Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial.

BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. OBJECTIVE: The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). METHODS AND ANALYSIS: Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. CONCLUSIONS: The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

Sex and age differences in the incidence of acute myocardial infarction during the COVID-19 pandemic in a Swedish health-care region without lockdown: a retrospective cohort study.

BACKGROUND: The incidence of acute myocardial infarction has decreased during the COVID-19 pandemic, but sex and age differences in this change in incidence have not been tested. Thus, we aimed to compare the incidence of acute myocardial infarction in a health-care region in Sweden during the COVID-19 pandemic with previous years and to evaluate sex and age differences. METHODS: We did a retrospective, observational cohort study using data from a national registry of patients admitted to coronary care units in Sweden. All patients admitted to one of three hospitals in Region Jönköping County with a diagnosis of acute myocardial infarction during the COVID-19 pandemic (March 1 to July 31, 2020) or reference period (March 1 to July 31, 2017-19) were included. The incidence of acute myocardial infarction (ST-elevation and non-ST-elevation) was calculated for both study periods. Participants were grouped according to sex and age (<70 years vs ≥70 years). The incidence and the incidence rate ratio (IRR) between the two study periods was calculated for each group and compared between groups using the Breslow-Day test. FINDINGS: The study included 1088 participants, 846 who were admitted for acute myocardial infarction during the reference period and 242 who were admitted during the COVID-19 pandemic period. The IRR of acute myocardial infarction for the COVID-19 period compared with the reference period was 0·85 (95% CI 0·73-0·98). The IRR for acute myocardial infarction was significantly lower among women aged 70 years or older (0·56 [0·40-0·78]) than among men aged 70 years or older (0·97 [0·77-1·23]; p=0·0074). INTERPRETATION: The incidence of acute myocardial infarction decreased predominantly among women aged 70 years or older during the COVID-19 pandemic. This highlights potential sex differences in health effects of the COVID-19 pandemic, which should be further elucidated. FUNDING: None.