Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting.

Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy. This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants. No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.

Dried blood spot sampling coupled with liquid chromatography-tandem mass for simultaneous quantitative analysis of multiple cardiovascular drugs.

Dried Blood Spots (DBS) revolutionize therapeutic drug monitoring using LC-MS for the precise quantification of cardiovascular drugs (CDs), enabling personalized treatment adapted to patient-specific pharmacokinetics with minimal invasiveness. This study aims to achieve simultaneous quantification of eight CDs in DBS, overcoming physicochemical challenges. A two-step protein precipitation method was used for simple and precise sample preparation. The drugs were analyzed using LC-MS/MS in ESI positive-ion mode, showing high sensitivity and linearity, with a correlation coefficient (r2) exceeding 0.999, after being separated on a reversed-phase chromatography by gradient elution of DW-acetonitrile containing 0.1 % formic acid + 2 mM ammonium formate. The validation results indicate good selectivity, with no observed matrix effect and carry-over. The intra- and inter-day accuracy and precision were within 6 % for most drugs, except for digoxin and deslanoside at low therapeutic levels where the variation was within 20 %. Stability tests confirmed suitable DBS handling and storage conditions, indicating drug stability for at least 30 days at room temperature. The analysis of whole spot has demonstrated remarkable precision and reliability in all target drugs. The analysis of 3 mm internal diameter discs, punched in and out of DBS, presumed to contain 3 µL of blood, showed acceptable accuracy for most drugs, with less polar drugs like digoxin and deslanoside showing lower accuracy, indicating a need for further correction due to non-uniform drug distribution. Consequently, the developed LC-MS/MS method enables the quantification of multiple CDs in a single DBS analysis, while suggesting the potential for accuracy-based analysis.

Safety of cardiovascular disease drugs approved between 2014 and 2021 in the US: a pharmacovigilance analysis.

BACKGROUND: Recently FDA-approved drugs for cardiovascular disease (CVD) require robust post-marketing surveillance. The objective of this study was to assess their safety using a large pharmacovigilance database. RESEARCH DESIGN AND METHODS: We analyzed adverse event (AE) reports for 17 drugs approved from 2014 to 2021, utilizing the FDA Adverse Event Reporting System (FAERS). Descriptive and disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and its 95% confidence interval. RESULTS: Among the 43,664,773 AE reports 97,702 (0.22%) were related to newly approved CVD drugs. No AEs were reported for finerenone and evinacumab. The results from the disproportionality analyses revealed potential risks of acute kidney injury (ROR = 8.24, 95% CI: 6.05-11.22), cardiac failure (ROR = 4.80, 95% CI: 3.82-6.05), and hypotension (ROR = 3.98, 95% CI: 3.44-4.61) among sacubitril/valsartan users. Additionally, ivabradine was found to be associated with tachycardia (ROR = 11.94, 95% CI: 8.35-17.08), abnormal feeling (ROR = 4.40, 95% CI: 2.70-7.18), and dizziness (ROR = 2.56, 95% CI: 1.68-3.90). CONCLUSIONS: This study identified specific safety concerns related to recently approved CVD drugs. Further research is required to understand the underlying mechanisms and clinical implications of these findings.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Sensitive "release-on-demand" fluorescent genosensors for probing DNA damage induced by commonly used cardiovascular drugs: Comparative study.

Cardiovascular drugs (CVDs) are agents working on the heart and the vascular system to treat many cardiovascular disorders. Such disorders represent the leading cause for morbidity and mortality worldwide. The treatment regimen includes different administered drugs on chronic basis. The cumulative drugs in human body coincides with exposure to electromagnetic radiations from different sources leading to drug-radiation interaction that may lead to drug photosensitization. Such photosensitization may lead to mutagenesis, cancer, and cell death due to molecular damage to DNA. This work involves the application of two bioluminescent genosensors; Terbium chloride and EvaGreen are utilized to investigate potential DNA damage caused by frequently used CVDs following UVA irradiation. A variety of CVDs are investigated. Ten drugs; Amiloride, Atorvastatin, Captopril, Enalapril, Felodipine, Hydrochlorothiazide, Indapamide, Losartan, Triamterene and Valsartan are studied. The study's findings showed that such drugs induced DNA damage following UVA irradiation. The induced DNA damage altered the fluorescence of terbium chloride and EvaGreen genosensors, proportionally. The results are confirmed by viscosity measurements reflecting the possible intercalation of CVDs with DNA. Also, the work is applied on calf thymus DNA to mimic the actual biological variability. The demonstrated bioluminescent genosensors provide automatic, simple and low-cost methods for assessing DNA-drug interactions.

