Cardiovascular Pharmacotherapy Research Articles

Management of cardiac emergencies in women: a clinical consensus statement of the Association for Acute CardioVascular Care (ACVC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the Heart Failure Association (HFA), and the European Heart Rhythm Association (EHRA) of the ESC, and the ESC Working Group on Cardiovascular Pharmacotherapy.

Cardiac emergencies in women, such as acute coronary syndromes, acute heart failure, and cardiac arrest, are associated with a high risk of adverse outcomes and mortality. Although women historically have been significantly underrepresented in clinical studies of these diseases, the guideline-recommended treatment for these emergencies is generally the same for both sexes. Still, women are less likely to receive evidence-based treatment compared to men. Furthermore, specific diseases affecting predominantly or exclusively women, such as spontaneous coronary dissection, myocardial infarction with non-obstructive coronary arteries, takotsubo cardiomyopathy, and peripartum cardiomyopathy, require specialized attention in terms of both diagnosis and management. In this clinical consensus statement, we summarize current knowledge on therapeutic management of these emergencies in women. Key statements and specific quality indicators are suggested to achieve equal and specific care for both sexes. Finally, we discuss several gaps in evidence and encourage further studies designed and powered with adequate attention for sex-specific analysis.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic cardiovascular disease and heart failure. The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolemia, type 2 diabetes, obesity and heart failure, the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of cardiovascular diseases.

Nose-to-Heart Approach: Unveiling an Alternative Route of Acute Treatment.

Intranasal (IN) administration has emerged as a novel approach for rapid systemic absorption, with potential applicability in the management of acute cardiovascular events. This review explores the evolution of IN cardiovascular pharmacotherapy, emphasizing its potential in achieving systemic effects and bypassing the first-pass metabolism associated with oral administration. The extensive vascularization of nasal mucosa and a porous endothelial basement membrane facilitate efficient drug absorption into the bloodstream. The IN route ensures a critical swift onset of action, which allows self-administration in at-home settings. For instance, etripamil nasal spray, a first-in-class formulation, exemplifies the therapeutic potential of this approach in the treatment of spontaneous supraventricular tachycardia. The review critically assesses studies on IN formulations for angina, acute myocardial infarction, hypertensive episodes, and cardiac arrhythmias. Preclinical evaluations of beta-blockers, calcium-channel blockers, and antianginal drugs demonstrate the feasibility of IN administration for acute cardiovascular events. A small number of clinical trials have revealed promising results, emphasizing the superiority of IN drug delivery over oral administration in terms of bioavailability and onset of action. Unambiguously, the limited clinical trials and patient enrollment pose challenges in generalizing experimental outcomes. However, the nose-to-heart approach has clinical potential.

First-in-human trial of PCSK9 gene editing therapy for lowering cholesterol: a new frontier in cardiovascular pharmacotherapy? News from AHA.

First-in-human trial of PCSK9 gene editing therapy for lowering cholesterol: a new frontier in cardiovascular pharmacotherapy? News from AHA.

Arg389Gly beta-1-adrenergic receptor polymorphism determines neutrophil-stunning-associated cardioprotection by metoprolol

