Cardiovascular Pharmacotherapy Research Articles

The ESC Working Group on Cardiovascular Pharmacotherapy: continuity through transformation.

The ESC Working Group on Cardiovascular Pharmacotherapy: continuity through transformation.

Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity.

Statins are drugs used in cardiovascular pharmacotherapy to decrease hypercholesterolemia and lower the risk of atherosclerosis. Statins also increase the risk of rhabdomyolysis, which is often minimized in comparison with large relative risk reductions of cardiovascular disease reported in clinical trials. By contrast, absolute risk reductions of cardiovascular disease are often clinically insignificant and unreported in statin clinical trials. Additionally, cytotoxic effects of statins inhibit cancer cell proliferation and reduce cancer risk, but other studies found that statins are carcinogenic. Due to an inverse association between incidence of cancer and atherosclerosis, the indication to prescribe statins likely biases the association of statins with cancer prevention. Dietary patterns associated with atherosclerosis and cancer contain inverse amounts of cholesterol and phosphate, an essential mineral that stimulates tumorigenesis. Accordingly, lower cancer risk is associated with high dietary cholesterol intake and increased risk of atherosclerosis. Furthermore, serum is exposed to excessive inorganic phosphate that could increase cancer risk as rhabdomyolysis induced by statins releases phosphate from skeletal muscle breakdown. Increased risk of comorbid conditions associated with statins may share the mediating factor of phosphate toxicity. More research is warranted on statins in the cause and prevention of cancer.

Sex-specific association of cardiovascular drug doses with adverse outcomes in atrial fibrillation

ObjectivesSex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women...

Transluminal balloon angioplasty and stenting of coronary arteries after prior orthotopic heart transplantation: a case report

Introduction. Today, heart failure (HF) is the most common natural outcome of diseases that are not diagnosed and treated in time. Despite the advances in cardiovascular pharmacotherapy, orthotopic heart transplantation is a generally recognized gold standard for the treatment of end-stage heart failure.Brief description. The article describes a 55-year-old male patient admitted to the Cardiology Dispensary (Kabardino-Balkarian Republic) with a clinical picture of non-ST segment elevation acute coronary syndrome (ACS). Earlier in 2017, the patient underwent orthotopic heart transplantation (OHT) for end-stage HF due to dilated cardiomyopathy. Hypertension was registered 2,5 years after surgery, and clinical manifestations of HF were registered for 5 years. In 2024, coronary angiography revealed subtotal stenosis of 95% in the middle segment of the anterior descending artery. Intraoperatively, the consensus assessed the risk and made a decision on surgical endovascular treatment of the stenosis. The postoperative period was uneventful.Discussion. The presented case is an example of timely diagnosis of coronary artery disease in a transplanted heart and successful transluminal balloon angioplasty and stenting of the anterior descending artery.

News in cardiovascular pharmacotherapy from the ACC.24 Meeting.

News in cardiovascular pharmacotherapy from the ACC.24 Meeting.

Comprehensive disease state reviews: A guide to live and virtual implementation in a therapeutics course

Background: Pharmacy curricula often teach disease states in silos, covering one disease at a time. This approach may inadequately prepare students for caring for patients with multiple coinciding disease states. The purpose of this “how-to” guide is to detail an approach to implementing a comprehensive, capstone-style disease state review into pharmacy therapeutics courses. Methods: This manuscript describes the use of a drug-class review, individual disease-state patient cases, and then layered, multi-disease-state cases that build upon individual cases in an integrated cardiovascular pharmacotherapy course. It also describes pre- and post-test assessments to supplement learning outcomes. Results: The educational activity significantly improved student performance between the pre- and post-tests. Informal feedback indicated appreciation for the real-world applicability of the activity. Conclusion: While cardiovascular examples are provided, this approach could be integrated into any therapeutics-type course. Benefits for students include providing a space to explore therapeutic decision-making for patients with multiple common, overlapping disease states. Faculty also benefit from this design, as once created, it is a robust and comprehensive review that can be used year after year regardless of changes in guidelines.

Recent advances in cardiology – Hot trials from the American Heart Association Annual Scientific Meeting 2023

ABSTRACT Cardiovascular (CV) diseases are the leading causes of death worldwide in both sexes alike. However, there have been significant developments in CV pharmacotherapy, percutaneous intervention, and systems of care over the past three decades in parallel. Several landmark studies were presented and discussed in American Heart Association (AHA) 2023 Scientific Sessions held in Philadelphia. The dapagliflozin-myocardial infarction (MI) and SELECT discussed the CV benefits of newer antidiabetic drugs. The AZALEA-TIMI and ARTESIA evaluated newer anticoagulants in atrial fibrillation. VERVE-101 and LEPODISIRAN studies were related to lipid-lowering in clinical practice. The ESPRIT trial demonstrated the benefits of intensive blood lowering, while KARDIA-1 tested a new RNA-based therapeutic agent for blood pressure lowering. The MINT trial evaluated strategies for blood transfusion in anemia concomitant with acute MI. ORBITA-2 study demonstrated the positive impact of percutaneous coronary intervention for angina control in stable coronary artery disease. Hence, these studies encompassed almost all aspects of cardiology, including heart failure, acute coronary syndrome, lipidology, anticoagulation, hypertension, obesity, and coronary intervention.

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 (CVDs) 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 CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; 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 CVDs.

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.

Differences in Cardiovascular Phenotype and Pharmacotherapy Between Patients with ESKD Based on Transplant Eligibility

Differences in Cardiovascular Phenotype and Pharmacotherapy Between Patients with ESKD Based on Transplant Eligibility

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.

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.