Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: Practical Considerations on the Choice of Agent and Dosing.

Direct or new oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have recently revolutionized the field of antithrombotic therapy for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (NVAF). Randomized controlled trials have shown that these agents have at least comparable efficacy with vitamin K antagonists along with superior safety, at least in what concerns intracranial hemorrhage. As a result, NOACs are indicated as first-line anticoagulation therapy for NVAF patients with at least one risk factor for stroke or systemic embolism. The rapid introduction, however, of NOACs in a field dominated for decades by vitamin antagonists and the variety of agents and dosing schemes may create difficulties in decision making. In the present article, we attempt to determine a practical approach to the choice of agent and dose in different clinical scenarios by considering not only the results of seminal randomized trials and post hoc analyses but also data from real-world patient populations as well as the recently available possibility of rapid NOAC reversal.

New-onset atrial fibrillation and clinical outcome in non-cardiac intensive care unit patients.

BACKGROUND: Data regarding new onset atrial fibrillation (nAF) in general, non-cardiac, intensive care unit (ICU) patients are limited. However, it has been suggested that nAF is associated with worse clinical outcome in these patients. OBJECTIVE: The purpose of the present work was to study the prognostic impact of nAF, in this setting. METHODS: We prospectively studied all patients admitted to a single ICU for a period of 12 months. Patients admitted for brief post-operative monitoring, patients with chronic, intermittent atrial fibrillation and atrial fibrillation present upon admission, were excluded. Death during ICU stay (ICUD) was the pre-specified study end-point. Length of stay (LOS) for survivors was also reported. A number of factors related to the occurrence of nAF and the present disease were recorded for each patient. RESULTS: The study population was comprised of 133 patients. Twenty (15%) of them manifested nAF. The end-point of ICUD was observed in 27.1% of the patients. The median LOS reported was 8 days. Patients with nAF seemed to have significantly worse prognosis, compared to those who did not manifest nAF (OR=3.35, 95%CI:1.26-8.92; P=0.016). Additionally, nAF patients appear to require significantly extended LOS (P=0.01). Nevertheless, when the effect of nAF on ICUD was adjusted for sepsis, there was no statistically significant difference between those that manifested nAF and the rest of the patients. CONCLUSION: Patients suffering nAF seem to have worse prognosis during ICU stay. However, a direct impact of nAF on mortality was not documented.

Dabigatran plasma levels, aPTT and thromboelastography in patients with AF: implications for allowing early non-elective surgical procedures.

According to current recommendations, patients on dabigatran should stop the drug 24-96 h before scheduled surgery. This may seem too long for non-elective cases. The aim of our study was to assess the number of patients on dabigatran who could theoretically undergo surgery 12 h post last drug dosing. We measured dabigatran plasma trough concentration by Hemoclot assay in 75 consecutive patients receiving dabigatran. Coagulation was assessed by aPTT and thromboelastography (TEG). Plasma levels ≤30 ng/ml were considered low. TEG parameters measured were clot reaction time (R), clot growth index (k), angle (α), maximal amplitude (MA) and the percentage of clot lysed after 30 min (LY30). Twelve patients (16%) had low plasma dabigatran levels 11.6 ± 0.9 h post last dosing. These patients compared to those with higher levels had significantly different aPTT (37.7 ± 4.4 vs. 49.6 ± 9.2 s; p < 0.001) and TEG R (6.7 ± 1.3 vs. 8.4 ± 2.6 min; p = 0.002). Only three of the patients with low levels had an aPTT >40 s. Within those with levels >30 ng/ml, four patients (6.4%) had plasma dabigatran levels ≥200 ng/ml, all with aPTT >65 s and TEG R >11 min. When the analysis was restricted to patients with creatinine clearance >80 ml/min, six (27.3%) had low plasma dabigatran levels. In this theoretical study, with a low risk population, it is suggested that one-sixth of patients receiving dabigatran have low drug concentrations at 12 h. Further studies are needed to confirm that such patients with low trough levels can actually undergo safely early surgery if necessary.

Epidemiology, reperfusion management, and outcomes of patients with myocardial infarction in Greece: The ILIAKTIS study.

