IMPORTANCE: Acute coronary syndromes (ACS) are characterized by a sudden reduction in blood supply to the heart and include ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and ...unstable angina. Each year, an estimated more than 7 million people in the world are diagnosed with ACS, including more than 1 million patients hospitalized in the US. OBSERVATIONS: Chest discomfort at rest is the most common presenting symptom of ACS and affects approximately 79% of men and 74% of women presenting with ACS, although approximately 40% of men and 48% of women present with nonspecific symptoms, such as dyspnea, either in isolation or, more commonly, in combination with chest pain. For patients presenting with possible ACS, electrocardiography should be performed immediately (within 10 minutes of presentation) and can distinguish between STEMI and non–ST-segment elevation ACS (NSTE-ACS). STEMI is caused by complete coronary artery occlusion and accounts for approximately 30% of ACS. ACS without significant ST-segment elevation on electrocardiography, termed NSTE-ACS, account for approximately 70% of ACS, are caused by partial or intermittent occlusion of the artery and are associated with ST-segment depressions (approximately 31%), T-wave inversions (approximately 12%), ST-segment depressions combined with T-wave inversions (16%), or neither (approximately 41%). When electrocardiography suggests STEMI, rapid reperfusion with primary percutaneous coronary intervention (PCI) within 120 minutes reduces mortality from 9% to 7%. If PCI within 120 minutes is not possible, fibrinolytic therapy with alteplase, reteplase, or tenecteplase at full dose should be administered for patients younger than 75 years without contraindications and at half dose for patients 75 years or older (or streptokinase at full dose if cost is a consideration), followed by transfer to a facility with the goal of PCI within the next 24 hours. High-sensitivity troponin measurements are the preferred test to evaluate for NSTEMI. In high-risk patients with NSTE-ACS and no contraindications, prompt invasive coronary angiography and percutaneous or surgical revascularization within 24 to 48 hours are associated with a reduction in death from 6.5% to 4.9%. CONCLUSIONS AND RELEVANCE: Each year, an estimated more than 7 million people are diagnosed with ACS worldwide. For patients with STEMI, coronary catheterization and PCI within 2 hours of presentation reduces mortality, with fibrinolytic therapy reserved for patients without access to immediate PCI. For high-risk patients with NSTE-ACS without contraindications, prompt invasive coronary angiography followed by percutaneous or surgical revascularization is associated with lower rates of death.
Summary Background The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and ...validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation. Methods We developed and internally validated a new biomarker-based risk score for major bleeding in 14 537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov , numbers NCT00412984 and NCT00262600 , respectively. Findings The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers GDF-15, cTnT-hs, and haemoglobin, and clinical history previous bleeding) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0·68 95% CI 0·66–0·70 vs 0·61 0·59–0·63 vs 0·65 0·62–0·67, respectively; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0·71 95% CI 0·68–0·73 vs 0·62 0·59–0·64 for HAS-BLED vs 0·68 0·65–0·70 for ORBIT; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores. Interpretation The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation. Funding BMS, Pfizer, Boehringer Ingelheim, Roche Diagnostics.
The prognostic implication of adiposity on clinical outcomes in atrial fibrillation (AF) patients treated with oral anticoagulation is unclear.
A total of 17 913 patients in the Apixaban for ...Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial had body mass index (BMI) measured at baseline. For the primary analysis, BMI was categorized as normal (18.5 to <25 kg/m
), overweight (25 to <30 kg/m
), and obese (≥30 kg/m
). Waist circumference (WC) was defined as high if >102 cm for men and >88 cm in women. Outcomes were stroke or systemic embolism, a composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), all-cause mortality, and major bleeding. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) across categories of BMI and WC adjusting for established risk factors and treatment allocation. At baseline, 4052 (22.6%) patients had a normal BMI, 6702 (37.4%) were overweight, and 7159 (40.0%) were obese. In multivariable analyses, higher BMI was associated with a lower risk of all-cause mortality overweight: HR 0.67 (95% CI 0.59-0.78); obese: HR 0.63 (95% CI 0.54-0.74), P < 0.0001 and the composite endpoint overweight: HR 0.74 (95% CI 0.65-0.84); obese: HR 0.68 (95% CI 0.60-0.78), P < 0.0001 compared with normal BMI. In women, high WC was associated with a 31% lower risk of all-cause mortality (P = 0.001), 27% lower risk of the composite endpoint (P = 0.001), and 28% lower risk of stroke or systemic embolism (P = 0.048) but not in men. There was no significant association between adiposity and major bleeding.
In patients with AF treated with oral anticoagulants, higher BMI and WC are associated with a more favourable prognosis.
