The Impact of Mandatory Vaccination Law in Italy on MMR Coverage Rates in Two of the Largest Italian Regions (Emilia-Romagna and Sicily): An Effective Strategy to Contrast Vaccine Hesitancy.

BACKGROUND: Vaccine hesitancy has increased worldwide, leading to reduction in vaccination coverage rates. In particular, reduction in the coverage for the trivalent Measles-Mumps-Rubella vaccine has led to an increase of measles cases. The aim of this study is to analyze the coverage rates for the MMR vaccine in the Emilia-Romagna Region (RER) and Sicily Region (SR) between 2009 and 2018, and to correlate any significant change to index events which could have modified the trend of vaccination rates. METHODS: Official aggregate data on vaccination coverage at 24 months provided by the RER and the SR were analyzed through trend analysis and related to important index events. RESULTS: The two regions showed similar results; both achieved the lowest coverage rates in 2015 and both showed an increase in the rates after the introduction of mandatory vaccinations for access to schools. In 2018, both reached the starting point before the decrease. CONCLUSION: Our results confirm the effectiveness of legislative coercive measures in favor of vaccination. A potential decrease in the coverage rates may be observed as a result of an attenuation of the positive effects of coercive measures over time. It is thus necessary to combine these measures together with information campaigns and political initiatives at different levels (i.e. national, regional).

Vaccine Hesitancy and Mandatory Immunizations in Emilia-Romagna Region: the case of MMR vaccine.

BACKGROUND AND AIM: An increase of vaccine hesitancy has spread worldwide and lead to reduction in coverage rates. The trivalent Measles-Mumps-Rubella (MMR) vaccine has been one of the most targeted leading due to possible (but never proven) adverse effects. This resulted in an increase of measles cases. The aim of the study is to analyze the 24-months coverage rates for the MMR vaccine in Emilia-Romagna Region (RER) between 2007 and 2018 and to correlate any significant changes to index events. METHODS: Official aggregate data on vaccination coverage at 24-month provided by the RER and the Italian Ministry of health were analyzed and discussed. RESULTS: From 2012 to 2015 a significant reduction in vaccination rates has been registered. In the following years an increase was recorded temporarily related to national and regional laws. CONCLUSION: The mandatory vaccination strategies seem to be in the short period effective in RER to counteract the growing population neegative attitudes towards vaccination and mitigate vaccine hesitancy.

Post Cardiovascular Surgery Atrial Fibrillation. Biomarkers Determining Prognosis.

BACKGROUND: New onset of atrial fibrillation (AF) after cardiovascular surgery is associated with increased risk of complications and length of hospital stay. Identification of patients at high risk of post-operative AF (POAF) may help to act with preventive strategies having clinical and economic relevance. OBJECTIVE: The focus of this review is to summarize findings on biomarkers of myocardial fibrosis (PICP and PIIINP), profibrotic mediators (TGF-beta1), extracellular matrix remodeling (MMP-9), myocardial stretch (BNP and NTpro-BNP), inflammation (interleukins, C-reactive protein and sCD40L), and myocardial necrosis (high-sensitivity troponin T), biomarkers, that can be used in clinical practice to stratify patients at risk for POAF. METHOD: We searched English-language studies on MEDLINE and PubMed. Evidence synthesis was based on cohort studies, clinical trials and meta-analysis data. International clinical practice guidelines were reviewed, as well. RESULTS: Factors such as cardiac remodelling, atrial pressure, surgery trauma, inflammation, oxidative stress, and sympathetic/parasympathetic activation have been implicated in the development of POAF. On the basis of multifactorial mechanism underlying the onset of POAF, several studies have investigated the predictive value of some serum biomarkers. To date, there are promising preliminary data on the clinical utility of PICP, PIINP, TGF-ß1 and sCD40L, whereas data on NT-proBNP, BNP, CRP, IL- 6, and hs-cTnT are controversial. CONCLUSION: Although some studies have shown promising results, there is a need for future larger studies with longer follow-up, before applying biomarkers as tools for POAF risk-stratification into clinical practice.

Sex Differences in Outcomes After STEMI: Effect Modification by Treatment Strategy and Age.