OBJECTIVE: Acute myocardial infarction (AMI) is one of the leading causes of death; however, updated data regarding clinical presentation and current management are missing in Greece. This study aimed to prospectively record the demographic and clinical characteristics of a representative sample of patients suffering from AMI, their management, and short-term outcomes. METHODS: ILIAKTIS is a national, prospective, multicenter, noninterventional study conducted under the auspices of Hellenic Society of Cardiology (HCS) and the European Initiative Stent - Save a Life. From 1st April 2020 to 30th June 2020, consecutive adult patients with STEMI or NSTEMI were enrolled in the 50 participating hospitals, appropriately selected to match the geographical and population distribution in the Greek territory. RESULTS: In total, 1862 patients (mean age: 64.2 ± 13.2 yrs.; 77.2% males) with AMI were enrolled. More patients presented with NSTEMI (56.8%) than with STEMI (43.2%). Primary PCI (pPCI) was the preferable treatment option for STEMI patients in PCI-hospitals (76.9% vs. 39.9% for non-PCI, p < .001) and thrombolysis in non-PCI-hospitals (47.3% vs. 17.9% for PCI-hospitals, p < .001). The mean length of hospital stay was 5.6 days. In-hospital mortality was less likely in NSTEMI compared to that in STEMI patients (aOR = 0.30; 95% CI 0.18 to 0.49). Patients initially admitted in non-PCI-hospitals showed increased risk for in-hospital (aOR = 2.29; 95% CI 1.20 to 4.42) and 30-day mortality (aOR = 1.88; 95% CI 1.20 to 2.96). CONCLUSION: This study shows that the proportion of STEMI and NSTEMI patients managed interventionally has significantly increased, resulting in better clinical outcomes compared to previous Greek surveys.

Outcome of patients with acute myocardial infarction admitted in hospitals with or without catheterization laboratory: results from the HELIOS registry.

AIMS: To compare the treatment and outcomes of myocardial infarction patients in hospitals with and without catheterization laboratory. METHODS AND RESULTS: The Hellenic Infarction Observation Study was a countrywide registry of acute myocardial infarction, conducted during 2005-2006. The registry enrolled 1840 patients with myocardial infarction from 31 hospitals with a proportional representation of all types of hospitals and of all geographical areas. Out of these patients, 645 (35%) were admitted in 11 hospitals with and 1195 (65%) in 20 hospitals without catheterization laboratory. Patients admitted in hospitals with catheterization laboratory in comparison with patients admitted in hospitals without were younger (66+/-14 vs. 68+/-13, P<0.004) with less diabetes (27 vs. 33%, P<0.001), but without other baseline differences (female 27 vs. 25%, prior myocardial infarction 20 vs. 17%, Killip class>1 22 vs. 23%). Reperfusion rates for ST-segment elevation myocardial infarction were 67% (43% lytic, 24% primary percutaneous coronary interventions) versus 56% (55% lytic, 1% percutaneous coronary interventions; P<0.01). In-hospital outcomes in hospitals with versus in hospitals without laboratory were: mortality 6.5 versus 8.3% (NS), stroke 2.2 versus 1.1% (NS), major bleeding 1.1 versus 0.6% (NS), and heart failure 11 versus 16% (P<0.01). In multivariate regression analysis, being admitted in a hospital without catheterization laboratory was not an independent predictor of increased in-hospital mortality (odds ratio=1.18, 95% confidence interval: 0.72-1.93, P=0.505). CONCLUSION: Although the majority of acute myocardial infarction patients was admitted in hospitals without catheterization laboratory, these patients do not have a survival disadvantage, provided they are treated with lytic therapy, medical secondary prevention drugs, and eventual revascularization according to current guidelines.

Anticoagulation therapy in elderly patients with atrial fibrillation: results from the Registry of Atrial Fibrillation To Investigate the Implementation of New Guidelines (RAFTING).

