Frequency and preventability of adverse drug events in the outpatient setting.

BACKGROUND: Limited data exist regarding adverse drug events (ADEs) in the outpatient setting. The objective of this study was to determine the incidence, severity, and preventability of ADEs in the outpatient setting and identify potential prevention strategies. METHODS: We conducted an analysis of ADEs identified in a retrospective electronic health records review of outpatient encounters in 2018 at 13 outpatient sites in Massachusetts that included 13 416 outpatient encounters in 3323 patients. Triggers were identified in the medical record including medications, consultations, laboratory results, and others. If a trigger was detected, a further in-depth review was conducted by nurses and adjudicated by physicians to examine the relevant information in the medical record. Patients were included in the study if they were at least 18 years of age with at least one outpatient encounter with a physician, nurse practitioner or physician's assistant in that calendar year. Patients were excluded from the study if the outpatient encounter occurred in outpatient surgery, psychiatry, rehabilitation, and paediatrics. RESULTS: In all, 5% of patients experienced an ADE over the 1-year period. We identified 198 ADEs among 170 patients, who had a mean age of 60. Most patients experienced one ADE (87%), 10% experienced two ADEs and 3% experienced three or more ADEs. The most frequent drug classes resulting in ADEs were cardiovascular (25%), central nervous system (14%), and anti-infective agents (14%). Severity was ranked as significant in 85%, 14% were serious, 1% were life-threatening, and there were no fatal ADEs. Of the ADEs, 22% were classified as preventable and 78% were not preventable. We identified 246 potential prevention strategies, and 23% of ADEs had more than one prevention strategy possibility. CONCLUSIONS: Despite efforts to prioritise patient safety, medication-related harms are still frequent. These results underscore the need for further patient safety improvement in the outpatient setting.

A Calculated Risk: Evaluation of QTc Drug-Drug Interaction (DDI) Clinical Decision Support (CDS) Alerts and Performance of the Tisdale Risk Score Calculator.

INTRODUCTION: A risk factor for a potentially fatal ventricular arrhythmia Torsade de Pointes is a prolongation in the heart rate-corrected QT interval (QTc) ≥ 500 milliseconds (ms) or an increase of ≥ 60 ms from a patient's baseline value, which can cause sudden cardiac death. The Tisdale risk score calculator uses clinical variables to predict which hospitalized patients are at the highest risk for QTc prolongation. OBJECTIVE: To determine the rate of overridden QTc drug-drug interaction (DDI)-related clinical decision support (CDS) alerts per patient admission and the prevalence by Tisdale risk score category of these overridden alerts. Secondary outcome was to determine the rate of drug-induced QTc prolongation (diQTP) associated with overrides. METHODS: Our organization's enterprise data warehouse was used to retrospectively access QTc DDI alerts presented for patients aged ≥ 18 years who were admitted to Brigham and Women's Hospital during 2022. The QTc DDI CDS alerts were included if shown to a physician, fellow, resident, physician assistant, or nurse practitioner when entering the order in inpatient areas for patients with a length of stay of at least 2 days. Variables collected for the Tisdale calculator included age, sex, whether patient was on a loop diuretic, potassium level, admission QTc value, admitting diagnosis of acute myocardial infarction, sepsis, or heart failure, and number of QTc-prolonging drugs given to the patient. RESULTS: A total of 2649 patients with 3033 patient admissions had 18,432 QTc DDI alerts presented that were overridden. An average of 3 unique QTc DDI alerts were presented per patient admission and the alerts were overridden an average of 6 times per patient admission. Overall, 6% of patient admissions were low risk (score ≤ 6), 64% moderate risk (score 7-10), and 30% high risk (score ≥ 11) of QTc prolongation. The most common QTc DDI alerts overridden resulting in an diQTP were quetiapine and propofol (11%) and amiodarone and haloperidol (7%). The diQTP occurred in 883 of patient admissions (29%) and was more frequent in those with higher risk score, with 46% of patient admissions with diQTP in high risk, 23% in moderate risk, and 8% in low risk. CONCLUSION: Use of the Tisdale calculator to assess patient-specific risk of QT prolongation combined with CDS may improve overall alert quality and acceptance rate, which may decrease the diQTP rate.

