen Loss.

BACKGROUND: Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer. METHODS AND RESULTS: Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months (P<0.001) and less variance of percent coverage at 9 months, 99.7% (interquartile range, 99.1-100) versus 99.6% (interquartile range, 96.8-99.9; difference, 0.10; 95% confidence interval, 0.00-1.05; P<0.001). No significant difference was observed in major adverse cardiac events or angiographic end points. CONCLUSIONS: Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01742507.

Comparison of Single Nucleotide Polymorphism genotyping of CYP2C19 by Loop-mediated isothermal amplification and real-time PCR melting curve analysis.

BACKGROUND: CYP2C19, a member of cytochrome P450 enzymes, is involved in various drug metabolisms, such as Clopidogrel. Common Single Nucleotide Polymorphisms (SNPs) of CYP2C19 gene, CYP2C19*2 and CYP2C19*3, are liable for the poor metabolism of Clopidogrel. It is crucial to identify poor metabolizers for alternative treatment as poor metabolism of Clopidogrel has been shown to correlate with worse clinical outcome in acute coronary syndrome (ACS) patients. METHOD: A genotyping method, Loop-mediated isothermal amplification (LAMP) was employed in this study. CYP2C19*2 and CYP2C19*3 were adapted from Iwasaki M. et al. with modifications in the reaction mixtures and end-point detection method where simpler visual detection using SYBR® Safe was employed instead of a more technical and equipment demanding real-time PCR. Real-time PCR melting curve analysis is a common method for SNPs analysis and hence chosen as a reference for results obtained from the LAMP assay. RESULTS: The CYP2C19-LAMP assay successfully detected CYP2C19*2 and CYPC19*3 mutants. The typing results of CYP2C19-LAMP assay, performed in triplicates, were concordant with the real-time PCR melting curve analysis results. CONCLUSION: CYP2C19-LAMP assay using SYBR® Safe dye for visual detection of end-point result is a simple, rapid and cost-effective method for CYP2C19 genotyping.

Characteristics and outcomes of medically managed patients with non-ST-segment elevation acute coronary syndromes: Insights from the multinational EPICOR Asia study.

BACKGROUND: Many patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are medically managed without coronary revascularization. The reasons vary and may impact prognosis. METHODS: EPICOR Asia (NCT01361386) is a prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8 countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non-significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3) significant CAD (CAG+ CAD+). We compared baseline differences between patients medically managed and patients undergoing revascularization, and also between the medically managed groups. Adverse events were reported and compared up to 2years. RESULTS: Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339 (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups, respectively. There were marked differences in the proportion of medically managed patients among the 8 countries/regions (13-81%). Medically managed patients had higher mortality at 2years compared with revascularization (8.7% vs. 3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more likely to have pre-existing cardiovascular disease, and had the highest 2-year mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality differences persisted after adjusting for other patient risk factors. CONCLUSIONS: Medically managed NSTE-ACS patients are a heterogeneous group with different risk stratification and variable prognosis. Identification of reasons underlying different management strategies, and key factors adversely influencing long-term prognosis, may improve outcomes.

Global geographical variations in ST-segment elevation myocardial infarction management and post-discharge mortality.

BACKGROUND: There is a shortage of information on regional variations in ST-segment elevation myocardial infarction (STEMI) management and prognosis at a global level. We aimed to compare patient profiles, in-hospital management and post-discharge mortality across several world regions. METHODS: In total, 11,559 patients with STEMI were enrolled in two prospective studies of acute coronary syndrome survivors: EPICOR (4943 patients from 555 hospitals in 20 countries in Europe and Latin America recruited between September 2010 and March 2011) and EPICOR Asia (6616 patients from 218 hospitals in eight Asian countries recruited between June 2011 and May 2012). Comparisons were performed by eight pre-defined regions: Northern Europe (NE), Southern Europe (SE), Eastern Europe (EE), Latin America (LA), China (CN), India (IN), Southeast Asia (SA), and South Korea/Hong Kong/Singapore (KS). RESULTS: Reperfusion therapy rates ranged between 53.9% (IN) and 81.2% (SE), primary percutaneous coronary intervention (PCI) between 24.8% (IN) and 65.6% (NE) and fibrinolysis between 8.1% (CN) and 34.2% (SA). Median time to primary PCI (h) ranged from 3.9 (NE) to 20.9 (IN) and to fibrinolysis from 2.4 (SE) to 6.3 (IN). Two-year mortality ranged between 2.5% in NE and 7.4% in LA. Regional variations in mortality persisted after adjustment for reperfusion therapy and known prognostic factors. CONCLUSIONS: Among patients with STEMI, there is a wide regional variation in clinical profiles, hospital care and mortality. Substantial room for improvement remains at a global level for increasing reperfusion rates, reducing delays and post-discharge mortality in patients with STEMI.

Evaluation of Early Healing Profile and Neointimal Transformation Over 24 Months Using Longitudinal Sequential Optical Coherence Tomography Assessments and 3-Year Clinical Results of the New Dual-Therapy Endothelial Progenitor Cell Capturing Sirolimus-Eluting Combo Stent: The EGO-Combo Study.

BACKGROUND: Current monotherapy drug-eluting stents are associated with impaired healing, neoatherosclerosis, and late stent thrombosis. The healing profile and neointimal transformation of the first dual-therapy endothelial progenitor cell-capturing sirolimus-eluting stent are unknown. METHODS AND RESULTS: In this prospective, single-center study, 61 patients treated with the Combo stent had optical coherence tomography at baseline, early follow-up (4 monthly groups in a 1:2:2:1 ratio from 2 to 5 months), 9 months, and 24 months. Optical coherence tomography early strut coverage increased from 77.1% to 92.5% to 92.7% to 94.9% between 2 and 5 months. At 9 months, the major adverse cardiac event rate was 1.64%, and angiographic in-stent late loss was 0.24 mm (0.08-0.40). The 36-month major adverse cardiac event rate was 3.3%. From 9 to 24 months, neointimal regression was confirmed by optical coherence tomography: neointimal thickness (median [first quartile and third quartile]), 0.14 mm (0.08 and 0.21) versus 0.12 mm (0.07 and 0.19), P<0.001; neointimal volume, 29.9 mm(3) (22.1 and 43.2) versus 26.2 mm(3) (19.6 and 35.8), P=0.003; and percent neointimal volume, 17.8% (12.2 and 21.2) versus 15.7% (11.2 and 19.4), P=0.01. No definite or probable late stent thrombosis was recorded. CONCLUSIONS: With additional endothelial progenitor cell-capturing technology, the Combo stent exhibits a unique late neointimal regression (from 9 to 24 months) that has not been reported in any drug-eluting stents, translating into good 36-month clinical results with minimal restenosis and no late stent thrombosis. This is the first study testing the concept of using a longitudinal sequential optical coherence tomography protocol to continuously document early healing profile and late neointimal transformation, predicting long-term outcomes of a new novel stent platform. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01274234, NCT01756807, and NCT02263313.