Effect of Cangrelor on Infarct Size in ST-Segment Elevation Myocardial Infarction Treated By Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarct (MI) size in the pre-clinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction (MVO) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods: This was a Phase 2, multi-center, randomized, double-blind, placebo controlled clinical trial conducted between November 2017 to November 2021 in six cardiac centers in Singapore (NCT03102723). Patients were randomized to receive either cangrelor or placeboinitiated prior to the PPCI procedure on top of oral ticagrelor. The key exclusion criteria included: presenting <6 hours of symptom onset, prior MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance (CMR). The primary efficacy endpoint was acute MI size by CMR within the first week expressed as percentage of the left ventricle mass ( %LVmass). MVO was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety endpoint was Bleeding Academic Research Consortium (BARC)-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test [reported as median (1st quartile- 3rd quartile)] and categorical variables were compared by Fisher's exact test. A 2-sided P<0.05 was considered statistically significant. Results: Of 209 recruited patients, 164 patients (78% ) completed the acute CMR scan. There were no significant differences in acute MI size [placebo: 14.9 (7.3 - 22.6) %LVmass versus cangrelor: 16.3 (9.9 - 24.4)%LVmass, P=0.40] or the incidence [placebo: 48% versus cangrelor: 47%, P=0.99] and extent of MVO [placebo:1.63 (0.60 - 4.65)%LVmass versus cangrelor: 1.18 (0.53 - 3.37)%LVmass, P=0.46] between placebo and cangrelor despite a two-fold decrease in platelet reactivity with cangrelor. There were no BARC-defined major bleeding events in either group in the first 48 hours. Conclusions: Cangrelor administered at time of PPCI did not reduce acute MI size or prevent MVO in STEMI patients given oral ticagrelor despite a significant reduction of platelet reactivity during the PCI procedure.

Multifactorial risk factors for hospital readmissions among patients with symptoms of advanced heart failure.

AIMS: Economic burden of heart failure is attributed to hospital readmissions. Previous studies assessing risk factors for readmissions have focused on single group of risk factors, were limited to 30-day readmissions, or did not account for competing risk of mortality. This study investigates the biological, socio-economic, and behavioural risk factors predicting hospital readmissions while accounting for the competing risk of mortality. METHODS AND RESULTS: In this prospective cohort study, we recruited 250 patients hospitalized with symptoms of advanced heart failure [New York Heart Association (NYHA) Class III and IV] between July 2017 and April 2019. We analysed their baseline survey data and their hospitalization records over the next 4.5 years (July 2017 to January 2022). We used a joint-frailty model to determine the multifactorial risk factors for all-cause and unplanned hospital readmissions and mortality. At the time of recruitment, patients' mean (SD) age was 66 (12) years, majority being male (72%) and NYHA class IV (68%) with reduced ejection fraction (72%). 87% of the patients had poor self-care behaviours, 51% had diabetes and 56% had weak grip strength. Within 2 years of a hospital admission, 74% of the patients had at least one readmission. Among all readmissions during follow-up, 68% were unplanned. Results from the multivariable regression analysis shows that the independent risk factors for hospital readmissions were biologic-weak grip strength [hazard ratio (95% CI): 1.59 (1.06, 2.13)], poor functional status [1.79 (0.98, 2.61)], diabetes [1.42 (0.97, 1.86)]; behavioural-poor self-care [1.66 (0.84, 2.49)], and socio-economic-preference for maximal life extension at high cost for those with high education [1.98 (1.17, 2.80)]. Risk factors for unplanned hospital readmissions were similar. A higher hospital readmission rate increased the risk of mortality [1.86 (1.23, 2.50)]. Other risk factors for mortality were biologic-weak grip strength [3.65 (0.57, 6.73)], diabetes [2.52 (0.62, 4.42)], socio-economic-lower education [2.45 (0.37, 4.53)], and being married [2.53 (0.37, 4.69)]. Having a private health insurance [0.40 (0.08, 0.73)] lowered the risk for mortality. CONCLUSIONS: Risk factors for hospital readmissions and mortality are multifactorial. Many of these factors, such as weak grip strength, diabetes, poor self-care behaviours, are potentially modifiable and should be routinely assessed and managed in cardiac clinics and hospital admissions.

Percutaneous Edge-to-Edge Mitral Valve Repair for Functional Mitral Regurgitation.

