Time-to-event comparative effectiveness of NOACs vs VKAs in newly diagnosed non-valvular atrial fibrillation patients.

Objective: To investigate the difference in the time-to-event probabilities of ischaemic events, major bleeding and death of NOAC vs VKAs in newly diagnosed non-valvular atrial fibrillation patients. Design: Retrospective observational cohort study. Setting: UK's Clinical Practice Research Data linked to the Hospital Episode Statistics inpatient and outpatient data, mortality data and the Patient Level Index of Multiple Deprivation. Participants: Patients over 18 years of age, with an initial diagnosis of atrial fibrillation between 1st-Mar-2011 and 31-July-2017, without a record for a valve condition, prosthesis or procedure previous to initial diagnosis, and without a record of oral anticoagulant treatment in the previous year. Intervention: Oral anticoagulant treatment with either vitamin K antagonists (VKAs) or the newer target-specific oral anticoagulants (NOACs). Main Outcome Measures: Ischaemic event, major bleeding event and death from 15 days from initial prescription up to two years follow-up. Statistical Analysis: Treatment effect was defined as the difference in time-to-event probability between NOAC and VKA treatment groups. Treatment and outcomes were modelled using an ensemble of parametric and non-parametric models, and the average and conditional average treatment effects were estimated using one-step Targeted Maximum Likelihood Estimation (TMLE). Heterogeneity of treatment effect was examined using variable importance methods in Bayesian Additive Regression Trees (BART). Results: The average treatment effect of NOAC vs VKA was consistently close to zero across all times, with a temporal average of $0.00[95\%0.00,0.00]$ for ischaemic event, $0.00\%[95\%-0.01,0.01]$ for major bleeding and $0.00[95\%-0.01,0.01]$ for death. Only history of major bleeding was found to influence the distribution of treatment effect for major bleeding, but its impact on the associated conditional average treatment effect was not significant. Conclusions: This study found no statistically significant difference between NOAC and VKA users up to two years of medication use for the prevention of ischaemic events, major bleeding or death.

Anomalous aortic origin of coronary arteries: an alternative to the unroofing strategy

OBJECTIVES Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden death in children and young adults. The most threatening anatomy is an interarterial and an intramural course, both probably involved in ischaemic phenomena and sudden death. The treatment of interarterial AAOCA remains controversial. Most of the published studies describe the results of the unroofing technique. Our study aims to evaluate the results of a different surgical approach. METHODS From 2005 to 2019, 61 patients were operated on for an interarterial AAOCA (median age 14.7 years). Forty patients had a right AAOCA, and 21 patients had a left AAOCA including 5 patients with intraseptal course. Seventy percent of patients were symptomatic. Five patients had an aborted sudden cardiac death. Two surgical techniques were used: an ‘anatomical’ repair for 35 patients (15 left and 22 right AAOCA) or a coronary translocation with creation of a neo-ostia in 19 patients (1 left and 18 right AAOCA). The 5 left AAOCA patients with an intra-septal course required a complete release of the coronary artery from the septum. RESULTS There was no early or late postoperative death. Three patients had an acute postoperative ischaemic event. Two patients required immediate angioplasty and stenting: 1 patient (7 years) with a hypoplastic right AAOCA and 1 patient (66 years) for inadequate tailoring after septal release. The third patient required an immediate surgical revision (H-2) for left AAOCA thrombosis at the level of the pericardial patch with full myocardial recovery at discharge. During follow-up, 1 patient with right AAOCA translocation and chronic chest pain required subsequent stenting and finally a coronary artery bypass grafting 2 years after initial surgery. One patient who had an asymptomatic mild right coronary stenosis 1 year after anatomical repair was successfully treated by angioplasty alone. All patients but 1 who underwent coronary translocation are totally asymptomatic. All patients with anatomical repair or septal release are free from ischaemic symptoms. CONCLUSIONS Anatomical repair might provide a better protective option for these patients. Unlike unroofing, it treats the entire intramural segment, relocates the ostium at the appropriate sinus level and corrects any acute take-off angle.

Longer term stroke risk in intracerebral haemorrhage survivors

ObjectiveTo evaluate the influence of intracerebral haemorrhage (ICH) location on stroke outcomes.MethodsWe included patients recruited to a UK hospital-based, multicentre observational study of adults with imaging confirmed spontaneous ICH. The outcomes of interest were occurrence of a cerebral ischaemic event (either stroke or transient ischaemic attack) or a further ICH following study entry. Haematoma location was classified as lobar or non-lobar.ResultsAll 1094 patients recruited to the CROMIS-2 (Clinical Relevance of Microbleeds in Stroke) ICH study were included (mean age 73.3 years; 57.4% male). There were 45 recurrent ICH events (absolute event rate (AER) 1.88 per 100 patient-years); 35 in patients presenting with lobar ICH (n=447, AER 3.77 per 100 patient-years); and 9 in patients presenting with non-lobar ICH (n=580, AER 0.69 per 100 patient-years). Multivariable Cox regression found that lobar ICH was associated with ICH recurrence (HR 8.96, 95% CI 3.36 to 23.87, p<0.0001); similar results were found in multivariable completing risk analyses. There were 70 cerebral ischaemic events (AER 2.93 per 100 patient-years); 29 in patients presenting with lobar ICH (AER 3.12 per 100 patient-years); and 39 in patients with non-lobar ICH (AER 2.97 per 100 patient-years). Multivariable Cox regression found no association with ICH location (HR 1.13, 95% CI 0.66 to 1.92, p=0.659). Similar results were seen in completing risk analyses.ConclusionsIn ICH survivors, lobar ICH location was associated with a higher risk of recurrent ICH events than non-lobar ICH; ICH location did not influence risk of subsequent ischaemic events.Trial registration numberNCT02513316.

