Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Effect of renin angiotensin system inhibitors on long-term major cardiovascular outcomes in patients with high atherosclerotic cardiovascular risk

Abstract The advantage of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with preserved LV systolic function is uncertain. We aimed to investigate the effects of ACEI/ARB in high atherosclerotic risk patients without overt heart failure (HF) on long-term major cardiovascular outcomes (MACEs). The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. The patients with ejection fraction < 50% were excluded. Among 8513 recruited patients, there were 4246 patients included into final analysis after propensity score matching. At 5-years follow-up, Cox regression analysis showed that ACEI/ARB was significantly associated with reduced risk of all-cause mortality or non-fatal myocardial infarction, non-fatal stroke and HF hospitalization (HR 0.82, 95% CI 0.70–0.96, P = 0.011). The benefit was driven by the reduced all-cause mortality and HF. Subgroup analysis demonstrated that ACEI/ARB decreased risk of long-term MACEs in patients with diabetes (HR 0.77, 95% CI 0.63–0.94, P = 0.011) and patients not taking statin (HR 0.57, 95% CI 0.40–0.82, P = 0.002). We demonstrated that the use of ACEI/ARB was associated with reduced risk of long-term MACEs in a large cohort of high atherosclerotic risk patients. Reduction of all-cause mortality and HF were likely the main contributors to the benefit of ACEI/ARB

Clinical Characteristics and In-Hospital Mortality in Patients with STEMI during the COVID-19 Outbreak in Thailand

Background: Nowadays, current evidence on the effects of the COVID-19 outbreak on ST-elevation myocardial infarction (STEMI) patients is discrepant. The aim of this study was to compare and identify any changes in STEMI patients between the pre-COVID-19 period and during the COVID-19 outbreak. Methods: We conducted a retrospective cohort study to evaluate consecutive STEMI patients admitted from 1 September 2018 to 30 September 2021. We designated 14 March 2020 as the commencement of the COVID-19 outbreak in Thailand. Results: A total of 513 consecutive STEMI patients were included in this study: 330 (64%) admitted during the pre-COVID-19 outbreak period and 183 (36%) admitted during the COVID-19 outbreak. There was a significant 45% decline in the number of STEMI cases admitted during the COVID-19 outbreak period. During the outbreak, STEMI patients had significantly increased intra-aortic balloon pump (IABP) insertion (23% vs. 15%, p-value = 0.004), higher high-sensitivity troponin T level (11,150 vs. 5213, p-value &lt; 0.001), and lower pre- and post-PCI TIMI flow. The time-to-diagnosis (59 vs. 7 min, p-value &lt; 0.001), pain-to-first medical contact (FMC) time (250 vs. 214 min, p-value = 0.020), FMC-to-wire-crossing time (39 vs. 23 min, p-value &lt; 0.001), and pain-to-wire-crossing time (292 vs. 242 min, p-value = 0.005) were increased in STEMI patients during the outbreak compared with pre-outbreak. There was no statistical difference in in-hospital mortality between both periods (p-value = 0.639). Conclusions: During the COVID-19 outbreak, there was a significant decline in the total number of admitted STEMI cases. Unfortunately, the time-to-diagnosis, pain-to-FMC time, FMC-to-wire-crossing time, and pain-to-wire-crossing time were significantly delayed during the COVID-19 outbreak. However, in-hospital mortality showed no significant differences between these two time periods. Highlights: 45% decline in the number of STEMI cases admitted and a significant delay in the treatment timeline during the COVID-19 outbreak. In-hospital mortality showed no significant difference between these two periods. Our study will motivate healthcare professionals to optimize treatments, screenings, and infectious control protocols to reduce the time from the onset of chest pain to wire crossing in STEMI patients during the outbreak

Additional file 2: of Very late presentation of anomalous origin of the left coronary artery from the pulmonary artery: case report

Coronary angiography. (AVI 1512 kb

Additional file 1: of Very late presentation of anomalous origin of the left coronary artery from the pulmonary artery: case report

Transthoracic echocardiograhy. (MP4 3235 kb

Modes of death and clinical outcomes in adult patients with hypertrophic cardiomyopathy in Thailand

Abstract Background There are limited data about modes of death and major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM) in South East Asian population. The aim of the study was to examine modes of death and clinical outcomes in Thai patients with HCM. Methods Between January 1, 2009 and December 31, 2013, 166 consecutive patients with HCM diagnosed in our institution were evaluated. Five patients were excluded because of non-Thai ethnic groups (n = 3) and diagnosis of myocardial infarction at initial presentation documented by coronary angiography (n = 2). The final study population consisted of 161 patients with HCM. HCM-related deaths included: (1) sudden cardiac death (SCD) – death due to sudden cardiac arrest or unexpected sudden death; (2) heart failure – death due to refractory heart failure; or (3) stroke - death due to embolic stroke associated with atrial fibrillation. MACEs included: (1) SCD, sudden unexpected aborted cardiac arrest, fatal, or nonfatal ventricular arrhythmia (ventricular fibrillation or sustained ventricular tachycardia); (2) heart failure (fatal or non-fatal), or heart transplantation; or (3) stroke - fatal or non-fatal embolic stroke associated with atrial fibrillation. Results One hundred and sixty-one Thai patients with HCM (age 66 ± 16 years, 58% female) were enrolled. Forty-two patients (26%) died over a median follow-up period of 6.8 years including 25 patients (16%) with HCM-related deaths (2%/year). The HCM-related deaths included: heart failure (52% of HCM-related deaths; n = 13), SCD (44% of HCM-related deaths; n = 11), and stroke (4% of HCM-related deaths, n = 1). The SCDs occurred in 6.8% of patients (1%/year). Eighty-four major MACEs occurred in 65 patients (41, 5%/year). The MACEs included: 40 heart failures in which 2 patients underwent heart transplants; 22 SCDs and nonfatal ventricular arrhythmias; and 22 fatal or nonfatal strokes. Conclusions The most common mode of death in adult patients with HCM in Thailand was heart failure followed by SCD. About one-third of the patients experiencing heart failure died during the 6.8 years of follow-up. SCDs occurred in 7% of patients (1%/year), predominantly in the fourth decade or later