sacubitril and Drug-Related-Side-Effects-and-Adverse-Reactions

Frailty is highly prevalent in heart failure populations and a major risk factor for adverse drug reactions (ADRs) and adverse drug events (ADEs). This review aimed to describe the prevalence, causality and severity of ADRs or ADEs from heart failure medications among frail compared with non-frail older adults.. A systematic search of CENTRAL, MEDLINE, Embase, Ageline, CINAHL, International Pharmaceutical Abstracts, PsychInfo, Scopus, registries and citations prior to 18 May 2021 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Risk of bias and quality of evidence were assessed. Eligible studies included randomised controlled trials (RCTs) and observational studies of people diagnosed with heart failure, aged ≥ 65 years, with frailty defined by an objective measurement, and reported ADRs/ADEs from/with heart failure medications.. Two reviewers screened 2419 articles; interrater reliability kappa = 0.88. Three observational studies (n = 2596), a secondary analysis of two RCTs (n = 2098) and two cohort studies (n = 498) were included in a narrative synthesis. Frail patients in randomised trials of sacubitril/valsartan, aliskiren, or enalapril had twice the risk of mortality (hazard ratio [HR] 2.09, 1.62-2.71) and hospitalisations (HR 1.82, 1.37-2.41) compared with robust patients, which may reflect responsiveness to medications and/or factors unrelated to medication use. Hospitalisations from falls, tiredness and nausea were probably attributable to digoxin and possibly preventable according to the Naranjo and Hallas scales, respectively.. The potential harms from heart failure medications in frail older people are poorly studied and understood. Clinical trials and pharmacovigilance studies should include frailty as a covariate to inform medication optimisation for this vulnerable and growing population.. Prospero registration number: CRD 42021253762.

Topics: Aged; Aminobutyrates; Biphenyl Compounds; Drug-Related Side Effects and Adverse Reactions; Frailty; Heart Failure; Humans; Pharmaceutical Preparations; Prevalence

Between 2012 and 2017, the FDA approved 29 therapies for a cardiovascular disease (CVD) indication. Due to the limited literature on patient safety outcomes for recently approved CVD medications, this study investigated adverse drug reports (ADRs) reported in the FDA Adverse Event Reporting System (FAERS).. A disproportionality analysis of spontaneously reported ADR was conducted. Reports in FAERS from Quarter 1, 2012, through Quarter 1, 2019, were compiled, allowing a 2-year buffer following drug approval in 2017. Top 10 reported ADRs and reporting odds ratios (ROR; confidence interval (CI)), a measure of disproportionality, were analyzed and compared to drugs available prior to 2012 as appropriate.. Of 7,952,147 ADR reports, 95,016 (1.19%) consisted of reports for newly approved CVD medications. For oral anticoagulants, apixaban had significantly lower reports for anemia and renal failure compared to dabigatran and rivaroxaban but greater reports for neurological signs/symptoms, and arrhythmias. Evaluating heart failure drugs, sacubitril/valsartan had greater reports for acute kidney injury, coughing, potassium imbalances, and renal impairment but notably, lower for angioedema compared to lisinopril. Assessing familial hypercholesterolemia drugs, alirocumab had greater reports for joint-related-signs/symptoms compared to other agents in this category. A newer pulmonary arterial hypertension treatment, selexipag, had greater reports of reporting for bone/joint-related-signs/symptoms but riociguat had greater reports for hemorrhages and vascular hypotension.. Pharmacovigilance studies allow an essential opportunity to evaluate the safety profile of CVD medications in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved CVD medications.

Topics: Adverse Drug Reaction Reporting Systems; Aminobutyrates; Arrhythmias, Cardiac; Biphenyl Compounds; Cardiovascular Agents; Cardiovascular Diseases; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance; United States; United States Food and Drug Administration