4114Efficacy of alirocumab treatment after acute coronary syndrome according to new ACC/AHA guidelines for lipid-lowering therapy

Background The 2018 ACC/AHA cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with LDL-C ≥1.8 mmol/L despite maximally tolerated statin therapy who are considered “very high-risk” on the basis of history of multiple ischaemic events or an ischaemic event and multiple high-risk conditions. Purpose We examined the frequency of major adverse cardiovascular events (MACE) and efficacy of PCSK9 inhibition with alirocumab to reduce MACE in patients with recent acute coronary syndrome (ACS) categorized as very high-risk or not very high-risk by guideline criteria. Methods Patients in ODYSSEY OUTCOMES (n=18,924) with recent ACS and residual dyslipidaemia despite optimal statin therapy were randomized to alirocumab or placebo and followed for median 2.8 years. The primary MACE outcome was a composite of coronary heart disease death, non-fatal myocardial infarction (MI), ischaemic stroke, or hospitalization for unstable angina. Results Of 18,924 randomized patients, 11,935 (63.1%) were categorized as very high-risk and 6989 (36.9%) as not very high risk (per ACC/AHA guidelines criteria). In the very high-risk category, 4450 (37.3%) had a prior ischaemic event plus the trial-qualifying index ACS (MI, 3633; stroke, 524; peripheral artery disease, 759); 7485 (62.7%) had no ischaemic event before the index ACS but had ≥2 high-risk conditions (diabetes, 3319; age ≥65 years, 3087; current smoking, 2371; chronic kidney disease, 1583). In the placebo group, the incidence of MACE was higher among those in the very high-risk category (14.4%) vs those not at very high-risk (5.6%). Overall, alirocumab reduced the risk of MACE vs placebo (9.5% vs 11.1%, hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.78–0.93; P=0.003), with consistent relative reductions in both risk categories (very high risk HR 0.84, 95% CI 0.76–0.92; not very high risk HR 0.86, 95% CI 0.70–1.06). However, the absolute reduction in MACE with alirocumab was greater among patients classified as very high-risk (2.1%) vs not very high risk (0.8%), and greater in particular among those classified as very high risk based on multiple ischaemic events (2.4%, Figure). Conclusions Application of 2018 ACC/AHA cholesterol guidelines criteria accurately identifies patients with ACS and dyslipidaemia who are at very high risk for recurrent MACE, and who derive a large absolute benefit from alirocumab treatment. Patients categorized as very high-risk based upon multiple ischaemic events derive a particularly large absolute benefit from treatment with alirocumab. Acknowledgement/Funding Supported by Sanofi and Regeneron Pharmaceuticals

Diabetes and lower extremity arterial disease

The risk of lower extremity arterial disease (LEAD) is markedly increased among patients with diabetes and ischaemic event rates are more frequent in LEAD populations with than among those without diabetes. A multidisciplinary approach to LEAD diabetic patients is essential. Proper diagnosis and management is crucial in this selected group of patients to reduce cardiovascular burden and decrease limb adverse events. This chapter reviews the clinical implications of LEAD in diabetic patients, diagnostic strategies, and management.

Antiplatelet therapy following ischaemic stroke – Continue or change pre-existing therapy?

Introduction Antiplatelet therapy is routinely prescribed early after ischaemic stroke. Many patients will already be taking antiplatelet therapy and it is unknown whether these patients should continue the same antiplatelet treatment or switch to a different regimen. Methods We selected patients with ischaemic stroke from the Virtual International Stroke Trials Archive database who were prescribed antiplatelets both before and after their stroke and who had detailed records of adverse events after stroke. We compared patients who changed to a new antiplatelet regimen after their stroke to those who continued the same regimen. The primary outcome was recurrent ischaemic stroke within 90 days after their index stroke and the secondary outcome was intracranial haemorrhage (ICH) or extracranial haemorrhage (ECH). We used logistic regression analysis and adjusted for age and baseline NIHSS. Results A total of 1129 participants were included. Of these, 538 subjects changed antiplatelet regimen post stroke and 591 continued the same regimen. A recurrent ischaemic event occurred in 4.1% of subjects who changed regimen and 4.3% who continued unchanged (adjusted OR = 0.93; 95% CI 0.54–1.75, p = 0.929). The incidence of ICH and ECH within the first 90 days was similar in both groups (2.4% vs. 2.6% (adjusted OR = 1.02; 95% CI 0.48–2.18, p = 0.955) and 4.7% vs. 2.9% (adjusted OR = 1.82; 95% CI 0.96–3.43, p = 0.065), respectively). Discussion The analysis was performed using a non-randomised registry data. Conclusion In patients who suffer ischaemic stroke whilst taking antiplatelets, a change in antiplatelet regimen was not associated with an altered risk of early recurrent ischaemic stroke rate or bleeding. However, the results must be interpreted in view of the low event rates.