Annals of Pharmacotherapy

Background: Loop diuretics play a crucial role in symptom management in patients with fluid overload. There is a paucity of data regarding optimal diuretic dose at hospital discharge for acute decompensated heart failure (ADHF) patients requiring loop diuretics. Objective: To compare all-cause 30-day readmission in ADHF patients on chronic loop diuretics who had an increase in loop diuretic dose at discharge (relative to their preadmission dose) with patients without a change or a decrease in loop diuretic dose at discharge. Methods: This was a multicenter, retrospective cohort study. Institutional review board approval was obtained. Patients admitted with a primary discharge diagnosis of heart failure, evidence of fluid overload, and reduced ejection fraction were included. Patients were divided into 2 groups based on total daily loop diuretic dose at discharge: those discharged on an increased dose and those discharged on a dose less than or equal to their preadmission dose. Results: A total of 131 patient admissions met inclusion criteria; 50 had an increase in loop diuretic dose at discharge, and 81 were discharged with no change or a decrease in diuretic dose. Patients in the increased dose group had an all-cause 30-day readmission rate of 20% compared with 38% of patients with no change or a decrease in diuretic dose (adjusted odds ratio = 0.320; 95% CI = 0.117-0.873). Conclusion: In patients admitted for ADHF with reduced ejection fraction and evidence of fluid overload, an increase in loop diuretic dose at discharge was associated with a reduced rate of 30-day hospital readmission.

Background: The use of preventive cardiovascular medication by patients with low cardiovascular disease (CVD) risk is potentially inappropriate. Objective: The aim of this study was to identify barriers to and enablers of deprescribing potentially inappropriate preventive cardiovascular medication experienced by patients and general practitioners (GPs). Methods: A total of 10 GPs participating in the ECSTATIC trial (Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care) audiotaped deprescribing consultations with low-CVD-risk patients. After initial conventional content analysis, 2 researchers separately coded all barriers to and enablers of deprescribing medication using framework analysis. We performed a within-case and cross-case analysis to explore barriers and enablers among both patients and GPs. Results: Patients (n = 49) and GPs (n = 10) expressed barriers and enablers with regard to the appropriateness of the medication and the deprescribing process. A family history for CVD was identified as a barrier to deprescribing medication for both patients and GPs. Patients feared possible consequences of deprescribing and were influenced by the opinion of their GP. Additionally, a presumed disapproving opinion from specialists influenced the GPs’ willingness to deprescribe medication. Conclusions: Patients appreciated discussing their doubts regarding deprescribing potentially inappropriate preventive cardiovascular medication. Furthermore, they acknowledged their GP’s expertise and took their opinion toward deprescribing into consideration. The GPs’ decisions to deprescribe were influenced by the low CVD risk of the patients, additional risk factors, and the alleged specialist’s opinion toward deprescribing. We recommend deprescribing consultations to be patient centered, with GPs addressing relevant themes and probable consequences of deprescribing preventive cardiovascular medication.

Background: Hyperkalemia occurs frequently in an inpatient setting, for which sodium polystyrene sulfonate (SPS) is a common treatment modality. Few studies have investigated the dose-response of SPS. Objective: To quantify the change in serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS. Secondary objectives were to compare the proportion of patients attaining post–SPS dose normokalemia between dosing groups and to investigate the effect of certain characteristics on SPS dose-response. Methods: The reduction in serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS administered to adult inpatients was evaluated through a retrospective chart review. Ottawa Hospital Research Ethics Board approval was obtained prior to data collection. Results: A total of 118 patients were included in the analysis. Serum potassium levels were reduced by 0.39, 0.69, 0.91, and 0.22 mEq/L following 15-, 30-, and 60-g oral doses and a 30-g rectal dose of SPS, respectively. A greater proportion of patients (50% vs 23%) remained hyperkalemic in the 15-g versus the 60-g group (P = 0.018), and all patients in the rectal group remained hyperkalemic. No patient in any group experienced postdose hypokalemia. The influence of all studied interindividual characteristics on SPS dose-response was clinically nonsignificant. Conclusion: Mild hyperkalemia can be effectively treated with a single 60-g oral dose of SPS as monotherapy, with minimal risk of hypokalemia. Moderate to severe hyperkalemic episodes warrant alternative therapy. The potassium-lowering effect is correlated to SPS dose and is independent of interindividual characteristics.

Background: Atypical antipsychotic use among children and adolescents is a cause for concern secondary to metabolic adverse effects. There have been reports of weight gain, metabolic syndrome, dyslipidemia, glucose abnormalities, and decreased insulin sensitivity in children aged 4 to 19 years using atypical antipsychotics. Objective: To determine the prevalence of antidiabetic and antilipidemic medication use among children and adolescents receiving atypical antipsychotics and to evaluate whether the odds of receiving antidiabetic and antilipidemic medication differs among atypical antipsychotic agents. Methods: This retrospective cross-sectional study included Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010, to July 31, 2011. The participants were categorized into atypical antipsychotic exposed and unexposed. The prevalence of antidiabetic and antilipidemic medication use within the groups was computed. Logistic regression was used to calculate the odds of receiving antidiabetic or antilipidemic medication after controlling for age, sex, and race. Results: A total of 299593 and 4922 beneficiaries were identified in unexposed and exposed groups, respectively. The prevalence of antidiabetic medication use was 0.32% in the unexposed and 1.40% in the exposed group (P < 0.0001). Prevalence of antilipidemic medication use was 0.09% in the unexposed and 0.35% in the exposed group (P < 0.0001). Risperidone and quetiapine users had lower odds than olanzapine users of receiving antidiabetic medication. No differences between the odds of receiving antilipidemic medication among the different antipsychotics (P = 0.1653) were observed. Conclusions: Prevalence of antidiabetic and antilipidemic medication use was significantly higher among children and adolescent atypical antipsychotic users in a Virginia Medicaid population.

