Key Points for Pharmacists From the ACC Expert Consensus Decision Pathway for Patients Hospitalized With Heart Failure.

Heart failure (HF) is a complex condition, and its clinical course often includes periods of decompensation that represent a deterioration in clinical status. During these periods, patients may experience worsening HF symptoms requiring hospitalization. Heart failure that necessitates hospitalization increases the risk of mortality and rehospitalization. In order to help facilitate appropriate care of patients hospitalized with HF, the American College Cardiology (ACC) published an expert consensus decision pathway (ECDP) that focuses on a multidisciplinary approach. The ECDP is divided into multiple nodes and pharmacists play integral roles in each one. There are many opportunities for pharmacists to optimize medical therapy, reinforce adherence, and provide medication and disease state education throughout hospitalization. This review article will highlight inpatient medication management of HF for hospital pharmacists.

Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease.

BACKGROUND: Spironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 and potassium < 5.0 mEq/L prior to initiation; however, spironolactone is prescribed outside these parameters. The objective of this study was to evaluate the safety and tolerability of spironolactone in patients with HF and chronic kidney disease (CKD). METHODS: This single-center, retrospective cohort study evaluated patients ≥ 18 years with HF and CKD stages 3-5 who received ≥ 48 h of spironolactone therapy and were hospitalized from February 2018 to August 2019. The primary outcome was incidence of hyperkalemia (potassium ≥ 5.5 mEq/L). RESULTS: Overall, 121 patients were evaluated: 52.1% (n = 63) had an EF > 40% and 47.9% (n = 58) had an EF ≤ 40% with 69.4% (n = 84) CKD stage 3, 24.8% (n = 30) stage 4, and 5.8% (n = 7) stage 5. Spironolactone was initiated prior to admission (PTA) for 54.5% (n = 66) of patients, while 45.5% (n = 55) of orders were initiated during hospitalization. Eight patients (6.6%) experienced inpatient hyperkalemia-all with PTA spironolactone. Patients who experienced inpatient hyperkalemia had a numerically lower eGFR that was not statistically significant (35.40 vs. 38.22 mL/min/1.73 m2; p = 0.730). Patients with CKD stage 3 (n = 4) had numerically higher rates of inpatient hyperkalemia than stages 4 (n = 1) or 5 (n = 3) (50%, 12.5%, and 37.5% respectively; p < 0.05). CONCLUSION: Spironolactone may be safe to initiate in hospitalized patients with HF and CKD; however, appropriateness of therapy must be assessed upon admission to the hospital. Larger studies are needed for conclusive results.

Predictors of Student Failure or Poor Performance on Advanced Pharmacy Practice Experiences.

Objective. To determine factors predictive of student failure or poor performance on advanced pharmacy practice experiences (APPEs) at a single pharmacy program. Methods. This retrospective cohort evaluated students entering the Doctor of Pharmacy (PharmD) program from 2012-2014 at St. Louis College of Pharmacy. Students who received a grade of F for one or more APPEs (failure group) were compared to all other students (non-failure group). A secondary evaluation compared students with a C or F on one or more APPEs (poor performers) to all other students (non-poor performers). Data were collected on didactic and experiential performance, identifiable professionalism issues from introductory pharmacy practice experiences (IPPEs), and academic honor code violations. Univariable and multivariable logistic regressions were performed to determine factors associated with APPE failure and poor performance. Results. A total of 669 students were analyzed. Twenty-eight students (4.2%) failed one or more APPEs and 81 students (12.1%) were identified as poor performers (grade of C or F). For the primary outcome, professional grade point average (GPA) of less than 2.7, practicum failure, IPPE professionalism issue(s), and pharmacotherapy course failure were identified for inclusion in the multivariable analysis. The IPPE professionalism issue(s) (HR 4.8 [95% CI 1.9-12.4]) and pharmacotherapy course failure (HR 4.2 [95% CI, 1.6-11.1]) were associated with APPE failure on multivariable regression. On the secondary analysis, the same variables were identified for multivariable regression, with professional GPA of less than 2.7 (HR 2.7 [95% CI 1.5-5]), IPPE professionalism issue(s) (HR 3.9 [95% CI 2.2-6.9]), and pharmacotherapy course failure (HR 2.0 [95% CI 1.1-3.7]) associated with poor performance. Conclusion. Poor academic performance and/or identified unprofessional behavior while completing IPPEs are associated with APPE failure and poor performance. Interventions should be aimed at identifying at-risk students and addressing risk factors prior to APPEs.

