Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial

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On the search for the right definition of heart failure with preserved ejection fraction

The definition of heart failure with preserved ejection fraction (HFpEF) has evolved from a clinically based “diagnosis of exclusion” to definitions focused on objective evidence of diastolic dysfunction and/or elevated left ventricular filling pressures. Despite advances in our understanding of HFpEF pathophysiology and the development of more sophisticated imaging modalities, the diagnosis of HFpEF remains challenging, especially in the chronic setting, given that symptoms are provoked by exertion and diagnostic evaluation is largely conducted at rest. Invasive hemodynamic study, and in particular — invasive exercise testing, is considered the reference method for HFpEF diagnosis. However, its use is limited as opposed to the high number of patients with suspected HFpEF. Thus, diagnostic criteria for HFpEF should be principally based on non-invasive measurements. As no single non-invasive variable can adequately corroborate or refute the diagnosis, different combinations of clinical, echocardiographic, and/or biochemical parameters have been introduced. Recent years have brought an abundance of HFpEF definitions. Here, we present and compare four of them: 1) the 2016 European Society of Cardiology criteria for HFpEF; 2) the 2016 echocardiographic algorithm for diagnosing diastolic dysfunction; 3) the 2018 evidence-based H2FPEF score; and 4) the most recent, 2019 Heart Failure Association HFA-PEFF algorithm. These definitions vary in their approach to diagnosis, as well as sensitivity and specificity. Further studies to validate and compare the diagnostic accuracy of HFpEF definitions are warranted. Nevertheless, it seems that the best HFpEF definition would originate from a randomized clinical trial showing a favorable effect of an intervention on prognosis in HFpEF

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor.The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group.Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the dual antiplatelet therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in postacute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic treatment (DATT) appear after a longer time from ACS (more than two years) and/or from cessation of DAPT (more than one year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials

Legitimacy and potential savings in automatic substitution of biological products in Poland, the example of insulin

Currently in Poland there is no regulation aiming at framing the complexity of substitution process arising at pharmacy level. In practice such process exists in variety type of products, both generic and biological scope. Lack of integrity in terms of this process between authorised medical professions who held it, might lead to further costs both for the health care system and patients. The aim of the study is to explain, that the economic advantage, which very often is the result of performed substitution process, in some types of products such as bio-logical ones, should be preceded with the decision of the treating physi-cian. Only then, in the cooperation between persons prescribing and dispensing certain medicinal product the process of substitution may fully use its potential of money saving along with the control over a certain patient. The study brings the yet unknown classification of dif-ferences in costs between actually performed automatic substitution of products containing human insulin in the pharmacy setting in Poland in four year period in five Voivodeships

A policy view: gaps and weaknesses of substitution between biological products in law and economics dimension: the example of insulin

The purpose of the study is to analyze the act of substitution between biological products. Diabetes mellitus notes the greatest increase in the projected causes of deaths globally till 2030. The proper drug substitution process may help to increase the control over the disease management. In this paper authors try to identify and explain the challenges for the health policies and legislations in emerging markets and low- and middle-income countries. Analysis of retrospective data covering prescribed-dispensed insulin products was performed. The study is based on the law and economics approach with the application of the planning theory and modeling. The study shows the scope of substitution process of insulin and highlights the necessity of univocal legal approach profiled for this therapy area. Prognosis of created base model indicates at constant presence of substitution process of insulin. Substitution is to bring financial savings for patients, it is yet however unknown whether savings arising from the act of purchase will still have positive impact on undertaken therapy process in long-term period. These findings may inform about important factors and how emerging markets and low- and middle-income countries can increase progress of the substitution process