Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial.

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a "postmortem" analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Effects of pharmacological interventions on mortality in patients with Takotsubo syndrome: a report from the SWEDEHEART registry.

AIMS: Takotsubo syndrome (TS) is a heart condition mimicking acute myocardial infarction. TS is characterized by a sudden weakening of the heart muscle, usually triggered by physical or emotional stress. In this study, we aimed to investigate the effect of pharmacological interventions on short- and long-term mortality in patients with TS. METHODS AND RESULTS: We analysed data from the SWEDEHEART (the Swedish Web System for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry, which included patients who underwent coronary angiography between 2009 and 2016. In total, we identified 1724 patients with TS among 228 263 individuals in the registry. The average age was 66 ± 14 years, and 77% were female. Nearly half of the TS patients (49.4%) presented with non-ST-elevation acute coronary syndrome, and a quarter (25.9%) presented with ST-elevation myocardial infarction. Most patients (79.1%) had non-obstructive coronary artery disease on angiography, while 11.7% had a single-vessel disease and 9.2% had a multivessel disease. All patients received at least one pharmacological intervention; most of them used beta-blockers (77.8% orally and 8.3% intravenously) or antiplatelet agents [aspirin (66.7%) and P2Y12 inhibitors (43.6%)]. According to the Kaplan-Meier estimator, the probability of all-cause mortality was 2.5% after 30 days and 16.6% after 6 years. The median follow-up time was 877 days. Intravenous use of inotropes and diuretics was associated with increased 30 day mortality in TS [hazard ratio (HR) = 9.92 (P < 0.001) and HR = 3.22 (P = 0.001), respectively], while angiotensin-converting enzyme inhibitors and statins were associated with decreased long-term mortality [HR = 0.60 (P = 0.025) and HR = 0.62 (P = 0.040), respectively]. Unfractionated and low-molecular-weight heparins were associated with reduced 30 day mortality [HR = 0.63 (P = 0.01)]. Angiotensin receptor blockers, oral anticoagulants, P2Y12 antagonists, aspirin, and beta-blockers did not statistically correlate with mortality. CONCLUSIONS: Our findings suggest that some medications commonly used to treat TS are associated with higher mortality, while others have lower mortality. These results could inform clinical decision-making and improve patient outcomes in TS. Further research is warranted to validate these findings and to identify optimal pharmacological interventions for patients with TS.

Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure.

Dapagliflozin in Myocardial InfarctionA total of 4017 patients with acute myocardial infarction, but no diabetes or chronic heart failure, were randomly assigned 10 mg of dapagliflozin or placebo. The primary outcome was a composite of death, hospitalization for heart failure, and five cardiometabolic outcomes analyzed using the win ratio method. There were significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval, 1.20 to 1.50), which was driven by the cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure was not different between the two groups.

Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease.

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Socioeconomic status is associated with process times in the emergency department for patients with chest pain.

Objective: Emergency department length of stay (EDLOS) is linked to crowding and patient outcomes whereas worse prognosis in low socioeconomic status remains poorly understood. We studied whether income was associated with ED process times among patients with chest pain. Methods: This was a registry-based cohort study on 124,980 patients arriving at 14 Swedish EDs between 2015 and 2019 with chest pain as their chief complaint. Individual-level sociodemographic and clinical data were linked from multiple national registries. The associations between disposable income quintiles, whether the time to physician assessment exceeded triage priority recommendations as well as EDLOS were evaluated using crude and multivariable regression models adjusted for age, gender, sociodemographic variables, and ED-management circumstances. Results: Patients with the lowest income were more likely to be assessed by physician later than triage recommendations (crude odds ratio [OR] 1.25 (95% confidence interval [CI] 1.20-1.29) and have an EDLOS exceeding 6 h (crude OR 1.22 (95% CI 1.17-1.27). Among patients subsequently diagnosed with major adverse cardiac events, patients with the lowest income were more likely to be assessed by a physician later than triage recommendations, crude OR 1.19 (95% CI 1.02-1.40). In the fully adjusted model, the average EDLOS was 13 min (5.6%) longer among patients in the lowest income quintile, 4:11 [h:min], (95% CI 4:08-4:13), compared to patients in the highest income quintile, 3:58 (95% CI 3:56-4:00). Conclusions: Among ED chest pain patients, low income was associated with longer time to physician than recommended by triage and longer EDLOS. Longer process times may have a negative impact due to crowding in the ED and delay diagnosis and timely treatment of the individual patient.

