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.).

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.

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.

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.

Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex-related outcomes from DETO2X-AMI.

BACKGROUND: The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI). METHODS: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex. RESULTS: Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found (P= .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment. CONCLUSION: Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age.

Association between ß-blocker dose and cardiovascular outcomes after myocardial infarction: insights from the SWEDEHEART registry.

AIMS: Dose-dependent effects of ß-blockers on survival and cardiovascular outcomes after myocardial infarction (MI) are not well understood. We investigated the long-term risk of cardiovascular events in patients with different doses of ß-blockers after MI. METHODS AND RESULTS: This was a nationwide observational study linking morbidity, mortality, socioeconomic, and medication data from Swedish national registries. Between 2006 and 2015, 97 575 unique patients with first-time MI were included. In total, 33 126 (33.9%) patients were discharged with ≥50% of the target ß-blocker dose and 64 449 (66.1%) patients with <50% of the target ß-blocker dose used in previous randomized trials. The primary composite endpoint was re-infarction or all-cause death within 1 year from discharge. Multivariable adjusted 1-year follow-up estimates using mixed effects Cox regression [HR (95% CI)] showed that patients treated with ≥50% of the target dose had a similar risk of the composite endpoint [1.03 (0.99-1.08)] and a somewhat higher risk when stroke, atrial fibrillation, or heart failure hospitalization were added to the composite endpoint [1.08 (1.04-1.12)], compared with patients on <50% of the target ß-blocker dose. Results remained similar up to 5 years of follow-up and consistent across relevant patient subgroups, including patients who developed heart failure during the index hospitalization. CONCLUSIONS: In contrast to doses of ß-blockers used in previous trials, ≥50% of the target ß-blocker dose was not associated with superior cardiovascular outcomes up to 5 years as compared with <50% of the target dose. Contemporary randomized clinical trials are needed to clarify the optimal dose of ß-blockers after MI.

Helicobacter pylori screening in clinical routine during hospitalization for acute myocardial infarction.

BACKGROUND: Potent antithrombotic therapy has significantly improved prognosis for patients with acute myocardial infarction (AMI), however, at a price of increased bleeding risk. Chronic gastric infection with Helicobacter pylori (Hp) commonly causes upper gastrointestinal bleeding and is proposed as a risk factor for subsequent bleeding post AMI. The prevalence of active Hp in a current AMI population and the feasibility of Hp screening as part of routine clinical care are unclear. OBJECTIVE: To determine the prevalence of active Hp infection in a contemporary AMI cohort and to establish the feasibility of Hp diagnosis as part of routine clinical MI care. DESIGN: Multicenter, prospective cohort study. SETTING: Two university hospitals in Stockholm, Sweden. PARTICIPANTS: Patients admitted for AMI between November 6, 2019 and April 4, 2020. After written informed consent, Hp diagnostics was performed with a bedside urea breath test (Diabact, Mayoly Spindler) incorporated into routine care during the hospitalization period. EXPOSURE: Positive test for Hp infection. MAIN OUTCOMES AND MEASURES: The primary outcome was the prevalence of Hp infection. Secondary aims included predictive factors in patient characteristics and outcomes which were obtained from linkage with national registries. Predefined subgroup analyses included stratification for proton pump inhibitor use and infarct type. RESULTS: Three hundred and ten consecutive AMI patients (median age 67; 23% female; 41% ST-elevation MI [STEMI]) were enrolled. Overall, the Hp prevalence was 20% (95%CI, 15.5-24.7). Hp positive status was significantly more common in smokers compared with nonsmokers (36% vs 21%, respectively; P < .05) and in patients presenting with STEMI compared with Non-STEMI (26% vs 15%, respectively; P = .02). The latter observation remained significant after multivariable adjustment. After exclusion of 97 subjects with current proton pump inhibitor use, the Hp prevalence was 24% (95%CI, 18.9-31.0). CONCLUSIONS: Active Hp infection is common in a contemporary AMI population and may represent a modifiable risk factor for upper gastrointestinal bleeding, which has been hitherto disregarded. Hp screening as part of clinical routine during AMI hospitalization was feasible. A future randomized trial is needed to determine whether routine Hp screening and subsequent eradication therapy reduces bleeding complications and improves prognosis. KEY POINTS: Question: Is Helicobacter pylori (Hp) infection sufficiently common in patients with acute myocardial infarction (AMI) to consider systematic screening, and can Hp diagnostics be performed during AMI hospitalization? FINDINGS: In this multicenter prospective cohort study of 310 consecutive AMI patients, Hp infection was established in at least 20% of patients. Infected patients were significantly more likely to be active smokers and to present with ST-elevation MI. Meaning: Hp screening as part of clinical routine during AMI hospitalization was feasible. Given the high Hp prevalence detected, Hp diagnostics and eradication to reduce bleeding complications and to improve prognosis after AMI should be further investigated.