Coronary artery disease management in older adults: revascularization and exercise training.

The mean age of patients with coronary artery disease (CAD) is steadily increasing. In older patients, there is a tendency to underutilize invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multi-vessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on sub-analyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients.

Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome: individual patient data meta-analysis.

BACKGROUND AND AIMS: Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients. METHODS: MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819). RESULTS: Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63-1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44-0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18-0.95; P = .037). There was no significant difference in mortality. CONCLUSIONS: No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.

Non-ST-elevation acute coronary syndromes with previous coronary artery bypass grafting: a meta-analysis of invasive vs. conservative management.

BACKGROUND AND AIMS: A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Eligible studies were RCTs of routine invasive vs. a conservative or selective invasive strategy in patients presenting with NSTE-ACS that included patients with previous CABG. Summary data were collected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Summary data were obtained from 11 RCTs, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477 routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40). CONCLUSIONS: This is the first meta-analysis assessing the effect of a routine invasive strategy in patients with prior CABG who present with NSTE-ACS. The results confirm the under-representation of this patient group in RCTs of invasive management in NSTE-ACS and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered RCT.

Management of Acute Coronary Syndrome in the Older Adult Population: A Scientific Statement From the American Heart Association.

Diagnostic and therapeutic advances during the past decades have substantially improved health outcomes for patients with acute coronary syndrome. Both age-related physiological changes and accumulated cardiovascular risk factors increase the susceptibility to acute coronary syndrome over a lifetime. Compared with younger patients, outcomes for acute coronary syndrome in the large and growing demographic of older adults are relatively worse. Increased atherosclerotic plaque burden and complexity of anatomic disease, compounded by age-related cardiovascular and noncardiovascular comorbid conditions, contribute to the worse prognosis observed in older individuals. Geriatric syndromes, including frailty, multimorbidity, impaired cognitive and physical function, polypharmacy, and other complexities of care, can undermine the therapeutic efficacy of guidelines-based treatments and the resiliency of older adults to survive and recover, as well. In this American Heart Association scientific statement, we (1) review age-related physiological changes that predispose to acute coronary syndrome and management complexity; (2) describe the influence of commonly encountered geriatric syndromes on cardiovascular disease outcomes; and (3) recommend age-appropriate and guideline-concordant revascularization and acute coronary syndrome management strategies, including transitions of care, the use of cardiac rehabilitation, palliative care services, and holistic approaches. The primacy of individualized risk assessment and patient-centered care decision-making is highlighted throughout.

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

Overcoming professional barriers encountered by women in interventional cardiology: an EAPCI statement.

Despite the increasing proportion of female medical and nursing students, there is still a significant under-representation of women working as healthcare providers in interventional cardiology, with very few of them reaching senior leadership, academic positions, or acting principal investigators, as well as actively involved in company advisory boards. In this position paper, we will describe the current status of women working in interventional cardiology across Europe. We will also provide an overview of the most relevant determinants of the under-representation of women at each stage of the interventional cardiology career path and offer practical suggestions for overcoming these challenges.

Tailoring antiplatelet therapy in older patients with coronary artery disease.

The older population represents a unique subset of patients due to a higher rate of comorbidities and risk factors, which can lead to a higher rate of ischemic and bleeding events. As a result, older adults are mainly underrepresented or excluded from randomized trials. Although the advancement in the percutaneous coronary intervention field with the development of new technologies, techniques, and potent antiplatelet therapy led to a reduction of ischemic risk, there is still a concern regarding bleeding hazards. Apart from the global utilization of less invasive trans-radial approach and proton pump inhibitors to reduce bleeding risk, proper tailoring of antiplatelet therapy in the older person is imperative. So far, several antiplatelet drugs have been introduced in different clinical scenarios, with dual antiplatelet therapy (combination of acetylsalicylic acid and P2Y12 inhibitor) recommended after percutaneous coronary intervention. The decision on the choice of antiplatelet drug and the DAPT duration is challenging and should be based on the relationship between ischemia and bleeding with the purpose of reducing ischemic events but not at the expense of increased bleeding complications. This is particularly important in the older population, where the evidence is obscure. The main objective of this review is to summarize the available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention.