Randomized evaluation of routine beta-blocker therapy after myocardial infarction quality of life (RQoL): design and rationale of a multicentre, prospective, randomized, open, blinded endpoint study.

Aims: Most cases of acute myocardial infarction (MI) in Sweden are treated with long-term ß-blocker therapy as secondary prevention. Case studies and patient reports have indicated negative effects of ß-blockers including symptoms of depression, fatigue, sexual dysfunction, and general low mood, all related to reduced quality of life (QoL). To date, no recent large-scale, randomized trial has explored the effects of ß-blockers on these factors. Methods and results: The ongoing Randomized Evaluation of Decreased Usage of beta-bloCkErs after myocardial infarction (REDUCE): quality of life (RQoL) study is a multicentre, prospective, randomized pre-specified substudy aiming to evaluate the effects of ß-blockers on self-reported measures of QoL. Following randomized allocation to long-term ß-blocker or no ß-blocker treatment, patients complete a total of six baseline measures pertaining to QoL, sexual functioning, and perceived side effects. Data collection is optionally carried out online through a unique and secure portal and repeated again at two follow-up time points. Recruitment began in July 2018. Data from the first 100 patients showed that at the first follow-up, 93% had completed the questionnaires, which decreased to 81% at the second follow-up. The method of digital data collection was utilized by over half of the patients recruited so far. Conclusion: Data from the first 100 patients indicate success in terms of study design and recruitment. The RQoL substudy investigates the effects of ß-blockers on self-reported measures of QoL in MI patients and will potentially contribute to the limited knowledge of QoL-related side effects reported in conjunction with ß-blocker use. Clinical trial registration: Eudra CT number, 2017-002336-17; Clinical trial.gov identifier, NCT03278509.

Risk factors for severe COVID-19 in the young-before and after ICU admission.

BACKGROUND: Factors associated with severe COVID-19 and death among young adults are not fully understood, including differences between the sexes. The aim of this study was to identify factors associated with severe COVID-19 requiring intensive care and 90-day mortality among women and men below 50 years of age. METHODS: A register-based study using data from mandatory national registers, where patients with severe COVID-19 admitted to the ICU with need for mechanical ventilation (cases) between March 2020 and June 2021 were matched regarding age, sex, and district of residence with 10 population-based controls. Both the study population and the controls were divided into groups based on age (< 50 years, 50-64, and ≥ 65 years) and sex. Multivariate logistic regression models including socioeconomic factors were used to calculate odds ratios (OR) with 95% confidence intervals (CIs) for associations between severe COVID-19 in the population to compare the magnitude of the risk associations for co-morbidities in the different age categories, and subsequently factors associated with 90-day mortality among patients admitted to ICU. RESULTS: In total, 4921 cases and 49,210 controls (median age 63 years, 71% men) were included. The co-morbidities with the strongest associations with severe COVID-19 for the young population compared to older patients were chronic kidney disease (OR 6.80 [3.61-12.83]), type 2 diabetes (OR 6.31 [4.48-8.88]), hypertension (OR 5.09 [3.79-6.84]), rheumatoid arthritis (OR 4.76 [2.29-9.89]), obesity (OR 3.76 [2.88-4.92]), heart failure (OR 3.06 [1.36-6.89]), and asthma (OR 3.04 [2.22-4.16]). When comparing women vs. men < 50 years of age, stronger associations were seen for women regarding type 2 diabetes (OR 11.25 [6.00-21.08] vs OR 4.97 [3.25-7.60]) and hypertension (OR 8.76 [5.10-15.01] vs OR 4.09 [2.86-5.86]). The factors associated with 90-day mortality in the young were previous venous thromboembolism (OR 5.50 [2.13-14.22]), chronic kidney disease (OR 4.40 [1.64-11.78]) and type 2 diabetes (OR 2.71 [1.39-5.29]). These associations with 90-day mortality were foremost driven by the female population. CONCLUSION: Chronic kidney failure, type 2 diabetes, hypertension, rheumatoid arthritis, obesity, heart failure, and asthma were the strongest risk factors associated with severe COVID-19 requiring ICU-care in individuals < 50 years compared to the older population. However, after ICU admission, previous thromboembolism, chronic kidney failure, and type 2 diabetes were associated with increased 90-day mortality. The risk associations for co-morbidities were generally stronger among younger individuals compared to older and in women compared to men.

