Duration of dual antiplatelet therapy in acute coronary syndrome

Despite a large volume of evidence supporting the use of dual antiplatelet therapy in patients with acute coronary syndrome, there remains major uncertainty regarding the optimal duration of therapy. Clinical trials have varied markedly in the duration of therapy, both across and within trials. Recent systematic reviews and meta-analyses suggest that shorter durations of dual antiplatelet therapy are superior because the avoidance of atherothrombotic events is counterbalanced by the greater risks of excess major bleeding with apparent increases in all-cause mortality with longer durations. These findings did not show significant heterogeneity according to whether patients had stable or unstable coronary heart disease. Moreover, the potential hazards and benefits may differ when applied to the general broad population of patients encountered in everyday clinical practice who have markedly higher bleeding and atherothrombotic event rates. Clinicians lack definitive information regarding the duration of therapy in patients with acute coronary syndrome and risk scores do not appear to be sufficiently robust to address these concerns. We believe that there is a pressing need to undertake a broad inclusive safety trial of shorter durations of therapy in real world populations of patients with acute coronary syndrome. The clinical evidence would further inform future research into strategies for personalised medicine

Rationale and design of PREvalence of DyspneA in patients treated with TicagrelOR (PREDATOR) program

Background: Ticagrelor, a reversible P2Y12 inhibitor, is a mainstay of antiplatelet strategy in patients withacute coronary syndrome (ACS). However, a large number of ticagrelor-induced dyspnea decrease patients’adherence and reduce an overall efficacy of the therapy. Design: The PREDATOR program consists of phase III and IV, multicenter, randomized, double-blind,placebo-controlled clinical trials and preceding pilot studies that assesses the prevalence and treatmentof ticagrelor-induced dyspnea in coronary artery disease (CAD) and ACS patients. The PREDATOR LDis designed to evaluate the occurrence of dyspnea after 180 mg ticagrelor loading dose, and relief ofdyspnea by theophylline administration in low-to-high risk acute coronary syndromes without ST-segmentelevation (NSTE-ACS) and stable CAD designated to undergo invasive treatment. The PREDATOR MD isa cross-over trial in stable CAD patients 1 year after percutaneous coronary intervention for ACS. Enrolledpatients will be randomized to one of four antiplatelet treatment regimens (ticagrelor 2x90 mg, ticagrelor2x60 mg, ticagrelor 2x45 mg or clopidogrel 75 mg [morning]+placebo [evening]) or placebo and will beassessed for dyspnea at the day 7, then undergo a switch of treatment and reassessment at day 14. Thesample size will be estimated based on preceding pilot studies. Discussion: The PREDATOR LD is expected to prospectively assess dyspnea rate with a loading doseof ticagrelor, and analyze a potential of theophylline to elevate symptoms of ticagrelor-induced dyspnea,while the PREDATOR MD will prospectively assess dyspnea and adverse events rate with a maintenancedose of P2Y12 inhibitors prospectively assess. All evaluations will be conducted using standardizedmetrics for dyspnea quantification

Is There Long-Term Clinical Equipoise Between CABG and PCI for Isolated Left Anterior Descending Artery Disease?

© 2023 Society for Cardiovascular Angiography and Interventions Foundation. Published by Elsevier Inc. on behalf of the Society for Cardiovascular Angiography and Interventions Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

PURPOSE OF THE STUDY: Statins and ezetimibe reduce low-density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50%-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholesterolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. STUDY DESIGN: We used data from a lipid-lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, and 69 cases also received statins. We used LDL-c thresholds 1.5-5.5 mmol/L to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. RESULTS: In 72 patients, TC and LDL-c targets were not met by 64 and 53 patients, respectively. We judged using the NICE TAG that only one patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. CONCLUSIONS: We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost-effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics

When a meta-analysis equals a single large-scale trial with meaningful follow-up

© 2021 The Author(s). Published on behalf of the European Society of Cardiology. All rights reserved. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/eurheartj/ehab460This commentary refers to ‘Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis’, by E.P. Navarese et al. doi:10.1093/ eurheartj/ehab246 and the discussion piece ‘In the pool: dilution or drowning?’, by V. Dayan et al. doi:10.1093/ eurheartj/ehab443Peer reviewe

