Ticagrelor is a powerful P2Y12 inhibitor with pleiotropic effects in the cardiovascular system. Consistently, we have reported that in patients with stable coronary artery disease (CAD) and concomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronary intervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markers of endothelial function, compared with clopidogrel. The objective of this study was to investigate the mechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses of RNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markers of inflammation and oxidative stress, such as RORγt (T helper 17 cells marker), FoxP3 (regulatory T cells marker), NLRP3, ICAM1, SIRT1, Notch ligands JAG1 and DLL4, and HES1, a Notch target gene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels of SIRT1 and HES1 mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negative correlation among changes in both SIRT1 and HES1 mRNA and serum levels of Epidermal Growth Factor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment in our previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positively regulates HES1 and SIRT1, two genes playing a protective role in the context of inflammation and oxidative stress. Our observations confirm and expand previous studies showing that the beneficial effects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity to reduce systemic inflammation and oxidative stress.

IntroductionDespite the availability of diverse evidence-based diagnostic and treatment options, many patients with acute coronary syndrome (ACS) still fail to receive effective, safe and timely diagnoses and therapies. The Association of Acute CardioVascular Care of the European Society of Cardiology has proposed and retrospectively validated a set of ACS-specific quality indicators. Combining these indicators with the principles of clinical governance—a holistic, patient-centred approach intended to promote continuous quality improvement—we designed the clinical governance programme in patients with ACS.Methods and analysisThis is a multicentre quality improvement initiative exploring multiple dimensions of care, including diagnosis, therapy, patient satisfaction, centre organisation and efficiency in all comers patients with ACS.The study will enrol ≈ 5000 patients prospectively (ie, at the time of the first objective qualifying ACS criterion) with a 1-year follow-up. Consecutive inclusion will be promoted by a simplified informed consent process and quantified by the concordance with corresponding hospital administrative records using diagnosis-related group codes of ACS.Coprimary outcome measures are (1) timely reperfusion in patients with ST-elevation ACS and (2) optimal medical therapy at discharge in patients with confirmed acute myocardial infarction. Secondary outcomes broadly include multiple indicators of the process of care. Clinical endpoints (ie, death, myocardial infarction, stroke and bleeding) will be adjudicated by a clinical event committee according to predefined criteria.Ethics and disseminationThe study has been approved by local ethics committee of all study sites. As a quality improvement initiative and to promote consecutive inclusion of the population of interest, a written informed consent will be requested only to patients who are discharged alive. Dissemination will be actively promoted by (1) the registration site (ClinicalTrials.Gov ID NCT04255537), (2) collaborations with investigators through open data access and sharing.

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Aims The prognostic implication of periprocedural myocardial infarction (MI) in older patients has been less investigated. The aim of this study is to assess the relationship between large periprocedural MI and long-term mortality in older patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI). Methods This is a pooled analysis of older NSTEACS patients who were included in the FRASER and HULK studies. Periprocedural MI was defined in agreement with the Society for Cardiovascular Angiography and Interventions definition. The primary outcome was all-cause mortality. The secondary outcome was cardiovascular mortality. The predictors of periprocedural MI and the relationship with scales of physical performance, namely Short Physical Performance Battery and grip strength, were also investigated. Results The study included 586 patients. Overall, periprocedural MI occurred in 24 (4.1%) patients. After a median follow-up of 1023 (740–1446) days, the primary endpoint occurred in 94 (16%) patients. After multivariable analysis, periprocedural MI emerged as an independent predictor of all-cause mortality (hazard risk 4.30, 95% confidence interval 2.27–8.12). This finding was consistent for cardiovascular mortality (hazard risk 7.45, 95% confidence interval 3.56–15.67). SYNTAX score, multivessel PCI and total stent length were independent predictors of large periprocedural MI. At hospital discharge, patients suffering from periprocedural MI showed poor values of Short Physical Performance Battery and grip strength as compared with others. Conclusion In a cohort of older NSTEACS patients undergoing PCI, large periprocedural MI occurred in around 4% of patients and was associated with long-term occurrence of all-cause and cardiovascular mortality. Clinical trial registration ClinicalTrials.gov: NCT02324660 and NCT03021044.

Aims Using the principles of clinical governance, a patient-centred approach intended to promote holistic quality improvement, we designed a prospective, multicentre study in patients with acute coronary syndrome (ACS). We aimed to verify and quantify consecutive inclusion and describe relative and absolute effects of indicators of quality for diagnosis and therapy. Methods and results Administrative codes for invasive coronary angiography and acute myocardial infarction were used to estimate the ACS universe. The ratio between the number of patients included and the estimated ACS universe was the consecutive index. Co-primary quality indicators were timely reperfusion in patients admitted with ST-elevation ACS and optimal medical therapy at discharge. Cox-proportional hazard models for 1-year death with admission and discharge-specific covariates quantified relative risk reductions and adjusted number needed to treat (NNT) absolute risk reductions. Hospital codes tested had a 99.5% sensitivity to identify ACS universe. We estimated that 7344 (95% CI: 6852–7867) ACS patients were admitted and 5107 were enrolled—i.e. a consecutive index of 69.6% (95% CI 64.9–74.5%), which varied from 30.7 to 79.2% across sites. Timely reperfusion was achieved in 22.4% (95% CI: 20.7–24.1%) of patients, was associated with an adjusted hazard ratio (HR) for 1-year death of 0.60 (95% CI: 0.40–0.89) and an adjusted NNT of 65 (95% CI: 44–250). Corresponding values for optimal medical therapy were 70.1% (95% CI: 68.7–71.4%), HR of 0.50 (95% CI: 0.38–0.66), and NNT of 98 (95% CI: 79–145). Conclusion A comprehensive approach to quality for patients with ACS may promote equitable access of care and inform implementation of health care delivery. Registration ClinicalTrials.Gov ID NCT04255537