Association of anxiety or depression with risk of recurrent cardiovascular events and death after myocardial infarction: A nationwide registry study.

BACKGROUND: Depression and anxiety are risk factors for patients with myocardial infarction (MI). However, the association of a previous psychiatric diagnosis of anxiety or depression, or only such self-reported symptoms, with cardiovascular outcomes and mortality post-MI has not been previously examined in the same nationwide cohort. METHODS: We linked demographic, socioeconomic and clinical data from four nationwide Swedish registries for patients enrolled in cardiac rehabilitation (CR) after first-time MI (2006-2015, N = 45,096). After multiple imputation, we applied Cox regression to estimate the post-MI outcome risk for patients with a previous psychiatric diagnosis of anxiety/depression (Diagnosis), patients with no formal diagnosis but self-reported symptoms of anxiety/depression (Symptoms), versus patients with neither Diagnosis nor Symptoms (Reference). RESULTS: During one-year follow-up, fully adjusted models showed that patients with Diagnosis had a higher risk (hazard ratio [95%CI]) of all-cause mortality (1.86 [1.36, 2.53]), reinfarction (1.14 [1.06, 1.22]), their composite (1.15 [1.07, 1.23]), and an extended cardiovascular composite (1.19 [1.12, 1.26]), versus Reference, even though 77% reported no symptoms at the time of MI. In patients with Symptoms, estimates were also elevated yet somewhat attenuated compared to Reference. Findings were overall robust across multiple sensitivity analyses. CONCLUSIONS: Both a previous diagnosis, and present self-reported symptoms of anxiety or depression are associated with an increased risk of death and recurrent cardiovascular events in adults with first-time MI. Only screening for present symptoms is inadequate for assessing this excessive risk. Assessment of both psychiatric history and self-reported symptoms seems warranted for these patients.

Hyperoxemia after reperfusion in cardiac arrest patients: a potential dose-response association with 30-day survival.

BACKGROUND: Hyperoxemia may aggravate reperfusion brain injury after cardiac arrest. The aim of this study was to study the associations between different levels of hyperoxemia in the reperfusion period after cardiac arrest and 30-day survival. METHODS: Nationwide observational study using data from four compulsory Swedish registries. Adult in- and out-of-hospital cardiac arrest patients admitted to an ICU, requiring mechanical ventilation, between January 2010 and March 2021, were included. The partial oxygen pressure (PaO2) was collected in a standardized way at ICU admission (± one hour) according to the simplified acute physiology score 3 reflecting the time interval with oxygen treatment from return of spontaneous circulation to ICU admission. Subsequently, patients were divided into groups based on the registered PaO2 at ICU admission. Hyperoxemia was categorized into mild (13.4-20 kPa), moderate (20.1-30 kPa) severe (30.1-40 kPa) and extreme (> 40 kPa), and normoxemia as PaO2 8-13.3 kPa. Hypoxemia was defined as PaO2 < 8 kPa. Primary outcome was 30-day survival and relative risks (RR) were estimated by multivariable modified Poisson regression. RESULTS: In total, 9735 patients were included of which 4344 (44.6%) were hyperoxemic at ICU admission. Among these, 2217 were classified as mild, 1091 as moderate, 507 as severe, and 529 as extreme hyperoxemia. Normoxemia was present in 4366 (44.8%) patients and 1025 (10.5%) had hypoxemia. Compared to the normoxemia group, the adjusted RR for 30-day survival in the whole hyperoxemia group was 0.87 (95% CI 0.82-0.91). The corresponding results for the different hyperoxemia subgroups were; mild 0.91 (95% CI 0.85-0.97), moderate 0.88 (95% CI 0.82-0.95), severe 0.79 (95% CI 0.7-0.89), and extreme 0.68 (95% CI 0.58-0.79). Adjusted 30-day survival for the hypoxemia compared to normoxemia group was 0.83 (95% CI 0.74-0.92). Similar associations were seen in both out-of-hospital and in-hospital cardiac arrests. CONCLUSION: In this nationwide observational study comprising both in- and out-of-hospital cardiac arrest patients, hyperoxemia at ICU admission was associated with lower 30-day survival.

Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells.