Importance: Previous works have shown that women hospitalized with ST-segment elevation myocardial infarction (STEMI) have higher short-term mortality rates than men. However, it is unclear if these differences persist among patients undergoing contemporary primary percutaneous coronary intervention (PCI). Objective: To investigate whether the risk of 30-day mortality after STEMI is higher in women than men and, if so, to assess the role of age, medications, and primary PCI in this excess of risk. Design, Setting, and Participants: From January 2010 to January 2016, a total of 8834 patients were hospitalized and received medical treatment for STEMI in 41 hospitals referring data to the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry (NCT01218776). Exposures: Demographics, baseline characteristics, clinical profile, and pharmacological treatment within 24 hours and primary PCI. Main Outcomes and Measures: Adjusted 30-day mortality rates estimated using inverse probability of treatment weighted (IPTW) logistic regression models. Results: There were 2657 women with a mean (SD) age of 66.1 (11.6) years and 6177 men with a mean (SD) age of 59.9 (11.7) years included in the study. Thirty-day mortality was significantly higher for women than for men (11.6% vs 6.0%, P < .001). The gap in sex-specific mortality narrowed if restricting the analysis to men and women undergoing primary PCI (7.1% vs 3.3%, P < .001). After multivariable adjustment for comorbidities and treatment covariates, women under 60 had higher early mortality risk than men of the same age category (OR, 1.88; 95% CI, 1.04-3.26; P = .02). The risk in the subgroups aged 60 to 74 years and over 75 years was not significantly different between sexes (OR, 1.28; 95% CI, 0.88-1.88; P = .19 and OR, 1.17; 95% CI, 0.80-1.73; P = .40; respectively). After IPTW adjustment for baseline clinical covariates, the relationship among sex, age category, and 30-day mortality was similar (OR, 1.56 [95% CI, 1.05-2.3]; OR, 1.49 [95% CI, 1.15-1.92]; and OR, 1.21 [95% CI, 0.93-1.57]; respectively). Conclusions and Relevance: Younger age was associated with higher 30-day mortality rates in women with STEMI even after adjustment for medications, primary PCI, and other coexisting comorbidities. This difference declines after age 60 and is no longer observed in oldest women.

Primary failure of eruption: Clinical and genetic findings in the mixed dentition.

OBJECTIVE: To test the hypothesis that mutations in the parathyroid hormone 1 receptor ( PTH1R) include effects in both primary and permanent teeth. MATERIALS AND METHODS: DNA was extracted from saliva samples of 29 patients (8 familial and 21 sporadic) who presented with clinical evidence of infraoccluded teeth, and their unaffected relatives (N = 22). Sequencing followed by mutational analysis of the coding regions of PTH1R gene was completed for all individuals (N = 29). RESULTS: Eight of 29 cases revealed a heterozygous pathogenic variant in the PTH1R gene; five of eight variants represented distinct mutations based on comparison with the dbSNP, HGMD, and ESP databases. One mutation (c.1765 T>C p.Trp89Arg) was found to segregate within a family (n = 3). In silico analyses for all variants revealed a putative pathogenic effect. A genotype-phenotype correlation was reported as defined by a functional mutation in PTH1R and corresponding effects on one or more posterior teeth only; unilateral or bilateral involvement, infraoccluded primary teeth. CONCLUSIONS: Novel mutations were reported in the PTH1R gene that included PFE-affected primary molars, thus providing the basis for using a genetic diagnostic tool for early diagnosis leading to proper management.

Acute Coronary Syndrome: The Risk to Young Women.

BACKGROUND: Although acute coronary syndrome (ACS) mainly occurs in patients >50 years, younger patients can be affected as well. We used an age cutoff of 45 years to investigate clinical characteristics and outcomes of "young" patients with ACS. METHODS AND RESULTS: Between October 2010 and April 2016, 14 931 patients with ACS were enrolled in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry. Of these patients, 1182 (8%) were aged ≤45 years (mean age, 40.3 years; 15.8% were women). The primary end point was 30-day all-cause mortality. Percentage diameter stenosis of ≤50% was defined as insignificant coronary disease. ST-segment-elevation myocardial infarction was the most common clinical manifestation of ACS in the young cases (68% versus 59.6%). Young patients had a higher incidence of insignificant coronary artery disease (11.4% versus 10.1%) and lesser extent of significant disease (single vessel, 62.7% versus 46.6%). The incidence of 30-day death was 1.3% versus 6.9% for the young and older patients, respectively. After correction for baseline and clinical differences, age ≤45 years was a predictor of survival in men (odds ratio, 0.24; 95% confidence interval, 0.10-0.58), but not in women (odds ratio, 1.35; 95% confidence interval, 0.50-3.62). This pattern of reversed risk among sexes held true after multivariable correction for in-hospital medications and reperfusion therapy. Moreover, younger women had worse outcomes than men of a similar age (odds ratio, 6.03; 95% confidence interval, 2.07-17.53). CONCLUSION: ACS at a young age is characterized by less severe coronary disease and high prevalence of ST-segment-elevation myocardial infarction. Women have higher mortality than men. Young age is an independent predictor of lower 30-day mortality in men, but not in women. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/. Unique identifier: NCT01218776.

Delayed Care and Mortality Among Women and Men With Myocardial Infarction.

BACKGROUND: Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. METHODS AND RESULTS: We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). CONCLUSIONS: Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01218776.

Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome).

Myotonic dystrophy, or Steinert's disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewing, breathing, and phonation. We present a case report of a 15-year-old boy with anterior open bite, upper and lower dental crowding, bilateral crossbite, and constriction of the upper jaw with a high and narrow palate. The patient's need was to improve his quality of life. Because of the severity of skeletal malocclusion, it was necessary to schedule a combined orthodontic and surgical therapy in order to achieve the highest aesthetic and functional result. Although therapy caused an improvement in patient's quality of life, the clinical management of the case was hard. The article shows a balance between costs and benefits of a therapy that challenges the nature of the main problem of the patient, and it is useful to identify the most appropriate course of treatment for similar cases.