Flecainide is well-tolerated and effective in patient with atrial fibrillation at 12 months: a retrospective study.

INTRODUCTION: Current atrial fibrillation (AF) guidelines recommend flecainide as a first-line rhythm control option in patients without structural heart disease. While there is proven efficacy in clinical trials and guideline support, it is hypothesized that flecainide may be underutilized due to negative outcomes in the CAST trial and that adverse effects are less common than previously perceived. METHODS: This retrospective chart review evaluated patients ⩾18 years initiated on flecainide for AF from August 2011 to October 2016 by a cardiology provider at the study site. Exclusion criteria included: <5 days of flecainide therapy, AF due to a reversible cause, and inadequate documentation. The primary outcome was efficacy of flecainide at maintaining symptomatic control at 6 and 12 months. Secondary outcomes included characterization of alterations in rhythm control strategies and documented normal sinus rhythm per electrocardiogram at 6 and 12 months. RESULTS: Of the 326 patients identified, 144 patients were included. After 6 and 12 months, 102 patients (70.8%) and 89 patients (61.8%) of the 144 were symptomatically controlled. Atenolol use (p = 0.024), female sex (p = 0.006), hypertension (p = 0.040), and dronedarone failure (p = 0.012) were associated with flecainide discontinuation at 6 months. At 12 months, only previous propafenone failure (p = 0.032) was significant. Of the 144 patients, 16 (11.1%) reported adverse effects with dizziness, hot flashes, bradycardia, and headache (1.4% each) being the most common. CONCLUSION: Flecainide is a well-tolerated medication, even at 12 months, with very minor adverse effects. These results support the utility of flecainide in guideline recommended patient populations.

Evaluating the safety and tolerability of inpatient sacubitril/valsartan initiation in a community hospital.

Background: Sacubitril/valsartan has been incorporated into guidelines based on the results of the PARADIGM-HF trial, which demonstrated reduced mortality in stable patients with heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan is recommended in addition to other HF therapies in place of an angiotensin-converting-enzyme inhibitor or angiotensin-receptor-blocker. Objectives: To evaluate the safety and tolerability of sacubitril/valsartan initiation in a community hospital. Design/methods: This single-center, retrospective review evaluated patients that received ≥24 hours of sacubitril/valsartan therapy August 2015-March 2018. The primary outcome included the incidence of hypotensive events during hospitalization. Secondary outcomes included: incidence of inpatient acute kidney injury (AKI) and hyperkalemia, rates of inpatient discontinuation, and change in ejection fraction (EF) ≥30 days after initiation. Results: Of the 59 patients included, 21 (35.6%) experienced a hypotensive event. A total of 6 patients (10.2%) discontinued therapy while inpatient, which was more likely in patients that developed AKI (n = 3; p = 0.005) or those who experienced a hypotensive event (n = 5; p = 0.018). There was a significant difference in mean EF from baseline to ≥ 30 days post-initiation (24.8% vs. 33.2%; p = 0.018). Conclusion: Careful patient selection and monitoring for hypotension, AKI, and hyperkalemia can help increase successful outcomes and improve patient safety.

Evaluation of the Safety and Effectiveness of Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation and Coexisting Valvular Heart Disease.

