Palliative Pharmacotherapy for Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Cardiovascular disease exacts a heavy toll on health and quality of life and is the leading cause of death among people ≥65 years of age. Although medical, surgical, and device therapies can certainly prolong a life span, disease progression from chronic to advanced to end stage is temporally unpredictable, uncertain, and marked by worsening symptoms that result in recurrent hospitalizations and excessive health care use. Compared with other serious illnesses, medication management that incorporates a palliative approach is underused among individuals with cardiovascular disease. This scientific statement describes palliative pharmacotherapy inclusive of cardiovascular drugs and essential palliative medicines that work synergistically to control symptoms and enhance quality of life. We also summarize and clarify available evidence on the utility of guideline-directed and evidence-based medical therapies in individuals with end-stage heart failure, pulmonary arterial hypertension, coronary heart disease, and other cardiomyopathies while providing clinical considerations for de-escalating or deprescribing. Shared decision-making and goal-oriented care are emphasized and considered quintessential to the iterative process of patient-centered medication management across the spectrum of cardiovascular disease.

Key Articles and Guidelines in the Management of Pericardial Syndromes.

Over the past two decades, emerging literature has shaped the management of pericardial syndromes and has evolved abundantly towards the creation of European guidelines for the diagnosis and management of pericardial diseases. However, since the publication of the European guidelines in 2015, more data surrounding the management of pericardial syndromes have been published. Comprehensive reference materials with the most updated literature are warranted and can be pivotal in helping pharmacists make evidence-based and clinical decisions for patients diagnosed with pericardial syndromes. This compilation of key articles and guidelines will serve as a resource for pharmacists who are responsible for the care of patients with pericardial syndromes.

Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity.

Objective: To review clinical data regarding the newly approved drug setmelanotide, an injectable melanocortin 4 receptor (MC4R) agonist, for chronic weight management in adults and children aged 6 years and older with monogenic obesity. Data Sources: A literature review was performed by searching MEDLINE, SCOPUS, and EMBASE for all relevant English-language articles published between January 1, 1996, and November 30, 2021, using search terms obesity, setmelanotide, Imcivree, and MC4R agonist. Study Selection/Data Extraction: This review included two phase 2, two phase 3, and one ongoing clinical trial evaluating the efficacy and/or safety of setmelanotide. Data Synthesis: Setmelanotide demonstrates statistically significant weight loss with at least a 10% decrease in body weight after 1 year and decreased appetite in phase 2 and phase 3 clinical trials. The most common adverse effects included injection site reaction (96%), skin hyperpigmentation (78%), nausea (56%), headache (41%), and diarrhea (37%). Place in Therapy: Setmelanotide is the first and only Food and Drug Administration-approved medication for the treatment of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, and leptin receptor deficiency in patients with obesity. It may be used in children and adults who have received genetic testing and exhibited extreme obesity before age five. Setmelanotide is a daily subcutaneous injection and may be difficult to afford for patients. Conclusion: Setmelanotide is an effective treatment in patients with obesity and indicated genetic disorders.

A systematic review of the drug-drug interaction between statins and colchicine: Patient characteristics, etiologies, and clinical management strategies.

Colchicine and statins are frequently co-prescribed for prevention and treatment of cardiovascular diseases, auto-inflammatory diseases, and gout. Both are substrates and inhibitors of the cytochrome P-450 (CYP) 3A4 isozyme and P-glycoprotein so that taken together, they represent a clinically significant interaction. Data suggest the interaction may be associated with potentially life-threatening myopathies and rhabdomyolysis. The purposes of this systematic review (SR) were to gather and appraise evidence surrounding the statin-colchicine drug interaction and discuss related risk-mitigation strategies. An electronic literature search was performed. Twenty-one articles met the protocol to be included in the qualitative analysis: 18 case reports/series, 2 retrospective observational cohort studies, and 1 retrospective case-control study. Thirty-eight patients developed an adverse drug event (ADE) receiving statin-colchicine combination therapy; 25 (66%) patients developed myopathy; 10 (26%) patients developed rhabdomyolysis, and three (8%) patients developed neuromyopathy. Over 70% of patients developed ADEs on simvastatin or atorvastatin, and 80% of studies reported moderate-to-high intensity statins. Colchicine dosing varied but ranged between 0.5 to 1.5 mg daily. Sixty-two percent of patients in the case reports/series had comorbid renal disease. Seven studies (33% of all included studies) reported patients taking concomitant interacting medications at the CYP3A4 and/or P-glycoprotein efflux pump. Seventeen studies (81% of all included studies) reported ADEs leading to hospitalization. A multivariate analysis from one case-control study identified risk factors prognosticating myopathy ADEs in patients taking statin-colchicine therapy: comorbid renal disease and/or cirrhosis, colchicine doses 1.2 mg daily or greater, and concomitant interacting medications. Clinicians must be cognizant that the statin-colchicine drug interaction may lead to patient harm and thus should employ risk-mitigation strategies for statin-associated muscle symptoms. Future studies are warranted to validate clinically relevant risk factors that are strongly associated with the complications owing to the statin-colchicine drug interaction.

