Severity and Hospitalization Cost Related to Warfarin-Related Adverse Events in a Tertiary Malaysian Hospital.

Introduction: Oral anticoagulant is essential for the treatment and prevention of thromboembolism. Warfarin is an effective oral anticoagulant in prevention and treatment of thromboembolism. However, warfarin is frequently associated with adverse event (AE) requiring hospitalization. Method: We performed a retrospective cohort study of all patients admitted to a large tertiary public hospital for warfarin-related AEs. Patients were grouped based on bleeding severity and the direct medical cost was also calculated. Results: During the 4 years study period, a total of 224 patients were admitted for warfarin-related AEs. Mean age of patients admitted was 65.1 years (standard deviation [SD] = 11.5). More than half, 59.6%, of them were on warfarin for prevention of stroke in atrial fibrillation or atrial flutter. Major bleeding occurred among 50.9% of the patients with gastrointestinal bleed, 34 (29.8%), as the common site of bleed. Patients with major bleed had longer median hospital stay of 4 days (interquartile range [IQR] = 5) compared to 3 (IQR = 3) days in non-major bleed. There were 17 (14.9%) death among the major bleeders. Mean medical cost for managing warfarin-related AEs was USD 708.08. Conclusion: The admitted patients were equally distributed in terms of bleeding severity. Medical cost incurred for managing warfarin-related AEs increased with the severity of bleeding.

Comparison of Bleeding Rates between Oral Anticoagulants in Combination with Dual Antiplatelet Therapy (Triple Therapy) in a Real-World Cohort.

Background: Triple antithrombotic therapy including an anticoagulant, P2Y12 inhibitor, and aspirin increases bleed risk up to 27%. The components of this regimen can vary, which may impact bleed risk. Objective: To compare the safety of various triple antithrombotic regimens. Methods: An Institutional Review Board approved retrospective cohort study was conducted from 2014 to 2017. Patients admitted to a large urban health system on triple therapy were evaluated for inclusion. The primary outcome compared rates of International Society of Thrombosis and Hemostasis major and clinically relevant nonmajor bleeding during index admission or within 90 days in patients receiving warfarin, rivaroxaban, or apixaban; aspirin; and a P2Y12 inhibitor. A multivariable logistic regression assessed the association between bleeding, antithrombotic use, and relevant confounding variables. Results: Three hundred and seventy-two patients were included: 238 patients received warfarin, 63 received rivaroxaban, and 71 received apixaban. Forty-five patients (12.1%) experienced a bleed, 25 of which (55.6%) were major. The rate of bleeding was 12.2% (n = 29) with warfarin, 14.3% (n = 9) with rivaroxaban, and 9.9% (n = 7) with apixaban (P = .7335). The use of prasugrel versus clopidogrel (OR 4.35, 95% CI 1.20-15.72; P = .025) and admission hemoglobin less than 12 mg/dL (OR 2.54, 95% CI 1.28-5.04; P = .008) were identified as risk factors associated with bleeding in the model. Conclusion: In patients on triple antithrombotic therapy, choice of oral anticoagulant did not impact bleeding rates, but use of prasugrel and a low baseline hemoglobin were associated with increased bleed rates which warrants further investigation.

The Safety and Efficacy of Verapamil Versus Diltiazem Continuous Infusion for Acute Rate Control of Atrial Fibrillation at an Academic Medical Center.

PURPOSE: Due to critical shortages of intravenous diltiazem in 2018, the Ohio State University Wexner Medical Center (OSUWMC) adopted intravenous verapamil as an alternative. However, there is a paucity of data supporting the use of intravenous verapamil infusions for rate control in the acute treatment of atrial arrhythmias. The purpose of this study was to determine the safety and efficacy of intravenous verapamil as compared with diltiazem for the acute treatment of atrial arrhythmias. METHODS: This retrospective, case-control study compared patients who received verapamil infusions between June 1 and September 30, 2018, with patients who received diltiazem infusions between June 1 and September 30, 2017, at OSUWMC. Patients were matched 1:1 based on age, sex, and the presence of comorbid heart failure with reduced ejection fraction (≤40%). RESULTS: A total of 73 patients who received at least 1 verapamil infusion and 73 patients who received at least 1 diltiazem infusion met inclusion criteria. The composite need for inotrope or vasopressor was similar for both groups (5% with verapamil versus 4% with diltiazem, P = .999). The rate of hypotension was similar between groups (37% versus 33% experiencing a systolic blood pressure <90 mm Hg, P = .603, and 27% versus 23% experiencing a mean arterial pressure <65 mm Hg, P = .704), as was the rate of bradycardia (19% versus 18%, P = .831). The efficacy outcomes of this study were similar for both groups, with 89% of patients in the verapamil group and 90% of patients in the diltiazem group achieving a heart rate less than 110 beats per minute (P = .785). CONCLUSION: Intravenous verapamil and diltiazem infusions had similar safety and efficacy outcomes when used for acute treatment of atrial arrhythmias in the institutional setting.

The Interaction Between Rosuvastatin and Ticagrelor Leading to Rhabdomyolysis: A Case Report and Narrative Review.

OBJECTIVE: Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. METHOD: We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. RESULTS: The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. CONCLUSION: Future pharmacokinetic studies are warranted to better understand the interaction.

Post-Discharge Initiation of Angiotensin Receptor-Neprilysin Inhibitor in an Inotrope-Dependent Patient in the Outpatient Setting: A Case Report.

