Antithrombotic Therapy in High Bleeding Risk, Part I: Percutaneous Cardiac Interventions.

Antithrombotic therapy after cardiac percutaneous interventions is key for the prevention of thrombotic events but is inevitably associated with increased bleeding, proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which in some cases may outweigh the expected benefit of reducing thrombotic events. Because the response to antithrombotic agents varies widely among patients, there has been a relentless effort toward the identification of patients at high bleeding risk (HBR), in whom modulation of antithrombotic therapy may be needed to optimize the balance between safety and efficacy. Among patients undergoing cardiac percutaneous interventions, recent advances in technology have allowed for strategies of de-escalation to reduce bleeding without compromising efficacy, and HBR patients are expected to benefit the most from such approaches. Guidelines do not extensively expand upon the topic of de-escalation strategies of antithrombotic therapy in HBR patients. In this review, we discuss the evidence and provide practical recommendations on optimal antithrombotic therapy in HBR patients undergoing various cardiac percutaneous interventions.

Acute Coronary Syndrome in Elderly Patients: How to Tackle Them?

Elderly patients diagnosed with acute coronary syndromes (ACS) represent a growing demographic population. These patients typically present more comorbidities and experience poorer outcomes compared to younger patients. Furthermore, they are less frequently subjected to revascularization procedures and are less likely to receive evidence-based medications in both the short and long-term periods. Assessing frailty is crucial in elderly patients with ACS because it can influence management decisions, as well as risk stratification and prognosis. Indeed, treatment decisions should consider geriatric syndromes, frailty, polypharmacy, sarcopenia, nutritional deficits, prevalence of comorbidities, thrombotic risk, and, at the same time, an increased risk of bleeding. Rigorous clinical assessments, clear revascularization criteria, and tailored approaches to antithrombotic therapy are essential for guiding personalized treatment decisions in these individuals. Assessing frailty helps healthcare providers identify patients who may benefit from targeted interventions to improve their outcomes and quality of life. Elderly individuals who experience ACS remain significantly underrepresented and understudied in randomized controlled trials. For this reason, the occurrence of ACS in the elderly continues to be a particularly complex issue in clinical practice, and one that clinicians increasingly have to address, given the general ageing of populations. This review aims to address the complex aspects of elderly patients with ACS to help clinicians make therapeutic decisions when faced with such situations.

Antithrombotic Therapy in High Bleeding Risk, Part II: Noncardiac Percutaneous Interventions.

Over the past decades, there have been great advancements in the antithrombotic management of patients undergoing percutaneous interventions, but most of the available evidence derives from studies conducted in the setting of cardiac interventions. Antithrombotic treatment regimens used in patients undergoing percutaneous cardiac interventions, in particular coronary, are frequently extrapolated to patients undergoing noncardiac interventions. However, the differences in risk profile of the population treated and the types of interventions performed may translate into differences is the safety and efficacy associated with antithrombotic therapy. Noncardiac percutaneous interventions are commonly performed in patients at high bleeding risk, which may indeed impact outcomes, hence underscoring the importance of risk stratification to guide clinical decision-making processes. In this review, we appraise the available evidence on antithrombotic therapy in high-bleeding-risk patients undergoing noncardiac percutaneous interventions.

How to Manage Beta-Blockade in Older Heart Failure Patients: A Scoping Review.

Beta blockers (BBs) play a crucial role in enhancing the quality of life and extending the survival of patients with heart failure and reduced ejection fraction (HFrEF). Initiating the therapy at low doses and gradually titrating the dose upwards is recommended to ensure therapeutic efficacy while mitigating potential adverse effects. Vigilant monitoring for signs of drug intolerance is necessary, with dose adjustments as required. The management of older HF patients requires a case-centered approach, taking into account individual comorbidities, functional status, and frailty. Older adults, however, are often underrepresented in randomized clinical trials, leading to some uncertainty in management strategies as patients with HF in clinical practice are older than those enrolled in trials. The present article performs a scoping review of the past 25 years of published literature on BBs in older HF patients, focusing on age, outcomes, and tolerability. Twelve studies (eight randomized-controlled and four observational) encompassing 26,426 patients were reviewed. The results indicate that BBs represent a viable treatment for older HFrEF patients, offering benefits in symptom management, cardiac function, and overall outcomes. Their role in HF with preserved EF, however, remains uncertain. Further research is warranted to refine treatment strategies and address specific aspects in older adults, including proper dosing, therapeutic adherence, and tolerability.