Impact of antibiotic choice on readmission in adults experiencing an acute COPD exacerbation.

PURPOSE: The impact of antibiotic therapy in managing acute chronic obstructive pulmonary disease (COPD) exacerbations requiring hospitalization remains unclear. We conducted a study to assess the impact of antibiotic therapy on the rate of 30-day readmission after discharge from a hospital stay for an acute COPD exacerbation. Additional study outcomes analyzed included the effects of antibiotic therapy on hospital length of stay, in-hospital mortality, 90-day and 12-month readmission rates, and time to next COPD exacerbation. METHODS: The study was an institutional review board-approved, retrospective, observational review of adult patients at a tertiary academic medical center. The medical records of patients 18 years of age or older who were hospitalized for an acute COPD exacerbation between January 2008 and December 2014 were evaluated. Included patients were stratified by receipt of guideline-appropriate, guideline-inappropriate, or no antibiotic therapy. Nonparametric data were analyzed using the Kruskal-Wallis test (nonparametric) and categorical data via χ 2 test, respectively. RESULTS: Three hundred twenty-five subjects were included; there were no significant differences in baseline characteristics in the 3 study groups. Sixty-eight percent of patients (n = 223) received antibiotics. The percentage of patients readmitted within 30 days did not differ between cohorts: 11.9% (appropriate therapy) vs 13.2% (nonappropriate therapy) vs 12.2% (no antibiotics) (P = 0.95 for all comparisons). Additionally, no detectable differences in 90-day or 12-month readmission rate, length of hospital day, or in-hospital mortality were found. However, a trend toward increased time to next COPD exacerbation was noted in those receiving antibiotics vs no antibiotics (352 days vs 192 days, P = 0.07). CONCLUSION: Treatment of COPD exacerbations with antibiotics did not impact readmission rates, length of hospital stay, in-hospital mortality, or time to next exacerbation. More investigation is warranted to assess the effect of antibiotics on time to next exacerbation, as well as comparative effectiveness between antibiotic classes.

Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection.

Predicting risk for major adverse cardiovascular events (MACE) is an evidence-based practice that incorporates lifestyle, history, and other risk factors. Statins reduce risk for MACE by decreasing lipids, but it is difficult to stratify risk following initiation of a statin. Genetic risk determinants for on-statin MACE are low-effect size and impossible to generalize. Our objective was to determine high-level epistatic risk factors for on-statin MACE with GWAS-scale data. Controlled-access data for 5890 subjects taking a statin collected from Vanderbilt University Medical Center's BioVU were obtained from dbGaP. We used Random Forest Iterative Feature Reduction and Selection (RF-IFRS) to select highly informative genetic and environmental features from a GWAS-scale dataset of patients taking statin medications. Variant-pairs were distilled into overlapping networks and assembled into individual decision trees to provide an interpretable set of variants and associated risk. 1718 cases who suffered MACE and 4172 controls were obtained from dbGaP. Pathway analysis showed that variants in genes related to vasculogenesis (FDR = 0.024), angiogenesis (FDR = 0.019), and carotid artery disease (FDR = 0.034) were related to risk for on-statin MACE. We identified six gene-variant networks that predicted odds of on-statin MACE. The most elevated risk was found in a small subset of patients carrying variants in COL4A2, TMEM178B, SZT2, and TBXAS1 (OR = 4.53, p < 0.001). The RF-IFRS method is a viable method for interpreting complex "black-box" findings from machine-learning. In this study, it identified epistatic networks that could be applied to risk estimation for on-statin MACE. Further study will seek to replicate these findings in other populations.

Managing acute and recurrent idiopathic pericarditis.

Pericarditis is the most common form of pericardial disease and may be associated with significant morbidity and mortality. Management of idiopathic pericarditis includes pharmacologic therapies, non-pharmacologic therapies, and surgery. This article describes the diagnosis and management of idiopathic causes of pericarditis, incorporating recommendations included in the European Society of Cardiology guidelines.