Comparison of P2Y12 Inhibitors in Acute Coronary Syndromes in the Australian Population.

BACKGROUND: Clopidogrel in combination with aspirin after acute coronary syndromes (ACS) reduces recurrent ischaemic events compared to aspirin alone. Further reductions in events have been demonstrated when clopidogrel is replaced by ticagrelor or prasugrel albeit with increases in bleeding. There are few studies documenting the patterns of use of P2Y12 inhibitors or their association with outcomes in the Australian population. AIMS: To describe the patterns of use of each P2Y12 inhibitor and to determine the associations between initial P2Y12 inhibitor use and outcomes. METHODS: Data were extracted from Cooperative National Registry of ACS, Guideline Adherence and Clinical Events (CONCORDANCE)-a prospective database of patients presenting to 43 sites across Australia with ACS. Patients were stratified based on first antiplatelet agent received. Baseline clinical characteristics were compared between these patient groups and hospital investigations, management as well as in-hospital and 12 months outcomes (death, a composite of cardiac-related death, myocardial infarction, and stroke, and major bleeding) were compared between the three treatment cohorts after adjustment for differences in baseline characteristics. RESULTS: Mean ages of the clopidogrel (n=7,537), ticagrelor (n=1,878), and prasugrel (n=347) cohorts were 65, 63, and 58 yrs respectively (p<0.0001), the mean Global Registry of Acute Coronary Events (GRACE) risk scores were 107, 104, and 102 (p=0.0016). The ticagrelor and prasugrel cohorts were more likely to receive percutaneous coronary intervention (PCI) (clopidogrel 52%, ticagrelor 66%, prasugrel 88%, p<0.0001), and evidence based medications (≥4 guideline indicated medications: clopidogrel 76%, ticagrelor 82%, prasugrel 93%, p<0.0001). Patients treated with ticagrelor and prasugrel were less likely to experience in-hospital death (clopidogrel 2.5%, ticagrelor 1.4%, prasugrel 1.2%, p=0.05), major adverse cardiac events (MACE) (clopidogrel 5.1%, ticagrelor 3.0%, prasugrel 3.5% [p=0.01]), or bleeding (clopidogrel 8.4%, ticagrelor 4.6%, prasugrel 7.5% [p<0.001]) compared to clopidogrel. These differences were no longer apparent after multivariable adjustment. There was no difference in outcomes between cohorts at 12 months. CONCLUSIONS: In Australia, ticagrelor and prasugrel are used in younger patients who are more likely to undergo percutaneous coronary intervention (PCI) and receive evidence based therapy. Patients receiving clopidogrel were more likely to experience in hospital ischaemic or bleeding events but this was explained by their higher baseline risk. Selection of therapy was not associated with any difference in outcomes at 12-month follow-up, but our findings suggest there is room for improvement towards guideline-driven usage of P2Y12 inhibitors.

In Hospital Outcomes for High-Risk Percutaneous Coronary Intervention (PCI) in Patients Referred From a Rural Centre to Metropolitan Sites.

BACKGROUND: Cardiac Society of Australia and New Zealand (CSANZ) guidelines recommend elective high-risk percutaneous coronary intervention (PCI) is not performed in sites greater than 1 hour from cardiac surgery. METHODS: In hospital outcomes for all patients from Orange Health Service (OHS) from January 2017 to January 2020 who were transferred electively to tertiary centres in Sydney for high risk PCI were examined. RESULTS: One hundred and fourteen (114) patients were identified, with 1,259 PCIs performed at OHS over the same period without transfer. The mean age of these 114 patients was 71 years, with 74.6% male. Receiving hospitals were Royal Prince Alfred Hospital, Sydney, NSW (66.7%), Concord Repatriation General Hospital, Concord, NSW (19.3%) and Strathfield Private Hospital, Strathfield, NSW (14%). The definition of high risk and indication for transfer included at least one of: moderate or greater calcification of the target lesion or proximal segment (34%), single or multiple target lesions that in aggregate jeopardised over 50% of remaining viable myocardium (27%), degenerated saphenous vein grafts (14.8%), chronic total occlusions (7.0%) and severe left ventricular (LV) impairment (3.9%). American Heart Society/American College of Cardiology (AHA/ACC) lesion types were A (1%), B1 (4.2%), B2 (40.2%), and C (54.6%). PCI was performed via the femoral route in 96.2%. The mean procedure duration was 72 minutes, mean combined fluoroscopy time was 19 minutes and mean radiation dose as defined by Reference Air Kerma was 1,630 mGy. Complications occurred in 13 patients and were: acute vessel dissection requiring stenting (4), perforation (2), acute vessel closure (4), puncture site related (1), and life-threatening arrhythmia (2). There were no cases of emergent coronary artery bypass graft (CABG) or death. CONCLUSION: This contemporary cohort of high-risk patients transferred electively from a regional PCI centre to a tertiary cardiac unit underwent lengthy PCI procedures, with high radiation doses, and a modest rate of peri-procedural complications, but had otherwise excellent procedural and clinical outcomes.

Relation of Body Mass Index to Outcomes in Acute Coronary Syndrome.

