Temporal Effect of CYP3A4/5 Induction on Ticagrelor's Pharmacodynamic Effects: A Case Series.

Ticagrelor is contraindicated in combination with cytochrome P450 3A4 and 3A5 enzyme (CYP3A4/5) inducers due to increased clearance, causing diminished antiplatelet effects. The emergent nature of acute coronary syndromes (ACS) may preclude scrutinization of home medications before P2Y12 inhibitor administration. The purpose of this case series is to establish the temporal impact of CYP3A4/5 enzyme induction on ticagrelor's pharmacodynamic effect by utilizing VerifyNow platelet aggregation studies. This was a retrospective case series of three patients who were taking a CYP3A4/5-inducing medication and loaded with ticagrelor for ACS. The duration of ticagrelor's antiplatelet effect was dramatically shortened in the presence of background CYP3A4/5 induction. The offset of antiplatelet effect, defined by platelet reactivity units (PRU), was 10-24 hours in the presence of CYP3A4/5 enzyme induction compared to the anticipated 36-48 hours. This was consistent across CYP3A4/5-inducing medications including carbamazepine, phenobarbital, and phenytoin. This study demonstrates rapid return of platelet function after a ticagrelor loading dose in the presence of CYP3A4/5-inducing medications. Monitoring of PRU every 6-12 hours with subsequent loading with clopidogrel or prasugrel should be considered. Larger scale studies are warranted to confirm these results.

Evaluating Guideline Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction Post-coronary Artery Bypass Grafting.

Background: Limited evidence regarding the use of guideline directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG) is available. Objective: The purpose of this study was to characterize prescription of HFrEF GDMT use before and after CABG. Methods: A retrospective analysis of adult patients with an ejection fraction ≤40% undergoing CABG was performed. The primary objective was to evaluate patients receiving HFrEF GDMT, defined as a heart failure beta-blocker (HFBB) and a renin-angiotensin inhibitor preoperatively and postoperatively. Secondary outcomes included dosing, percent of patients on each individual therapy, mineralocorticoid receptor antagonist (MRA) use, and the combination thereof. The follow up period was 1 year. Results: Thirty-eight patients met criteria for inclusion. Prior to CABG, 52.6% of patients were receiving HFrEF GDMT. The prescribing rate of HFrEF GDMT was not significantly higher at any point within 1 year postoperatively (P = .299). The rate of renin-angiotensin inhibitors, HFBB, and aldosterone antagonists use significantly increased from 13.2% preoperatively to 36.8% at 1 year after CABG (P = .022). Doses of individual therapies were not significantly different across all time points preoperatively and postoperatively. Conclusion: HFrEF GDMT use and doses of individual therapies after CABG were not maximized. Collaborative efforts between cardiac surgeons, heart failure cardiologists, and pharmacists could be used to optimize HFrEF GDMT use and dose titration.

Meta-Analysis Comparing Bivalirudin Versus. Unfractionated Heparin in Adult Patients With Extracorporeal Membrane Oxygenation.

Introduction: Unfractionated heparin (UFH) has traditionally been the agent of choice in patients on extracorporeal membrane oxygenation (ECMO). However, direct thrombin inhibitors (DTI) have recently garnered more attention in ECMO because of their advantages over UFH. Given the heterogeneous results of multiple recent published studies, we performed a meta-analysis to describe pooled outcomes between bivalirudin and UFH anticoagulation in patients on ECMO. Methods: Relevant studies were identified from MEDLINE and Google Scholar database searches through April 23, 2022. The primary efficacy outcome was thromboembolism (TE), and secondary efficacy outcomes included all-cause mortality and circuit thrombosis. The primary safety outcome was major bleeding. Results: A total of 6 studies were included in the meta-analysis. Bivalirudin use was associated with significantly lower risk of TE (OR 0.61; 95% CI 0.38-.99; P = .05; I2 = 0%) and circuit thrombosis (OR 0.51; 95% CI .32-.80; P = .004; I2 = 0%) compared with UFH. There was no significant difference in all-cause mortality risk (OR 0.75; 95% CI .52-1.09; P = .13; I2 = 30%) between the bivalirudin and UFH groups. No significant difference in the risk of major bleeding between 2 groups was found (OR 0.67; 95% CI 0.25-1.81; P = .43; I2 = 80%). Conclusion: These data support that bivalirudin is a reasonable alternative to UFH in patients on ECMO. Randomized controlled trials are needed to confirm bivalirudin's efficacy and safety results compared with UFH.

Sacubitril/Valsartan Off-Label Uses for Heart Failure.

