BACKGROUND:Sex differences in the diagnostic yield of invasive coronary angiography (ICA) in non-ST-elevation acute coronary syndrome (NSTE-ACS) are well established, but contemporary population-level data incorporating high-sensitivity troponin era cohorts and cross-national validation remain limited. OBJECTIVES:The objectives of the study were to assess sex differences in diagnostic yield, revascularization rates, and 1-year outcomes in patients undergoing first-time ICA for suspected NSTE-ACS. METHODS:Using data from the Swedish Coronary Angiography and Angioplasty Registry with validation in the Western Denmark Heart Registry. Adults without previously known coronary artery disease (CAD) undergoing first-time ICA for suspected NSTE-ACS were included. The primary outcome was the absence of significant CAD, defined as a normal angiography or <50% stenosis in all major epicardial vessels. Multivariable Poisson regression models were used to estimate adjusted risk ratios (aRRs). Secondary outcomes were 1-year major adverse cardiovascular events, comparing women and men with and without obstructive CAD using Kaplan-Meier estimates and adjusted Cox proportional hazards models. RESULTS:A total of 74,883 and 17,863 patients were included from Sweden and Western Denmark. Women had approximately twice the proportion without significant CAD compared to men in Swedish Coronary Angiography and Angioplasty Registry (40.9% vs 17.2%; aRR: 2.59; 95% CI: 2.51-2.67) and Western Denmark Heart Registry (50.1% vs 25.2%; aRR: 2.01; 95% CI: 1.95-2.08). In women below the age of 50 without any traditional cardiovascular risk factors, 74.8% had no significant CAD. CONCLUSIONS:In 2 population-based cohorts undergoing first-time ICA for suspected NSTE-ACS, 40 to 50% of women had no significant CAD, approximately twice the proportion to men, highlighting ongoing challenges in risk stratification of patients referred for ICA.

Aims Structured care through enrollment and data collection in quality registries may lead to better care and improved outcomes. We investigated differences in admission characteristics, clinical management and outcomes between patients with acute myocardial infarction enrolled vs. non-enrolled in the SWEDEHEART quality registry.Methods and results We linked health records from all hospitalisations (n = 47 342) due to a first or recurrent myocardial infarction between 2006 and 2021 in the region of Stockholm, Sweden, to SWEDEHEART. We compared non-enrolled vs. enrolled patients in terms of characteristics, invasive procedures, use of and adherence to guideline-recommended medications, in-hospital mortality, and clinical outcomes after discharge. Non-enrolled participants (n = 6 113, 13%) were older, had more chronic kidney disease and other comorbidities. They underwent fewer coronary angiographies and fewer coronary interventions. Non-enrolled participants were less likely to initiate aspirin (HR 0.88, 95% CI 0.84-0.91), beta-blockers (HR 0.87, CI 0.84-0.90), renin-angiotensin system inhibitors (HR 0.73, CI 0.69-0.76), and statins (HR 0.59, CI 0.56- 0.61). They were also less likely to adhere to treatments, in part explained by their comorbid profile. Even after extensive adjustments, non-enrolled patients had higher in-hospital and long-term mortality (HR 1.15, 95% CI 1.09-1.21), and more reinfarction/stroke (HR 1.16, 95% CI 1.08-1.26) than enrolled patients.Conclusion Patients non-enrolled in SWEDEHEART received less evidence-based care and had worse short- and long-term outcomes. This study identifies a non-negligible population in need of better care and provides support for the value of structured care models in improving patient outcomes through closer monitoring and better treatment.

BACKGROUND:Adherence to guideline-recommended drug treatment for heart failure (HF) is lower among patients managed in primary care compared with cardiology care. Understanding more about the patient group managed in primary care only is important. AIM:To compare the sociodemographic characteristics, comorbidities, care use, and drug dispensation of older patients with HF managed exclusively in primary care with those who are also managed in cardiology care. DESIGN AND SETTING:A register-based study using real-world administrative data from Stockholm, Sweden. METHOD:The study population comprised all individuals aged ≥60 years resident in Stockholm on 31 December 2022 with an HF diagnosis. The Total Population Register and several national health registers were linked, providing information on comorbidities, HF hospital admissions, primary care visits, and dispensed drugs. Individuals were categorised into those managed exclusively in primary care or those who were also managed in cardiology care by the absence/presence of an in-/outpatient appointment with a cardiologist during the past 5 years. RESULTS:HF was prevalent in 33 872 of 524 250 (6.5%) individuals of whom 50.4% (n = 17 067) were exclusively managed in primary care. Among patients also managed in cardiology care, two-thirds of HF drugs were prescribed by primary care. Primary care-managed patients were on average 3 years older, more often female, of lower socioeconomic status, had fewer comorbidities, received fewer guideline-recommended drugs, and had lower rates of admissions to hospital for HF than cardiology care-managed patients. Residing in a nursing home and having dementia were the factors most strongly associated with exclusive primary care management. CONCLUSION:Primary care manages the majority of individuals with HF, who are typically older than those patients who are also managed in cardiology care. These characteristics may explain differences in drug use.

