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.

Oxygen Therapy in Suspected Acute Myocardial Infarction.

BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110 .).

Discontinuation of smokeless tobacco and mortality risk after myocardial infarction.

BACKGROUND: Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. METHODS AND RESULTS: All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). CONCLUSIONS: In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction.

BACKGROUND: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%-49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high. METHODS AND RESULTS: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within-person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within-person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later. CONCLUSIONS: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.

Patients' experiences of clinical trial participation involving a product remotely assessing study drug adherence.

Background: The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with acute medical conditions. The registry-based randomized DAPA-MI clinical trial recruited patients during hospitalization for myocardial infarction and provided study drugs in bottles with smart caps that used wireless technology to transmit monitoring data. This interview study aimed to investigate patients' experience of participation in a clinical trial and their attitude to the new bottle cap technology. Methods: A subset of patients participating in the DAPA-MI trial were recruited from four hospitals in Sweden. Semi-structured interviews were conducted and analysed using manifest content analysis. Results: Video interviews were performed including 21 patients (four women and 17 men). The median age was 59 years (range 44-80). Four categories of patients' experiences were identified. A willingness to contribute consisted of patients' positive attitudes to participation and to be a part of development and research. The perception of information emphasized the value of the oral information as well as the importance of time for reflection. Be in a vulnerable condition highlighted the impaired ability to perceive and remember in the acute medical condition. Adaptation to a new technology described the overall positive experiences of the smart bottle cap to evaluate adherence. Conclusions: Patients' experiences of trial participation were in general positive but some challenges in the acute setting of a myocardial infarction were revealed. The smart bottle cap was well accepted, despite some handling difficulties.

Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure.

BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. METHODS: In this international registry-based, randomized, double-blind trial, patients without prior diabetes or chronic heart failure, presenting with acute MI and impaired left ventricular systolic function, were randomly assigned 10 mg of dapagliflozin or placebo, given once daily. The primary outcome was the hierarchical composite of death, hospitalization for heart failure, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease of 5% or greater at the last visit using the win ratio analysis method. The key secondary outcome was the same hierarchical composite excluding the body weight component. RESULTS: We enrolled 4017 patients of whom 2019 were assigned to dapagliflozin and 1998 to placebo. The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval [CI], 1.20 to 1.50; P<0.001). The win ratio outcome, which was adopted in a change of analysis during trial performance because of low event accrual, was mainly driven by the added cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure occurred in 50/2019 (2.5%) patients assigned to dapagliflozin and 52/1998 (2.6%) patients assigned to placebo (hazard ratio, 0.95; 95% CI, 0.64 to 1.40). The rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified. CONCLUSIONS: In patients with acute MI as noted above, after approximately 1 year of treatment with dapagliflozin there were significant benefits with regard to improvement in cardiometabolic outcomes but no impact on the composite of cardiovascular death or hospitalization for heart failure compared with placebo. (Funded by AstraZeneca; ClinicalTrial.gov number, NCT04564742.)

Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts.

BACKGROUND: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure. DESIGN: Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers. METHODS: Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure. RESULTS: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use. CONCLUSION: Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.