We assessed the association of BMI with all-cause and cardiovascular (CV) mortality in a contemporary acute coronary syndrome cohort. Patients from the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events and Global Registry of Acute Coronary Events between 2009 and 2019, were divided into BMI subgroups (underweight: <18.5, healthy: 18.5 to 24.9, overweight: 25 to 29.9, obese: 30 to 39.9, extremely obese: >40). Logistic regression was used to determine the association between BMI group and outcomes of all cause and CV death in hospital, and at 6 months. 8,503 patients were identified, mean age 64 ± 13, 72% male. The BMI breakdown was: underweight- 95, healthy- 2,140, overweight- 3,258, obese- 2,653, extremely obese- 357. Obese patients were younger (66 ± 12 vs 67 ± 13), with more hypertension, diabetes, and dyslipidemia vs healthy (all p < 0.05). Obese had lower hospital mortality than healthy: all-cause: 1% versus 4%, aOR (95% CI): 0.49(0.27, 0.87); CV: 1% versus 3%, 0.51(0.27, 0.96). At 6-month underweight had higher mortality than healthy: all-cause: 11% versus 4%, 2.69(1.26, 5.76); CV: 7% versus 1%, 3.54(1.19, 10.54); whereas obese had lower mortality: all-cause: 1% versus 4%, 0.48(0.29, 0.77); CV: 0.4% versus 1%, 0.42(0.19, 0.93). When BMI was plotted as a continuous variable against outcome a U-shaped relationship was demonstrated, with highest event rates in the most obese (>60). In conclusion, BMI is associated with mortality following an acute coronary syndrome. Obese patients had the best outcomes, suggesting persistence of the obesity paradox. However, there was a threshold effect, and favorable outcomes did not extend to the most obese.

Impact of medical consultation frequency on risk factors and medications 6 months after acute coronary syndrome.

OBJECTIVE: Initiatives that support primary care to better enable delivery of optimal prevention services are of great importance. The purpose of this study was to examine the frequency of medical consultations by patients with acute coronary syndrome (ACS) in the 6 months after hospital discharge and to determine whether the frequency of visits was associated with differences in lifestyle, clinical measures and medication prescription. METHODS: We conducted a retrospective subgroup analysis of data collected in the Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE), which is an ongoing (prospective) clinical initiative providing continuous real-time reporting on the clinical characteristics, management and outcomes of patients admitted to Australian hospitals with ACS. We compared clinical measures, medications, smoking status and receipt of cardiac rehabilitation with frequency of medical consultations 6 months after hospital discharge. RESULTS: Patients with ACS visited their general practitioner (GP) a mean of 4.4 (± 3.8) times and their cardiologist 1.2 (± 0.9) times in the 6-month period after their index admission. Patients who saw a GP in the 6-month period had significantly higher rates of participation in cardiac rehabilitation, receipt of dietary advice and prescription of cardioprotective medications. Factors associated with increased frequency of GP visits were older age groups (oldest fourth vs youngest fourth incidence rate ratio (IRR) 1.08; 95% CI 1.01, 1.14), being female (male vs female IRR 0.83; 95% CI 0.80, 0.86), diagnosis of ST-segment elevation myocardial infarction (STEMI) (STEMI vs non-STEMI IRR 1.08; 95% CI 1.04, 1.13; STEMI vs unstable angina IRR 1.01; 95% CI 0.95, 1.06), being a current smoker (IRR 1.09; 95% CI 1.05, 1.15), history of cardiovascular disease (IRR 1.06; 95% CI 1.01, 1.12), history of diabetes (IRR 1.25; 95% CI 1.21, 1.31), inpatient revascularisation (IRR 0.95; 95% CI 0.91, 0.99), receipt of cardiac rehabilitation referral (IRR 0.93; 95% CI 0.89, 0.97), and discharged on four or more out of five indicated medications (IRR 1.04; 95% CI 1.00, 1.08). CONCLUSION: The majority of ACS survivors in this study saw their GP frequently and their cardiologist at least once during the 6 months after index admission. Seizing these opportunities to engage, manage and support patients is important for strengthening prevention in primary care.

Cerebrovascular events in young adults after surgical repair of tetralogy of Fallot.

Increasing numbers of children who have undergone intracardiac repair of tetralogy of Fallot have survived to adulthood, but often have residual haemodynamic and/or electrical abnormalities. We report the unusual observation of 4 instances of cerebrovascular accidents in young adults subsequent to surgical repair of tetralogy of Fallot.

Intramolecular [4 + 2] cycloadditions of iminoacetonitriles: a new class of azadienophiles for hetero Diels-Alder reactions.

Iminoacetonitriles participate as reactive dienophiles in stereoselective intramolecular hetero Diels-Alder reactions which afford substituted quinolizidines. The cycloadduct with exo-oriented cyano group is obtained as the major or exclusive product of the reaction as a consequence of the alpha-amino nitrile anomeric effect The alpha-amino nitrile moieties incorporated in the cycloadducts constitute latent iminium ions, which upon exposure to mild protic or Lewis acids are unmasked, setting the stage for further useful synthetic transformations. For example, reductive decyanation with NaBH3CN excises the cyano group, while Bruylants reaction with Grignard reagents and acetylides lead to alpha-substituted amines. The substrates for these [4 + 2] cycloadditions are prepared from readily available alcohols via a Mitsunobu coupling reaction with the previously unknown, easily prepared reagent HN(Tf)CH2CN followed by cesium carbonate promoted elimination of trifluoromethanesulfinate.