Objectives The aim of this study was to determine the risk of major clinical and thromboembolic events after cardioversion for atrial fibrillation in subjects treated with apixaban, an oral factor Xa ...inhibitor, compared with warfarin. Background In patients with atrial fibrillation, thromboembolic events may occur after cardioversion. This risk is lowered with vitamin K antagonists and dabigatran. Methods Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, we conducted a post-hoc analysis of patients undergoing cardioversion. Results A total of 743 cardioversions were performed in 540 patients: 265 first cardioversions in patients assigned to apixaban and 275 in those assigned to warfarin. The mean time to the first cardioversion for patients assigned to warfarin and apixaban was 243 ± 231 days and 251 ± 248 days, respectively; 75% of the cardioversions occurred by 1 year. Baseline characteristics were similar between groups. In patients undergoing cardioversion, no stroke or systemic emboli occurred in the 30-day follow-up period. Myocardial infarction occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Major bleeding occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Death occurred in 2 patients (0.5%) receiving warfarin and 2 patients receiving apixaban (0.6%). Conclusions Major cardiovascular events after cardioversion of atrial fibrillation are rare and comparable between warfarin and apixaban. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ARISTOTLE; NCT00412984 )
Background Device-detected subclinical atrial fibrillation (AF) refers to infrequent, short-lasting, asymptomatic AF that is detected only with long-term continuous monitoring. Subclinical AF is ...common and associated with an increased risk of stroke; however, the risk of stroke with subclinical AF is lower than for clinical AF, and very few patients with subclinical AF alone have been included in large AF anticoagulation trials. The net benefit of anticoagulation in patients with subclinical AF is unknown. Design ARTESiA is a prospective, multicenter, double-blind, randomized controlled trial, recruiting patients with subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor, and who have additional risk factors for stroke. Patients with clinical AF documented by surface electrocardiogram will be excluded from the study. Participants will be randomized to receive either apixaban (according to standard AF dosing) or aspirin 81 mg daily. The primary outcome is the composite of stroke, transient ischemic attack with diffusion-weighted magnetic resonance imaging evidence of cerebral infarction, and systemic embolism. Approximately 4,000 patients will be enrolled from around 230 clinical sites, with an anticipated mean follow-up of 36 months until 248 adjudicated primary outcome events have occurred. Summary ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with subclinical AF and additional risk factors.
Atrial fibrillation (AF) is associated with an increased risk of stroke, which is currently estimated by clinical characteristics. The cardiac biomarkers N-terminal fragment B-type natriuretic ...peptide (NT-proBNP) and cardiac troponin high-sensitivity (cTn-hs) are independently associated with risk of stroke in AF. Our objective was to develop and validate a new biomarker-based risk score to improve prognostication of stroke in patients with AF.
A new risk score was developed and internally validated in 14 701 patients with AF and biomarkers levels determined at baseline, median follow-up of 1.9 years. Biomarkers and clinical variables significantly contributing to predicting stroke or systemic embolism were assessed by Cox-regression and each variable obtained a weight proportional to the model coefficients. External validation was performed in 1400 patients with AF, median follow-up of 3.4 years. The most important predictors were prior stroke/transient ischaemic attack, NT-proBNP, cTn-hs, and age, which were included in the ABC (Age, Biomarkers, Clinical history) stroke risk score. The ABC-stroke score was well calibrated and yielded higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001). Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups.
A novel biomarker-based risk score for predicting stroke in AF was successfully developed and internally validated in a large cohort of patients with AF and further externally validated in an independent AF cohort. The ABC-stroke score performed better than the presently used clinically based risk score and may provide improved decision support in AF.
NCT00412984, NCT00799903.
Patients with diabetes and recent worsening heart failure that had led to hospitalization were randomly assigned to receive sotagliflozin or placebo. At a median of 9 months, the total number of ...deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure was significantly lower with sotagliflozin than with placebo.
This trial compared weekly injections of efpeglenatide, an exendin-based glucagon-like peptide-1 receptor agonist, at a dose of 4 or 6 mg with placebo in participants with known type 2 diabetes and ...either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor. The risk of cardiovascular events was lower with efpeglenatide.
This trial compared the oral HIF-PHI daprodustat with conventional erythropoiesis-stimulating agents for the treatment of anemia in patients with chronic kidney disease receiving dialysis. ...Daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes.
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with ...varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease.
Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated.
Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI 0.78-0.91), cardiovascular mortality (HR 0.84; 95% CI 0.76-0.93) hospitalization for HF (HR 0.69; 95% CI 0.64-0.74), myocardial infarction (HR 0.91; 95% CI 0.84-0.99), and composite kidney outcome (HR 0.62; 95% CI 0.56-0.70). There was no significant effect on the risk of stroke (HR 0.98; 95% CI 0.86-1.11). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI 0.84-1.01) or amputation (OR 1.25; 95% CI 0.97-1.62). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI 1.39-5.86).
In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke.
PDF
