Factor VIII Inhibitor Bypassing Activity (FEIBA) Reversal for Apixaban and Rivaroxaban in Patients With Acute Intracranial and Nonintracranial Hemorrhage.

BACKGROUND: The clinical use of factor VIII inhibitor bypassing activity (FEIBA) for factor Xa (FXa) inhibitor reversal is derived from small studies with notable variation in patient eligibility for use, dosage regimens, concurrent supportive care, and outcome measures. Consequently, additional effectiveness and safety data are warranted to expand the literature evaluating FEIBA for FXa inhibitor reversal. OBJECTIVE: This study sought to determine the incidence of observed effective hemostasis within 24 hours of post-FEIBA® administration as well as in-hospital and 30-day post-discharge incidences of thromboembolic event (TEE) and mortality between apixaban and rivaroxaban in the intracranial hemorrhage (ICH) and non-ICH populations. METHODS: This case series evaluated patients between January 1, 2014 through July 1, 2019 who received at least one FEIBA® dose for apixaban or rivaroxaban reversal secondary to acute ICH or non-ICH. Patient demographics, FEIBA® dosages, adjunct treatments, effectiveness, and safety outcomes were retrospectively collected from electronic medical record review. Modified hemostasis outcomes, adapted from criteria previously published by Sarode et al., TEE, and mortality between apixaban and rivaroxaban in the ICH and non-ICH populations were evaluated. RESULTS: Among the 104 patients evaluated, 62 received apixaban and 42 rivaroxaban. Thirty apixaban and 25 rivaroxaban users experienced ICH, whereas 32 apixaban and 17 rivaroxaban users experienced non-ICH. Among the combined ICH and non-ICH populations, effective hemostasis occurred in 89%, TEE in 8%, and mortality in 13%. No statistically significant differences were observed within ICH and non-ICH populations receiving apixaban or rivaroxaban regarding effective hemostasis, TEE, or mortality. CONCLUSION AND RELEVANCE: The combined ICH and non-ICH overall rates of effective hemostasis, TEE, and mortality were comparable to preexisting studies of FEIBA for factor Xa inhibitor reversal. The limitations inherent to the study design warrant a randomized controlled trial with an active comparator to confirm these observations.

ß-Blockers and the Rate of Chronic Obstructive Pulmonary Disease Exacerbations.

Objective: To review the rate of exacerbations relative to ß-blocker use in patients with chronic obstructive pulmonary disease (COPD). Data Sources: A MEDLINE search (1953 to May 2019) was performed using the search terms beta-blockers, chronic obstructive pulmonary disease, and exacerbations. An EMBASE search was also performed using the search terms chronic obstructive lung disease and beta adrenergic receptor blocking agents (1970 to May 2019). References from the review of literature citations were also identified. Study Selection and Data Extraction: English-language studies assessing COPD exacerbations in patients prescribed a ß-blocker were included. Any article not addressing exacerbations was excluded. Data Synthesis: A total of 15 articles were included; 7 articles showed no change, 1 provided mixed results, and 7 indicated a significant decrease in COPD exacerbations in a variety of exacerbation severities. Two of the studies differentiated between cardioselective and noncardioselective ß-blockers. Relevance to Patient Care and Clinical Practice: This work represents an initial assessment of the use of ß-blockers to reduce COPD exacerbations. The findings raise the question if ß-blockers should be used more frequently in patients with COPD. Conclusions: Based on the limited number of studies that address ß-blocker use in COPD, it appears that exacerbations are not increased and may be decreased. A randomized, placebo-controlled trial is in progress to possibly provide more definitive answers to this question. Until the trial is complete, ß-blockers should not be withheld in COPD patients who have concurrent cardiovascular conditions, especially where there is a mortality benefit.

Effectiveness and Safety Comparison for Systemic Corticosteroid Therapy With and Without Inhaled Corticosteroids for COPD Exacerbation Management.

BACKGROUND: Only 1 small, single-center study has evaluated the combination of systemic plus inhaled corticosteroid (ICS) routes for chronic obstructive pulmonary disease (COPD) exacerbation management. This study aims to further improve the existing quantity and quality of evidence regarding the utility for combination therapy in the management of COPD exacerbation. OBJECTIVES: To evaluate length of hospital stay, readmission rate, incidence of infection, and mortality in hospitalized patients who experience a COPD exacerbation and receive systemic corticosteroid therapy with or without concurrent ICS. METHODS: Design: retrospective cohort study. PARTICIPANTS AND SETTING: patients at least 18 years old admitted between May 31, 2015, and May 31, 2016, for an acute COPD exacerbation at any of 7 Indiana University Health system hospitals. INTERVENTIONS: patients who received an oral or intravenous systemic corticosteroid either with or without concurrent ICS therapy. RESULTS: This study included 241 patients. No significant difference was found between rates of 30-day readmission or inpatient mortality. Patients receiving concurrent therapy had longer lengths of stay versus those who only received systemic corticosteroid therapy (6.35 ± 3.98 vs 4.99 ± 2.89 days, P = 0.0039). Differences in the rates of antifungal use and mechanical ventilation did not statistically differ. Conclusion and Relevance: There was no significant benefit demonstrated when adding ICS to systemic corticosteroid therapy for COPD exacerbation management. These preliminary findings build on the limited evidence on how best to manage corticosteroid therapy in the inpatient setting, but a large, prospective trial remains warranted to confirm these findings given the design, size, and concern for selection bias limitations in the present study.