Sacubitril/valsartan is an angiotensin receptor/neprilysin inhibitor that the Food and Drug Administration has indicated to reduce the risk of cardiovascular hospitalization and death in patients with left ventricular ejection fraction below normal and with no specified ejection-fraction cut-off. However, clinically significant patient groups were excluded or minimally represented in sacubitril/valsartan's pivotal clinical trials. Clinicians often encounter scenarios in which a sacubitril/valsartan off-label use may be beneficial, but limited resources are available to evaluate the efficacy and safety in these patients. This state-of-the-art review describes contemporary literature for sacubitril/valsartan Food and Drug Administration off-label indications to help clinicians assess its appropriateness in these selected, clinically important groups of patients: those with acute decompensated heart failure, acute coronary syndrome, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, adult congenital heart disease, cardiomyopathy in dialysis patients, right ventricular failure, or durable left ventricular assist device.

Atrial Fibrillation Management: A Comprehensive Review with a Focus on Pharmacotherapy, Rate, and Rhythm Control Strategies.

Atrial fibrillation (AF) is an increasingly common arrhythmia encountered in clinical practice that leads to a substantial increase in utilization of healthcare services and a decrease in the quality of life of patients. The prevalence of AF will continue to increase as the population ages and develops cardiac comorbidities; thus, prompt and effective treatment is important to help mitigate systemic resource utilization. Treatment of AF involves two tenets: prevention of stroke and systemic embolism and symptom control with either a rate or a rhythm control strategy. Historically, due to the safe nature of medications like beta-blockers and non-dihydropyridine calcium channel blockers, used in rate control, it has been the initial strategy used for symptom control in AF. Newer data suggest that a rhythm control strategy with antiarrhythmic medications with or without catheter ablation may lead to a reduction in major adverse cardiovascular events, particularly in patients newly diagnosed with AF. Modulation of factors that promote AF or its complications is another important aspect of the overall holistic management of AF. This review provides a comprehensive focus on the management of patients with AF and an in-depth review of pharmacotherapy of AF in the rate and rhythm control strategies.

Risk of pump thrombosis and stroke in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding.

Gastrointestinal (GI) bleeding is a common complication following the placement of continuous-flow left ventricular assist devices (LVADs) in patients with advanced heart failure. Secondary events arising as a result of GI bleeding have not been well-described. Furthermore, attribution of these events to bleeding is complicated by the interruption or de-intensification of antithrombotic therapy, while bleeding is controlled. The purpose of this study was to assess the incidence of pump thrombosis and ischemic stroke in patients with LVADs who experience GI bleeding, while on support. This was a single-center, retrospective, observational cohort study of consecutive patients with LVADs implanted from January 2012 to June 2018. Patients were assigned to comparator groups based on whether they experienced GI bleeding while on LVAD support. The primary endpoint assessed was the composite of pump thrombosis or ischemic stroke. Secondary endpoints assessed included incidence of pump thrombosis or ischemic stroke. A total of 250 patients were included after screening for exclusion criteria, 101 (40.4%) in the GI bleeding group, and 149 (59.6%) in the non-bleeding group. The incidence of pump thrombosis or ischemic stroke was not significantly greater in patients experiencing GI bleeding [23 (22.8%) vs. 21 (14.1%); P = .09]; however, the incidence of ischemic stroke alone was significantly greater [17 (16.8%) vs. 10 (6.7%); P = .01]. We conclude that GI bleeding in LVAD patients may be associated with a greater risk of ischemic stroke.

Anticoagulation of Impella with a Bivalirudin Purge Solution.

The use of percutaneous ventricular assist devices (VADs) in the acute management of cardiogenic shock is becoming increasingly common. The Impella is a percutaneous VAD, which requires a heparin-containing purge solution to prevent thrombosis and maintain proper pump functionality. In this report, we describe two patients with heparin-induced thrombocytopenia (HIT) supported with an Impella using a bivalirudin-containing purge solution. Case 1 involved a 39-year-old man with cardiogenic shock, initially implanted with an intraaortic balloon pump, who developed HIT early in his hospital course. His worsening hemodynamics necessitated the placement of an Impella and later venoarterial extracorporeal membrane oxygenation until he eventually underwent durable left VAD implantation. Case 2 involved a 69-year-old man who had an Impella implanted for worsening cardiogenic shock. HIT was suspected shortly after device insertion, necessitating switching his anticoagulation to bivalirudin. He was successfully bridged directly to heart transplantation. Both patients' courses resulted in therapeutic anticoagulation without major bleeding or thrombotic events. These cases demonstrate the safe and effective use of bivalirudin-containing purge solutions for patients with confirmed HIT requiring temporary mechanical circulatory support with Impella.