Helicobacter pylori (H. pylori) has been associated with cardiovascular diseases. The pro-inflammatory H. pylori virulence factor cytotoxin-associated gene A (CagA) has been detected in serum exosomes of H. pylori-infected subjects and may exert systemic effects throughout the cardiovascular system. The role of H. pylori and CagA in vascular calcification was hitherto unknown. The aim of this study was to determine the vascular effects of CagA through human coronary artery smooth muscle cell (CASMC) osteogenic and pro-inflammatory effector gene expression as well as interleukin 1ß secretion and cellular calcification. CagA upregulated bone morphogenic protein 2 (BMP-2) associated with an osteogenic CASMC phenotype switch and induced increased cellular calcification. Furthermore, a pro-inflammatory response was observed. These results support that H. pylori may contribute to vascular calcification through CagA rendering CASMCs osteogenic and inducing calcification.

Association Between CKD, Obesity, Cardiometabolic Risk Factors, and Severe COVID-19 Outcomes.

Introduction: Chronic kidney disease (CKD) is a risk factor for acquiring severe COVID-19, but underlying mechanisms are unknown. We aimed to study the risk associated with CKD for severe COVID-19 outcomes in relation to body mass index (BMI) and diabetes because they are common risk factors for both CKD and severe COVID-19. Methods: This nationwide case-control study with data from mandatory national registries included 4684 patients (cases) admitted to the intensive care units (ICUs) requiring mechanical ventilation and 46,840 population-based controls matched by age, sex, and district of residency. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between severe COVID-19 and exposures with adjustment for confounders, in subgroups by BMI, and matched by type 2 diabetes. Results: The median age was 64 years, and 27.7% were female. CKD was observed in 5.4% of the cases and 1.5% of the controls, whereas 1.9% and 0.3% had end-stage CKD, respectively. CKD was associated with severe COVID-19 (OR, 2.20 [95% CI, 1.85-2.62]), continuous renal replacement therapy (CRRT) in ICU (OR, 7.36 [95% CI, 5.39-10.05]), and death any time after ICU admission (OR, 2.51 [95% CI, 1.96-3.22]). The risk associated with CKD for severe COVID-19 did not differ significantly by weight but was higher in those without diabetes (OR, 2.76 [95% CI, 2.15-3.55]) than in those with diabetes (OR, 1.88 [95% CI, 1.37-2.59]). Conclusion: CKD, especially end-stage CKD, is an important risk factor for severe COVID-19 and death after ICU admission also in patients with normal BMI and without type 2 diabetes.

Design and rationale of randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI).

AIMS: Most trials showing benefit of beta-blocker treatment after myocardial infarction (MI) included patients with large MIs and are from an era before modern biomarker-based MI diagnosis and reperfusion treatment. The aim of the randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI) trial is to determine whether long-term oral beta-blockade in patients with an acute MI and preserved left ventricular ejection fraction (EF) reduces the composite endpoint of death of any cause or recurrent MI. METHODS AND RESULTS: It is a registry-based, randomized, parallel, open-label, multicentre trial performed at 38 centres in Sweden, 1 centre in Estonia, and 6 centres in New Zealand. About 5000 patients with an acute MI who have undergone coronary angiography and with EF ≥ 50% will be randomized to long-term treatment with beta-blockade or not. The primary endpoint is the composite endpoint of death of any cause or new non-fatal MI. There are several secondary endpoints, including all-cause death, cardiovascular death, new MI, readmission because of heart failure and atrial fibrillation, symptoms, functional status, and health-related quality of life after 6-10 weeks and after 1 year of treatment. Safety endpoints are bradycardia, AV-block II-III, hypotension, syncope or need for pacemaker, asthma or chronic obstructive pulmonary disease, and stroke. CONCLUSION: The results from REDUCE-AMI will add important evidence regarding the effect of beta-blockers in patients with MI and preserved EF and may change guidelines and clinical practice.

Long-term antithrombotic therapy after coronary artery bypass grafting in patients with preoperative atrial fibrillation. A nationwide observational study from the SWEDEHEART registry.

AIMS: To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). METHODS AND RESULTS: From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. CONCLUSION: In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC.

Immigrant background and socioeconomic status are associated with severe COVID-19 requiring intensive care.