Background: Existing data suggest that selective serotonin uptake inhibitors (SSRIs) may have an impact on urinary frequency. Objective: To evaluate the impact of SSRIs and selective noradrenaline reuptake inhibitors (SNRIs) on nocturnal urinary frequency. Methods: This was a retrospective study comparing nocturnal urinary frequency in individuals on SSRI or SNRI therapy versus no therapy during nocturnal polysomnography in a 14-month period at a sleep center. Results: A total of 316 individuals were studied: 94 in the SSRI/SNRI group and 222 controls. No statistically significant difference was found in nocturnal urinary frequency between those on SSRI/SNRI therapy and the control group (0.40 vs 0.34 bathroom visits/night, P = 0.40). The degree of urinary frequency was higher in sertraline users (0.61 bathroom visits/night) compared with duloxetine users (0.18 visits/night, 2-tailed P = 0.04). A post hoc analysis suggested that the difference between these 2 agents is a class effect (SSRIs vs SNRIs, 2-tailed P = 0.03). The sample size did not allow conclusive comparison of either the SSRI or the SNRI group with the control group. Conclusion: SSRI/SNRI agents as a combined group do not appear to have a significant impact on nocturnal urinary frequency. The SSRIs and SNRIs may have an opposite effect on nocturnal frequency.

Objective: To review the role of heart rate in myocardial ischemia and heart failure with reduced ejection fraction (HFrEF) as well as ivabradine’s pharmacology and pharmacokinetics, clinical trials, and place in therapy. Data Sources: We conducted MEDLINE searches from 1980 to October 2015 using the terms heart failure, HFrEF, angina, f-channel inhibitor, and ivabradine, with forward and backward citation tracking. Study Selection and Data Extraction: English-language trials assessing ivabradine were obtained. Studies and narrative reviews of the topic areas were incorporated if they provided relevant data to inform the practicing clinician. Data Synthesis: In the SIGNIFY (Study Assessing the Morbidity-Mortality Benefits of the I_f Inhibitor Ivabradine in Patients with Coronary Artery Disease) trial, there was no difference in the primary composite end point of cardiovascular (CV) mortality or nonfatal myocardial infarction with ivabradine use in patients with stable coronary artery disease (CAD) versus placebo (P = 0.20). In the subgroup with Canadian Cardiovascular Society angina class ≥II, there was an 18% increase in the primary end point with ivabradine versus placebo (P = 0.02). In HFrEF patients, ivabradine reduced CV mortality or heart failure hospitalizations versus placebo, as seen in the SHIFT (Systolic Heart failure treatment with the I_f inhibitor ivabradine Trial; P < 0.05). Conclusions: The SIGNIFY trial negated much of the enthusiasm for using ivabradine in CAD. Ivabradine is a promising therapy in HFrEF based on the results of the SHIFT, but it is an adjunctive therapy, not a substitute for drugs with proven mortality benefits.

Objective: To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. Data Sources: Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. Study Selection and Data Extraction: Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. Data Synthesis: The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. Conclusions: The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

Objective: To evaluate safety and efficacy data for potassium-binding resins in renin-angiotensin-aldosterone system (RAAS)-associated hyperkalemia. Data Sources: A search of MEDLINE (EBSCOhost; 1946 to February 2016) was conducted using the terms hyperkalemia, rennin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonists, resin, and binder. Results were limited to human trials in English language journals. References of identified articles were reviewed to identify other relevant articles. Study Selection and Data Extraction: Concurrent potassium-binding agents and RAAS inhibitor use literature were reviewed. Inclusion criteria a 2-week minimum therapy duration with hyperkalemia or high-risk patients receiving concurrent RAAS-inhibiting agents. Seven articles met inclusion criteria: 1 retrospective case series for sodium polystyrene sulfonate (SPS), 1 noncontrolled study using patiromer, and 5 randomized, placebo-controlled trials using 3 different agents—2 patiromer, 2 sodium zirconium cyclosilicate (SZC), and 1 cross-linked polyelectrolyte (CLP). Data Synthesis: SPS efficacy data are limited to a mean potassium reduction of 1.8 mEq/L in a 14-patient uncontrolled case series. CLP did not reduce hyperkalemia incidence compared with placebo. Patiromer effectively maintained potassium at 0.45 to 0.72 mmol/L lower than placebo while allowing spironolactone dose titration in more patients (91% vs 74%, P = 0.019). SZC also safely and effectively normalized and maintained potassium levels in patients receiving RAAS inhibitors (71%-85% vs 48% for placebo, P < 0.01). Conclusions: Currently, the literature does not support SPS and CLP for preventing RAAS inhibitor–associated hyperkalemia. Patiromer and SZC safely and effectively lower serum potassium and prevent hyperkalemia redevelopment in patients receiving RAAS inhibitors for up to 4 and 8 weeks,0 respectively.

Asthma is a frequent comorbidity in hospitalized children and adults. Patients with a history of asthma may have no breathing complaints or abnormal chest exam findings to trigger care for this comorbidity during hospitalization. Consequently, this may lead to a potential missed opportunity to discuss asthma as a comorbidity and ongoing issue to ensure its optimal management at home. Our goal is to raise awareness that such patient encounters may represent opportunities for health care professionals to optimize asthma management. Despite focusing on the present illness and limited time availability, asthma care may be improved in a time-efficient manner in these patients.