Cardiovascular/anti-inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer. METHODS: We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023. MAIN OUTCOMES AND MEASURES: The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival. RESULTS: We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival). CONCLUSIONS AND RELEVANCE: Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.

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.

Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used diabetes and obesity medications but have been associated with gastrointestinal (GI) adverse events. However, real-world evidence on comparative GI adverse reaction profiles is limited. OBJECTIVES: This study aimed to evaluate GI adverse events among GLP-1 RA users and compare semaglutide, dulaglutide, liraglutide, and exenatide safety regarding the GI adverse reaction profile. METHODS: This retrospective cross-sectional analysis utilized real-world data on 10,328 adults with diabetes/obesity in the National Institutes of Health All of Us cohort. New GLP-1 RA users were identified, and GI adverse events were examined. Logistic regression determined factors associated with GI adverse events. RESULTS: The mean age of the study population was 61.4 ± 12.6 years, 65.7% were female, 51.3% were White, and they had a high comorbidity burden. Abdominal pain (57.6%) was the most common GI adverse event, followed by constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%). Dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than semaglutide and exenatide. Liraglutide and exenatide had the highest pancreatitis (4.0% and 3.8%, respectively). Compared to semaglutide, dulaglutide and liraglutide had higher odds of abdominal pain, and nausea and vomiting. They also had higher odds of gastroparesis than semaglutide. No significant differences existed in GI bleeding or pancreatitis risks between the GLP-1 RAs. CONCLUSIONS: In this real-world cohort, GI adverse events were common with GLP-1 RAs. Differences in GI safety profiles existed between agents, with exenatide appearing safer than other GLP-1 RAs, except for gastroparesis. These findings can inform GLP-1 RA selection considering GI risk factors. Further studies are needed to evaluate the causal relationship and GLP-1 RA safety with concomitant medication use.

Comparative assessment of high-risk cardiovascular medication knowledge between practising and student nurses: a descriptive multi-centre study.

Aim To examine unexplored knowledge of cardiovascular highrisk medications and perception thereof among practising nurses and students in the Kingdom of Saudi Arabia (KSA). Methods The multicentre cross-sectional quantitative study used an online survey dichotomised into a knowledge test (true/false and multiple choice questions) and a perception assessment (closed-ended questions). Four hundred and eighteen nurses participated in the study. Results In the knowledge test, 19 (4.5%) participants scored high (≥71%), while 83 (19.8%) and 316 (75.5%) demonstrated moderate (score ≥51-70%) and poor performance (score ≤50%), respectively. In a comparative analysis, the knowledge level of staff nurses was significantly higher than the students but not the other nurses' cohort. Nurses' specialty and region of KSA were strongly associated with the knowledge level. Emergency room nurses and those belonging to the eastern region of KSA exhibited higher knowledge levels than other subgroups. A vast majority of nurses, 128 (30.6 %), rated their knowledge of medicines as somewhat sufficient, while quoting insufficient knowledge 226 (54.1%) as the major cause of medication errors. Three hundred and sixteen (75%) nurses expressed interest in undergoing specialised training in high-alert medication-based therapy preferably in a classroom setting by 279 (66.7%). Conclusion This study revealed a marked knowledge deficit in high-risk cardiovascular drugs among nurses. The pharmacological curriculum in nursing schools should be tailored to be clinically oriented and reinforced with problem-based learning. Continued pharmacology education focusing on high-risk drugs should be implemented among nurses to safeguard patient lives by mitigating the risks of medication error.

Efficacy of BAY 60-2770, a soluble guanylate cyclase activator, for coronary spasm in animal models.

