Current concepts in coronary artery revascularisation.

Coronary artery revascularisation can be performed surgically or percutaneously. Surgery is associated with higher procedural risk and longer recovery than percutaneous interventions, but with long-term reduction of recurrent cardiac events. For many patients with obstructive coronary artery disease in need of revascularisation, surgical or percutaneous intervention is indicated on the basis of clinical and anatomical reasons or personal preferences. Medical therapy is a crucial accompaniment to coronary revascularisation, and data suggest that, in some subsets of patients, medical therapy alone might achieve similar results to coronary revascularisation. Most revascularisation data are based on prevalently White, non-elderly, male populations in high-income countries; robust data in women, older adults, and racial and other minorities, and from low-income and middle-income countries, are urgently needed.

Acute, periprocedural and longterm antithrombotic therapy in older adults: 2022 Update by the ESC Working Group on Thrombosis

The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.

Implantable Cardioverter-Defibrillators for Primary Prevention in Patients With Ischemic or Nonischemic Cardiomyopathy: A Systematic Review and Meta-analysis.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have a role in preventing cardiac arrest in patients at risk for life-threatening ventricular arrhythmias. PURPOSE: To compare ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic or nonischemic cardiomyopathy. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, and EMBASE databases, as well as several Web sites, from 1 April 1976 through 31 March 2017. STUDY SELECTION: Randomized controlled trials, published in any language, comparing ICD therapy with conventional care and reporting mortality outcomes (all-cause, sudden, any cardiac, or noncardiac) in the primary prevention setting. DATA EXTRACTION: 2 independent investigators extracted study data and assessed risk of bias. DATA SYNTHESIS: Included were 11 trials involving 8716 patients: 4 (1781 patients) addressed nonischemic cardiomyopathy, 6 (4414 patients) ischemic cardiomyopathy, and 1 (2521 patients) both types of cardiomyopathy. Mean follow-up was 3.2 years. An overall reduction in all-cause mortality, from 28.26% with conventional care to 21.37% with ICD therapy (hazard ratio [HR], 0.81 [95% CI, 0.70 to 0.94]; P = 0.043), was found. The magnitude of reduction was similar in the cohorts with nonischemic (HR, 0.81 [CI, 0.72 to 0.91]) and ischemic (HR, 0.82 [CI, 0.63 to 1.06]) disease, although the latter estimate did not reach statistical significance. The rate of sudden death fell from 12.15% with conventional care to 4.39% with ICD therapy (HR, 0.41 [CI, 0.30 to 0.56]), with a similar magnitude of reduction in patients with ischemic (HR, 0.39 [CI, 0.23 to 0.68]) and those with nonischemic disease (HR, 0.44 [CI, 0.17 to 1.12]). Noncardiac and any cardiac deaths did not differ significantly by treatment. LIMITATION: Heterogeneous timing of ICD placement; heterogeneous pharmacologic and resynchronization co-interventions; trials conducted in different eras; adverse events and complications not reviewed. CONCLUSION: Overall, primary prevention with ICD therapy versus conventional care reduced the incidence of sudden and all-cause death. PRIMARY FUNDING SOURCE: None.

The left atrial appendage: from embryology to prevention of thromboembolism.

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches.

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation.

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers.

Platelet P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention: An Emerging Option for Antiplatelet Therapy De-escalation.

Antiplatelet therapy is considered essential for secondary prevention of ischemic heart disease. After percutaneous coronary intervention (PCI), temporary dual antiplatelet therapy (DAPT), a combination consisting of aspirin and an oral P2Y12 receptor blocker, is recommended. In the long term, this strategy results in more bleeding than antiplatelet therapy with aspirin alone. Therefore, to reduce bleeding, an increasing trend has been to keep DAPT as short as clinically acceptable, after which aspirin monotherapy is continued. Another option to diminish bleeding is to discontinue aspirin at the moment of DAPT cessation after PCI, and to continue on P2Y12 blocker monotherapy. This survey reviews the evidence on P2Y12 blocker monotherapy. Some clinical guidance will be provided on when and in whom P2Y12 inhibitor monotherapy may be applied after DAPT cessation following PCI.

Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions.

Oral inhibitors of the platelet P2Y12 receptor are indispensable in the treatment of ST-elevation myocardial infarction (STEMI), improving outcomes and even reducing mortality in some studies. However, these drugs are limited by delayed absorption and suboptimal platelet inhibition at the time of primary percutaneous coronary intervention. Despite efforts to achieve faster and more sustained platelet inhibition, strategies such as prehospital administration, higher loading doses, and crushed formulations have not led to improved coronary reperfusion. Parenteral glycoprotein IIb/IIIa inhibitors act sooner and are more potent than oral P2Y12 inhibitors, but their use has been limited by the increased risk of major bleeding and thrombocytopenia. Hence, there is a clinical need to refine drugs that deliver rapid, effective, yet safe platelet inhibition in the setting of STEMI. Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients.

[Managing patients with left ventricular thrombosis after acute myocardial infarction: current evidence, uncertainties, and future perspectives]. / Il paziente con trombosi ventricolare sinistra dopo infarto miocardico acuto: tra evidenze disponibili, incertezze e prospettive future.

The incidence of left ventricular thrombosis (LVT) after acute myocardial infarction has declined significantly in recent decades, thanks to advances in the field of revascularization and antithrombotic therapy. Despite oral anticoagulation, embolic events are the most feared complication of LVT. From a pathophysiological point of view, the development of LVT depends on Virchow's triad, that is, endothelial damage caused by myocardial infarction, blood stasis due to left ventricular dysfunction, and hyper-coagulability determined by inflammation. The diagnostic modalities of LVT include transthoracic echocardiography preferably implemented by contrast administration, and cardiac magnetic resonance. Most thrombi develop in the first 2 weeks after acute myocardial infarction, so the role of systematic screening with short to medium term repeated imaging appears limited. Vitamin K antagonists remain the cornerstone of therapy, since the effectiveness of direct oral anticoagulants remains to be established. Only weak evidence supports the routine use of prophylactic anticoagulant therapy, even in high-risk patients.

Intracoronary bolus of glycoprotein IIb/IIIa inhibitor as bridging or adjunctive strategy to oral P2Y12 inhibitor load in the modern setting of ST-elevation myocardial infarction.

BACKGROUND: In the acute management of ST-elevation myocardial infarction (STEMI), glycoprotein IIb/IIIa inhibitors (GPIs) bolus not followed by intravenous infusion is potentially advantageous given their fast onset and offset of action, but clinical evidence in a contemporary setting is limited. METHODS: We collected data from consecutive STEMI patients admitted to the cardiac catheterization laboratory of the IRCCS A. Gemelli University Polyclinic Foundation from October 2017 to September 2019. RESULTS: Out of 423 consecutive STEMI patients, 297 met the inclusion and exclusion criteria and were included in the study. Of them, 107/297 (36%) received an intracoronary GPI bolus-only during primary percutaneous coronary intervention (PPCI) not followed by intravenous infusion and 190/297 (64%) received standard antithrombotic therapy. Of the 107 GPI-treated, 22/107 (21%) had P2Y12 inhibitor pretreatment (adjunctive strategy) and 85/107 (79%) did not (bridging strategy). During hospital staying, there was no difference in the primary safety endpoint of TIMI major+minor bleeding (P=0.283), TIMI major (P=0.267) or TIMI minor (P=0.685) bleeding between groups. No stroke event occurred in the GPI group. Despite patients receiving GPI having a significantly higher intraprocedural ischemic burden, no significant differences were found in the efficacy outcomes between groups. Consistent findings were observed for patients receiving GPIs bolus before (bridging strategy) or after (adjunctive strategy) P2Y12 inhibitors, compared to those receiving standard therapy. Multivariate logistic regression analyses did not find any independent predictors significantly associated to the primary and secondary composite endpoints. CONCLUSIONS: In a contemporary real-world population of STEMI patients undergoing PPCI, the use of intracoronary GPIs bolus-only in selected patients at high ischemic risk is safe and could represent a useful antithrombotic strategy both in those pretreated and in those naïve to P2Y12 inhibitors.

