Drug-induced heart failure

Maxwell, C.; Jenkins, Antoine T.

doi:10.2146/ajhp100637

Cited by 25 publications

(12 citation statements)

References 88 publications

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“…Potential confounders data acquired: BMI, weight, height, and smoking status last recorded before the index date, alcohol abuse, and drug abuse; history of chronic diseases, known to be associated with HF, diagnosed before cohort entry to avoid adjusting for factors affected by exposure: diabetes mellitus, hypertension, hyperlipidaemia, ischaemic heart disease, peripheral vascular disease, carotid artery disease, atrial fibrillation, other arrhythmias, valvular heart disease, chronic renal failure, and cirrhosis; medications known to be potentially associated with HF (Maxwell and Jenkins, 2011), dispensed in the last year before the index date; other antineoplastic and immunomodulating agents dispensed in the last year before the index date; and radiotherapy (all fields) during follow-up until index date. Antiarrhythmic drugs used were assessed before cohort entry because these drugs, in addition to being a potential cause for HF, can also be on the causal path between exposure and HF (when prescribed for an arrhythmia caused by exposure to chemotherapy or to a tyrosine kinase-targeting drug).…”

Section: Methodsmentioning

confidence: 99%

Tyrosine kinase-targeting drugs-associated heart failure

et al. 2017

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Background:The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF).Methods:A nested case–control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012. Each new case of HF was matched to up to 30 controls from the cohort on calendar year of cohort entry, age, gender, and duration of follow-up. Main outcome measure was odds ratio (OR) with 95% confidence interval (CI) of new-onset HF.Results:There were 936 incident cases of HF during 71 742 person-years of follow-up. Trastuzumab (OR 1.90, 95% CI 1.46–2.49), cetuximab (OR 1.72, 1.10–2.69), panitumumab (OR 3.01, 1.02–8.85), and sunitinib (OR 3.39, 1.78–6.47) were associated with increased HF risk. Comorbidity independently associated with higher risk in a multivariable conditional regression model was diabetes mellitus, hypertension, chronic renal failure, ischaemic heart disease, valvular heart disease, arrhythmia, and smoking.Conclusions:Trastuzumab, cetuximab, panitumumab, and sunitinib are associated with increased risk for new-onset HF.

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Section: Methodsmentioning

confidence: 99%

Tyrosine kinase-targeting drugs-associated heart failure

et al. 2017

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“…Other conditions associated with an increased risk of HFPEF include sleep apnea,(34) chronic obstructive pulmonary disease,(35) renal dysfunction,(31) dyslipidemia/cardiac steatosis,(36) rheumatoid arthritis and other systemic inflammatory diseases,(37–40) and select medications (especially antineoplastic therapy)(41) although the exact and independent role of these contributing conditions to the risk of HFPEF remains to be determined.…”

Section: Risk Factorsmentioning

confidence: 99%

Epidemiology of Heart Failure with Preserved Ejection Fraction

Andersson

Vasan

2014

Heart Failure Clinics

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Heart failure with preserved ejection fraction (HFPEF) is a common condition, especially among the elderly and in women, with the reported prevalence approaching 10% in women over the age of 80 years. With an increasing prevalence of hypertension, obesity, atrial fibrillation, and diabetes, and the growing elderly segment of the general population, the prevalence of HFPEF is projected to increase further. HFPEF presents a diagnostic challenge. As a consequence, studies differ widely in their reported incidence and mortality rates associated with this condition, although there is agreement that between a third and one half of heart failure patients in the community have HFPEF. Although several consensus statements and guidelines have been published during the last decade, some of the recent randomized clinical trials have reported low mortality rates, raising doubts whether all patients diagnosed with HFPEF do actually suffer from HFPEF (as opposed to misdiagnosis) or if the condition is heterogeneous by nature in terms of its etiology and prognosis. The overall reported prognosis of patients with HFPEF remains poor, with patients experiencing substantial comorbidity, high rates of repeated hospitalizations, and a high mortality. In both community-based and hospital-based cohorts, HFPEF was recently reported to be associated with approximately 159 (154–165) deaths per 1000 person-years.