Abstract Background Cardioprotective strategies to limit infarct size (IS) have become crucial. The damaged inflicted on the myocardium is the result of the processes of Ischemia and Reperfusion (I/R). In the clinical trial METOCARD-CNIC, it was shown that the intravenous (i.v.) pre-reperfusion administration of the β1-selective antagonist metoprolol reduces IS and improves long-term cardiac function in patients after acute myocardial infarction (1). However, the small sample size precludes a definite conclusion. Despite not having demonstrated a solid clinical benefit in terms of hard endpoints reduction, the clinical guidelines for the management of ST-Elevation Myocardial Infarction (STEMI) recommend the early administration of i.v. β-blockers in patients undergoing Primary Coronary Intervention. Additionally, our group has recently described that the beneficial effect of metoprolol against myocardial I/R injury is due to neutrophil stunning (2), which represents a one-of-a-kind property not shared by other i.v. β-blockers, such as atenolol or propranolol (3). Purpose Since β1-adrenergic receptor (ADRB1) is one of major targets of pharmacological therapy, great efforts are now underway to account for the relevance of the polymorphic variation. Here we explore whether the cardioprotection exerted by metoprolol is dependent on genetic polymorphisms in human ADRB1. Methods Patients included in the METOCARD-CNIC trial were grouped into the different variants for the ADRB1, rs1801252 and rs1801253 (SerGly49 and Arg389Gly, respectively), which might affect their response to the beta-1 modulation exerted by metoprolol on neutrophils and thus its cardioprotective effect. Additionally, the polymorphic-dependent effect of metoprolol on neutrophil migration was evaluated in healthy volunteers, whose neutrophils were exposed across the transwell filter to the CXCL1 in the presence or absence of metoprolol. Drug-receptor interaction properties were evaluated in silico. Results We found that Arg389Gly polymorphism of the human ADRB1 impacts the cardioprotective effect of metoprolol in STEMI patients. Therefore, Arg389 homozygosity was associated with lower infarcts (Figure 1) and better long-term left ventricle ejection fraction when metoprolol was intravenously administered prior reperfusion. Moreover, the disrupting effect of metoprolol on neutrophil migration was only observed in Arg389 homozygote volunteers (Figure 2). These differences were attributed to alterations in the drug-receptor complex stability when Gly residues are present in position 389 of the ADRB1. Conclusions From our perspective, these results are the first showing a polymorphic implication in drug response against myocardial I/R injury. All the data presented refine cardiovascular pharmacotherapy, and have major implications for the prospective clinical trial design aiming at positioning metoprolol as the beta-blocker of choice to reduce hard endpoints in STEMI patients.CardioprotectionNeutrophil migration

From statistical inference to machine learning: A paradigm shift in contemporary cardiovascular pharmacotherapy.

Heart failure with reduced ejection fraction (HFrEF) poses significant challenges for clinicians and researchers, owing to its multifaceted aetiology and complex treatment regimens. In light of this, artificial intelligence methods offer an innovative approach to identifying relationships within complex clinical datasets. Our study aims to explore the potential for machine learning algorithms to provide deeper insights into datasets of HFrEF patients. To this end, we analysed a cohort of 386 HFrEF patients who had been initiated on sodium-glucose co-transporter-2 inhibitor treatment and had completed a minimum of a 6-month follow-up. In traditional frequentist statistical analyses, patients receiving the highest doses of beta-blockers (BBs) (chi-square test, P = .036) and those newly initiated on sacubitril-valsartan (chi-square test, P = .023) showed better outcomes. However, none of these pharmacological features stood out as independent predictors of improved outcomes in the Cox proportional hazards model. In contrast, when employing eXtreme Gradient Boosting (XGBoost) algorithms in conjunction with the data using Shapley additive explanations (SHAP), we identified several models with significant predictive power. The XGBoost algorithm inherently accommodates non-linear distribution, multicollinearity and confounding. Within this framework, pharmacological categories like 'newly initiated treatment with sacubitril/valsartan' and 'BB dose escalation' emerged as strong predictors of long-term outcomes. In this manuscript, we not only emphasize the strengths of this machine learning approach but also discuss its potential limitations and the risk of identifying statistically significant yet clinically irrelevant predictors.

Cardiovascular pharmacotherapy in patients with triple negative breast cancer before and after anthracycline treatment

Cardiovascular pharmacotherapy in patients with triple negative breast cancer before and after anthracycline treatment

The European Society of Cardiology working group on cardiovascular pharmacotherapy.

The European Society of Cardiology working group on cardiovascular pharmacotherapy.