Ischemia with non-obstructive coronary arteries (INOCA), caused by coronary artery spasm, has gained increasing attention owing to the poor quality of life of impacted patients. Therapeutic options to address INOCA remain limited, and developing new therapeutic agents is desirable. Herein, we examined whether soluble guanylate cyclase (sGC) activators could be beneficial in preventing coronary spasms. In organ chamber experiments with isolated canine coronary arteries, prostaglandin F2α-, endothelin-1-, 5-hydroxytryptamine-, and potassium chloride-induced contractions were suppressed by the sGC activator BAY 60-2770 (0.1, 1, and 10 nM). In isolated pig coronary arteries, BAY 60-2770 (0.1, 1, and 10 nM) could prolong the cycle length of phasic contractions induced by 3,4-diaminopyridine, as well as lower the peak and bottom tension of the contraction in a concentration-dependent manner. Additionally, BAY 60-2770 (1 pM‒0.1 µM) evoked a concentration-related relaxation to a greater extent in small (first diagonal branch) coronary arteries than in large (left anterior descending) coronary arteries. In vasopressin-induced angina model rats, pretreatment with BAY 60-2770 (3 µg/kg) suppressed electrocardiogram S-wave depression induced by arginine vasopressin without affecting changes in mean blood pressure and heart rate. These findings suggest that BAY 60-2770 could be valuable in preventing both large and small coronary spasms. Therefore, sGC activators could represent a novel and efficacious therapeutic option for INOCA. Significance Statement The sGC activator BAY 60-2770 exerted antispastic effects on the coronary arteries in animal vasospasm models as proof-of-concept studies. These data can help to support potential clinical development with sGC activators, suitable for human use in patients with vasospastic angina.

Prevalence of Cardiovascular Drugs and Oral Anticoagulant Use among Persons with and without Parkinson's Disease.

INTRODUCTION: Cardio- and cerebrovascular diseases are common among persons with Parkinson's disease (PD), but it is unknown how the prevalence of cardiovascular drug and oral anticoagulant use changes in relation to PD diagnosis. METHODS: We investigated the prevalence of cardiovascular drug and oral anticoagulant use among persons with and without PD among 17,541 persons who received incident PD diagnosis in 2001-2015 in Finland and their 116,829 matched comparison persons. Prevalence was calculated in 6-month time windows from 5 years before to 5 years after PD diagnosis (index date) and compared to a matched cohort without PD using generalized estimating equations. RESULTS: Persons with PD had higher prevalence of any cardiovascular drugs (unadjusted OR = 1.15; 95% CI: 1.11-1.18) and oral anticoagulants (unadjusted OR = 1.16; 95% CI: 1.11-1.22) before index date than those without PD. After index date, persons with PD had lower prevalence of cardiovascular drugs (0.94; 95% CI: 0.91-0.96), and no difference was observed for oral anticoagulants. Prevalence of any cardiovascular drugs on the index date was 66 and 61% for persons with and without PD, respectively. ß-blockers were the most common cardiovascular drugs in both cohorts. Warfarin was the most common oral anticoagulant, but the use of direct oral anticoagulants increased during the last years of follow-up. CONCLUSION: Orthostatic hypotension and weight loss likely explain the decreased cardiovascular drug use after PD diagnosis. Results with oral anticoagulants may reflect clinical assessment of benefits being larger than risks, despite the risks associated with their use in persons with PD.

Drug-related problems in older adults in outpatient settings: Results from a 6-year long prospective study in a tertiary hospital of north India.

AIM: Drug-related problems (DRPs) are a common cause of hospitalization in older patients. So far, these issues have been studied in hospitalized settings, and evidence on patterns and outcomes of DRPs, such as adverse drug reactions, is relatively scarce in older outpatients. The main aim of this study was to provide a comprehensive description and possible solutions for DRPs in older adults in outpatient settings. METHODS: The study was carried out from January 2015 to September 2021 in a tertiary hospital in north India. Patients aged ≥50 years with DRPs were enrolled. DRPs causing hospitalization, drug interactions and drug-disease interactions were identified, along with preventive measures. RESULTS: Of 10 400 patients registered, 1031 DRPs occurred in 666 patients (9.9%). Adverse drug reactions were the major DRPs (n = 933, 8.9%). Metabolic disorders were the commonest DRP in individuals aged ≥65 years compared with gastrointestinal disorders in the 50-64 years group. Drug interactions and drug-disease interactions contributed to 20.1% and 7.9% of patients, respectively. Nearly 15.8% of DRPs directly led to hospitalization, with drug-induced metabolic disturbances and movement disorders as the common causes. The Naranjo scale was not applicable in 35.3% of patients, and drug interactions were the commonest cause. Frequent monitoring, omission of unnecessary drugs, slow titration and proper instructions on therapy, together, could avoid one-third of DRPs. CONCLUSION: One out of 10 prescriptions of older outpatients carries a DRP. New-onset metabolic and neurological disturbances should prompt a thorough drug history. A multifaceted holistic approach can prevent significant drug-related morbidity and requires future evaluation. Geriatr Gerontol Int 2024; 24: 285-291.