BACKGROUND: Patients with atrial fibrillation aged 75 years or older have a CHA2DS2VASc score that dictates oral anticoagulants. We recorded physicians' anticoagulation attitudes in elderly patients with atrial fibrillation and assessed the impact of stroke and bleeding risk. METHODS: Atrial Fibrillation To Investigate the Implementation of New Guidelines , a countrywide prospective registry performed in Greece during 2010, a period when only vitamin-K antagonists (VKA) were available, enrolled 1127 patients with atrial fibrillation diagnosis during Emergency Departments visit in 31 representative hospitals; 807 patients had known atrial fibrillation and of those, 342 aged 75 years or older. We recorded preadmission anticoagulation treatment and associated it with clinical characteristics and stroke/bleeding risk. RESULTS: Patients on VKA (n = 207; 61%) were younger (81 ±â€Š4 vs. 83 ±â€Š5; P < 0.001) but no other significant differences were noticed, including mean CHA2DS2VASc (high: 2-4, very high: >4) or modified HASBLED (low: 0-2, high: >2) scores. VKA were prescribed in 65% of patients with very high CHA2DS2VASc score as compared with 55% of those with high score (P = 0.065). VKA were used equally in low or high-modified HASBLED score (61% vs. 59%; P = 0.78). The interaction between CHA2DS2VASc and HASBLED was significant (P < 0.001) in patients on VKA; in patients with low HASBLED, VKA use was similar in high versus very high CHA2DS2VASc score (58 vs. 64%), whereas in patients with high HASBLED, VKA use tended to be higher in very high versus high CHA2DS2VASc score (66 vs. 43%). CONCLUSION: In this countrywide atrial fibrillation registry, 61% of elderly patients received VKA, a decision driven mainly by stroke risk. VKA use was not higher in patients with low bleeding risk.

Younger age potentiates post myocardial infarction survival disadvantage of women.

BACKGROUND: Female patients with acute myocardial infarction (MI) exhibit higher unadjusted in-hospital mortality rates compared to male patients. However, contradictory evidence exists on whether this survival disadvantage disappears after adjustment for age and other prognostic factors. This study, based on a countrywide survey of consecutive unselected patients with acute MI, examined whether female gender is an independent predictor of poor short-term outcome and less intensive in-hospital treatment. METHODS: Data on a total of 7433 patients were analyzed. RESULTS: The mean age was 64+/-13 years and the proportion of females in this population was 23%. Univariate and multivariate predictors of in-hospital mortality in female patients were estimated. Unadjusted in-hospital mortality rates of women were significantly higher compared to men (17.7 vs. 8.6, p<0.001). In multivariate analysis, female gender was an independent predictor of in-hospital mortality in the total population [relative risk (RR)=1.29, 95% confidence interval (CI)=1.02-1.64, p=0.036]. The RR of women for in-hospital death was exaggerated among younger patients, aged <55 years (RR=3.84, 95% CI=1.07-13.74, p=0.039). Female gender was also independently and inversely associated with administration of thrombolytic treatment (RR=0.724, 95% CI=0.630-0.831, p=<0.001). CONCLUSION: Although female gender is an independent predictor of higher post-MI in-hospital mortality with a pronounced effect among younger patients, women are less likely to receive thrombolysis than men. Based on the results from this countrywide study, we should consider women, especially of younger age, as patients at particular high risk, who contrary to common practice, deserve more intensive and aggressive in-hospital treatment.

A Tongue Lesion as a Sign of a Systemic Disease.

Amyloidosis is the extracellular fibril deposition of a variety of proteins, many of which circulate as plasma ingredients. It is a disease difficult to identify due to its nonspecific symptoms and manifestations. Amyloidosis of the tongue, either isolated or part of the systemic disease, is rare and its features resemble those of a tumor. We report the case of a patient with amyloidosis who presented with a tongue lesion, weakness, nonspecific arthritis, and dyspnea on exertion that resulted in multiorgan system failure.

Clinical profile and therapeutic management of patients with atrial fibrillation in Greece: results from the Registry of Atrial Fibrillation to Investigate New Guidelines (RAFTING).

