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.

Empagliflozin-A New Chance for Patients with Chronic Heart Failure.

The heart failure (HF) epidemic is one of the challenges that has been faced by the healthcare system worldwide for almost 25 years. With an ageing world population and a fast-paced lifestyle that promotes the development of cardiovascular disease, the number of people suffering from heart failure will continue to rise. To improve the treatment regimen and consequently the prognosis and quality of life of heart failure patients, new therapeutic solutions have been introduced, such as an inclusion of Sodium-glucose co-transporter 2 (SGLT-2) inhibitors in a new treatment regimen as announced by the European Society of Cardiology in August 2021. This article focuses on the SGLT2 inhibitor empagliflozin and its use in patients with heart failure. Empagliflozin is a drug originally intended for the treatment of diabetes due to its glycosuric properties, yet its beneficial effects extend beyond lowering glycemia. The pleiotropic effects of the drug include nephroprotection, improving endothelial function, lowering blood pressure and reducing body weight. In this review we discuss the cardioprotective mechanism of the drug in the context of the benefits of empagliflozin use in patients with chronic cardiac insufficiency. Numerous findings confirm that despite its potential limitations, the use of empagliflozin in HF treatment is advantageous and effective.

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid, diabetes, and antithrombotic trials.

This review article aims to explain the important issues that data safety monitoring boards (DSMB) face when considering early termination of a trial and is specifically addressed to the needs of clinical and research cardiologists. We give an insight into the overall background and then focus on the three principal reasons for stopping trials, i.e. efficacy, futility, and harm. The statistical essentials are also addressed to familiarize clinicians with the key principles. The topic is further highlighted by numerous examples from lipid trials and antithrombotic trials. This is followed by an overview of regulatory aspects, including an insight into industry-investigator interactions. To conclude, we summarize the key elements that are the basis for a decision to stop a randomized clinical trial (RCT).

Vulnerable plaques and patients: state-of-the-art.

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of 'high-risk' plaques occurring in 'vulnerable' patients.

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid and diabetes trials.

Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.

Cardiovascular Imaging and Theranostics in Cardiovascular Pharmacotherapy.

Imaging plays a pivotal role in the diagnostic and prognostic assessment of cardiovascular diseases. During the past two decades, there has been an expansion of the available imaging techniques, some of which are now part of routine clinical practice. Cardiovascular imaging of atherosclerosis is a useful instrument, and it can corroborate and expand pathophysiological evidence on cardiovascular disease, providing proof of concept for medical therapy and can predict its responsiveness, and it may be able to be used as surrogate endpoints for clinical trials. Theranostics is an emerging therapy that combines imaging and therapeutic functions, using imaging-based therapeutic delivery systems. Theranostics could partially overcome current imaging limitations and translate experimental evidence and large-scale trials assessing clinical endpoints, rationalising cardiovascular drug development and paving the way to personalised medicine. The medical community cannot overlook the use of cardiovascular imaging as a complementary and supportive adjunct to trials investigating clinical endpoints, which remain the mainstay for investigating the efficacy and safety of cardiovascular pharmacotherapy.

Farmacoterapia de la insuficiencia cardíaca: análisis de casos de pacientes hospitalizados en un centro de salud privado en Costa Rica / Pharmacotherapy of heart failure: analysis of cases of hospitalized patients in a private health center in Costa Rica

Resumen Introducción y objetivos: La insuficiencia cardíaca es una patología que afecta a la población adulta mundial; se estima que más de 23 millones de personas en el mundo la padecen, siendo esta una de las principales causas de mortalidad cardiovascular. Dicha investigación buscó evaluar la terapia utilizada en un ambiente hospitalario privado y su correlación con respecto a las guías internacionales; todo esto con el fin de proyectar el posible impacto sobre la morbimortalidad del paciente. Métodos: Se llevó a cabo un estudio observacional retrospectivo analizando múltiples variables obtenidas de los expedientes físicos y electrónicos de todos los pacientes adultos hospitalizados por insuficiencia cardiaca en el Hos pital Clínica Bíblica enero 2014 y diciembre 2016, para comparar la farmacoterapia utilizada con la definida por las guías terapéuticas seleccionadas. Resultados: Se analizaron 72 pacientes, de los cuales 35% estaba entre 81-90 años, 58% eran hombres; 61% estuvieron hospitalizados entre 1-5 días (61%), 9 ingresaron por rehospitalización y el resto fue por primera vez; 69 fueron egresados y 3 fallecieron. La estrategia terapéutica más utilizada en estos pacientes fue un betabloqueador en conjunto con un antagonista del receptor de angiotensina y un diurético de asa. Un 78% mantuvo un tratamiento adecuado según las guías. Conclusiones: El abordaje farmacoterapéutico de los pacientes con falla cardiaca fue satisfac torio, estuvo en la mayoría de los casos de acuerdo con las guías clínicas, por lo que se podría esperar beneficios en torno a la mortalidad, tiempo de hospitalización y tasa de rehospitalización.