What is the context?The older population represents a unique subset of patients due to a higher rate of comorbidities, risk factors, and unfavorable prognostic features, which can lead to a higher rate of ischemic and bleeding events. They are either excluded or underrepresented in most randomized clinical trials, which is why guidelines recommendation should be taken cautiously. Thus, the decision on the choice of antiplatelet therapy and its duration after percutaneous coronary intervention in older adults is challenging and should be tailored to a particular patient to avoid bleeding complications but not at the expense of increased ischemic events.What is new?In this review, we summarize all available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention. In particular, several recommended approaches in patients with high bleeding risk, are thoroughly discussed in this review: De-escalation strategies with discontinuation of one antiplatelet drugDe-escalation strategy with switching between P2Y12 inhibitorsDe-escalation strategy based on dose reductionFinally, based on the current knowledge on factors contributing to high bleeding risk and the aforementioned antiplatelet modification approaches, in this review, we propose antiplatelet algorithm after percutaneous coronary intervention in older adults.What is the impact?The review provides comprehensive knowledge on antiplatelet therapy in older population and may help in tailoring antiplatelet therapy in this unique subset of patients.

The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030.

Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.

Ticagrelor with or without Aspirin in High-Risk Patients after PCI.

BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

Contemporary device management of cardiogenic shock following acute myocardial infarction.

Despite advances in the overall management of acute myocardial infarction (AMI), cardiogenic shock in the setting of AMI (CS-AMI) continues to be associated with poor patient outcomes. There are multiple devices that can be used in CS-AMI to support the failing circulation, although their utility in improving outcomes as compared with conventional pharmacotherapy of vasopressors and inotropes remains to be established. This contemporary review provides an update on the evidence base for each of these techniques. In CS-AMI, acute thrombotic occlusion of a major epicardial artery leads to hypoxia and myocardial ischaemia in the territory subtended by that vessel. The resultant regional dysfunction in myocardial contractility can severely compromise stroke volume and result in acute circulatory failure, systemic hypoperfusion, lactic acidosis, multi-organ failure and ultimately death.

Gender differences in the assessment, decision-making and outcomes for ventricular assist devices and heart transplantation: An analysis from a UK transplant center.

PURPOSE: There are marked gender differences in all etiologies of advanced heart failure. We sought to determine whether there is evidence of gender-specific decision making for transplant assessments, and how gender effects outcomes. METHODS: Retrospective analysis of adult heart transplant assessments at a single UK center between April 2015 and March 2020. RESULTS: Females were 32% of referrals (N = 137 females, 285 males), with marked differences between diagnoses - 11% ischemic and 43% of adult congenital. Females were younger, shorter, weighed less, and had lower pulmonary pressures. Females were much less likely to receive a ventricular assist device (13%). Blood type "O" females were relatively more likely compared to males to receive a transplant (45%). Comparing males and females who received a ventricular assist device, both had similar levels of high pulmonary pressures, indicating consistent decision-making based on hemodynamics to implant a device. Overall survival was better for females (in noncongenital patients), and this was due to female patients who were not accepted for transplant or a ventricular assist device being more often "too well for transplant," rather than in males when they were more often "unsuitable." CONCLUSIONS: Marked gender differences exist at all stages of the heart transplant assessment pathway. Appropriate decision-making based on clinical grounds is shown with less transplants in male blood type "O"s and hemodynamic criteria for ventricular assist device implantation in both genders. Further studies are needed to determine if there is a wider community bias in advanced heart failure treatments for females.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.

Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR.

AIMS: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. METHODS AND RESULTS: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. CONCLUSIONS: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

Prognostically relevant periprocedural myocardial injury and infarction associated with percutaneous coronary interventions: a Consensus Document of the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI).

A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant 'major' periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI.

Ticagrelor monotherapy in patients with chronic kidney disease undergoing percutaneous coronary intervention: TWILIGHT-CKD.

AIMS: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD. CONCLUSION: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes.

AIMS: To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). METHODS AND RESULTS: In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). CONCLUSIONS: Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.

An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group.

This consensus document, a summary of the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), appraises the importance of ischaemia with non-obstructive coronary arteries (INOCA). Angina pectoris affects approximately 112 million people globally. Up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease, more common in women than in men, and a large proportion have INOCA as a cause of their symptoms. INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. INOCA can result from heterogeneous mechanism including coronary vasospasm and microvascular dysfunction and is not a benign condition. Compared to asymptomatic individuals, INOCA is associated with increased incidence of cardiovascular events, repeated hospital admissions, as well as impaired quality of life and associated increased health care costs. This consensus document provides a definition of INOCA and guidance to the community on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.

Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS.

AIMS: The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS: We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION: Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.