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia with significant morbidity, including a 5-fold increase in stroke risk. The management of AF, including antithrombotic therapy (AT), varies considerably among countries. Representative data concerning AF features and management in Greece are generally lacking. METHODS: The Registry of Atrial Fibrillation To Investigate New Guidelines (RAFTING) is a country-wide prospective observational study of AF in Greece that enrolled consecutive patients with a diagnosis of AF in emergency departments of 31 hospitals of different types according to the population's geographical distribution. RESULTS: RAFTING enrolled 1127 patients, 51% females, aged 71 ± 12 years. Paroxysmal AF was present in 54% of patients and newly diagnosed AF in 28%; 68% of patients with a previous AF history had undergone a median of 4 cardioversions. A high rate of comorbidities was present, including arterial hypertension in 75% and heart failure in 40%. The median CHADS2 and CHA2DS2VASc scores were 2 and 3, respectively; AT had been prescribed in 87% of non-newly diagnosed patients, with warfarin being prescribed in 56% of them. Among all patients on warfarin, INR values were within therapeutic range in 34% of cases during inhospital measurement. Hospital admission occurred in 82% of cases, with in-hospital mortality 0.8%. CONCLUSIONS: RAFTING provides updated insights into the current features and management of AF in Greece. The majority of patients have a sufficiently high risk to warrant oral anticoagulation and further attempts to comply with the existing guidelines are warranted.

Epidemiological characteristics and in-hospital management of acute coronary syndrome patients in Greece: results from the TARGET study.

INTRODUCTION: Conduction of national surveys is needed to depict temporal trends in the risk profile, type of implemented treatment strategy and outcome of patients with acute coronary syndromes (ACS). The TARGET study is a multicenter, observational study that aimed to evaluate the epidemiological characteristics, management pattern and outcome of ACS patients in Greece. METHODS: A total of 418 consecutive patients with ACS (44.7% STEMI, 34.2% NSTEMI, 21.1% unstable angina) from 17 centers (52.9% with catheterization facilities) were enrolled in the study (78.0% males, 63.9 ± 12.9 years). RESULTS: Overall, 67.9% of the patients had hypertension, 27.5% were diabetics and 57.4% had dyslipidemia. Thrombolytic therapy (60.7% tenecteplase, 38.2% reteplase) was administered in 22.7% of the study population, while invasive management was performed in 40.2% of patients (27.0% PCI and 1.0% CABG) during the index hospitalization. In-hospital all-cause mortality was 1.9%, with 12.2% of patients experiencing adverse clinical events. Evidence-based medications were prescribed to the majority of enrolled patients during hospitalization and upon discharge (97% and 94% received aspirin, 93% and 84% clopidogrel, 87% and 86% beta-blockers, 96% and 93% statins, respectively). CONCLUSION: The prevalence of modifiable risk factors exhibits an increasing trend among ACS patients in Greece. The prescription pattern of evidence-based medications has improved considerably, while there remains considerable room for improvement in expanding the implementation of invasive management in realworld clinical practice.

Inadequate heart rate control is associated with worse quality of life in patients with coronary artery disease and chronic obstructive pulmonary disease. The RYTHMOS study.

INTRODUCTION: Significant evidence shows that elevated heart rate (HR) is an independent risk factor in patients with coronary artery disease (CAD) and influences their prognosis. In addition, patients with chronic obstructive pulmonary disease (COPD) have more frequent episodes of angina and their compliance with heart rate agents, such as beta blockers, is poor. The purpose of the multicenter observational RYTHMOS study was to evaluate the role of heart rate management in the prognosis and quality of life in patients with CAD and COPD. METHODS: Baseline data from 280 patients, enrolled in 22 hospitals representing all types of hospital and all geographical areas of the country, were analyzed. All patients had either a prior myocardial infarction or angiographically documented CAD, and COPD verified either after spirometry or from a clinical evaluation by pulmonologists. RESULTS: The mean age of the enrolled patients was 71.8 ± 9.3 years, 76% were males, mean body mass index was 28.6 ± 7.9 kg/m2, 76.3% had hypertension, 31% had diabetes mellitus, and 53.5% of them suffered from heart failure. About 31% of the patients had an angina episode the week before the enrollment and the Canadian Cardiovascular Society (CSS) classification was class I, II, III and IV in 55%, 30%, 14% and 1%, respectively. The mean resting HR was 72.5 bpm; 51% of the patients had resting HR>70 bpm and 22% of them had HR80 bpm. Only 52.8% of the study patients were receiving beta-blockade (BB) therapy; they were more likely to have resting HR70 bpm (57.4% vs. 42.7%, p<0.001). 16.4% of the patients were receiving ivabradine and they had a higher initial HR compared to the others (78.5 vs. 71.3, p<0.001). Multivariate analysis showed that diabetes mellitus was independently associated with HR>70 bpm. Patients with resting HR>70 bpm had significantly more frequent angina episodes (p<0.001), were less satisfied with treatment (p<0.001), and had a lower quality of life (p<0.001). CONCLUSION: The baseline data of this study showed that patients with CAD and COPD present inadequate HR control and frequent angina episodes. Apart from the special characteristics of these patients related to COPD management, underuse of BB therapy largely contributes to the inadequate control of HR. Patients with HR>70 bpm had significantly worse quality of life.