Abstract Pharmacotherapy of heart failure: analysis of cases of hospitalized patients in a private health center in Costa Rica Objective: Heart failure is a disease that affects a highly proportion of the adult population worldwide; about 23 million people endure this ailment, being one of the main causes of cardiovascular mortality. Therefore, the aim was to evaluate the correlation between the current therapy in a hospital setting and international guidelines, as well as the impact on morbidity and mortality. Methods: Observational prospective study, to analyze multiple variables from physical and electronic registers from all hospitalized patients for heart failure at Hospital Clínica Bíblica from January 2014 to December 2016, with the intention to compare the prescribed therapy at the hospital with selected therapeutical guidelines. Results: There were 72 patients, from which 35% were between 81 and 90 years old, 58% were men, 61% were hospitalized between 1-5 days, 9 were readmitted and 63 had their first admission, 69 were discharged and 3 perished. Conclusions: The pharmacotherapeutic approach in patients with heart failure has had a satisfactory evolution, and it's according to clinical guidelines, which could have repercussions regarding the reduction of mortality rates, hospitalization stays and rehospitalization rates.

Predialysis Cardiovascular Disease Medication Adherence and Mortality After Transition to Dialysis.

BACKGROUND: Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among patients with advanced chronic kidney disease and mortality following their transition to dialysis. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 32,348 US veterans who transitioned to dialysis during 2007 to 2011. PREDICTORS: Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. OUTCOMES: Post-dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. RESULTS: Mean age of the cohort was 72±11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC>80%, there were 14,006 deaths (mortality rate, 283 [95% CI, 278-288]/1,000 patient-years]); among patients with PDC>60% to 80%, there were 3,882 deaths (mortality rate, 294 [95% CI, 285-304]/1,000 patient-years); among patients with PDC≤60%, there were 720 deaths (mortality rate, 291 [95% CI, 271-313]/1,000 patient-years). Compared with patients with PDC>80%, the adjusted HR for post-dialysis therapy initiation all-cause mortality for patients with PDC>60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC≤60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post-dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. LIMITATIONS: Large number of missing values; results may not be generalizable to women or the general US population. CONCLUSIONS: Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.

Risk of gastrointestinal bleeding and cardiovascular events due to NSAIDs in the diabetic elderly population.

OBJECTIVE: We assessed gastrointestinal bleeding (GIB) and cardiovascular (CV) risks such as myocardial infarction or stroke associated with non-steroidal anti-inflammatory drug (NSAID) use among elderly patients with diabetes. METHODS: Using a nationwide claims database covering 2008-2012, we conducted a cohort study of patients with diabetes aged ≥65 years. Among the 117 610 patients, NSAID users and non-users were propensity score matched, excluding any who had experienced a potentially confounding event in the year prior to cohort entry. Multivariate Cox regression models treating death as competing risk were used. RESULTS: There were 2184 (1.86%) cases of GIB and NSAID users had an adjusted HR (aHR) of 1.68 (95% CI 1.54 to 1.83) of GIB risk after adjusting for age, sex, comorbidities and recent medications compared to NSAID non-users. There were 9333 (7.94%) cases of myocardial infarction or stroke with an aHR of 1.20 (95% CI 1.15 to 1.25). The risk of GIB was higher in patients with liver disease and renal failure, while that of CV events was higher in patients who received anticoagulants, antiplatelet agents, aspirin and selective serotonin reuptake inhibitors. The number needed to harm was 111 for GIB and 77 for CV events. Among different NSAIDs, nimesulide increased the risk of GIB and ketorolac increased the risk of CV events compared to celecoxib (aHR 2.60 and 3.13, respectively). CONCLUSIONS: Elderly patients with diabetes treating NSAIDs had a significantly higher risk of both upper GIB and CV events compared to NSAID non-users, and the risk varied among different NSAIDs regardless of cyclooxygenase-2 activity.