AIMS:In the randomized DAPA-MI clinical trial, 10 mg of dapagliflozin once daily improved cardiometabolic outcomes versus placebo after acute myocardial infarction (MI) in patients without established diabetes or heart failure (HF). We assessed associations between baseline left ventricular ejection fraction (LVEF) and cardiometabolic outcomes in DAPA-MI. METHODS:The primary outcome, assessed using the win ratio method, was the hierarchical composite of death, hospitalization for HF, non-fatal MI, atrial fibrillation/flutter, Type 2 diabetes, New York Heart Association classification at last visit and body weight decrease of ≥5% from baseline to last visit. For the present analysis, patients were categorized using LVEF at randomization (<50% or ≥50%). RESULTS:Of the DAPA-MI participants with available LVEF data who received ≥1 dose of study drug (n = 3751), 2913 (77.7%) had LVEF <50% and 838 (22.3%) had LVEF ≥50%. The primary hierarchical composite outcome resulted in a win ratio favouring dapagliflozin of 1.38 (95% CI: 1.21, 1.57; P < 0.001) in patients with LVEF <50% and 1.32 (1.00, 1.73; P = 0.048) in patients with LVEF ≥ 50% (P interaction = 0.76). In a sensitivity analysis excluding patients with LVEF <30%, the primary hierarchical composite outcome resulted in a win ratio favouring dapagliflozin of 1.40 (95% CI: 1.22, 1.61; P < 0.001). There were no significant interactions between baseline LVEF and any secondary outcomes. CONCLUSIONS:Regardless of baseline LVEF, dapagliflozin resulted in significant cardiometabolic benefits versus placebo, although there was no impact on the composite of cardiovascular death or hospitalization for HF.

Abstract Background The burden and outcomes of inflammation in people with atherosclerotic cardiovascular disease (ASCVD) are poorly defined, particularly beyond the controlled settings of trials and research cohorts. Methods We conducted a longitudinal observational study of adults with ASCVD undergoing C-reactive-protein (CRP) testing in routine healthcare in Stockholm, Sweden. After excluding CRP tests associated with acute illness and patients with medications/conditions that bias CRP interpretation, the systemic inflammation of participants was defined over a 3-month ascertainment window. Baseline determinants of CRP≥2 mg/L were explored with logistic regression, and baseline CRP categories were compared via Poisson and Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events (MACE), heart failure hospitalization, and all-cause death. Result After applying inclusion/exclusion criteria, we identified 84,399 adults with ASCVD with a mean age of 71 years and of which 54% were men. In total, 60% had CRP≥2 mg/L. At baseline, female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anemia, were associated with CRP≥2 mg/L. Conversely, the use of RASi, antiplatelets, and lipid-lowering therapy were associated with lower odds. Over a median follow-up of 6.4 years and compared to people with CRP <2 mg/L, those with CRP≥2 mg/L had a higher rate of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications during follow-up (P<0.05 for all). They also had a higher rate of MACE [adjusted hazard ratio (HR), 1.30; 95% CI, 1.27–1.33], heart failure hospitalization [1.24; 1.20–1.39], and all-cause death [1.35; 1.20–1.30]. Results were consistent across subgroups and more granular CRP categories, and robust to the exclusion of extreme CRP values or early events. Conclusions Two in three adults with ASCVD have systemic inflammation. A CRP≥2 mg/L is associated with excess healthcare resource utilization as well as increased rates of MACE, heart failure, and death.

