Abbreviated Versus Standard Dual Antiplatelet Therapy Times After Percutaneous Coronary Intervention in Patients With High Bleeding Risk With Acute Coronary Syndrome: Insights From the SWEDEHEART Registry.

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.

Comparison between ticagrelor and clopidogrel in myocardial infarction patients with high bleeding risk.

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 ≥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.

Association of CHA2DS2-VASc and HAS-BLED to frailty and frail outcomes: From the TREAT-AF study.

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.

Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function.

ABSTRACT: 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.

Association of Ischemic and Bleeding Events With Mortality Among Patients in Sweden With Recent Acute Myocardial Infarction Receiving Antithrombotic Therapy.

Importance: Antithrombotic treatment after myocardial infarction (MI) should be individualized based on the patient's risk of ischemic and bleeding events. Uncertainty remains regarding the relative prognostic importance of the 2 types of events, and further study would be useful. Objectives: To compare the association of ischemic vs bleeding events with mortality in patients with a recent MI and assess whether the relative mortality risk for the 2 types of events has changed over the past 2 decades. Design, Setting, and Participants: A cohort study based on nationwide registers in Sweden, 2012-2017, was conducted. Data were analyzed between July 2021 and May 2022. Patients with MI who were discharged alive with antithrombotic therapy (antiplatelet therapy or oral anticoagulation) were included in the analysis. Main Outcomes and Measures: The incidence of a first ischemic event (hospitalization for MI or ischemic stroke) or bleeding event (hospitalization with bleeding) up to 1 year after discharge and the mortality risk up to 1 year after each type of event were assessed. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) for 1-year mortality after an ischemic and bleeding event vs no event, and after an ischemic vs bleeding event. Adjusted HRs for mortality after ischemic vs bleeding events were compared among patients discharged in 1997-2000, 2001-2011, and 2012-2017. Results: Of 86 736 patients discharged after MI in 2012-2017 (median age, 71 [IQR, 62-80] years; 57 287 [66.0%] men), 4039 individuals experienced a first ischemic event (5.7 per 100 person-years) and 3399 experienced a first bleeding event (4.8 per 100 person-years). The mortality rate was 46.2 per 100 person-years after an ischemic event and 27.1 per 100 person-years after a bleeding event. The aHR for 1-year mortality vs no event was 4.16 (95% CI, 3.91-4.43) after an ischemic event and 3.43 (95% CI, 3.17-3.71) after a bleeding event. When the 2 types of events were compared, the aHR was 1.27 (95% CI, 1.15-1.40) for an ischemic vs bleeding event. There was no statistically significant difference in the aHR of an ischemic vs bleeding event in 1997-2000, 2001-2011, and 2012-2017. Conclusions and Relevance: In this nationwide cohort study of patients with a recent MI, postdischarge ischemic events were more common and associated with higher mortality risk compared with bleeding events.

Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease.

BACKGROUND: Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed. OBJECTIVES: This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD. METHODS: The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged ≥65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival. RESULTS: There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.0-6.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure. CONCLUSIONS: Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk.

Safety of early hospital discharge following admission with ST-elevation myocardial infarction treated with percutaneous coronary intervention: a nationwide cohort study.

BACKGROUND: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy. AIMS: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS: Using nationwide data from the SWEDEHEART registry, we identified patients with STEMI treated with primary PCI during the period 2009-2017, of whom 8,092 (26.4%) were identified as low risk with the PAMI-II score. Low-risk patients were stratified according to their length of hospital stay (≤2 days vs >2 days). The primary endpoint was major adverse cardiovascular events (MACE, including death, reinfarction treated with PCI, stroke or heart failure hospitalisation) at one year, assessed using a Cox proportional hazards model with propensity score as well as an inverse probability weighting propensity score of average treatment effect to adjust for confounders. RESULTS: A total of 1,449 (17.9%) patients were discharged ≤2 days from admission. After adjustment, the one-year MACE rate was not higher for patients discharged at >2 days from admission than for patients discharged ≤2 days (4.3% vs 3.2%; adjusted HR 1.31, 95% confidence interval [CI]: 0.92-1.87, p=0.14), and no difference was observed regarding any of the individual components of the main outcome. Results were consistent across all subgroups with no difference in MACE between early and late discharge patients. CONCLUSIONS: Nationwide observational data suggest that early discharge of low-risk patients with STEMI treated with PCI is not associated with an increase in one-year MACE.