Validez y confiabilidad de un instrumento para identificar factores que influyen en la adherencia al tratamiento en personas con factores de riesgo cardiovascular

Introducción: Es necesario contar con instrumentos válidos y confiables para identificar los factores que influyen en la adherencia al tratamiento en personas con factores de riesgo cardiovascular. En Colombia, Bonilla y Gutiérrez diseñaron un instrumento que cuenta con validez facial y de contenido. Sin embargo, no se ha demostrado la validez de constructo. Objetivo: Determinar la validez de constructo y confiabilidad del instrumento, factores que influyen en la adherencia al tratamiento farmacológico y no farmacológico en personas con factores de riesgo cardiovascular. Metodología: Investigación metodológica. Participaron 694 personas con factores de riesgo de enfermedad cardiovascular residentes en tres ciudades de Colombia (Neiva, Espinal y Tunja). Se realizó un análisis factorial exploratorio (extracción de componentes principales y rotación Varimax), análisis factorial confirmatorio (estimación de máxima verosimilitud) y una prueba de confiabilidad global y por dimensiones (alfa de Cronbach y Test-retest). Resultados: El análisis factorial exploratorio reportó un instrumento de 30 ítems con estructura de 4 factores (varianza total acumulada de 42,6 %). Los índices de ajuste del modelo propuesto indicaron ajuste absoluto excelente y ajuste incremental aceptable. El alfa de Cronbach global fue 0,86, lo que indica alta confiabilidad. Discusión: El estudio proporciona evidencia de un instrumento más robusto que otras versiones. Los instrumentos estandarizados para medir factores que influyen en la adherencia pueden ser muy útiles para la investigación y la práctica si cumplen con pruebas psicométricas de fiabilidad y validez. Conclusión: Se pone a disposición de los investigadores y del personal de salud un instrumento válido y confiable. Se recomienda su uso en poblaciones similares a la de este estudio.

Introduction: It is necessary to have valid and reliable instruments to identify the factors that influence adherence to treatment in people with cardiovascular risk factors. In Colombia, Bonilla y Gutierrez designed an instrument that has face and content validity. However, construct validity has not been demonstrated. Objective: To determine the construct validity and reliability of the instrument, factors that influence adherence to pharmacological and non-pharmacological treatment in people with cardiovascular risk factors. Methodology: Methodological research. A total of 694 people with risk factors for cardiovascular disease residing in three Colombian cities (Neiva, Espinal and Tunja) participated. Exploratory factor analysis (extraction of principal components and Varimax rotation), confirmatory factor analysis (maximum likelihood estimation) and global and dimensional reliability test (Cronbach's alpha and Test-retest) were performed. Results: The exploratory factor analysis reported a 30-item instrument with a 4-factor structure (total cumulative variance of 42.6%). The fit indices of the proposed model indicated excellent absolute fit and acceptable incremental fit. The overall Cronbach's alpha was 0.86, indicating high reliability. Discussion: The study provides evidence of a more robust instrument than other versions. Standardized instruments to measure factors that influence adherence can be very useful for research and practice if they meet psychometric tests of reliability and validity. Conclusion: A valid and reliable instrument is made available to researchers and health personnel. Its use is recommended in populations similar to that of this study.

Can Pharmaceutical Excipients Threaten the Aquatic Environment? A Risk Assessment Based on the Microtox® Biotest.

The ecotoxicological impact of pharmaceuticals has received considerable attention, primarily focusing on active pharmaceutical ingredients (APIs) while largely neglecting the potential hazards posed by pharmaceutical excipients. Therefore, we analyzed the ecotoxicity of 16 commonly used pharmaceutical excipients, as well as 26 API-excipient and excipient-excipient mixtures utilizing the Microtox® test. In this way, we assessed the potential risks that pharmaceutical excipients, generally considered safe, might pose to the aquatic environment. We investigated both their individual ecotoxicity and their interactions with tablet ingredients using concentration addition (CA) and independent action (IA) models to shed light on the often-overlooked ecotoxicological consequences of these substances. The CA model gave a more accurate prediction of toxicity and should be recommended for modeling the toxicity of combinations of drugs with different effects. A challenge when studying the ecotoxicological impact of some pharmaceutical excipients is their poor water solubility, which hinders the use of standard aquatic ecotoxicity testing techniques. Therefore, we used a modification of the Microtox® Basic Solid Phase protocol developed for poorly soluble substances. The results obtained suggest the high toxicity of some excipients, i.e., SLS and meglumine, and confirm the occurrence of interactions between APIs and excipients. Through this research, we hope to foster a better understanding of the ecological impact of pharmaceutical excipients, prompting the development of risk assessment strategies within the pharmaceutical industry.