Safety and efficacy of P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary interventions.

Introduction: Antiplatelet therapy represents a key strategy for the prevention of thrombotic complications in patients with both acute and chronic coronary syndromes, particularly those undergoing percutaneous coronary intervention (PCI). Nevertheless, dual antiplatelet therapy (DAPT) is associated with a bleeding risk proportionate to its duration. Ever growing appreciation of the prognostic implications associated with bleeding and the development of safer stent platforms over the past years have led to a number of novel antiplatelet treatment strategies being tested among patients undergoing PCI. Areas covered: P2Y12 inhibitor monotherapy after ashort course DAPT has emerged as ableeding reduction strategy to mitigate such risk while still preventing thrombotic complications. In this review we describe the latest evidence regarding the safety and efficacy of P2Y12 inhibitor monotherapy in patients undergoing PCI in different clinical settings. Expert opinion: P2Y12 inhibitor monotherapy after a brief period of DAPT has emerged as an effective approach to reduce the risk of bleeding without any tradeoff in efficacy (i.e., thrombotic complications). This strategy has shown consistent findings in a number of different clinical settings of patients undergoing PCI. Nevertheless, unanswered questions on the ideal patient and the precise P2Y12 monotherapy regimen warrant further investigation.

Sustained safe and effective anticoagulation using Edoxaban via percutaneous endoscopic gastrostomy.

Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non-valvular atrial fibrillation, leading to a significantly increase in the use of these compounds in clinical practice. However, there is no compelling evidence supporting the use of direct oral anticoagulant in individuals who are intubated or have a percutaneous endoscopic gastrostomy (PEG): patients with several co-morbidities are underrepresented in clinical trials, so the best long-term strategy for anticoagulation is difficult to ascertain. The aim of the present report was to evaluate the safety and efficacy of edoxaban administered via PEG in a patient with heart failure and a history of atrial fibrillation affected by amyotrophic lateral sclerosis (ALS). A 71-year-old man with atrial fibrillation, advanced ALS, type II diabetes mellitus, and hypertension presented to the emergency department with dyspnoea and tachycardia. Because vitamin K antagonist and rivaroxaban 15 mg were dropped because of difficult international normalized ratio control (time in therapeutic range <30%) and severe haematuria, respectively, edoxaban 30 mg (crushed pill) daily was administered based on the patient's weight of 58 kg. Mean edoxaban plasma concentration-time profiles were measured, as anti-Xa activity, 2 h before and at 2, 6, and 22 h after drug administration and then compared with the pharmacokinetic profile of edoxaban 30 mg in healthy subjects. An additional testing of steady-state peak plasma concentration of edoxaban after 10 days and a 30 day follow-up were evaluated. The values of the pharmacokinetic parameters, analysed with a non-compartmental analysis by PKSolver module, showed that Cmax and AUC0→t were only slightly higher than those observed in healthy subjects, while the half-life and observed clearance were significantly longer and lower, respectively, than in normal subjects. Steady-state peak plasma concentration of edoxaban was very similar to the levels reported in healthy subjects, and neither relevant bleeding nor thromboembolic event was reported at a 30 day follow-up. These results support safe and effective anticoagulation with edoxaban 30 mg but suggest caution with the use of full dose of edoxaban (60 mg daily) in this kind of patients. We report, for the first time, a safe and effective anticoagulation based on the administration of edoxaban 30 mg daily through PEG in a patient with advanced ALS, acute respiratory, and heart failure, presenting with Takotsubo syndrome and atrial fibrillation.

Data from a multidisciplinary poll of 178 expert physicians on the usage of non-vitamin K Oral Anticoagulants in patients with atrial fibrillation and venous thromboembolism.