Epidemiology of Aortic Stenosis/Aortic Valve Replacement (from the Nationwide Swedish Renal Registry).

Contemporary data on the prevalence and incidence of aortic stenosis (AS) and aortic valve replacement (AVR) in patients initiating dialysis are scarce. This observational cohort study aimed to estimate (1) the point prevalence of AS and AVR at dialysis start and (2) the AS incidence and associated factors prospective to dialysis initiation. The study included 14,550 patients initiating dialysis registered in the Swedish Renal Registry between 2005 and 2018. AS was defined by the International Statistical Classification of Diseases, Tenth Revision codes, and AVR by the surgical procedure codes. Associations between covariates and outcomes were assessed in Cox regression models. The median age was 68 (57 to 77), 66% were males, and the point prevalence of AS and AVR was 3.4% and 1.1%, respectively. In those without known AS/AVR at dialysis initiation (n = 14,050), AS was diagnosed in 595 patients (incidence 16.3/1000 person-years, 95% confidence interval [CI] 15.1 to 17.7/1,000 person-years) during a median follow-up of 2.7 years (interquartile range 1.1 to 5.7). In adjusted Cox regression models, higher age (hazard ratio [HR] 1.03, 95% CI 1.02 to 1.04), male gender (HR 1.51, 95% CI 1.25 to 1.83), atrial fibrillation (HR 1.32, 95% CI 1.06 to 1.64), and hypertension (HR 1.65, 95% CI 1.03 to 2.65) were associated with incident AS. Peritoneal dialysis patients had a nonsignificant trend toward higher AS risk compared with hemodialysis (HR 1.18, 95% CI 0.99 to 1.40). About 20% of patients (n = 113) diagnosed with incident AS underwent AVR (incidence 3.1/1000 person-years, 95% CI 2.6 to 3.7/1,000). Only the male gender was associated with AVR (HR 2.07, 95% CI 1.30 to 3.30). In conclusion, the prevalence and incidence of AS and AVR in patients initiating dialysis are high. A fifth of newly diagnosed AS underwent AVR after dialysis onset.

Direct Oral Anticoagulant Adherence of Patients With Atrial Fibrillation Transitioned from Warfarin.

Background Reduced time in international normalized ratio therapeutic range (TTR) limits warfarin safety and effectiveness. In patients switched from warfarin to direct oral anticoagulants (DOACs), patient factors associated with low TTR could also increase risk of DOAC nonadherence. We investigated the relationship between warfarin TTR and DOAC adherence in warfarin-treated patients with atrial fibrillation switched to DOAC. Methods and Results Using data from the Veterans Health Administration, we identified patients with atrial fibrillation switched from warfarin to DOAC (switchers) or treated with warfarin alone (non-switchers). Logistic regression was used to evaluate association between warfarin TTR and DOAC adherence. We analyzed 128 605 patients (age, 71±9; 1.6% women; CHA2DS2-VASc 3.5±1.6); 32 377 switchers and 96 228 non-switchers. In 8016 switchers with international normalized ratio data to calculate 180-day TTR before switch, TTR was low (median 0.45; IQR, 0.26-0.64). Patients with TTR <0.5 were more likely to be switched to DOAC (odds ratio [OR],1.68 [95% CI,1.62-1.74], P<0.0001), as were those with TTR <0.6 or TTR <0.7. Proportion of days covered ≥0.8 was achieved by 76% of switchers at 365 days. In low-TTR individuals, proportion of days covered ≥0.8 was achieved by 70%, 72%, and 73% of switchers with TTR <0.5, 0.6, and 0.7, respectively. After multivariable adjustment, TTR <0.5 decreased odds of achieving 365-day proportion of days covered ≥0.8 (OR, 0.49; 0.43-0.57, P<0.0001), with similar relationships for TTR <0.6 and TTR <0.7. In non-switchers with TTR <0.5, long-term TTR remained low. Conclusions In patients with atrial fibrillation switched from warfarin to DOAC, most achieved adequate DOAC adherence despite low pre-switch TTRs. However, TTR trajectories remained low in non-switchers. Patients with low warfarin TTR more consistently achieved treatment targets after switching to DOACs, although adherence-oriented interventions may be beneficial.