Purpose: Angiotensin receptor-neprilysin inhibitor (ARNI) therapy has been reported to be initiated in patients on vasoactive medications during acute decompensated heart failure. However, there is no report regarding the safety of initiating ARNI therapy in patients receiving inotrope infusion in an outpatient setting. Summary: We described a case of initiating post-discharge ARNI therapy in a 41-year-old man with inotrope-dependent heart failure in an outpatient setting. Two weeks after the initiation of low dose sacubitril/valsartan, milrinone was successfully discontinued without any adverse effects. Conclusion: With close monitoring, ARNI therapy could be safely initiated in hemodynamically stable patients receiving intravenous inotrope, and further investigation is needed to confirm our findings.

Prevention of anthracycline-induced cardiotoxicity: a systematic review and network meta-analysis.

Background Anthracycline based chemotherapy is commonly used in many malignancies. While life expectancy increases with the use of this medication, cardiac toxicity causes a risk for patients' health due to anthracyclines. Objective This systematic review and meta-analysis emphasizes on prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Methods We conducted a systematic review of electronic databases including PubMed, Medline, EMBASE, ClinicalTrials.gov, Web of Science, and the Cochrane Library from inception to June 2019 collecting published articles on primary prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. We conducted a network meta-analysis and a pairwise meta-analysis in order to compare direct and indirect cardiac agents group with control group calculate left ventricular ejection fraction change. Primary studies results were pooled using random effects model, frequent network meta-analyses, and performed pairwise meta-analysis using netmeta and meta packages respectively in R software version 3.5.1. Results Twelve studies reported left ventricular ejection fraction outcome among 526 patients in the cardiac agent group and 508 in the control group. Based on Surface Under the Cumulative Ranking cure result, spironolactone was the best in left ventricular ejection fraction change and based on meta-analysis, cardiac group had 1.98 unit left ventricular ejection fraction more than the control group (MD = 1.98, 95% CI 0.15-3.81, p value = 0.03). Conclusions The amount of left ventricular ejection fraction used by cardiac agents in anthracycline-based chemotherapy was reduced to a lesser extent. The effective and ineffective drugs were spironolactone and metoprolol, respectively.

Lyme Carditis: A Case Report and Review of Management.

Purpose: A case report of a patient who presented with an acute onset, fluctuating atrioventricular (AV) block and was diagnosed with Lyme carditis is presented. Summary: A 55-year-old man with progressively worsening generalized malaise, flu-like symptoms, dyspnea on exertion, and near syncope was admitted with bradycardia (heart rate was between 20 and 30 beats per minute upon admission). He endorsed having several tick bites after which he developed erythema migrans on his arm and abdomen. An electrocardiogram (ECG) revealed a second-degree AV block, fluctuating between Mobitz type I and Mobitz type II heart block, with a P-R interval of 300 ms. A presumptive diagnosis of Lyme carditis was made based on a confirmed history of tick exposure, presence of erythema migrans, and AV block. The patient was started on ceftriaxone. On day 3 of hospitalization, patient's heart rate was between 50 and 60 beats per minute. A diagnosis of Lyme disease was confirmed based on serologic testing. A repeat ECG revealed a first-degree AV block with a P-R interval of 300 ms. On day 5 of hospitalization, a peripherally inserted central catheter line was placed and the patient was discharged to his home on a 28-day course of ceftriaxone. Patient's heart rate was 65 beats per minute on discharge day. Conclusion: Considering Lyme carditis as a differential diagnosis in patients with an AV block of an unknown etiology can result in a timely diagnosis and treatment of Lyme carditis.

Stability of 2 mg/mL Adenosine Solution in Polyvinyl Chloride and Polyolefin Infusion Bags.

Adenosine is a potent endogenous mediator of vasodilation. Compounded sterile solutions of adenosine are used in cardiac catheterization lab to perform stress tests on the heart. These tests are used to determine the fractional flow reserve (FFR) and are commonly used in the management and diagnosis of cardiovascular conditions. The purpose of this study was to assess the physical and chemical stability of 2 mg/mL adenosine in 0.9% Sodium Chloride Injection, USP in polyvinyl chloride [PVC]) and polyolefin infusion bags stored at room temperature (20°C-25°C) and under refrigeration (2°C-8°C). The compounding and analytical methods used in this study were very similar to those described in the prior publications from the authors' laboratory. To ensure a uniform starting concentration of all stability samples, a batch of 2 mg/mL adenosine solution was prepared and then packaged into empty PVC and polyolefin infusion bags. These stability samples were prepared in triplicate for each bag type and storage temperature (a total of 12 samples). The infusion bag samples were assessed for stability immediately after preparation and after 1 day, 3 days, 7 days, and 14 days. At each time point, the infusion bags were first visually inspected against a light background for color change, clarity, and particulates. Aliquots were drawn from each sample at each time point for pH analysis and high-performance liquid chromatography (HPLC) analysis. Over 14 days of storage at room temperature or refrigeration, no considerable change in visual appearance or pH was observed in any bags. All samples retained 90% to 110% of the initial drug concentration. No significant degradation peaks were observed in the HPLC chromatograms.

Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report.

Dofetilide's hepatotoxicity is not well described. In this case report, we describe acute hepatocellular jaundice related to dofetilide use in a 33-year-old male being treated for atrial fibrillation. Both viral and ischemic causes of hepatocellular damage were ruled out as unlikely in this case. This case report outlines a rare yet probable report of idiosyncratic dofetilide-induced liver injury.