BACKGROUND: Current guidelines recommend direct-acting oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF) and valvular heart disease (VHD) without a mechanical valve or moderate to severe mitral stenosis. However, real-world data to support the safety and efficacy of DOACs in this patient population are lacking. OBJECTIVE: Our objective was to assess the safety and effectiveness of DOACs in patients with AF and VHD. METHODS: This retrospective chart review evaluated patients aged ≥ 18 years with a diagnosis of AF and at least moderate VHD on echocardiogram. Patients were included if they received ≥ 1 month of DOAC therapy from December 2016 to December 2018. Patients were excluded if they received dual antiplatelet therapy or had additional indications for anticoagulation. The primary outcomes were incidence of stroke or systemic embolism (SSE) and major bleeding. RESULTS: In total, 200 patients were included (disease type: aortic, n = 50; mitral, n = 50; tricuspid, n = 50; multivalve, n = 50). Most patients received apixaban (n = 133 [66.5%]) followed by rivaroxaban (n = 50 [25%]) and dabigatran (n = 17 [8.5%]). No patients received edoxaban. The mean CHA2DS2-VASc score was 4.25 and was similar among DOAC cohorts (p = 0.380). The overall SSE rate was 3.5% and was highest for dabigatran (n = 3 [17.6%]) compared with the other DOACs (apixaban, n = 1 [0.8%]; rivaroxaban, n = 3 [6%]; p = 0.001). Rates were similar among different valve types (aortic, n = 3 [6%]; mitral, n = 1 [2%]; tricuspid, n = 2 [4%]; multivalve, n = 1 [2%]; p = 0.653). The overall rate of major bleeding was 5.5% and did not differ among the DOACs (apixaban, n = 5 [3.8%]; rivaroxaban, n = 4 [8%]; dabigatran, n = 2 [11.8%]; p = 0.264) or valve type (aortic, n = 3 [6%]; mitral, n = 2 [4%]; tricuspid, n = 2 [4%]; multivalve, n = 4 [8%]; p = 0.787). CONCLUSIONS: In patients with AF and VHD, rates of major bleeding were similar among the DOACs and valve types; however, more patients receiving dabigatran experienced SSE. Further studies are needed to validate these findings.

Evaluation of the effect of prior antiarrhythmic drug use on the success of atrial fibrillation catheter ablation.

WHAT IS KNOWN AND OBJECTIVE: Current guidelines recommend catheter ablation (CA) for atrial fibrillation (AF) refractory to at least one antiarrhythmic drug (AAD), but do not specify an adequate number of AADs to be trialed prior to considering ablation. The objective of this study was to evaluate the effect of CA success based on the number of AADs failed in patients with paroxysmal or persistent AF. METHODS: This retrospective cohort study evaluated patients with paroxysmal or persistent AF who underwent an initial CA at a community hospital. Patients with unknown AAD histories, those who did not achieve acute procedural success, or who were lost to follow-up or death unrelated to thromboembolic stroke within 6 months post-ablation were excluded. Catheter ablation success was defined as freedom from AF. The primary outcome was the incidence of AF or atrial flutter captured on an electrocardiogram or other recording device at 3, 6, 9 and 12 months after the procedure. RESULTS AND DISCUSSION: Overall, 99 out of 103 patients completed 1 year of follow-up. Of those patients, 34 of 99 (34.3%) experienced AF recurrence within 1-year post-ablation. There was no significant difference among the categories of number of failed AADs and the recurrence of AF within 12 months post-ablation for zero AADs, 1 AADs and ≥2 AADs (41.7%, 31.3% and 40%, respectively; P = 0.658). WHAT IS NEW AND CONCLUSION: The results of this study do not support preferentially performing CA on patients who have failed a certain number of AADs. Results are limited by the nature of the study design and a small sample size. Conclusive results would best be addressed by a prospective randomized trial.

A rare case of a gabapentin-induced cardiomyopathy.

WHAT IS KNOWN AND OBJECTIVE: Gabapentin, a γ-aminobutyric acid derivative, is used for the treatment of partial onset seizures, postherpetic neuralgia, diabetic neuropathy and a host of other neurological disorders. CASE DESCRIPTION: A 44-year-old woman with spinal stenosis was prescribed gabapentin for pain. Two months after initiating therapy, she was diagnosed with a new-onset non-ischaemic cardiomyopathy with an ejection fraction of 36% measured on a transthoracic echocardiogram. WHAT IS NEW AND CONCLUSION: A patient with suspected gabapentin-induced cardiomyopathy is reported. However, to date, gabapentin therapy has not been associated with risk of the developing a cardiomyopathy.