Do we reperfuse those in most need? Clinical characteristics of ST-elevation myocardial infarction patients receiving reperfusion therapy in the countrywide registry HELIOS.

INTRODUCTION: we analysed the clinical profile of patients with an ST-elevation myocardial infarction (STEMI) who arrived in hospital within 12 hrs from pain onset and either received reperfusion therapy (PCI or fibrinolytic therapy) or remained without reperfusion. METHODS: the Hellenic Infarction Observation Study (HELIOS) was a countrywide registry of acute myocardial infarction, conducted during 2005-2006. The registry enrolled 1840 patients with myocardial infarction from 31 hospitals, with a proportional representation of all types of hospitals and all geographical areas. RESULTS: of 870 patients with STEMI who were admitted within 12 hrs from pain onset, Group A received no reperfusion (n=289, 33.2%), group B underwent primary PCI (n=84, 9.7%) and group C received fibrinolysis (n=497, 57.1%). In groups A, B and C, respectively, mean age was 73 ± 13, 61 ± 12 and 62 ± 13 years (p<0.001). The prevalence of female sex was 33%, 14%, 18%, of diabetes 40%, 23%, 21%, of prior MI 23%, 10%, 11% and of Killip class 2-4 at admission 32%, 11%, 13%, respectively (all p<0.001). In a multivariate analysis, advanced Killip class, age, diabetes and pain to admission time >3 hrs were all independent variables related to no reperfusion therapy. CONCLUSION: reperfusion therapies are applied to relatively lower-risk patients. If a survival advantage is to be expected at the national level, more high-risk patients, such as the elderly, women, diabetics, and mainly those with advanced Killip class, should be considered for reperfusion strategies.

Statistical modelling of 10-year fatal cardiovascular disease risk in Greece: the HellenicSCORE (a calibration of the ESC SCORE project).

INTRODUCTION: Interest in the development of functions that estimate the likelihood of an individual suffering a future cardiovascular disease (CVD) event has increased in recent times (e.g. Framingham sheets, SCORE-Systematic COronary Risk Estimation, PROCAM, etc.). However, the estimates of absolute risk may show substantial variations between different populations, because of geographical, cultural, social, behavioural and genetic differences, as well as various methodological issues related to the predictive models employed. We sought to calibrate the SCORE equations to the Greek population. METHODS: We used the SCORE system that offers an estimation of total fatal CVD risk in "high" and "low" CVD risk European countries. The project pulls together a pool of datasets from 12 European countries and 2.7 million person-years of observation. A mathematical procedure to adjust the risk estimates for individual countries was applied, based on local mortality and risk factor prevalence data from the ATTICA epidemiological study, which enrolled 3042 men and women (18+ years old), from the Attica region of Greece. RESULTS: We present the calibration of the HellenicSCORE (equations, charts) by age group and sex, based on mortality data, as reported by the National Statistical Services, and prevalence data regarding smoking, total cholesterol and blood pressure levels, as reported by the ATTICA study. CONCLUSION: The proposed HellenicSCORE will hopefully result in better estimation of the risk of CVD death in Greece and enhance handling of CVD risk factors in the referent population.