Keeping It "Current": A Review of Treatment Options for the Management of Supraventricular Tachycardia.

OBJECTIVE: To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT). DATA SOURCES: A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies were considered if they were available in English and conducted in humans. DATA SYNTHESIS: PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations. CONCLUSIONS: With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).

Visfatin and Subclinical Atherosclerosis in Type 2 Diabetes: Impact of Cardiovascular Drugs.

Background and Objectives: The role of adipokines in the development of atherosclerosis in type 2 diabetes (T2DM) has not yet been fully elucidated. The effects of drugs on adipokine concentrations have only been evaluated in very few studies, although they may be of clinical importance. This study aimed to assess whether the concentrations of circulating adipokines could predict subclinical atherosclerosis in patients with T2DM, as well as their interactions with commonly used cardiovascular drugs. Materials and Methods: Our population-based cross-sectional multicentric study included 216 participants with T2DM but without previously diagnosed atherosclerosis. The carotid artery intima-media thickness (IMT), plaque and ankle-brachial index (ABI) metrics were measured. Resistin, visfatin, retinol-binding protein 4, high molecular weight adiponectin and leptin levels were evaluated using Luminex's xMAP technology. Results: Visfatin and resistin concentrations correlated positively with IMT (p = 0.002 and p = 0.009, respectively). The correlation of visfatin to IMT ≥ 1.0 mm was significant in males (p < 0.001). Visfatin had a positive correlation with IMT ≥ 1.0 mm or plaque (p = 0.008) but resistin only correlated with plaque (p = 0.049). Visfatin predicted IMT ≥ 1.0 mm or plaque in patients on ß-blocker monotherapy (p = 0.031). Visfatin lost its ability to predict subclinical atherosclerosis in patients taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or statins. After adjustments for risk factors for atherosclerosis and cardiovascular drugs, visfatin maintained an independent association with mean IMT (p = 0.003), IMT ≥ 1.0 mm or plaque (p = 0.005) and ABI ≤ 0.9 (p = 0.029). Conclusions: Visfatin could be used as a marker of subclinical atherosclerosis in patients with T2DM, especially in males. The assessment of visfatin concentration could aid in identifying individuals who could benefit from implementing preventive measures against atherosclerosis.

Marketing research of combined drugs for treatment of cardiovascular diseases.

The work is devoted to the results of complex marketing research of all combined cardiovascular drugs. The market of combined drugs from group C according to the ATC classification in 41 countries of the world during 2019-2022 was analyzed. Segment markets of the 27 European Union countries, Albania, Belarus, Bosnia and Hercegovina, Canada, Colоmbia, Great Britain, India, Moldova, Norway, Russian Federation, Switzerland, and Ukraine, were studied. The pharmaceutical market of Australia and the United States were also studied. The structure of this group of drugs was characterized, and the most common combinations in the analyzed markets were identified. It was found that group C09 is the most filled with combined drugs, and the number of combinations is most diverse in C09 drug groups that act on the renin-angiotensin system, C10 hypolipidemic drugs, C07 beta-blockers, and C03 diuretics, which are the drugs of the first choice for arterial hypertension and coronary heart disease. There are two promising areas for expanding the range of drugs that affect the cardiovascular system.

Impact of COVID-19 epidemic on antihypertensive drug treatment disruptions: results from a nationwide interrupted time-series analysis.

Background: The COVID-19 epidemic has disrupted care and access to care in many ways. It was accompanied by an excess of cardiovascular drug treatment discontinuations. We sought to investigate a deeper potential impact of the COVID-19 epidemic on antihypertensive drug treatment disruptions by assessing whether the epidemic induced some changes in the characteristics of disruptions in terms of duration, treatment outcome, and patient characteristics. Methods: From March 2018 to February 2021, a repeated cohort analysis was performed using French national health insurance databases. The impact of the epidemic on treatment discontinuations and resumption of antihypertensive medications was assessed using preformed interrupted time series analyses either on a quarterly basis. Results: Among all adult patients on antihypertensive medication, we identified 2,318,844 (18.7%) who discontinued their antihypertensive treatment during the first blocking period in France. No differences were observed between periods in the characteristics of patients who interrupted their treatment or in the duration of treatment disruptions. The COVID-19 epidemic was not accompanied by a change in the proportion of patients who fully resumed treatment after a disruption, neither in level nor in trend/slope [change in level: 2.66 (-0.11; 5.42); change in slope: -0.67 (-1.54; 0.20)]. Results were similar for the proportion of patients who permanently discontinued treatment within 1 year of disruption [level change: -0.21 (-2.08; 1.65); slope change: 0.24 (-0.40; 0.87)]. Conclusion: This study showed that, although it led to an increase in cardiovascular drug disruptions, the COVID-19 epidemic did not change the characteristics of these. First, disruptions were not prolonged, and post-disruption treatment outcomes remained unchanged. Second, patients who experienced antihypertensive drug disruptions during the COVID-19 outbreak were essentially similar to those who experienced disruptions before it.

