Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Multicenter comparison of antiplatelet treatment strategies for urgent/emergent neuroendovascular stenting.

BACKGROUND: Emergent neuroendovascular stenting presents challenges for the utilization of antiplatelet agents. METHODS: This was a multicenter, retrospective cohort of patients who underwent emergent neuroendovascular stenting. The primary endpoints were thrombotic and bleeding events in relation to the timing of antiplatelet administration, route of administration, and choice of intravenous (IV) agent and the study investigated practice variability in antiplatelet utilization. RESULTS: Five-hundred and seventy patients were screened across 12 sites. Of those, 167 were included for data analysis. For patients who presented with ischemic stroke, artery dissection and emergent internal carotid artery (ICA) stenting who received an antiplatelet agent prior to or during the procedure, 57% were given an IV antiplatelet agent; for patients who were given an antiplatelet agent after the procedure, 96% were given an oral agent. For patients who presented for aneurysm repair and received an antiplatelet agent prior to or during the procedure, 74% were given an IV agent; patients who were given an antiplatelet agent after the completion of the procedure were given an oral antiplatelet agent 90% of the time. In patients who presented with ischemic stroke, artery dissection and emergent ICA stenting who received oral antiplatelet agents post-procedure were more likely to have thrombotic events compared to those who received oral antiplatelet agents prior to or during the procedure (29% vs 9%; p = 0.04). There were no differences in the primary outcomes observed when comparing other antiplatelet treatment strategies. CONCLUSION: The optimal timing of antiplatelet administration in relation to stent placement and route of administration of antiplatelet agents is unclear. Timing and route of administration of antiplatelet agents may have an effect on thrombosis in emergent neuroendovascular stenting. Significant practice variation exists in antiplatelet agent utilization in emergent neuroendovascular stenting.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

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.

Lean into Clinical Pharmacy: An Experience in Implementing Key Performance Indicators and Gemba Walks into Clinical Pharmacy Services.

Purpose: The Lean methodology was applied to clinical metrics by a critical care pharmacy team. The experiences associated with the development and implementation of clinical metrics and their impact on daily workflow are described. Summary: The Lean methodology has been introduced into the healthcare system as a means of process improvement, which can eliminate waste through appropriate medication utilization. At OhioHealth Riverside Methodist Hospital, the department of pharmacy was tasked with the development of clinical metrics after a health system wide Gemba walk was initiated. The pharmacy department's critical care team developed a strategy identifying and evaluating clinical metrics pertaining to their everyday workflow. Each clinical metric was evaluated in accordance with a pre-defined goal. Metrics requiring heavy documentation and those in which the pharmacist does not have autonomous authority to manage were often challenging to implement and were less successful. Throughout this process, the lessons learned focused on generating ideas that were easily documented, evidence-based, and department specific. The critical care team discovered that the outcome of the most successful metrics highlighted clinical pharmacist value and data generated could be used to support funding for additional resources. Conclusion: The critical care pharmacy team developed a streamlined process to implement clinical metrics as means of identifying areas for improvement using the Lean methodology.

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.

Pharmacologic Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is responsible for 5% to 10% of all strokes in the United States annually and is a neurologic emergency with considerable morbidity and mortality. A common complication of aSAH is cerebral vasospasm (CVS) or narrowing of the cerebral arteries. While nearly 70% of aSAH patients will develop CVS, approximately 30% of those patients will go on to develop delayed cerebral ischemia, defined as symptomatic vasospasm or cerebral infarction demonstrated on imaging. While the pathophysiology of CVS is unclear, the prevention and treatment of this complication are a focus of ongoing research. Despite continued efforts, only one medication, nimodipine, is Food and Drug Administration approved for the improvement of neurologic outcomes by reducing the incidence and severity of ischemic deficits in patients with CVS during aSAH. This review provides nurse practitioners and the bedside nursing staff with a summary of the available literature on the pharmacologic management of CVS. It focuses on oral, intravenous, intra-arterial, and intraventricular medications available in the United States that may be utilized in the management of CVS.

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.