Diabetogenic effect of statins: a comprehensive review on the clinical relevance, underlying pathomechanisms and rationale for tailored statin therapy

Statins are potent hypolipidemic drugs effectively reducing low-density lipoprotein (LDL) cholesterol serum concentration, but also exerting a wide range of pleiotropic effects. In numerous clinical trials statins were proven to substantially decrease cardiovascular morbidity and mortality both in primary and secondary prevention. However, a growing body of evidence suggests that statins, although safe and generally well-tolerated, are associated with an increased occurrence of new-onset diabetes mellitus (DM). The aim of this review is to explore the relationship between statin therapy and new-onset DM, including its clinical relevance and underlying pathomechanisms, and to discuss the concept of tailored statin therapy. According to our recently published comprehensive network meta-analysis including 113,394 patients, the high-dose statin regimens were connected with an elevated risk of new-onset DM as compared with moderate-dose statin regimens and a gradient for the risk of new-onset DM across different types and doses of statins was demonstrated. There are multiple possible mechanisms explaining the diabetogenic effect of statins (e.g., decreased insulin secretion, induction of b-cell apoptosis, increased insulin resistance or compromised glucose transport into the cells). Statins are among the most widely used drugs worldwide and physicians should be aware of the fact that there is a risk of new-onset DM across different types and doses of statins. Selection of adequate statin that suits patient’s needs remains the challenge of hypolipidemic therapy. The identification of individuals who would benefit more from smaller doses and/or use of less diabetogenic compounds could help to optimize the treatment and reduce the number of patients developing DM. The non-pharmacological approach such as adequate physical activity, weight reduction and low fat diet should not be neglected either. These actions create a chance to decrease baseline LDL-cholesterol concentration and reduce the number of both cardiovascular and DM risk factors. All in all, statins with their exceptional cardiovascular benefits will undoubtedly defend their position of a cornerstone of cardiovascular prevention because profits derived from statin therapy far exceed the potential harms connected with statin-induced impairments of glucose metabolism

Intracoronary versus intravenous abciximab administration in STEMI patients: overview of current status and open questions

Objectives: To perform a systematic review to provide rationale for intracoronary (IC) abciximab administration in patients with ST-segment elevation myocardial infarction (STEMI), to summarize recent studies comparing IC vs. intravenous (IV) abciximab administration in this setting and to define questions that need to be answered in future trials determining the optimal abciximab regimen. Methods: A search covering the period from January 1993 to June 2011 was conducted by two independent investigators using MEDLINE, CENTRAL and Google Scholar databases. Proceedings from the scientific sessions of ACC, AHA, ESC, TCT and EuroPCR were also considered. Results: IC administration allows one to obtain a much higher concentration of abciximab than IV injection at the culprit lesion. Therefore it is hypothesized that IC abciximab administration provides more efficient GP IIb/IIIa receptor inhibition and more pronounced additional dose-dependent antiplatelet, antithrombotic, and antiinflammatory effects when compared to the IV route. Numerous observational and randomized studies comparing IC vs. IV abciximab in STEMI patients indicated improvement in different surrogate end points (infarct size, obstruction of coronary microcirculation, ST segment resolution, inflammatory mediators and markers of platelet activation) related to IC administration. The evidence supporting clinical benefits associated with IC injection of abciximab comes from one randomized and several non-randomized trials as most of the studies were underpowered to assess clinical outcomes. No difference in bleeding complications was observed between IC and IV regimens. Issues that need to be addressed in future studies include: the use of IC abciximab in combination with thrombectomy, the role of selective delivery systems, and the necessity of a prolonged IV infusion of abciximab after IC bolus administration. Conclusions: An accumulating body of evidence suggests the superiority of IC over IV abciximab administration in STEMI patients. However, further trials are warranted to establish the optimal strategy of abciximab treatment in this setting