Background and Aims The burden and outcomes of inflammation in patients with atherosclerotic cardiovascular disease (ASCVD) are not well defined beyond the controlled settings of trials and research cohorts. Methods This was an observational study of ASCVD adults undergoing C-reactive protein testing in Stockholm's healthcare (2007-21). After excluding C-reactive protein tests associated with acute illness or medications/conditions that bias C-reactive protein interpretation, systemic inflammation was evaluated over a 3-month ascertainment window. Determinants of C-reactive protein >= 2 mg/L were explored with logistic regression. C-reactive protein categories were compared via negative-binomial/Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events, heart failure hospitalization, and death. Results A total of 84 399 ASCVD adults were included (46% female, mean age 71 years, 59% with C-reactive protein >= 2 mg/L). Female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anaemia were associated with higher odds of C-reactive protein >= 2 mg/L. The use of renin-angiotensin system inhibitors, antiplatelets, and lipid-lowering therapy was associated with lower odds. Over a median of 6.4 years, compared with C-reactive protein < 2 mg/L, patients with C-reactive protein >= 2 mg/L had higher rates of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications (P < .05 for all). They also had a higher rate of major adverse cardiovascular events [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.27-1.33], heart failure (HR 1.24; 95% CI 1.20-1.30), and death (HR 1.35; 95% CI 1.31-1.39). Results were consistent across subgroups and granular C-reactive protein categories and robust to the exclusion of extreme C-reactive protein values or early events. Conclusions Three in five adults with ASCVD have systemic inflammation, which is associated with excess healthcare resource utilization and increased rates of cardiovascular events and death.

Abstract Background Dapagliflozin improved cardiometabolic outcomes compared with placebo following acute myocardial infarction (MI) in participants without prior diabetes mellitus (DM) or chronic heart failure (HF) in the DAPA-MI trial. Purpose Cardiometabolic outcomes were assessed in the DAPA-MI trial according to left ventricular ejection fraction (EF) at randomisation. Methods Participants were categorised according to whether baseline EF was ≥50 or <50%. Those without a baseline EF result and those who did not receive a dose of study drug were excluded. The primary objective was to determine the clinical effect of dapagliflozin 10 mg versus placebo assessed using a hierarchical composite outcome and analysed by the win ratio method. The primary outcome was the hierarchical composite, by order of perceived clinical importance, of death, hospitalization for HF (HHF), nonfatal MI, atrial fibrillation/flutter event, new diagnosis of type 2 DM, NYHA functional class at the last trial visit, and body weight decrease of ≥5% from baseline to the last trial visit. Time to first event of NYHA class II-IV or HHF and time to first event of NYHA class III-IV or HHF were assessed as endpoints of special interest. Hazard ratios (HR) with 95% confidence intervals (CI) were determined using Cox proportional hazards models. The main subgroup variable (baseline EF ≥50 or <50) and its interaction with treatment (P int) were included. Results 838 participants had EF≥50 and 2913 had EF<50 at baseline. The primary hierarchical composite outcome resulted in a win ratio for those with EF≥50 of 1.32 (CI 1.00-1.73) and 1.38 for those with EF<50 (CI 1.21-1.57; P int 0.8) (Figures). There were no significant interactions by EF for any of the secondary outcomes. In those with EF<50, a first event of NYHA class II-IV or HHF occurred in 435 (29.4%) participants in the dapagliflozin group and 485 (33.8%) in the placebo group (absolute risk difference [ARD] 4.4%; HR 0.83, CI 0.73-0.94, P<0.01). In those with EF≥50, this occurred in 81 (19.7%) and 93 (21.8%), respectively (ARD 2.1%; HR 0.96, CI 0.65-1.41, P=0.7; P int 0.47). In those with EF<50, a first event of NYHA class III-IV or HHF occurred in 77 (5.2%) in the dapagliflozin and 115 (8.0%) in the placebo groups (ARD 2.2%; HR 0.64, CI 0.48-0.85, P<0.01). In those with EF≥50, this occurred in 14 (3.4%) and 19 (4.4%), respectively (ARD 1.0%; HR 0.80, CI 0.40-1.60, P=0.5; P int 0.55). There was no significant effect of dapagliflozin on death/MI/stroke in either subgroup (EF<50: HR 0.96, CI 0.65-1.41; EF≥50: HR 0.83, CI 0.38-1.84; P int 0.75). Dapagliflozin increased the incidence of 5% weight loss in both of the EF subgroups with no significant interaction. Conclusions Dapagliflozin resulted in significant benefit in cardiometabolic outcomes compared with placebo regardless of baseline EF. The absolute reduction in HF symptoms or HHF with dapagliflozin, compared with placebo, was greatest in those with baseline EF<50.Figures