This data article contains data from a multidisciplinary questionnaires filled in by 178 expert physicians on the usage of non-vitamin K Oral Anticoagulants in patients with atrial fibrillation (AF) and for the treatment of patients with venous thromboembolism (VTE). The questionnaire consists of 9 statements of clinical complex AF and VTE cases and informative campaign on antithrombotic therapy for stroke prevention in AF. The data are potentially valuable for the scientific community, showing the doubts of different specialists (Internists, Pneumologists, Geriatricians, Cardiologists and Neurologists) with a large experience in prescribing oral anticoagulation in difficult AF and VTE cases (see full list of participants provided). The data obtained in some particular clinical cases such as CHA2DS2-VASc=1, comorbid coronary artery disease, frailty, advanced age, risk of falling and prior haemorrhagic stroke, can be compared with indications from published guidelines and recommendations for future insight and to be considered as a benchmark for future trials in the area or oral anticoagulation for AF and VTE. The data concerning informative campaign on antithrombotic therapy for stroke prevention showed the expert panel agreement on the inclusion of self monitoring of heart rhythm by pulse taking in subjects older than 64 years of age (81% agreement, item 3); knowledge that the risk of stroke associated with AF is almost twice the risk associated with hypertension (95% agreement, item 4); knowledge that the CHA2DS2-VASc score exerts a higher influence on stroke risk compared to AF duration (92% agreement, item 5); knowledge that stroke prevention in AF with a NOAC is more effective, does not cause any higher bleeding risk, and is equally simple compared to aspirin treatment (91% agreement, item 6). Data on strategies to optimise appropriate prescription of antithrombotic therapy showed agreement on the utility of short television advertisements about the risks of stroke associated with AF (79% agreement, item 8), on a campaign encouraging regular control of cardiac rhythm by pulse taking (77% agreement, item 1), on a campaign reporting the advantages of anticoagulation over no antithrombotic therapy (98% agreement, item 2) or of NOACs over aspirin (96% agreement, item 3) or on the practical use of NOAC (93% agreement, item 6) or on stroke and bleeding risk scores (87% agreement, item 7). See Colonna et al. (2017) [1] for further interpretation and discussion.

Aspirin therapy in primary cardiovascular disease prevention: a position paper of the European Society of Cardiology working group on thrombosis.

Although the use of oral anticoagulants (vitamin K antagonists) has been abandoned in primary cardiovascular prevention due to lack of a favorable benefit-to-risk ratio, the indications for aspirin use in this setting continue to be a source of major debate, with major international guidelines providing conflicting recommendations. Here, we review the evidence in favor and against aspirin therapy in primary prevention based on the evidence accumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, we argue for a pragmatic approach to using low-dose aspirin in primary cardiovascular prevention and suggest its use in patients at high cardiovascular risk, defined as ≥2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding.

Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta-analysis.

OBJECTIVES: To investigate the safety and efficacy of durable polymer drug eluting stents (DES) and biodegradable polymer biolimus eluting stents (biolimus-ES). DESIGN: Network meta-analysis of randomised controlled trials. DATA SOURCES AND STUDY SELECTION: Medline, Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) database search for randomised controlled trials comparing at least two of durable polymer sirolimus eluting stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer biolimus-ES. PRIMARY OUTCOMES: Safety (death, myocardial infarction, definite or probable stent thrombosis) and efficacy (target lesion and target vessel revascularisation) assessed at up to one year and beyond. RESULTS: 60 randomised controlled trials were compared involving 63,242 patients with stable coronary artery disease or acute coronary syndrome treated with a DES. At one year, there were no differences in mortality among devices. Resolute and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES, but not biodegradable polymer biolimus-ES, were associated with significantly reduced odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES. Compared with everolimus-ES, biodegradable polymer biolimus-ES were associated with significantly increased odds of myocardial infarction (by 29%), while Endeavor zotarolimus-ES and paclitaxel-ES were associated with significantly increased odds of stent thrombosis. All investigated DES were similar with regards to efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which were associated with significantly increased the odds of target lesion and target vessel revascularisations compared with other devices. Direction of results beyond one year did not diverge from the findings for up to one year follow-up. Bayesian probability curves showed a gradient in the magnitude of effect, with everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles. CONCLUSIONS: The newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety endpoints, differences become apparent, with everolimus-ES and Resolute zotarolimus-ES emerging as the safest stents to date.

New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease position paper.

Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.