Prognostic Impact of Multiple Drug Use at Discharge in Patients Hospitalized with Heart Failure.

The association between polypharmacy/multiple drug use (MDU) and prognosis in patients hospitalized with heart failure (HF) is unclear. It is also unknown whether the prognostic values of MDU vary depending on the presence/absence of a previous history of HF and preserved/reduced left ventricular ejection fraction (LVEF). We analyzed consecutive 1,034 patients hospitalized with HF (age, 74.9 ± 11.5 years; 58.7% male). MDU was defined as ≥5 drugs at discharge. The primary endpoint was a composite of all-cause death and HF readmission. MDU was observed in 695 patients (67.2%). Patients with MDU use had higher prevalences of a previous history of HF, reduced LVEF, and comorbidities than those without MDU. Cox proportional hazard analysis showed that MDU was significantly associated with the primary endpoint after adjustment for possible confounders (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.03-1.79; P = 0.030). There was significant interaction between the presence/absence of a history of HF and the prognostic impact of MDU (HF history [-]: HR, 0.86; 95% CI, 0.54-1.40; P = 0.553; HF history [+]: HR, 1.72; 95% CI, 1.16-2.55; P = 0.007; P for interaction = 0.005). However, there was no significant interaction between preserved/reduced LVEF and the prognostic impact of MDU (P for interaction = 0.274). In conclusion, MDU at discharge is an independent risk factor for the composite of death or HF readmission in patients hospitalized with HF. We observed a significant interaction between the presence of de novo versus recurrent HF and the prognostic value of MDU.

Acmella oleracea induced nanostructured Ca2Fe2O5 for evaluation of photo catalytic degradation of cardiovascular drugs and bio toxicity.

Biosynthesis of nanoparticles is increasingly becoming popular due to the demand for sustainable technologies worldwide. In the present investigation, Acmella oleracea plant extract fuelled combustion technique followed by calcination at 600 °C was adopted to prepare nanocrystalline Ca2Fe2O5. The prepared nano compound was characterised using X-ray powder diffraction (XRD), scanning electron microscopy (SEM), Ultra Violet (UV) spectroscopy, Infrared (IR) spectroscopy and its role was assessed for photocatalytic pollutant degradation along with bactericidal action in the concentration range of 1 µg/mL to 320 µg/mL. The photocatalytic degradation efficiency of pollutant drugs Clopidogrel Bisulphate and Asprin used for cardiovascular disorders is around 80% with 10 mg/L photocatalyst. The results showed that the photocatalytic activity increased with rising pH from 4, to 10, along with a significant antibacterial action against Enterococcus faecalis bacteria and a slight cytotoxic effect at high concentrations. The antibacterial property was reinforced by Minimum inhibitory concentrations (MIC) and Minimum bactericidal concentrations (MBC) studies with an average value of 0.103 at 600 nm which was further proved by significant anti-biofilm activeness. Adhesion tests in conjunction with cryogenic-scanning electron microscopy displayed a morphological change through agglomeration that caused an expansion in nano particles from 181 nm to 223.6 nm due to internalization followed by inactivation of bacteria. In addition, the non-toxicity of nano Ca2Fe2O5 was confirmed by subtle cytological changes in microscopic images of Allium Cepa root cells in the concentration range 0.01-100 µg/mL and a slight inhibition in HeLa cell proliferation indicated by IC50 value of 170.94 µg/mL. In total, the current investigation for the first time reveals the application of bio based synthesis of Nano Ca2Fe2O5 to new possibilities in bioremediation namely degrading cardiovascular pharmaceutical pollutants, endodontic antibacterial action and cytological activity.