Robin Hofmann

Background: The prognosis of myocardial infarction (MI) has improved in the past decades with the adoption of invasive management and potent antithrombotic therapy, but at a cost of an increase in bleeding complications. Helicobacter pylori (H. pylori) is a common infection that increases the risk of peptic ulcers and upper gastrointestinal bleeding (UGIB). Infection with H. pylori could be of particular importance for patients with coronary artery disease, partly as a risk factor for enhanced development of atherosclerosis and plaque rupture, but also for UGIB in combination with antithrombotic treatment post MI. Aims: The specific research questions are: 1. What is the prevalence of H. pylori infection in a current population of patients with MI? Is it feasible to perform H. pylori screening as part of routine clinical care? 2. How common is UGIB after MI in relation to other bleeding events and ischemic events? How has the incidence changed over time? 3. What is the prognostic impact of an UGIB after MI? How does it compare to the prognosis of UGIB without a prior MI? 4. Does systematic screening for H. pylori with subsequent eradication therapy in patients post MI significantly reduce the risk of UGIB and adverse cardiovascular outcomes, and does the treatment effect have an interaction with baseline clinical bleeding risk? We hypothesize that H. pylori is common in a current population of patients with MI and that screening in this population is feasible. We also believe that UGIB is one of the most common bleeding events after MI and associated with a poor prognosis. Applied in a randomized clinical trial, we believe that screening and treatment of H. pylori in patients with MI reduces the risk of UGIB. Furthermore, we believe that bleeding risk at baseline influences the effect of H. pylori screening and treatment on the risk of subsequent bleeding. Time plan: Two out of four planned studies are published or in manuscript form. The epidemiological study concerning the prognostic impact of UGIB is in the planning phase, with an aim of publishing late spring/early summer 2026. The randomized clinical trial is completed, with results to be announced August 2025. Subgroup analysis will begin thereafter, with an aim to publish results during spring 2026. Significance: Bleeding events after MI are associated with worse outcomes. Further evaluation of UGIB and H. pylori screening may provide insight into measures that can prevent these events.

BACKGROUND Prognosis for patients with atherosclerotic cardiovascular disease (CVD) has improved remarkedly due to the use of antithrombotic agents. However, this benefit is counterbalanced by an increase in hemorrhagic complications, typically upper gastrointestinal bleeding (UGIB). Helicobacter pylori (Hp) may play an important role in CVD for two reasons: First, Hp has been associated with atherosclerosis and development of CVD, but the underlying mechanism is unknown. Second, concomitant Hp infection and antithrombotic therapy substantially aggravate the risk for UGIB. Hp screening and treatment in an myocardial infarction population has not been evaluated in any larger randomized trial. Thus, it remains unknown if systematic screening and subsequent eradication therapy significantly reduces the risk of bleeding and improves prognosis. AIMS: We hypothesize that there may be a causal link between Hp infection and the development of atherosclerotic CVD. The aim of this project is to elucidate this potential link, and subsequently, to determine whether systematic screening and treatment of Hp significantly reduces the risk of UGIB and improves cardiovascular outcomes after MI. The specific research questions are: 1. Does active Hp infection contribute to the development of atherosclerosis and incident CVD events potentially in synergy with commensal gut microbial species in SCAPIS? 2. Does routine screening for Hp and subsequent eradication therapy significantly reduce the risk of UGIB and improve cardiovascular outcomes in patients with acute MI? 3. Can we identify subgroups of patients at highest risk for adverse events when adding Hp phenotype and biomarkers of inflammation, atherosclerosis and lipid metabolim to our risk assessment? Work plan: First EPM and SCAPIS applications are approved. Hp analysis in currently in planning including logistics. HELP-SWEDEHEART study completed enrollment (N=19200) and is currently in follow-up phase. Application for data linkage to national databases submitted. Study closure 17/1-2025. Primary data expected during spring 2025. Analysis work for observational and biomarker studies on-going or planned during fall 2024. Significance: Identification and treatment of risk factors for CVD is of crucial importance for primary and secondary prevention. The global prevalence of Hp is around 50 %, and a causal contribution to CVD would have a large impact on global health.

Background:Left ventricular (LV) thrombus is a serious complication of AMI associated with increased risk of stroke or systemic embolism (SSE). Warfarin has long been the standard treatment, but the better safety profile of the DOACs makes them an attractive alternative to warfarin. In the absense of adequately powered randomized studies, no recommendation for the treatment of LV thrombus is provided.Primary Objective: To evaluate the efficacy of apixaban versus warfarin with respect to thrombus resolution Secondary Objectives: To evaluate the safety and efficacy of apixaban versus warfarin with respect to bleeding outcomes, MACE, NACE, stroke and SSE, and the rate of LV thrombus recurrence at one year. Workplan:Two hundred twelve patients with LV thrombus detected on transthoracic echocardiography (TTE) within 1 to 28 days after an AMI will be randomized 1:1 to apixaban or warfarin. The primary outcome will be evaluated at 3 months. Secondary outcomes as outlined above, will be evaluated at 3 and 12 months.  Significance:It is important to evaluate the use of DOAC (apixaban) for LV thrombus since there are other indications where DOACs were believed to be as effective as warfarin, but randomized trials failed, such as for mechanical heart valves and rheumatic heart disease. If apixaban prove at least non-inferior to warfarin, apixaban would be the preferred drug due to its better safety profile and convenience. This study will inform LV thrombus treatment recommendations.