Search

Aim: To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants. Materials and methods: In SOUL, the effects of oral semaglutide, the first oral glucagon‐like peptide‐1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double‐blind, parallel‐group, placebo‐controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event‐driven trial will continue until 1225 first adjudication‐confirmed MACEs have occurred. Enrolment has been completed. Results: Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m2, glycated haemoglobin 63.5 mmol/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium‐glucose cotransporter‐2 inhibitors (26.7%) and dipeptidyl peptidase‐4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants. Conclusion: SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD. [ABSTRACT FROM AUTHOR]

The randomized, double-blind, cardiovascular outcomes trials LEADER (NCT01179048) and SUSTAIN 6 (NCT01720446) showed cardiovascular risk reduction in patients with type 2 diabetes treated with liraglutide and semaglutide, respectively, compared with placebo. This post hoc analysis examined the impact of microvascular disease at baseline on cardiovascular outcomes in these trials, and the efficacy of liraglutide (1.8 mg) and once-weekly semaglutide (0.5-1.0 mg) in patients with and without microvascular disease. In total, 9340 patients from LEADER and 3297 patients from SUSTAIN 6 were included in this analysis; of these, 5761 and 2356 had a history of microvascular disease at baseline and 3835 and 1640 had a history of both microvascular and macrovascular disease, respectively. Patients with microvascular disease were shown to have an increased risk of major adverse cardiovascular events compared with patients without microvascular disease (hazard ratio [95% confidence interval] in LEADER: 1.15 [1.03; 1.29], P = .0136; SUSTAIN 6: 1.56 [1.14; 2.17], P = .0064). Liraglutide and semaglutide consistently reduced cardiovascular risk in patients with and without microvascular disease. [ABSTRACT FROM AUTHOR]

The electrocardiogram (ECG) can be used for determining the presence, location and extent of jeopardized myocardium during acute coronary occlusion. Accordingly, the ECG has become essential in the treatment of patients with acute coronary syndrome (ACS). This thesis aims at optimizing the decision support, provided by the ECG, for choosing the best treatment strategy in the individual patient with ST-segment elevation acute myocardial infarction (STEMI). ECG recorded in the prehospital setting has become the standard of care in many communities, but to achieve the full advantage of this early approach it is important that the ECG is recorded from accurately placed electrodes to produce an ECG that resembles the standard 12-lead ECG. Accurate electrode placement is difficult especially in the acute setting, and we investigated an alternative lead system with fewer electrodes in easily identified positions. We showed that the system produced waveforms similar to the standard 12-lead ECG. However, occasional diagnostic errors were seen, compromising general acceptance of the system. Once the ECG has been recorded a decision regarding triage must be made on the basis of a correct ECG diagnosis. We found that trained paramedics can diagnose STEMI correctly in patients without ECG confounding factors, while the presence of ECG confounding factors decreased their ability substantially. Consequently, since many patients do present with ECG confounding factors, transmission to an on-call cardiologist for an early correct diagnosis is needed. We showed that time to pPCI was reduced by more than 1 hour by transmitting prehospital ECG to a cardiologist's handheld device for diagnosis, triage, and activation of the catheterization laboratory when needed. The optimal treatment strategy is dependent on the duration of ischemia however patient information is often inaccurate. Accordingly, it would be advantageous if the first available ECG can help identify patients who will benefit greatly from acute reperfusion therapy versus patients with modest effect. We showed that by recognizing the acuteness of the infarction process the initial ECG can identify a group of patients with no potential for myocardial salvage despite short symptom duration. Urgent transport for pPCI may then not be necessary in this group of patients, and conservative treatment may be an option. Conversely, we also identified a group of patients with a large potential for myocardial salvage with acute reperfusion therapy despite long symptom duration. We also investigated whether ST-segment elevation on the initial ECG could provide prognostic information and thereby decision support for appropriate triage. All patients regardless of ST-segment elevation seemed to have most clinical benefit from pPCI. However, only patients with the greatest amount of ST-segment elevation had a reduced mortality rate with pPCI suggesting that patients with minor infarcts may achieve similar benefit from fibrinolysis followed by transfer to angiography and PCI. Once the triage decision is settled, STEMI patients must undergo ECG monitoring and receive antithrombotic therapy for optimal prehospital care. STEMI patients transported over even short distances are in danger of developing arrhythmic complications, but appropriate treatment is available when primary ambulances are supported by physician-manned ambulances in urban areas. Prehospital antithrombotic therapy must be effective in preparing the patient for pPCI without causing bleeding. Heparin is currently the standard therapy, but we showed that the direct thrombin inhibitor bivalirudin may be an attractive alternative by causing less bleeding events, and a higher frequency of preprocedure thrombolysis in myocardial infarction (TIMI) 3 flow. After reperfusion therapy a decision regarding the need for further treatment is desirable. By determining ST-segment resolution in the post-reperfusion ECG we showed that the degree of ST-segment resolution at 90 minutes and 4 hours is important for risk stratification after fibrinolysis, but not after pPCI. Interestingly, we found that patients with compete ST-segment resolution treated with fibrinolysis had the highest risk of reinfarction. Consequently, transfer to a PCI-facility should be considered in all patients treated with fibrinolysis as the initial reperfusion therapy. Based on the findings in the present thesis we conclude that the ECG is an important tool for decision support in every step from symptom onset to post-reperfusion therapy in STEMI patients.

Introduction: Time to reperfusion is critical to the outcome of patients with ST-elevation myocardial infarction (MI). Other studies have indicated that wireless transmission of prehospital ECGs can reduce the time to reperfusion. This study evaluated the effect on time to treatment using prehospitalisation ECG transmission to a cardiologist's handheld device in patients with acute chest pain, as well as the potential effect of direct transfer of patients to the closest appropriate cardiological facility., Materials and Methods: During a one-year study period, prehospitalisation ECGs were transmitted for all patients with symptoms indicative of acute coronary syndrome. The ECGs were received on a handheld device by an attending cardiologist, and the patient was referred to PCI treatment if ST-elevation was found., Results: 152 transmissions were registered; 27 of these patients underwent primary PCI treatment. 135 (89%) of the attempted transmissions were successful. Compared to historic controls, there was an increased on-scene time usage of 7 minutes, including transfer. The median time spent from arrival at the hospital to the start of invasive treatment was low, 22 minutes. Compared to historic controls, we found a total reduction in time spent of 72 minutes (p< 0.01)., Discussion: The results indicate that it is possible to minimize the time delay to primary PCI treatment by direct transfer through consultation and use of wireless transmission of prehospitalisation-acquired ECGs to a handheld device carried by an attending cardiologist.