The presence and severity of functional mitral regurgitation (FMR) is associated with worse outcomes in patients with heart failure and reduced ejection fraction. Prior to the availability of percutaneous mitral valve repair, management for FMR has been limited to medical therapy, cardiac resynchronization therapy for a specific subset of patients and surgery which has yet to demonstrate mortality benefits. Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged in the past decade as an invaluable member of the armamentarium against FMR with the 2 landmark randomized controlled trials providing deep insights on patient selection. In addition, TEER has spurred the rapid advancement in our understanding of FMR. This article seeks to provide an overview as well as our current understanding on the role of TEER in FMR.

The clinical value and cost-effectiveness of treatments for patients with coronary artery disease.

BACKGROUND: The clinical value and cost-effectiveness of invasive treatments for patients with coronary artery disease is unclear. Invasive treatments such as coronary artery bypass grafting and percutaneous coronary intervention are frequently used as a starting treatment, yet they are much more costly than optimal medical therapy. While patients may transition into other treatments over time, the choices of starting treatments are likely important determinants of costs and health outcomes. The aim is to predict by how much costs and health outcomes will change from a decision to use different starting treatments for patients with coronary artery disease in an Asian setting. METHODS: A cost-effectiveness study using a Markov model informed by data from Singapore General Hospital was done. All patients with initial presentations of stable coronary disease and no acute coronary syndromes who received medical treatments and interventional therapies were included. We compare existing practice, where the starting treatment can be medical therapy or stent percutaneous coronary interventions or coronary artery bypass grafting, with alternate starting treatment strategies. RESULTS: When compared to 'existing practice' a policy of starting 14% of patients with coronary artery bypass grafting and 86% with optimal medical therapy showed savings of $1,743 per patient and 0.23 additional quality adjusted life years. A change to policy nationwide would save $10 million and generate 1,380 quality adjusted life years. CONCLUSIONS: Increasing coronary artery bypass grafting and use of medical therapy in the setting of coronary artery disease is likely to saves costs and improve health outcomes. A definitive study to address the question we investigate would be very difficult to undertake and so using existing data to model the expected outcomes is a useful tool. There are likely to be large and complex barriers to the implementation of any policy change based on the findings of this study.

Study protocol for a cohort study of patients with advanced heart failure in Singapore.

INTRODUCTIO: Understanding the symptom and health expenditure burden among patients with advanced congestive heart failure (CHF) and their family caregivers is essential to reform policy and practice needed to provide quality care to these patients at affordable prices. The proposed cohort study titled Singapore Cohort of Patients with Advanced Heart Failure aims to describe trajectories of quality of life among patients and their primary informal caregivers, quantify healthcare utilisation and expenditures, assess changes in patient and caregiver awareness of and preferences for knowing diagnostic and prognostic information, awareness and utilisation of palliative care services, preferences for treatments and decision making, perceived quality of care, self-care, caregiver psychological distress and caregiver burden. METHODS: This cohort study will recruit 250 patients with New York Heart Association Classification class III and IV CHF from inpatient wards at two public tertiary healthcare institutions in Singapore. Patients and their primary informal caregiver are being surveyed every 4 months until patients' death; caregivers are followed until 8 weeks postpatient death. Medical and billing records of patients are obtained and merged with patients' survey data. ETHICS AND DISSEMINATION: The study has been approved by an ethics board. Results from the study will be disseminated through publications and presentations targeting researchers, policy makers and clinicians interested in understanding and improving care for patients with advanced CHF. TRIAL REGISTRATION NUMBER: NCT03089034.

The use of drug-eluting stents in ST-elevation myocardial infarction.

Drug-eluting stents (DES) dramatically lower rates of restenosis in patients undergoing percutaneous coronary interventions. However, their use has extended beyond the initial approved indications into off-label scenarios such as ST-elevation myocardial infarction (STEMI). Multiple retrospective case series and 10 prospective randomised controlled trials have been published on the use of DES in STEMI patients, and these generally show reduced rates of target vessel revascularisation with a neutral effect on mortality. Three meta-analyses show similar findings with the composite endpoint of death, recurrent myocardial infarction, or re-intervention significantly lower in the DES group, although this was largely driven by a decrease in target vessel revascularisation. These studies also demonstrate that DES use in the setting of STEMI is not associated with increased risk of stent thrombosis compared to bare metal stents. In summary, current data support the efficacy of DES in reducing restenosis and re-intervention in patients who present with STEMI. From a safety standpoint, the use of DES in STEMI does not increase the risk of stent thrombosis, and there is no difference in overall mortality. The use of DES in STEMI patients should be individualised on a case-by-case basis given the importance of compliance with dual antiplatelet therapy.