Cardiometabolic Consequences of Targeted Anticancer Therapies.

ABSTRACT: Cardiometabolic disease (CMD) is the most common preventable cause of death in the world. A number of components are included in the spectrum of CMD, such as metabolic syndrome/obesity, hyperglycemia/diabetes, dyslipidemia, and hypertension, which are independently associated with cardiovascular disease risk. These conditions often occur together, and patients with cancer frequently undergo treatments that can generate or worsen CMD. This review highlights and presents mechanistic and epidemiological evidence regarding CMD in 4 categories of anticancer medications, namely, mTOR/PI3K-Akt inhibitors, multitargeted tyrosine kinase inhibitor, immune checkpoint inhibitor therapy, and endocrine therapy. Patients taking these medications need careful monitoring during therapy. There is a role for cardio-oncology and onco-primary care specialists in optimally managing patients at risk to mitigate CMD during treatment with these and other investigational anticancer medications.

Outcomes in patients with anthracycline-induced cardiomyopathy undergoing left ventricular assist devices implantation.

AIMS: Improved cancer survivorship has led to a higher number of anthracycline-induced cardiomyopathy patients with end-stage heart failure. We hypothesize that outcomes following continuous-flow LVAD (CF-LVAD) implantation in those with anthracycline-induced cardiomyopathy are comparable with other aetiologies of cardiomyopathy. METHODS AND RESULTS: Using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2008 to 2017, we identified patients with anthracycline-induced cardiomyopathy who received a CF-LVAD and compared them with those with idiopathic dilated (IDM) and ischaemic cardiomyopathies (ICM). Mortality was studied using the Cox proportional hazards model. Other adverse events were evaluated using competing risk models. Overall, 248 anthracycline-induced cardiomyopathy patients underwent CF-LVAD implantation, with a median survival of 48 months, an improvement compared with those before 2012 [adjusted hazards ratio (aHR): 0.53; confidence interval (CI): 0.33-0.86]. At 12 months, 85.1% of anthracycline-induced cardiomyopathy, 86.0% of IDM, and 80.2% of ICM patients were alive (anthracycline-induced cardiomyopathy vs. IDM: aHR: 1.12; CI: 0.88-1.43 and anthracycline-induced cardiomyopathy vs. ICM: aHR: 0.98; CI: 0.76-1.28). Anthracycline-induced cardiomyopathy patients had a higher major bleeding risk compared with IDM patients (aHR: 1.23; CI: 1.01-1.50), and a lower risk of stroke and prolonged respiratory support compared to ICM patients (aHR: 0.31 and 0.67 respectively; both P < 0.05). There was no difference in the risk of major infection, acute kidney injury, and venous thromboembolism. CONCLUSIONS: After receiving a CF-LVAD, survival in patients with anthracycline-induced cardiomyopathy is similar to those with ICM or IDM. Further research into differential secondary endpoints-related disparities is warranted.

Contemporary utilization patterns and outcomes of thrombolytic administration for ischemic stroke among patients with cancer.

BACKGROUND: Thrombolytic therapy significantly improves outcomes among patients with acute ischemic stroke. While cancer outcomes have dramatically improved, the utilization, safety, and mortality outcomes of patients with cancer who receive thrombolytic therapy for acute ischemic stroke are unknown. METHODS: Using a national database, we identified all hospitalizations for acute ischemic stroke requiring thrombolytic therapy between 2003 and 2015. Patients with contraindications to thrombolytic therapy were excluded. Following propensity score matching for comorbidity burden, trends in thrombolytic therapy use and its effect on in-hospital mortality, intracranial or all-cause bleeding, and the combined endpoint of mortality and all-cause bleeding, by presence/absence of cancer were evaluated. We also evaluated 30- and 90-day readmission rates post-thrombolytic therapy administration. RESULTS: We identified 237,687 acute ischemic stroke hospitalizations requiring thrombolytic therapy, of which 26,328 (11%) had an underlying cancer. Over the study period, thrombolytic therapy use increased across all acute ischemic stroke admissions, irrespective of cancer presence (12.4/1000 in 2003 to 81.1/1000 in 2015, P < 0.0001). However, thrombolytic therapy utilization differed by cancer presence (4.8% cancer vs.·5.1% non-cancer, P = 0.001). There was no difference in intracranial bleeding (9.6% vs. 9.7%), all-cause bleeding (13.2% vs. 13.2%), or in-hospital mortality (7.6% vs. 7.2%). While there was no difference in 30-day readmission rates by cancer presence (24% vs. 29%, P = 0.40), at 90-days, cancer patients saw higher readmission rates (17.2% vs. 13.3%, P = 0.02). CONCLUSIONS: Contemporary thrombolytic therapy use for acute ischemic stroke has risen, irrespective of presence of cancer. Yet, patients with comorbid cancer appear to see lower rates of thrombolytic therapy use for acute ischemic stroke, despite no difference in the rate of intracranial bleeding or mortality after adjustment for comorbidities.

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug.

Objective: The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Data Synthesis: Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.