Impact of Low-Fidelity Simulation Based Learning in a Cardiovascular Pharmacotherapy Module

To determine the impact of low-fidelity simulation (LFS) on the comprehension of 5 major cardiovascular diseases in a pharmacotherapy module. Study population included pharmacy students enrolled in the cardiovascular pharmacotherapy from 2020-2022. Baseline knowledge was obtained by comparing practice quiz answers to corresponding exam questions. Near the course end, answers from the LFS patient case involving the 5 diseases were compared to corresponding final exam questions. The percentage correct was compared to see if LFS has more impact than practice quizzes on exam grades. All groups showed approximately the same percentage correct exam questions from practice quizzes. LFS was superior to practice quizzes in percentage correct on exam questions in 4/5 disease states for the class enrolled in 2021. However, opposite results were shown for the class enrolled in 2022, with practice quizzes showing a larger improvement over the LFS activity on exam questions in all 5 disease states. Although data was mixed, the use of LFS is a viable addition to classroom learning in complicated pharmacotherapy courses. There is a paucity of literature published to date in the health sciences literature on the use of LFS; therefore, this adds to the body of evidence to support learning via simulation.

[Cardiovascular pharmacotherapy in old age].

Cardiovascular diseases are the most frequent cause of disability and death. Evidence-based pharmacotherapy is the basis for successful treatment of common diseases, such as hypertension, heart failure, coronary artery disease, and atrial fibrillation. The proportion of older people with several diseases (multimorbidity) who need five or more drugs daily (polypharmacy) is steadily increasing. Evidence on the efficacy and safety of drugs in these patients is, however, limited because they are often excluded or underrepresented in clinical trials. In addition, clinical guidelines mostly focus on single diseases and only occasionally deal with the challenges in the pharmacotherapy of older multimorbid patients with polypharmacy. This article describes the options and special features of pharmacotherapy for hypertension, chronic heart failure and dyslipidemia, as well as antithrombotic treatment in (very) old people.

Pharmacotherapy of heart failure A.D. 2023. Expert opinion of Working Group on Cardiovascular Pharmacotherapy, Polish Cardiac Society.

Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021-2022 in relation to Polish health care conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include: drugs blocking the renin-angiotensin-aldosterone system (preferably angiotensin receptor antagonist/neprilisin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect - options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers - carvedilol and nebivolol), mineralocorticoid receptor antagonist and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness of the above-mentioned has been confirmed in numerous prospective, randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent, additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or presence of arrhythmia. The manuscript emphasizes cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction. We propose practical guidelines for the use of medicines, the profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation or antiplatelet and anticoagulant therapy were also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF were discussed.

Not obtaining a medication the first time it is prescribed: primary non-adherence to cardiovascular pharmacotherapy.

Primary medication non-adherence describes the situation when a first prescription for a new medication is never filled. Primary non-adherence is an important, yet understudied aspect of reduced effectiveness of pharmacotherapy. This review summarizes the frequency, impact, reasons, predictors, and interventions regarding primary non-adherence to cardiovascular/cardiometabolic drugs. The current literature reveals a high prevalence of primary non-adherence. The individual risk of primary non-adherence is determined on multiple factors, e.g., primary non-adherence of lipid-lowering drugs is higher compared to antihypertensive medications. However, the overall rate of primary non-adherence is > 10%. Additionally, this review identifies specific areas for research to better understand why patients forgo evidence-based beneficial pharmacotherapy and to explore targeted interventions. At the same time, measures to reduce primary non-adherence-once proven to be effective-may represent an important new opportunity to reduce cardiovascular diseases.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus β-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Stability of Oral Liquid Dosage Forms in Pediatric Cardiology: A Prerequisite for Patient's Safety-A Narrative Review.