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.

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.

[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.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

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.

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.

Impact of coronary stenting on top of medical therapy and of inclusion of periprocedural infarctions on hard composite endpoints in patients with chronic coronary syndromes: a meta-analysis of randomized controlled trials.

INTRODUCTION: Composite endpoints are pivotal when assessing rare outcomes over relatively short follow-ups. Most randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with stent implantation to optimal medical therapy (OMT) in chronic coronary syndromes (CCS) patients included both hard and soft outcomes in their primary endpoint, with periprocedural myocardial infarctions (MIs) systematically allocated to the PCI arm. We meta-analyzed the above RCTs for composite hard endpoints, with and without periprocedural MIs. EVIDENCE ACQUISITION: This study is registered in PROSPERO CRD42020166754 and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration reporting. Patients had inducible ischemia, no left main disease nor severe left ventricular dysfunction. EVIDENCE SYNTHESIS: Six RCTs involving 10,751 patients followed for a mean of 4.4 years were included. PCI+OMT versus OMT alone was associated with no difference in the two co-primary composite endpoints of all-cause death/MI/stroke and cardiovascular death/MI including all-MIs (IRR 0.99; 95% CI 0.90-1.08 and IRR 0.95; 95% CI 0.83-1.08 respectively). After inclusion of spontaneous rather than all-MIs (i.e., excluding periprocedural MIs), the odds showed benefit of PCI+OMT for both co-primary endpoints (IRR 0.88; 95% CI 0.80-0.97, P<0.01 and IRR 0.81; 95% CI 0.69-0.95, P=0.01 respectively) with numbers needed to treat of 42 in both cases. CONCLUSIONS: Among CCS patients with inducible myocardial ischemia without severely reduced ejection fraction or left main disease, adding PCI to OMT reduces hard composite outcomes only after exclusion of periprocedural MIs. Continued efforts to define periprocedural MIs reproducibly, to assess their prognostic relevance and to prevent them are warranted.

Oral anticoagulants in fragile patients with percutaneous endoscopic gastrostomy and atrial fibrillation: the ORIGAMI pilot investigation.

BACKGROUND: Extensive data support the superior safety without any trade-off in efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation, deep venous thrombosis or pulmonary embolism. Whether DOACs may be successfully used to treat complex and fragile patients with percutaneous endoscopic gastrostomy (PEG) remains to be proven. The purpose of this pilot study was to evaluate the feasibility, anticoagulant effect, and preliminary safety/efficacy profile of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation. METHODS: In this prospective, single-arm, pilot study, 12 patients with PEG and guideline-recommended indication for anticoagulation for nonvalvular atrial fibrillation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. Quantitative measures of edoxaban's antifactor Xa activity were performed at steady state. Thromboembolic and bleeding events were assessed at one-month follow-up. RESULTS: Steady state edoxaban plasma levels were at therapeutic range in all patients; mean plasma concentration was 208.5 (±78.6) ng/mL. At one month follow-up, none had suffered a thromboembolic event; one developed minor bleeding, and one died from non-cardiovascular death, owing to sudden worsening of a pre-existing underlying severe condition. CONCLUSIONS: In this pilot investigation, we report for the first time that crushed edoxaban, administered at approved doses through PEG in fragile and complex patients, is feasible, results in therapeutic edoxaban concentrations, and is apparently effective and safe.