Background Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention. Methods and Results Patients from the SWEDEHEART (Swedish Web‐system for Enhancement and Development of Evidence‐Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12‐month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88–1.11], P =0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94–1.25]), or their components between groups. The results were consistent among all of the investigated subgroups. Conclusions In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

Abstract Background NT-proBNP-levels are often elevated in patients with atrial fibrillation (AF), but their clinical use and interpretation for predicting subsequent cardiovascular events has not been explored in an all-comers setting. Aim To determine whether NT-proBNP levels are associated with the risk of subsequent heart failure (CHF) and/or death in patients with AF and its relation to prior CHF diagnosis Method All patients with new-onset AF (defined by ICD-code I48) who had an NT-proBNP-level within +/- 14 days of the date of the AF date measured in a regional laboratory repository between 2000-2021 were included in the analysis cohort. Patients were categorized into NT-proBNP level (pg/mL) <1000, 1000-1999, ≥2000. If several NT-proBNP-levels were measured, the maximal value was used. The association between NT-proBNP level and the outcome CHF hospitalization and/or death within 3 years of diagnosis was assessed in Cox regression analyses adjusted for baseline characteristic and medications. Since there was an interaction (p<0.001) between Nt-proBNP-level and prior/new-onset CHF at time of AF diagnosis and no known CHF, two separate analyses were performed in patients with or new-onset CHF and those without prior CHF. Results There were 10559 patients with AF and no CHF, and 11 257 with AF and CHF. There were 14% of patients with new-onset CHF at time of new-onset AF diagnosis. These were grouped together with patients with known CHF. Patients with no prior CHF were younger (76 years (95% CI 68-83) vs 80 (72-87), p<0.001), and healthier with less often diabetes (18.4% vs 24.5%, p<0.001), prior myocardial infarction (12.0% vs 24.3%), a lower CHA2DS2-VASc score (3.0 vs 5.0, p<0.001) and a lower median NT-proBNP level (1650 pg/mL (95% CI 702-3549) vs 4240 pg/mL (2160-8860), p<0.001). Among patients with AF and no prior CHF, the incidence rate in the lowest NT-proBNP level was low, but increased with higher levels (Table). Adjusting for covariates and medications, the risk of both CHF hospitalization and CHF/death compared to the reference category NTproBNP< 1000 pg/mL was nearly 2 and 3 times higher among those who with initial NT-proBNP level 1000-1999 and ≥ 2000. Among patients with AF and known CHF, the incidence rate of CHF hospitalization or CHF hospitalization/death at the same NT-proBNP-strata was several times higher compared to patients without known CHF. Adjusting for covariates, the risk increased for CHF hospitalization or CHF/hospitalization similarly for each strata as for patients without known CHF. AF patients without known HF but with the highest elevation of NTproBNP-level had a risk of subsequent hospitalization of heart failure which was higher than those with known heart failure and lowest NTproBNP-level. Conclusion A higher NTproBNP-level in patients with AF identifies patients at higher risk of CHF hospitalization and/or death in both patients with no and prior CHF.Table

Abstract Background Treatment of myocardial infarction (MI) has improved over the last decades due to the implementation of early revascularization and medical therapies for secondary prevention. The impact of these treatment changes on survival in women and men has not been documented over a 30-year perspective. Purpose The aim of this study was to assess implementation of new treatment strategies and their effects on changes in long-term outcomes in all patients with MI in Sweden over 30 years. Methods In SWEDEHEART, the Swedish register for coronary heart disease, we investigated treatments and outcomes and their associations in patients admitted with MI between 1991-2021. Patients were stratified in 2-year blocks, starting with a 3-year block for 1991-1993. Primary outcome was 1-year risk of cardiovascular (CV) mortality. Effect of treatments on outcome was assessed comparing observed event rates with event rates standardized by logistic regression accounting for differences in baseline characteristics and treatment. Results A total of 433,524 cases with MI were hospitalized between 1991-2021. Between 1991-1993 and 2020-2021, treatment with reperfusion and revascularization increased from 34.7% to 77.3%; in-hospital PCI from 1.8% to 73.8 %; dual antiplatelet therapy (DAPT) from 0.0% to 73.8%; statins from 3.0% to 91.7%; beta-blockers from 66.4% to 88.3%; and renin-angiotensin-system (RAS) inhibitors from 21.6% to 81.6% (Figure 1A). During the same period, the rates of 1-year CV mortality decreased from 24.1% to 8.3%. For women, CV mortality decreased from 28.9% to 10.3% and for men from 21.7% to 7.3%. When comparing observed with standardized event rates, most of the mortality improvement was explained by the implementation of early revascularization with PCI (Figure 1B). Conclusions In this unique nationwide cohort of patients with MI over 30 years, there was a gradual implementation of revascularization and novel medical treatment. Concurrently, there was a gradual absolute reduction in 1-year risk of CV mortality with 16 percentage points, which was similar in women and men. Most of the improvement in survival was related to implementation of early revascularization strategies. Figure 1 (A) Temporal trends in treatment and (B) crude and standardized rates of cardiovascular mortality within 1 year in patients with myocardial infarction over 30 years in Sweden.

Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low-moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low-moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2), 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30-59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87-0.99) and OT-A (HR 0.90; 0.83-0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group (P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low-moderate intensity.

We thank Dr Dimitriadis et al. for their reflections regarding the importance of considering risk factors for ischaemia, when examining the risk of adverse clinical outcomes following dual antiplatelet therapy ( DAPT ) in myocardial infarction ( MI ) patients who are at high bleeding risk ( HBR ) . 1 In our previously published comparison of ticagrelor and clopidogrel in a cohort of HBR MI patients, we adjusted for several factors which are known to be associated with the risk of recurrent ischaemic events, including smoking st atus , diabetes mellitus , and prior revascularization therapy. 2 , 3 While data on procedural characteristics such as stent length and the complexity of percutaneous coronary intervention ( PCI ) was unavailable to us and could therefore not be adjusted for in our analyses, there are other studies which have examined the relationship between these risk factors for recurrent ischaemic events and the intensity of antiplatelet therapy in HBR patients. For instance, a recently published study found that early DAPT discontinuation was associated with similar ischaemic outcomes as compared with standard DAPT in both HBR patients who underwent complex PCI and those who did not present as complex PCI cases. 4 In contrast, standard DAPT was found to be superior to early DAPT discontinuation in complex PCI patients who were considered to have a lower bleeding risk. This suggests

Aims Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

BACKGROUND:Morbidity and mortality associated with high CHA2DS2-VASc and HAS-BLED scores is not specific to atrial fibrillation (AF). Frailty could be an important contributor to this morbidity and mortality while being mechanistically independent from AF. We sought to evaluate the association of stroke and bleeding risk to noncardiovascular frail events and the association of stroke prevention therapy to outcomes in frail patients with AF. METHODS:Using the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the Veterans Health Administration, we identified patients with newly diagnosed AF from 2004 to 2014. Baseline frailty was identified using a previously validated claims-based index requiring ≥2 of 12 ICD-9 diagnoses. Logistic regressions modeled the association between CHA2DS2-VASc and modified HAS-BLED and frailty. Cox proportional hazard regressions were used to evaluate the association between CHA2DS2-VASc and modified HAS-BLED and a composite of noncardiovascular frail events (fractures, urinary tract infections, bacterial pneumonia, or dehydration). We also evaluated the association of oral anticoagulant (OAC) use with stroke, bleeding, and 1-year mortality in frail patients and non-frail patients. RESULTS:In 213,435 patients (age 70 ± 11; 98% male; CHA2DS2-VASc 2.4 ± 1.7) with AF, 8,498 (4%) were frail. CHA2DS2-VASc > 0 and HAS-BLED > 0 were strongly associated with frailty (odds ratio [OR] 13.3 (95% CI: 11.6-15.2) for CHA2DS2-VASc 4+ and OR 13.4 (10.2-17.5) for HAS-BLED 3+). After adjusting for covariates, CHA2DS2-VASc, and HAS-BLED > 0 were associated with higher risk of non-cardiovascular frail events (hazard ratio [HR] 2.1 (95% CI: 2.0-2.2) for CHA2DS2-VASc 4+ and HR 1.4 (95% CI: 1.3-1.5) for HAS-BLED 3+). In frail patients, OAC use was associated with significantly lower risk of 1-year mortality (HR 0.82; 95% CI 0.72-0.94, P = .0031) but did not reach significance for risk of stroke (HR 0.80; 95% CI 0.55-1.18, P = .26) or major bleeding (HR 1.08; 95% CI 0.93-1.25, P = .34). CONCLUSIONS:High CHA2DS2-VASc and HAS-BLED scores are strongly associated with frailty. However, in frail patients, OAC use was associated with reduction in 1-year mortality. For this challenging clinical population with competing risks of frailty and frail events, focused prospective studies are needed to support clinical decision-making. Until then, careful evaluation of frailty should inform shared decision-making.