The development of safe and effective pediatric formulations is essential, especially in therapeutic areas such as pediatric cardiology, where the treatment requires multiple dosing or outpatient care. Although liquid oral dosage forms are considered the formulation of choice given the dose flexibility and acceptability, the compounding practices are not endorsed by the health authorities, and achieving stability can be problematic. The purpose of this study is to provide a comprehensive overview of the stability of liquid oral dosage forms used in pediatric cardiology. An extensive review of the literature has been performed, with a particular focus on cardiovascular pharmacotherapy, by consulting the current studies indexed in PubMed, ScienceDirect, PLoS One, and Google Scholar databases. Regulations and guidelines have been considered against the studies found in the literature. Overall, the stability study is well-designed, and the critical quality attributes (CQAs) have been selected for testing. Several approaches have been identified as innovative in order to optimize stability, but opportunities to improve have been also identified, such as in-use studies and achieving dose standardization. Consequently, the information gathering and the results of the studies can be translated into clinical practice in order to achieve the desired stability of liquid oral dosage forms.

Rapid response to the editor regarding the journal article 'Acute LDL-C reduction post ACS: strike early and strike strong: from evidence to clinical practice. A clinical consensus statement of the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Association of Preventive Cardiology (EAPC) and the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy'.

With great interest, I read the relevant consensus document led by Konstantin Krychtiuk highlighting the importance of early and aggressive reduction of low-density lipoprotein cholesterol (LDL-C) following acute coronary syndrome (ACS) event to improve clinical outcomes.1 While the ‘strike early and strong’ message is perfectly sound, I would wish to put more emphasis on the window of opportunity for lipid lowering among ACS patients before they receive an invasive management. Authors are to be commended for integrating early lipid lowering in their proposed management pathway; however, the concept of statin ‘pre-loading’ should be put more forward. The mechanisms behind very early statin use in ACS and their translation to clinical benefit are not fully elucidated; however, such effects could be explained by the multifactorial impact of statin treatment on molecular and cellular events that are fundamental to the pathogenesis of ACS. Such mechanisms, independent of the central action on atherogenic lipoproteins, include reduction of inflammation, modulation of thrombogenesis and thrombolysis, improvement of endothelial dysfunction, and amelioration of ischaemia/reperfusion injury.2 It has been previously shown in clinical studies that statin pre-loading before percutaneous coronary intervention (PCI) can limit periprocedural microcirculatory damage, significantly reduce ‘no-reflow’ phenomenon, and can elicit greater endothelial protection in both chronic and acute coronary syndrome populations.3,4,5 These beneficial pharmacodynamic effects of statin pre-loading in patients with ACS might translate to short-term reduction in adverse events, especially those that are coronary-driven.

Metabolic associated fatty liver disease and cardiovascular risk: The expert opinion of the Working Group on Cardiovascular Pharmacotherapy of the Polish Cardiac Society.

The diagnosis of metabolic associated fatty liver disease (MAFLD) is significant for patients' prognosis, as the disease accelerates the development of cardiovascular complications and, on the other hand, cardiometabolic conditions are risk factors for the development of fatty liver diseases. This expert opinion presents principles of MAFLD diagnosis and standards of management to reduce cardiovascular risks in patients with MAFLD.

Utilizing quantitative dried blood spot analysis to objectively assess adherence to cardiovascular pharmacotherapy among patients at Kenyatta National Hospital, Nairobi, Kenya.