A Multicenter Analysis of Factors Associated With Apixaban-Related Bleeding in Hospitalized Patients With End-Stage Renal Disease on Hemodialysis.

BACKGROUND: In 2014, the United States Food and Drug Administration approved a labeling change for apixaban to include recommendations for patients with severe renal impairment and patients with end-stage renal disease (ESRD) on hemodialysis (HD), though these recommendations are largely based on pharmacokinetic and pharmacodynamic data. OBJECTIVE: Identify variables associated with bleeding events in hospitalized patients with ESRD on HD receiving apixaban. METHODS: This retrospective, multicenter cohort study evaluated hospitalized patients with ESRD on HD receiving apixaban from January 1, 2013, through March 31, 2016. Correlational analysis and logistic regression were completed to identify factors associated with bleeding. RESULTS: A total of 114 adults were included in the analysis. The median length of stay (LOS) was 6.2 (interquartile range = 3.8-11.9) days and bleeding events occurred in a total of 17 patients (15%). A weak correlation was identified for higher cumulative apixaban exposure, increased number of HD sessions while receiving apixaban, and increased hospital LOS ( P < 0.05; correlation coefficient < 0.40). When controlling for confounders, logistic regression revealed that composite bleeding events were independently increased by continuation of outpatient apixaban (odds ratio = 13.07; 95% CI = 1.54-110.54; P = 0.018), increased total daily dose of apixaban (odds ratio = 1.72; 95% CI = 1.20 to 2.48; P = 0.003), and total HD sessions while receiving apixaban (odds ratio = 2.04; 95% CI = 1.06-3.92; P = 0.033). CONCLUSION: The association between these factors and increased bleeding should prompt concern for long-term anticoagulation with apixaban in patients with ESRD receiving chronic HD.

Hemopericardium and cardiac tamponade associated with dabigatran use.

OBJECTIVE: To describe 2 cases of hemopericardium following treatment with dabigatran. CASE SUMMARIES: A 70-year-old male with a history of dabigatran use presented with cough, fatigue, and bloody stools. The patient had a large hyperdense pericardial effusion caused by accumulation of bloody fluid, leading to hypotension and shock. Approximately 1000 mL of hemorrhagic fluid was drained from the pericardial space. A 77-year-old female was admitted for treatment of pneumonia and atrial fibrillation. Dabigatran was initiated and, after 6 doses, the patient developed abdominal pain, respiratory distress, and shock. She was diagnosed with pericardial effusion leading to cardiac tamponade. Pericardiocentesis and thoracentesis procedures removed a cumulative total of 2000 mL of bloody fluid. DISCUSSION: Dabigatran is an oral direct thrombin inhibitor approved for the reduction of stroke and systemic embolism risk in patients with nonvalvular atrial fibrillation. In December 2011, the Food and Drug Administration released a statement describing serious bleeding events associated with dabigatran use. According to the Naranjo scale, the cases presented here had probable associations between hemopericardium and dabigatran. While there is no known literature supporting this relationship, there are documented cases of warfarin-induced hemopericardium. CONCLUSIONS: These case reports highlight the potential for dabigatran to cause hemopericardium and cardiac tamponade. Additional reports may better elucidate (or characterize) the risk of dabigatran-induced hemopericardium and cardiac tamponade.

Use of cilostazol for secondary stroke prevention: an old dog with new tricks?

OBJECTIVE: To evaluate the safety and efficacy of cilostazol for secondary prevention of non-cardioembolic ischemic stroke. DATA SOURCES: PubMed and MEDLINE searches were performed (January 1970-September 2011) using the key words cilostazol, antiplatelet, aspirin, acetylsalicylic acid, secondary stroke prevention, ischemic stroke, intracerebral hemorrhage, intracranial, cerebrovascular accident, and transient ischemic attack. Additionally, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles published in English and relevant primary literature evaluating the efficacy and safety of cilostazol in the secondary prevention of atherosclerotic ischemic stroke were included. DATA SYNTHESIS: Antiplatelet therapy plays a vital role in the multifaceted approach to secondary stroke prevention. Current American Heart Association/American Stroke Association clinical guidelines for secondary stroke prevention support the use of aspirin, clopidogrel, and combination aspirin/extended-release dipyridamole. The antiplatelet, antithrombotic, and vasodilatory effects of cilostazol make it a potential alternative agent for atherosclerotic stroke prevention. Recent literature has demonstrated superior efficacy of cilostazol 100 mg twice daily for secondary stroke prevention compared to placebo and aspirin. Three clinical trials were reviewed (1 placebo-controlled, 2 aspirin-controlled), all of which were conducted in Japan or China. Cilostazol reduced the primary outcome of recurrence of stroke, with significantly fewer major bleeding events when compared to aspirin. CONCLUSIONS: Available literature suggests that cilostazol may be safer and more effective than aspirin in the secondary prevention of stroke in Asian patients. Further large-scale studies in more heterogeneous study populations are warranted to determine whether cilostazol is a viable therapeutic option for patients with a history of non-cardioembolic ischemic stroke.