To determine whether immigrant background and socioeconomic status were associated with increased risk to develop severe Coronavirus disease 2019 (COVID-19) requiring mechanical ventilation at the intensive care unit and to study their effects on 90-day mortality. Nationwide case-control study with personal-level data from the Swedish Intensive Care register linked with socioeconomic data from Statistics Sweden and comorbidity data from the national patient register. For each case of COVID-19 treated with mechanical ventilation at the intensive care unit (outcome), 10 population controls were matched for age, sex and area of residence. Logistic and Cox regression were used to study the association between the exposure (immigrant background, income and educational level) and 90-day mortality. In total, 4 921 cases and 49 210 controls were matched. In the adjusted model, the risk of severe COVID-19 was highest in individuals born in Asia (Odds ratio [OR] = 2.44, 95% confidence interval [CI] = 2.20-2.69), South America (OR = 2.34, 95% CI = 1.82-2.98) and Africa (OR = 2.11, 95% CI = 1.76-2.50). Post-secondary education was associated with a lower risk of severe COVID-19 (OR = 0.75, CI = 0.69-0.82) as was the highest (vs. lowest) income quintile (OR = 0.87, CI = 0.77-0.97). In the fully adjusted Cox-regression analysis birth region of Africa (OR 1.38, CI = 1.03-1.86) and high income (OR 0.75, CI 0.63-0.89) were associated with 90-day mortality. Immigrant background, educational level and income were independently associated with acquiring severe COVID-19 with need for mechanical ventilation.

Association between ß-blocker dose and quality of life after myocardial infarction: a real-world Swedish register-linked study.

BACKGROUND: ß-blockers are routinely administered to patients following myocardial infarction (MI), yet their potential effect on health-related quality of life (HRQoL) is not entirely understood. We investigated the relationship between two different doses of ß-blockers with HRQoL following MI. METHODS AND RESULTS: This nationwide observational study used Swedish national registries to collate sociodemographic, clinical, medication, and HRQoL {the latter operationalized using EuroQol [European Quality of Life Five Dimensions Questionnaire (EQ-5D)]}. Estimates at 6-10 weeks and 12-14 months post-MI follow-up from pooled linear and logistic models were calculated after multiple imputation. We identified 35 612 patients with first-time MI, discharged with ß-blockers, and enrolled in cardiac rehabilitation between 2006 and 2015. Upon discharge, patients were either dispensed <50% [24 082 (67.6%)] or ≥50% [11 530 (32.4%)] of the target dosage, as defined in previous trials. After adjusting for pre-defined covariates, neither the EQ-5D Index nor the Emotional Distress items were statistically different between groups. The EQ-VAS score was significantly lower in patients treated with ≥50% target ß-blocker dose than those treated with <50% of the target dose [-0.87 [-1.23, -0.46], P < .001]. Results were similar at the 12-month follow-up and across sub-groups separated by sex and age. CONCLUSION: No difference in HRQoL was found among patients taking <50% vs. ≥50% of the target ß-blocker dose, except for the EQ-VAS in which higher scores were reported in those taking a lower dose. The clinical meaningfulness of this statistical significance is likely low.

Incidence, associated outcomes, and predictors of upper gastrointestinal bleeding following acute myocardial infarction: a SWEDEHEART-based nationwide cohort study.

AIMS: Of all spontaneous bleeding complications in patients with acute myocardial infarction (MI), upper gastrointestinal bleeding (UGIB) is common and of specific interest since it could be prevented by several prophylactic measures. We aimed to determine the incidence, associated outcomes, and predictors of UGIB following acute MI. METHODS AND RESULTS: All patients with acute MI enrolled in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry from January 2007 to June 2016 and discharged alive on any antithrombotic therapy (n = 149 477) were followed regarding UGIB for 1 year. Associated outcomes were determined by Cox proportional hazards regression with UGIB as a time-dependent covariate, adjusting for baseline characteristics, invasive treatment, and medical treatment at discharge. Predictors of UGIB were determined by logistic regression and machine learning models.At 1 year, UGIB had occurred in 2230 patients (cumulative incidence 1.5%) and was significantly associated with an increased risk of all-cause death [hazard ratio (HR) 2.86, 95% confidence interval (CI) 2.58-3.16] and stroke (HR 1.80, 95% CI 1.32-2.45) but not with recurrent MI (HR 1.17, 95% CI 0.97-1.42). The most important predictors of UGIB were haemoglobin, age, systolic blood pressure, blood glucose, smoking status, previous upper gastrointestinal bleeding, and antithrombotic and gastroprotective treatment. CONCLUSION: After acute MI, readmission because of UGIB is common and significantly associated with poor prognosis. By using machine learning in addition to traditional logistic regression, new predictors of UGIB, such as blood glucose and smoking status, were identified.

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.