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.

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.

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.

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.

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.

Early Invasive Strategy for Unstable Angina: a New Meta-Analysis of Old Clinical Trials.

Randomized controlled trials (RCTs) were conflicting to support whether unstable angina versus non-ST-elevation myocardial infarction (UA/NSTEMI) patients best undergo early invasive or a conservative revascularization strategy. RCTs with cardiac biomarkers, in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1975-2013 were reviewed considering all cause mortality, recurrent non-fatal myocardial infarction (MI) and their combination. Follow-up lasted from 6-24 months and the use of routine invasive strategy up to its end was associated with a significantly lower composite of all-cause mortality and recurrent non-fatal MI (Relative Risk [RR] 0.79; 95% confidence interval [CI], 0.70-0.90) in UA/NSTEMI. In NSTEMI, by the invasive strategy, there was no benefit (RR 1.19; 95% CI, 1.03-1.38). In the shorter time period, from randomization to discharge, a routine invasive strategy was associated with significantly higher odds of the combined end-point among UA/NSTEMI (RR 1.29; 95% CI, 1.05-1.58) and NSTEMI (RR 1.82; 95% CI, 1.34-2.48) patients. Therefore, in trials recruiting a large number of UA patients, by routine invasive strategy the largest benefit was seen, whereas in NSTEMI patients death and non-fatal MI were not lowered. Routine invasive treatment in UA patients is accordingly supported by the present study.

Atypical Chest Pain in ACS: A Trap Especially for Women.

Not all acute coronary syndromes (ACS) exhibit the classic symptoms of chest pain. The diagnosis of ACS in patients without typical chest pain is often challenging. These patients are at increased risk for delayed or incorrect diagnosis, less aggressive treatment and high in-hospital mortality. The association between diabetes mellitus and absence of chest pain in ischemic heart disease is established. As well, it is known that women, more frequently than men, have atypical presentation. However, there is a lack of standardization in characterizing the population of patients with ACS and atypical presentation. The identification of other factors influencing and/or related with the absence of chest pain in ACS could be helpful for patients' outcomes. The object of our study was to examine the current literature on the clinical features, other than female gender and diabetes, associated with the atypical presentation of ACS. We found that patients with non-ST-elevation ACS more frequently than patients with ST-elevation myocardial infarction have atypical presentation. Atypical symptoms in aged population are common both among female and male. Subjects with history of comorbidities, specifically heart failure, chronic kidney disease, chronic obstructive pulmonary disease and stroke are less likely to report chest pain as chief complain of ACS.

Comparison of Early Versus Delayed Oral ß Blockers in Acute Coronary Syndromes and Effect on Outcomes.

The aim of this study was to determine if earlier administration of oral ß â€‹blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous ß blockers or remained free of any ß â€‹blocker treatment during hospital stay, 23 as timing of oral ß â€‹blocker administration was unknown, and 182 patients because they died before oral ß blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral ß blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early ß â€‹blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early ß â€‹blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score-matched analyses. In conclusion, in patients with ACSs, earlier administration of oral ß â€‹blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.

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.

Unfractionated heparin-clopidogrel combination in ST-elevation myocardial infarction not receiving reperfusion therapy.

OBJECTIVE: We sought explore the relative benefits of unfractionated heparin (UFH) compared with enoxaparin, alone or in combination with clopidogrel, in ST-segment elevation myocardial infarction (STEMI) patients not undergoing reperfusion therapy. METHODS: This is a propensity score study from The International Survey on Acute Coronary Syndromes in Transition Countries (ISACS-TC/NCT01218776) on patients admitted between October 2010-June 2013. There were a total of 1175 STEMI patients who did not receive mechanical or pharmacological reperfusion. Of these, 1063 were eligible for the aim of the study, being treated with UFH (522/1175; 44.4%) or enoxaparin (541/1175; 46%). Clopidogrel in combination with UFH or enoxaparin was given to 751 (63.9%) patients. The primary endpoint was in-hospital mortality. Secondary endpoints were intracranial hemorrhages, and clinically relevant bleedings. RESULTS: After adjustment for any confounders, UFH was associated with a lower risk of in-hospital mortality in clopidogrel users (multivariate adjusted regression analysis: odds ratio [OR]: 0.62, 95% Confidence Interval [CI] 0.41-0.94) as compared with clopidogrel non-users (OR: 0.94, 95% CI 0.55-1.60). The observed effect was not associated with combined enoxaparin and clopidogrel therapy. Major bleeding events were comparable in the enoxaparin group and UFH group (0.4% and 1.5% respectively, p = 0.06). The risk of major hemorrhage was nearly similar with combined UFH-clopidogrel therapy (1.4%) as compared with UFH alone (1.9%), p = 0.67. CONCLUSION: UFH - Clopidogrel combination was associated with a large mortality reduction in STEMI patients not undergoing reperfusion therapy and did not significantly increase the risk of major bleeding.