Evaluation of the impact of body mass index on warfarin requirements in hospitalized patients.

BACKGROUND: Despite well established empiric dose adjustments for drug and disease-state interactions, the impact of body mass index (BM) on warfarin remains unclear. The objective of this study is to evaluate warfarin requirements in hospitalized patients, stratified by BMI. METHODS: This retrospective review included two cohorts of patients: cohort A (patients admitted with a therapeutic international normalized ratio (INR)) and cohort B (newly initiated on warfarin during hospitalization). Exclusion criteria included: age under 18 years, pregnancy, INR (goal 2.5-3.5), and warfarin thromboprophylaxis post orthopedic surgery. The primary outcome was mean total weekly dose (TWD) of warfarin based on weight classification: underweight (BMI <18 kg/m2), normal/overweight (BMI 18-29.9 kg/m2), obese (BMI 30-39.9 kg/m2), and morbidly obese (BMI ⩾ 40 kg/m2). Data were extracted from two community hospitals in reverse chronologic order during July 2015-June 2013 until both study institutions evaluated 100 patients per cohort in each BMI classification or until all patients had been evaluated within the prespecified timeframe. RESULTS: A total of 585 patients were included in cohort A (26 underweight, 200 normal/overweight, 200 obese, 159 morbidly obese). There was a statistically significant difference in TWD as determined by one-way analysis of variance ( p < 0.05). A Tukey post hoc test revealed a statistically significantly higher TWD in morbidly obese (41.5 mg) compared with underweight (25.6 mg, p < 0.05), normal/overweight (28.8 mg, p < 0.05) and obese patients (32.4 mg, p < 0.05). In cohort B, 379 patients were evaluated (9 underweight, 166 normal/overweight, 152 obese, 52 morbidly obese). Overall, 191 patients had a therapeutic INR on discharge (88.9% underweight, 52.4% normal/overweight, 44.1% obese, 55.8% morbidly obese, p = 0.035). Of those, there was a statistically significant difference in TWD ( p = 0.021) with a higher TWD in the morbidly obese (41 mg) compared with underweight patients (24.4 mg, p = 0.017). CONCLUSIONS: Based on the results of this study, morbidly obese patients may require higher TWD to obtain and maintain a therapeutic INR.

Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Hemodialysis Patients.

Background: Enoxaparin, a low-molecular-weight heparin approved for prophylaxis in patients at risk for venous thromboembolism (VTE), offers several advantages compared with unfractionated heparin (UFH). Enoxaparin is primarily excreted through renal elimination and is currently not recommended in patients receiving hemodialysis (HD) due to potential increased bleeding complications. To date, there are limited safety and efficacy data supporting the use of enoxaparin in this patient population for VTE prophylaxis. Objective: The aim of this study was to compare the safety and efficacy of enoxaparin with UFH for deep venous thromboembolism (DVT) prophylaxis in medically ill HD patients. Methods and Results: This retrospective cohort study examined medically ill patients who received HD and were concomitantly prescribed enoxaparin or UFH for at least 2 consecutive days for VTE prophylaxis. A total of 225 patients (150 received UFH and 75 received enoxaparin) were evaluated in chronological order. The primary outcome was a composite of major, clinically relevant nonmajor, and minor bleeding based on International Society on Thrombosis and Haemostasis bleeding definitions. The secondary outcome was the occurrence of a confirmed thrombotic event. Baseline characteristics were similar between the cohorts. One patient in each cohort had a documented bleed (UFH = 0.7%, enoxaparin = 1.3%, P > .05) during the admission assessed; however, neither bleed was related to the prophylactic agent utilized. No patients developed a VTE during the index hospitalization. Conclusions: This study demonstrates that enoxaparin may be as safe and effective as UFH for VTE prophylaxis in medically ill patients receiving HD.

Comparison of the Safety and Effectiveness of Apixaban versus Warfarin in Patients with Severe Renal Impairment.