Pretreatment With P2Y12 Inhibitors in Patients With Chronic Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Report From the Swedish Coronary Angiography and Angioplasty Registry.

BACKGROUND: In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, the optimal timing of P2Y12 inhibitors' administration is uncertain. We compared pretreatment versus treatment in the catheterization laboratory (In-Cathlab) in a real-world population. METHODS: In Swedish Coronary Angiography and Angioplasty Registry, all patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, between 2006 and 2017 were identified. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography, outside the catheterization laboratory. Outcomes were net adverse clinical events including death, myocardial infarction, stroke, or bleeding within 30 days of the index procedure and in-hospital bleeding. RESULTS: We included 26 814 patients, 8237 in the In-Cathlab, and 18 577 in the pretreatment group. In-Cathlab treatment compared with pretreatment was associated with lower risk for net adverse clinical event (4.2 versus 5.1%, adjusted hazard ratio 0.79 [0.63-0.99]), bleeding (2.3 versus 2.6%, adjusted hazard ratio, 0.76 [0.57-1.01]). and in-hospital bleeding (1.9 versus 2.1%, adjusted odds ratio, 0.70 [0.51-0.96]). The risk for death, myocardial infarction, or stroke did not significantly differ between the groups. Among the In-Cathlab treated patients, 41% received ticagrelor or prasugrel and 59% clopidogrel. Treatment with ticagrelor or prasugrel was associated with higher risk for net adverse clinical events (5.4% versus 3.4%, adjusted hazard ratio, 1.66 [1.12-2.48]), bleeding (3.4 versus 1.6%, adjusted hazard ratio, 2.14 [1.34-3.42]), and in-hospital bleeding (2.9 versus 1.2%, adjusted odds ratio, 2.24 [1.29-3.90]) but similar risk for death, myocardial infarction, or stroke, compared with clopidogrel. CONCLUSIONS: In patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, pretreatment with P2Y12 inhibitors, before arrival to the catheterization laboratory, was not associated with improved clinical outcomes but was associated with increased risk for bleeding. Our data support clopidogrel administration in the catheterization laboratory as the standard of care. Graphic Abstract: A graphic abstract is available for this article.

High-sensitivity troponins in dialysis patients: variation and prognostic value.

BACKGROUND: Dialysis patients have a high prevalence of cardiovascular mortality but also elevated cardiac troponins (cTns) even without signs of cardiac ischaemia. The study aims to assess variation and prognostic value of high-sensitivity cTnI and cTnT in prevalent dialysis patients. METHODS: In 198 prevalent haemodialysis (HD) and 78 peritoneal dialysis (PD) patients, 4-monthly serum troponin I and T measurements were obtained. Reference change values (RCVs) were used for variability assessment and competing-risk regression models for survival analyses; maximal follow-up was 50 months. RESULTS: HD and PD patients had similar troponin levels [median (interquartile range) troponin I: 25 ng/L (14-43) versus 21 ng/L (11-37), troponin T: 70 ng/L (44-129) versus 67 ng/L (43-123)]. Of troponin I and T levels, 42% versus 98% were above the decision level of myocardial infarction. RCVs were +68/-41% (troponin I) and +29/-23% (troponin T). Increased variability of troponins related to higher age, male sex, protein-energy wasting and congestive heart failure, but not ischaemic heart disease or dialysis form. Elevated troponin T, but not troponin I, predicted death after adjusting for confounders. CONCLUSIONS: A large proportion of prevalent dialysis patients without current established or ongoing cardiac events have elevated levels of high-sensitivity cTns. Mortality risk was doubled in patients with persistently high troponin T levels. The large intraindividual variation of cTns suggests that serial measurements and reference change levels may be used to improve diagnostic utility. However, evidence-based recommendations require more data from large studies of dialysis patients with cardiac events.

Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices.

BACKGROUND: Kidney function may promote progression of AF. OBJECTIVE: We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED). METHODS: We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death. RESULTS: Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.37 per 10 years; 95% CI:1.22-1.54). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25). CONCLUSION: Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.

Comparing Effect Estimates in Randomized Trials and Observational Studies From the Same Population: An Application to Percutaneous Coronary Intervention.

Background To understand when results from observational studies and randomized trials are comparable, we performed an observational emulation of a target trial designed to ask similar questions as the VALIDATE (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy) randomized trial. The VALIDATE trial compared the effect of bivalirudin and heparin during percutaneous coronary intervention on the risk of death, myocardial infarction, and bleeding across Sweden. Methods and Results We specified the protocol of a target trial similar to the VALIDATE trial, then emulated the target trial in the period before the VALIDATE trial took place using data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry-the same registry in which the trial was undertaken. The target trial emulation and the VALIDATE trial both estimated little or no effect of bivalirudin versus heparin on the risk of death or myocardial infarction by 180 days (target trial emulation risk ratio for death, 1.21 [95% CI, 0.88 - 1.54]; VALIDATE trial hazard ratio for death, 1.05 [95% CI, 0.78 - 1.41]). The observational data, however, could not capture less severe cases of bleeding, resulting in an inability to define a bleeding outcome like the trial, and could not accurately estimate the comparative risk of death by 14 days, which may be the result of intractable confounding early in follow-up or the inability to precisely emulate the trial's eligibility criteria. Conclusions Using real-world data to emulate a target trial can deliver accurate effect estimates. Yet, even with rich observational data, it is not always possible to estimate the short-term effect of interventions or the effect on outcomes for which data are not routinely collected.

Prasugrel versus ticagrelor in patients with myocardial infarction undergoing percutaneous coronary intervention.

OBJECTIVE: The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes. METHODS: In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders. RESULTS: We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results. CONCLUSION: In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.

Validation of risk scores for ischaemic stroke in atrial fibrillation across the spectrum of kidney function.

AIMS: The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function. METHODS AND RESULTS: Overall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS2, Modified CHADS2, CHA2DS2-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2], mild CKD (eGFR 30-60 mL/min/1.73 m2), and advanced CKD (eGFR <30 mL/min/1.73 m2). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS2 score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration. CONCLUSION: In the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients.

Glucagon-like peptide-1 receptor agonists and the risk of cardiovascular events in diabetes patients surviving an acute myocardial infarction.

AIMS: Trial evidence indicates that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of cardiovascular (CV) events in patients with diabetes and myocardial infarction (MI). We aimed to expand this observation to routine care settings. METHODS AND RESULTS: Prospective observational study including all patients with diabetes surviving an MI and registered in the nationwide SWEDEHEART registry during 2010-17. Multivariable Cox regression analyses were used to estimate the association between GLP-1 RAs use and the study outcome, which was a composite of stroke, heart failure, Re-infarction, or CV death. Covariates included demographics, comorbidities, presentation at admission, and use of secondary CV prevention therapies. In total, 17 868 patients with diabetes were discharged alive after a first event of MI. Their median age was 71 years, 36% were women and their median estimated glomerular filtration rate was 75 mL/min/1.73m2. Of those, 365 (2%) were using GLP-1 RAs. During median 3 years of follow-up, 7005 patients experienced the primary composite outcome. Compared with standard of diabetes care, use of GLP-1 RAs was associated with a lower event risk [adjusted hazard ratio (HR) 0.72; 95% confidence interval (CI): 0.56-0.92], mainly attributed to a lower rate of re-infarction and stroke. Results were similar after propensity score matching or when compared with users of sulfonylurea. There was no suggestion of heterogeneity across subgroups of age, sex, chronic kidney disease, and STEMI. CONCLUSION: GLP-1 RAs use, compared with standard of diabetes care, was associated with lower risk for major CV events in healthcare-managed survivors of an MI.

Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Severe Obesity: A Nationwide Cohort Study.

BACKGROUND: The number of patients with myocardial infarction and severe obesity is increasing and there is a lack of evidence how these patients should be treated. The aim of this study was to investigate the association between metabolic surgery (Roux-en-Y gastric bypass and sleeve gastrectomy) and major adverse cardiovascular events in patients with previous myocardial infarction (MI) and severe obesity. METHODS: Of 566 patients with previous MI registered in the SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) undergoing metabolic surgery and registered in the nationwide Scandinavian Obesity Surgery Registry, 509 patients (Roux-en-Y gastric bypass n=465; sleeve gastrectomy n=44) could be matched 1:1 to a control with MI from SWEDEHEART, but no subsequent metabolic surgery regarding sex, age (±3 years), year of MI (±3 years), and body mass index (±3). The 2 groups were well matched, except for a lower proportion of reduced ejection fraction after MI (7% versus 12%), previous heart failure (10% versus 19%), atrial fibrillation (6% versus 10%), and chronic obstructive pulmonary disease (4% versus 7%) in patients undergoing metabolic surgery. RESULTS: The median (interquartile range) follow-up time was 4.6 (2.7-7.1) years. The 8-year cumulative probability of major adverse cardiovascular events was lower in patients undergoing metabolic surgery (18.7% [95% CI, 15.9-21.5%] versus 36.2% [33.2-39.3%], adjusted hazard ratio, 0.44 [95% CI, 0.32-0.61]). Patients undergoing metabolic surgery had also a lower risk of death (adjusted HR, 0.45 [95% CI, 0.29-0.70]; MI, 0.24 [0.14-0.41]) and new onset heart failure, but there were no significant differences regarding stroke (0.91 [0.38-2.20]) and new onset atrial fibrillation (0.56 [0.31-1.01]). CONCLUSIONS: In severely obese patients with previous MI, metabolic surgery is associated with a low risk for serious complications, lower risk of major adverse cardiovascular events, death, new MI, and new onset heart failure. These findings need to be confirmed in a randomized, controlled trial.

Incidence and Predictors of Out-of-Hospital Cardiac Arrest Within 90 Days After Myocardial Infarction.

BACKGROUND: The risk of sudden cardiac death (SCD) is high early after myocardial infarction (MI). Current knowledge and guidelines mainly rely on results from older clinical trials and registry studies. Left ventricular ejection fraction (LVEF) alone has not been proven a reliable predictor of SCD. OBJECTIVES: This study sought to identify the incidence and additional predictors of SCD early after MI in a contemporary nationwide setting. METHODS: The authors used data from SWEDEHEART, the Swedish Cardiopulmonary Resuscitation Registry, and the Swedish Pacemaker and Implantable Cardioverter-Defibrillator (ICD) Registry. Cases of MI, which had undergone coronary angiography and were discharged alive between 2009 to 2017 without a prior ICD, were followed up to 90 days. Cox regression models were used to assess associations between clinical parameters and out-of-hospital cardiac arrest (OHCA). RESULTS: Among 121,379 cases, OHCA occurred in 349 (0.29%) and non-OHCA death in 2,194 (1.8%). A total of 6 variables (male sex, diabetes, estimated glomerular filtration rate <30 ml/min/1.73 m2, Killip class ≥II, new-onset atrial fibrillation/flutter, and impaired LVEF [reference ≥50%] categorized as 40% to 49%, 30% to 39%, and <30%) were identified as independent predictors, were assigned points, and were grouped into 3 categories, where the incidence of OHCA ranged from 0.12% to 2.0% and non-OHCA death from 0.76% to 11.7%. Stratified by LVEF <40% alone, the incidence of OHCA was 0.20% and 0.76% and for non-OHCA death 1.1% and 4.9%. CONCLUSIONS: In this nationwide study, the incidence of OHCA within 90 days after MI was <0.3%. A total of 5 clinical parameters in addition to LVEF predicted OHCA and non-OHCA death better than LVEF alone.