The burden of cardiovascular disease (CVD) is rising in Kenya and non-adherence to cardiovascular pharmacotherapy is a growing global public health issue that leads to treatment failure, an increased risk of cardiac events and poor clinical outcomes. This study assessed adherence to selected cardiovascular therapy medications among CVD patients attending outpatient clinics at Kenyatta National Hospital, Kenya by determining drug concentration(s) in patient dried blood spot (DBS) samples. Patients who had been taking one or more of the five commonly prescribed CVD medications (amlodipine, atenolol, atorvastatin, losartan, and valsartan) for at least six months were enrolled. Each patient completed a short questionnaire about their medication history and then provided a finger-prick blood spot sample from which drug concentrations were determined by liquid chromatography-high resolution mass spectrometry analysis. Two hundred and thirty-nine patients (62.3% female) participated in the study. The median number of medications used by patients was 2 (IQR 75%-25% is 3-1). Less than half (117; 49.0%) of patients were adherent to their prescribed CVD pharmacotherapy. Binary regression analysis revealed a significant correlation between non-adherence and the number of medications in the treatment regimen (Odds Ratio (OR) 1.583; 95%CI: 0.949-2.639; P-value = 0.039) and that gender was not an independent predictor of medication adherence (OR 1.233; 95%CI: 0.730-2.083; P-value = 0.216). Valuable information about adherence to each medication in the patient's treatment regimen was obtained using quantitative DBS analysis showing that adherence to CVD medications was not uniform. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence to pharmacotherapies objectively, when combined with hyphenated mass spectrometry analytical techniques. This information can provide physicians with an evidence-based novel approach towards personalization and optimization of CVD pharmacotherapy and implementing interventions in the Kenyan population, thereby improving clinical outcomes.

Medical treatment of patients with cardiovascular diseases during the first year after hospitalization for COVID-19

Aim. To evaluate the medical treatment of patients with cardiovascular disease (CVD) during the first year of follow-up after hospitalization for coronavirus disease 2019 (COVID-19) in a prospective registry.Material and methods. The material for the study was obtained from the database of the TARGET-VIP inhospital registry. The registry included 1130 people. Of 863 patients discharged from the hospital with a diagnosis of COVID-19, 473 (548%) patients with CVD were selected, and 31 (40,8%) patients were selected from 76 patients in whom the diagnosis of COVID-19 was not confirmed with CVD.Results. At the stage of discharge from the hospital, the quality of therapy for CVD was insufficient on average, the frequency of proper prescriptions was 59,5%. During the first year, there was a significant trend towards a decrease in the prevalence of antihypertensive therapy for hypertension (p=0,018), anticoagulants for atrial fibrillation (p<0,001) and an increase in prescribing angiotensinconverting enzyme inhibitors/angiotensin receptor blockers for heart failure (p=0,037). The average prevalence of prescribing proper cardiovascular pharmacotherapy after 30-60 days and 6 months of follow-up was significantly less than at discharge from the hospital. In both groups of patients, when comparing the average frequency of compliance with proper prescriptions at all follow-up periods, as well as when comparing these indicators between groups, no significant differences were found, with the exception of the stage of 30-60 days after discharge from the hospital (p=0,009).Conclusion. In the TARGET-VIP registry after discharge from the hospital, the prevalence of proper appointments for CVD was insufficient. During the first year of observation, patients with CVD showed a significant decrease in the frequency of proper prescription of antihypertensive therapy for hypertension and anticoagulants for atrial fibrillation. When comparing groups of patients with confirmed and non-confirmed COVID-19, a higher average rate of adherence to proper prescriptions was found in patients with confirmed COVID-19. However, significant differences were found only 30-60 days after discharge.

Rules for the use of reduced doses of non-vitamin K antagonist oral anticoagulants in the prevention of thromboembolic complications in patients with atrial fibrillation. The opinion of the Working Group on Cardiovascular Pharmacotherapy of the Polish Cardiac Society

Rules for the use of reduced doses of non-vitamin K antagonist oral anticoagulants in the prevention of thromboembolic complications in patients with atrial fibrillation. The opinion of the Working Group on Cardiovascular Pharmacotherapy of the Polish Cardiac Society

The use of GLP-1 analogues in the treatment of diabetes in patients with cardiovascular diseases. The expert opinion of the Working Group of Cardiovascular Pharmacotherapy of the Polish Cardiac Society.

The use of GLP-1 analogues in the treatment of diabetes in patients with cardiovascular diseases. The expert opinion of the Working Group of Cardiovascular Pharmacotherapy of the Polish Cardiac Society.