STUDY OBJECTIVE: The U.S. Food and Drug Administration approval of the use of apixaban in patients with a creatinine clearance (CrCl) of < 15 ml/minute or in those receiving dialysis is based only on pharmacokinetic data as clinical trials of apixaban excluded patients with a CrCl of < 25 ml/minute or a serum creatinine concentration (SCr) of > 2.5 mg/dl. Thus, the objective of this study was to evaluate the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. DESIGN: Retrospective, matched-cohort study. SETTING: Community hospital. PATIENTS: A total of 146 adults who received at least one dose of apixaban (73 patients) or warfarin (73 patients) while hospitalized between January 30, 2014, and December 31, 2015, and had a CrCl of < 25 ml/minute or SCr of > 2.5 mg/dl, or who received peritoneal dialysis or hemodialysis, were included. Patients who were taking warfarin and had a therapeutic international normalized ratio on admission were matched consecutively in a 1:1 fashion in chronologic order to patients taking apixaban based on renal function and indication for anticoagulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was major bleeding. Secondary outcomes included the composite of bleeding (major bleeding, clinically relevant nonmajor bleeding, and minor bleeding) in addition to documented ischemic stroke or recurrent venous thromboembolism. A nonsignificant difference in the occurrence of major bleeding and composite bleeding was observed between patients who received apixaban compared with those who received warfarin (9.6% vs 17.8%, p=0.149, and 21.9% vs 27.4%, p=0.442, respectively). The occurrence of stroke was similar between the groups (7.5% in each group), and no recurrent venous thromboembolism events were noted in either group during the study period. CONCLUSION: Apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment.

Evaluation of Apixaban for the Treatment of Nonvalvular Atrial Fibrillation With Regard to Dosing and Safety in a Community Hospital.

Background: Apixaban, a direct factor Xa inhibitor, is approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Apixaban's compelling safety and efficacy data, combined with minimal laboratory monitoring, make it an attractive anticoagulant. Objectives: To characterize and evaluate the dosing and safety of apixaban for the treatment of nonvalvular atrial fibrillation at a community hospital. Design/Patients: A retrospective chart review evaluated patients ≥18 years of age who received at least 2 consecutive doses of apixaban from January 1, 2013 to June 30, 2016. Patients with multiple admissions were evaluated for each hospitalization. Patients were excluded if height, weight, or serum creatinine was not documented during hospital admission. Patients who received apixaban for the treatment or prophylaxis of venous thromboembolism were excluded. Prescribing patterns were characterized based on FDA-approved dosing regimens and patient demographics. Safety outcomes included incidences of major, clinically relevant nonmajor, and minor bleeding. Results: Of the 707 patients evaluated, 82% received an FDA-approved apixaban regimen. Of the 127 patients (18%) who received an unapproved regimen, 5.5% (7 patients) received an unapproved frequency and 94.5% (120 patients) received an unapproved dose. The majority (98 patients, 81.7%) were underdosed. Composite bleeding rates were 2.7%, with 1.8% major bleeds, 0.7% clinically relevant nonmajor bleeds, and 0.1% minor bleeds. Conclusions: The use of apixaban must be monitored in order to ensure FDA-approved dosing regimens are being prescribed and patients are not being underdosed.

Comparison of Clevidipine Versus Sodium Nitroprusside for the Treatment of Postoperative Hypertension in Cardiac Surgery Patients.

OBJECTIVE: To evaluate the efficacy and safety of clevidipine (CLV) versus sodium nitroprusside (SNP) for the treatment of hypertension (HTN) in postoperative cardiac surgery patients at a community hospital. METHODS: This single-center, retrospective, cohort study included cardiac surgery patients treated with CLV or SNP for postoperative systolic blood pressure (SBP) control. The primary efficacy outcome was defined as the mean number of times the SBP rose above 140 mm Hg. Secondary outcomes included a comparative cost analysis and a safety analysis. RESULTS: Forty patients were included in each arm. Patients who received CLV had a higher incidence of SBP readings greater than 140 mm Hg (p < .05). There were no differences in safety outcomes, number of patients who received as-needed (PRN) antihypertensives, or mean number of PRN antihypertensives required. There were differences in infusion duration (22.4 hours CLV vs 15.6 hours SNP; p = .035), number of infusions dispensed (2.8 CLV vs 1.3 SNP; p = .001), and length of hospital stay (12.33 days CLV vs 7.65 days SNP; p = .013). However, CLV was less expensive based on the AWP cost at the time of review. CONCLUSIONS: Although a difference in blood pressure control was seen between CLV and SNP, the safety profiles were similar between the 2 drugs. In addition, CLV remained less expensive than SNP for postoperative BP control.