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“…In randomized controlled trials of onychomycosis, complete cure rates reflecting both mycological and clinical cures for terbinafine and itraconazole range from approximately 35 to 50% (10). Moreover, both drug classes carry safety warnings pertaining to liver toxicity (11,12) and drug-drug interactions (13), with a small but significant percentage of more serious side effects (14)(15)(16). As a consequence, many patients choose not to pursue oral therapy.…”

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confidence: 99%

VT-1161 Dosed Once Daily or Once Weekly Exhibits Potent Efficacy in Treatment of Dermatophytosis in a Guinea Pig Model

Garvey

Hoekstra

Moore

et al. 2015

Antimicrob Agents Chemother

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c Current therapies used to treat dermatophytoses such as onychomycosis are effective but display room for improvement in efficacy, safety, and convenience of dosing. We report here that the investigational agent VT-1161 displays potent in vitro antifungal activity against dermatophytes, with MIC values in the range of <0.016 to 0.5 g/ml. In pharmacokinetic studies supporting testing in a guinea pig model of dermatophytosis, VT-1161 plasma concentrations following single oral doses were dose proportional and persisted at or above the MIC values for at least 48 h, indicating potential in vivo efficacy with once-daily and possibly once-weekly dosing. Subsequently, in a guinea pig dermatophytosis model utilizing Trichophyton mentagrophytes and at oral doses of 5, 10, or 25 mg/kg of body weight once daily or 70 mg/kg once weekly, VT-1161 was statistically superior to untreated controls in fungal burden reduction (P < 0.001) and improvement in clinical scores (P < 0.001). The efficacy profile of VT-1161 was equivalent to those for doses and regimens of itraconazole and terbinafine except that VT-1161 was superior to itraconazole when each drug was dosed once weekly (P < 0.05). VT-1161 was distributed into skin and hair, with plasma and tissue concentrations in all treatment and regimen groups ranging from 0.8 to 40 g/ml (or g/g), at or above the MIC against the isolate used in the model (0.5 g/ml). These data strongly support the clinical development of VT-1161 for the oral treatment of onychomycosis using either once-daily or once-weekly dosing regimens. F ungal infections of the skin, nails, and hair by dermatophytes, yeasts, and nondermatophyte molds are a common occurrence (1-3), with an estimated worldwide prevalence of 20% to 25% (1). In a survey of ambulatory records in the United States, these infections necessitated an average of 4 million physician visits per year from 1995 to 2004 (4), and the majority of these infections were caused by dermatophytes. The worldwide distribution of causative fungi and types of infection are dependent on geography, environment, and cultural factors (1, 2). Consistent with most of Europe and the United States (1, 2), a recent retrospective study found that onychomycosis (also referred to as tinea unguium) was the most common dermatophyte infection and that the absolute number of onychomycosis cases increased 10-fold over a 40-year period (5). This increase can be partly explained by the increases of two at-risk populations, the elderly (6) and diabetics (7). The most common species causing onychomycosis in Europe and the United States are Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum (8).Current oral treatment options for superficial fungal infections include allylamines, such as terbinafine, and azole-based fungal sterol 14␣-demethylase (CYP51) inhibitors (8, 9). The azoles fall into two classes defined by the moiety that binds the heme iron within the active site of CYP51, the imidazoles (e.g., ketoconazole), which are rarely used orally due...

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Drug-induced heart failure

Abstract: A variety of agents have been associated with drug-induced HF. Patients receiving agents that have been implicated in cases of new-onset HF or exacerbations of HF should be monitored for signs and symptoms of CV effects.

Cited by 25 publications

References 88 publications

Tyrosine kinase-targeting drugs-associated heart failure

Tyrosine kinase-targeting drugs-associated heart failure

Epidemiology of Heart Failure with Preserved Ejection Fraction

VT-1161 Dosed Once Daily or Once Weekly Exhibits Potent Efficacy in Treatment of Dermatophytosis in a Guinea Pig Model

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