Božidarka Knežević

Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry

Aims Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition. We sought to evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and either received reperfusion therapy or remained without reperfusion in Eastern Europe. Methods and results Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; NCT01218776) on STEMI patients admitted to 57 hospitals in Eastern European countries from January 2010 to February 2015. The primary endpoint was 30-day mortality. Of 7982 patients, 65 (0.8%) had a documented contraindication to reperfusion, 5973 (75.5%) received fibrinolysis ( n = 1032) or underwent primary percutaneous coronary intervention (p-PCI; n = 4941), and 1944 patients (24.6%) did not receive any reperfusion therapy. The overall unadjusted 30-day mortality rate was 7.9%. Thirty-day mortality rates were higher in non-reperfusion patients (16.0 vs. 5.0% in the p-PCI group and 7.4% in fibrinolysis group). The strongest factors associated with not attempting reperfusion therapy among these patients were female sex (OR 1.29 CI 1.07-1.56), age (OR 1.02; CI 1.01-1.03), prior MI (OR 1.79; CI 1.38-2.32), prior cerebrovascular events (OR 1.87; CI 1.30-2.68), chronic kidney disease (OR 1.76; CI 1.22-2.53), Killip class >1 (OR 1.31; CI 1.06-1.62), and time to admission >12 h (OR 15.9; CI 13.1-19.3). Conclusions A substantial number of patients are still not offered any reperfusion therapy in many Eastern European countries with economy in transition, and this was associated with increased 30-day mortality. Time from symptoms onset to admission >12 h was the highest ranking among factors related to lack of reperfusion therapy. Quality improvement efforts should focus on minimizing delay to hospital admission among STEMI patients.

Association between comorbidities and absence of chest pain in acute coronary syndrome with in-hospital outcome.

BACKGROUND To evaluate the impact of comorbidities on the management and outcomes of acute coronary syndrome (ACS) patients without chest pain/discomfort (i.e. ACS without typical presentation). METHODS Of the 11,458 ACS patients, enrolled by the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC; ClinicalTrials.gov: NCT01218776), 8.7% did not have typical presentation at the initial evaluation, and 40.2% had comorbidities. The odds of atypical presentation increased proportionally with the number of comorbidities (odds ratio [OR]: 1, no-comorbid; OR: 1.64, 1 comorbidity; OR: 2.52, 2 comorbidities; OR: 4.57, ≥3 comorbidities). RESULTS Stratifying the study population by the presence/absence of comorbidities and typical presentation, we found a decreasing trend for use of medications and percutaneous intervention (OR: 1, typical presentation and no-comorbidities; OR: 0.70, typical presentation and comorbidities; OR: 0.23, atypical presentation and no-comorbidities; OR: 0.18, atypical presentation and comorbidities). On the opposite, compared with patients with typical presentation and no-comorbidities (OR: 1, referent), there was an increasing trend (p<0.001) in the risk of death (OR: 2.00, OR: 2.52 and OR: 4.83) in the above subgroups. However, after adjusting for comorbidities, medications and invasive procedures, atypical presentation was not a predictor of in-hospital death. Independent predictors of poor outcome were history of stroke (OR: 2.04), chronic kidney disease (OR: 1.57), diabetes mellitus (OR: 1.49) and underuse of invasive procedures. CONCLUSIONS In the ISACS-TC, atypical ACS presentation was often associated with comorbidities. Atypical presentation and comorbidities influenced underuse of in-hospital treatments. The latter and comorbidities are related with poor in-hospital outcome, but not atypical presentation, per se.

The no-reflow phenomenon in the young and in the elderly

BACKGROUND The objectives of this study were to evaluate the incidence of no-reflow as independent predictor of adverse events and to assess whether baseline pre-procedural treatment options may affect clinical outcomes. METHODS Data were derived from the ISACS-TC registry (NCT01218776) from October 2010 to January 2015. No-reflow was defined as post-PCI TIMI flow grades 0-1, in the absence of post-procedural significant (≥25%) residual stenosis, abrupt vessel closure, dissection, perforation, thrombus of the original target lesion, or epicardial spasm. The outcome measure was in-hospital mortality. RESULTS No-reflow was identified in 128 of 5997 patients who have undergone PCI (2.1%). On multivariate analysis, patients with no-reflow were more likely to be older (OR: 1.20, 95% CI: 1.01-1.44), to have a history of hypercholesterolemia (OR: 1.95, 95% CI: 1.31-2.91) and to be admitted with a diagnosis of STEMI (OR: 2.96, 95% CI: 1.85-4.72). Angiographic characteristics associated with no-reflow phenomenon were: stenosis ≥50% of the right coronary artery, presence of multivessel disease and pre-procedural TIMI blood flow grades 0-1. No-reflow was highly predictive of in-hospital mortality (17.2% vs. 4.2%; adjusted OR: 4.60, 95% CI: 2.61-8.09). Administration of pre-procedural unfractioned heparin or 600mg clopidogrel loading dose was associated with less incidence of no-reflow (OR: 0.65, 95% CI: 0.43-0.99 and 0.61, 95% CI: 0.37-1.00, respectively). Aspirin, enoxaparin, and 300mg clopidogrel loading dose, did not significantly impact the occurrence of the no-reflow. CONCLUSIONS We found that pre-procedural administration of 600mg loading dose of clopidogrel and/or unfractioned heparin is associated with reduced incidence of no-reflow.