Comparative risk impact of edoxaban in the management of stroke and venous thromboembolism.

Edoxaban, a factor Xa inhibitor, was approved by the United States Food and Drug Administration in 2015 for stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism. It is the fourth target-specific oral anticoagulant to be approved. Edoxaban is noninferior for efficacy compared to warfarin for both approved indications. Edoxaban is superior to warfarin for the first major or clinically relevant nonmajor bleeding event in venous thromboembolism and major bleeding in nonvalvular atrial fibrillation. Edoxaban is dosed once daily for both indications and requires dose adjustment for renal function. In patients with nonvalvular atrial fibrillation, use is not recommended in patients with a creatinine clearance greater than 95 mL/min due to reduced efficacy. Edoxaban offers a new therapeutic alternative to the currently available options in the market.

Edoxaban, a Novel Oral Factor Xa Inhibitor.

OBJECTIVE: To evaluate the current literature and potential clinical role of edoxaban (Savaysa) for stroke prevention in nonvalvular atrial fibrillation (NVAF) and treatment of deep-vein thrombosis and pulmonary embolism. DATA SOURCES: A PubMed and Cochrane Central Register of Controlled trials search was conducted in February 2015 using the search terms edoxaban (ordu-176b) and atrial fibrillation, deep vein thrombosis, pulmonary embolism, or venous thromboembolism. Bibliographies of all retrieved articles were reviewed. All references included were published between 1998 and 2015. STUDY SELECTION/DATA EXTRACTION: All studies that included humans and contained data describing the use of edoxaban for either stroke prevention in patients with NVAF or the treatment of venous thromboembolism (VTE) were reviewed. DATA SYNTHESIS: Edoxaban is a target-specific oral anticoagulant, specifically a factor Xa inhibitor. It has been studied in 4 major randomized controlled trials for the prevention of stroke and systemic embolism in patients with NVAF. One randomized controlled trial was conducted for the treatment of VTE. Edoxaban demonstrated noninferiority of the primary efficacy end point compared with warfarin for both approved indications. The most common adverse effect is bleeding, similar to other anticoagulants. A dosing limitation exists related to patients treated for NVAF with creatinine clearance >95 mL/min; these patients experienced decreased efficacy. CONCLUSIONS: Edoxaban is a safe and effective anticoagulant to reduce the risk of stroke in patients with NVAF and for the treatment of VTE.

Extended-Duration Venous Thromboembolism Prophylaxis in Hospitalized Acutely Ill Medical Patients: A Review of the Evidence.

Objective: To evaluate the risks and benefits of extended-duration thromboprophylaxis (EDT) beyond hospitalization in acutely ill medical patients. Data Sources: PubMed was searched from inception (1946) through February 2015 for the search terms venous thrombosis/prevention and control, venous thromboembolism/prevention and control, anticoagulants, and aspirin. Study Selection and Data Extraction: Relevant clinical trials evaluating pharmacologic strategies for EDT were screened for inclusion. Bibliographies of articles were extensively reviewed for additional sources. Data Synthesis: Three studies, and one additional subgroup analysis, were identified for inclusion. Enoxaparin and rivaroxaban demonstrated a significant reduction in venous thromboembolism (VTE) with EDT, but the benefit with enoxaparin was limited to the highest risk groups and women. The improved efficacy in both studies was accompanied by a ~2.5-fold increase in risk of major hemorrhage. Apixaban was unable to demonstrate a reduction of VTE and was also associated with a significant increase in bleeding. Conclusions: EDT should not be routinely provided to all medically ill patients. It may be considered in patients at the highest risk for VTE, but careful consideration must be used due to the increased risk of bleeding.