Abstract Background and Aims In patients with severely decreased eGFR (stage 4-5 CKD), efficacy of treating patients to a lower blood pressure (BP) target is uncertain. The Systolic blood PRessure INtervention Trial (SPRINT) demonstrated lower rates of a composite cardiovascular (CVD) endpoint and death in the intensive treatment group with a target systolic blood pressure (SBP) of <120 mmHg. This study has influenced guidelines; the updated 2021 Kidney Disease Improving Global Outcomes (KDIGO) now suggest lowering the SBP to < 120 mmHg, if tolerated. In this study we set out to investigate the association between SBP and CVD in a large cohort of nephrology-referred patients with CKD stage 3-5. Method We included patients ≥18 years participating in the Swedish Renal Registry (SRR-CKD) who had a first registered eGFR <60 ml/min/1.73 m2 2006-2017 with at least one recorded BP measurement and two out-patient visits within one year. We excluded individuals with a recorded SBP <100 mmHg or prior kidney failure replacement treatment. After the initial one-year observation period, we followed patients until the primary or secondary outcome was attained, or until December 31, 2017. The achieved average systolic BP, measured during routine out-patient care using any standard electronic or manual blood pressure device, was categorized into a priori defined categories. To align with SPRINT, the primary endpoint was Major Cardiovascular Events (MACE) defined as the composite of first myocardial infarction (MI), non-MI acute coronary syndrome, stroke, heart failure, or death attributable to CVD. The secondary endpoints were the individual components of the primary composite endpoint, all-cause death, or a composite of the primary endpoint and death. Demographics, body mass index, underlying kidney disease, and laboratory values at the start of follow-up were obtained from the SRR-CKD. Information on comorbidity, including Charlson comorbidity index was gathered from a linkage with the National Patient Registry; medications were obtained from the National Prescribed drug register. The primary endpoint and secondary endpoints were assessed by cause-specific Cox proportional hazards regression, adjusting for age, sex, history of CVD, Charlson comorbidity, plasma albumin, phosphate, diuretics, RAASi, betablockers, eGFR, and diastolic blood pressure. Missing data were handled through multiple imputation. Results In total 15,668 patients with a median eGFR 23 ml/min/1.73 m2, mean age 71 years and 33% women were followed over a period of 2.8 years (IQR 1.4-5.0). There were 6359 patients (41%) experiencing the primary outcome; 2601 (17%) with a coronary artery event, 1427 (9%) MI, 1,345 (9%) cerebrovascular event, and 5,480 (35%) patients died. The unadjusted analysis showed a J-shaped relationship between SBP and the primary outcome, with the lowest risk of events in patients with SBP around 125 mmHg (Figure 1). In multivariable models, there was a higher risk of experiencing the primary outcome if the average SBP was >150 mmHg (HR 1.09;95%CI 1.0-1.19), the highest risk being in those with SBP above 160 mmHg (HR 1.40 with 95% CI 1.28-1.53) as compared to those with SBP 130-140 mmHg (Figure 2). We observed 30% lower risk of MI when the SBP was 100–120 mmHg after adjustments (HR 0.70 (95% CI 0.56–0.88) as compared to 130–140, and higher risk of MI at SBP >160 mmHg (1.78; 1.49–2.12) with 11% higher risk of MI with every 10 mmHg increase in SBP (HR 1.11; 1.07–1.14). The other cardiovascular endpoints, including all-cause mortality showed a similar pattern as the primary composite endpoint. Conclusion In patients with advanced stage CKD, SBP <120 mmHg is associated with lower risk of MI, but not with lower risk of other cardiovascular outcomes or all-cause mortality. A SBP >140 mmHg was associated with higher risk of most cardiovascular events including cardiovascular mortality and all-cause mortality.