Factors associated with use of percutaneous coronary intervention among elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI): Results from the ISACS-TC registry

BACKGROUND A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients. METHODS We evaluated 1315 STEMI patients aged ≥75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame. RESULTS Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89). CONCLUSIONS In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients.

Primary percutaneous coronary intervention in octogenarians

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 ≥70years old (mean age 76.8±5.1years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79years old (elderly) and 27.2% were ≥80years 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.

Invasive versus conservative strategy in acute coronary syndromes: The paradox in women's outcomes

BACKGROUND We explored benefits and risks of an early invasive compared with a conservative strategy in women versus men after non-ST elevation acute coronary syndromes (NSTE-ACS) using the ISACS-TC database. METHODS From October 2010 to May 2014, 4145 patients were diagnosed as having a NSTE-ACS. We excluded 258 patients managed with coronary bypass surgery. Of the remaining 3887 patients, 1737 underwent PCI (26% women). The primary endpoint was the composite of 30-day mortality and severe left ventricular dysfunction defined as an ejection fraction <40% at discharge. RESULTS Women were older and more likely to exhibit more risk factors and Killip Class ≥2 at admission as compared with men. In patients who underwent PCI, peri-procedural myocardial injury was not different among sexes (3.1% vs. 3.2%). Women undergoing PCI experienced higher rates of the composite endpoint (8.9% vs. 4.9%, p=0.002) and 30-day mortality (4.4% vs. 2.0%, p=0.008) compared with men, whereas those who managed with only routine medical therapy (RMT) did not show any sex difference in outcomes. In multivariable analysis, female sex was associated with favorable outcomes (adjusted HR for the composite endpoint: 0.72, 95% CI: 0.58-0.91) in patients managed with RMT, but not in those undergoing PCI (adjusted HR: 0.96, 95% CI: 0.61-1.52). CONCLUSIONS We observed a more favorable outcome in women than men when patients were managed with RMT. Women and men undergoing PCI have similar outcomes. These data suggest caution in extrapolating the results from men to women in an overall population of patients in the context of different therapeutic strategies.

SEX-RELATED DIFFERENCES IN ACUTE CORONARY CARE AMONG PATIENTS WITH MYOCARDIAL INFARCTION: THE ROLE OF PRE-HOSPITAL DELAY

We sought to investigate sex-related differences in access to care among patients with myocardial infarction (STEMI) in order to identify gender-related factors associated with outcomes. We studied 7457 patients enrolled in the ISACS-TC registry 2010-2014 ([ClinicalTrials.gov][1] [NCT01218776][2

DELAY TO HOSPITAL ADMISSION AND ACUTE CORONARY CARE IN THE ELDERLY AND IN THE VERY ELDERLY

Limited data are available in elderly patients, as most of the trials excluded old patients older than 70 years. Uncertainty about benefits and risks of invasive treatments are more pronounced in the setting of a very advanced age and concomitant acute coronary syndrome (ACS). This retrospective,

Optimizing prevention and guideline-concordant care in Montenegro

BACKGROUND Guidelines recommend use of evidence-based medications in patients discharged after an acute coronary syndrome (ACS). Yet the current rates of adherence in many eastern European countries are unknown. OBJECTIVE To determine whether 6month outpatient follow-up after ACS is associated with recommended rates of medication adherence in Montenegro. METHODS A prospective analysis was conducted in 585 ACS patients confirmed to be alive after ACS at 6month follow-up. The study was undertaken between 2012 and 2015, from 9 International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) hospitals in the Montenegro. The primary outcome was guideline-concordant care, defined as 100% compliance with 5 medications: aspirin, clopidogrel, beta-blockers, and statins in ACS patients, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [ACEI/ARB] for the subset of patients with left ventricular systolic dysfunction, as assessed by an ejection fraction less than 40% at discharge. In addition to the composite end point, the achievement of each single treatment measure was analyzed. Multivariate predictors of long-term medication adherence were also identified. RESULTS Guideline-concordant care (GCC) at discharge increased from 2012 to 2015 (adjusted OR for increase 1.51; CI 0.88-2.52). GCC over 6months was adhered in 73% of patients. In patients who did not achieve GCC, adherence was persistently high with 92.3% for aspirin, 91.3% for statins and 72% for ACE-inhibitors or angiotensin-receptor blockers (ARBs). Adherence was lower for clopidogrel (57.7%) and beta-blockers (64.4%). After adjusting for demographic and clinical differences, in-hospital referral to PCI and ST segment elevation myocardial infarction (STEMI) were associated with greater medication adherence at 6month follow-up. CONCLUSIONS In Montenegro, long-term adherence to evidence-based medication after ACS is high. Adherence to guideline-recommended therapies increased over time with participation to the ISACS-TC. The lower achievement of GCC in patients treated medically and in those with non-ST-segment elevation ACS needs particular attention.