Changes in Metabolic Parameters of Hemoglobin A1c, Weight, and Blood Pressure During and After COVID-19 Stay-at-Home Orders.

BACKGROUND: Due to the COVID-19 pandemic, a "state of emergency" was declared in North Carolina on March 10, 2020. Subsequent "stay-at-home" (SAH) orders restricted activities including use of fitness facilities, and teleworking was encouraged. This study investigates metabolic effects of these changes in activity level. METHODS: This retrospective prepost study included adults diagnosed with type 2 diabetes mellitus and hypertension with hemoglobin A1c (HbA1c), weight, and blood pressure (BP) measurements for 3 time periods: 3/10/2019-9/9/2019 ("pre-SAH"), 3/10/2020-9/9/2020 ("during SAH"), and 3/10/2021-9/9/2021 ("post-SAH"). The primary outcome was change in HbA1c pre-SAH to during SAH and during SAH to post-SAH. Secondary outcomes were changes in weight, systolic BP (SBP), and diastolic BP (DBP) over the same periods. Exploratory outcomes included health care utilization. Paired t test compared outcomes between time periods using Bonferroni-adjusted α of 0.025 for significance. RESULTS: Analysis included 301 participants with an average age of 69.8 years. HbA1c, SBP, and DBP trended up from pre-SAH to during SAH and then decreased post-SAH with a significant change only for DBP from during SAH to post-SAH (74.2 mmHg to 73.6 mmHg, P < .001). Weight trended down across the 3 study periods. In-office visits significantly decreased from pre-SAH to during SAH, and telehealth visits significantly decreased from during SAH to post-SAH (both P < .001). CONCLUSIONS: With the exception of DBP, findings reveal consistency in HbA1c, weight, and BP across time periods before, during, and after COVID-19 SAH orders in North Carolina.

Use of Cardioprotective Antidiabetic Medications in Adults With and Without Cardiovascular Disease, 2015 to March 2020.

BACKGROUND: Certain glucagon-like peptide-1 receptor (GLP-1) agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2-inhibitors) can reduce cardiovascular risk in individuals with type 2 diabetes and cardiovascular disease (CVD). However, these medications can be expensive, potentially limiting their use. Objectives: The primary objective was to characterize the use of cardioprotective GLP-1 agonists and SGLT2-inhibitors among adults with diabetes with and without CVD. The secondary objective was to investigate the association of socioeconomic factors and health care utilization with the use of these medications. METHODS: Adults aged ≥20 years old with self-reported diabetes, A1c ≥6.5%, or fasting glucose ≥126 mg/dL were identified using the 2015 to March 2020 National Health and Nutrition Examination Survey. The primary outcome was the use of cardioprotective GLP-1 agonists or SGLT2-inhibitors compared in individuals with and without CVD. Secondary analyses included identification of socioeconomic factors and health care utilization associated with the use of cardioprotective antidiabetic medications, stratified by CVD status. Weighted analyses were conducted to account for the complex survey design. RESULTS: Use of cardioprotective antidiabetic medications was higher in adults with CVD compared to those without CVD (7.8% vs. 4.6%, P = 0.02), which was driven by the use of cardioprotective SGLT2-inhibitors (4.6% versus 1.9%, P = 0.002). Lower income level and less frequent health care visits within the past year were associated with lower likelihood of using these medications. CONCLUSION AND RELEVANCE: Despite preferential use in individuals with diabetes and CVD, the prevalence of cardioprotective antidiabetic medication use remains relatively low. Disparities in use appear to exist based on income level and health care utilization.

Evaluation of the change in glycated hemoglobin for patients in an employee health program formerly managed by a pharmacist-run ambulatory care clinic.

PURPOSE: To evaluate the change in mean glycated hemoglobin (HbA1c) for patients with diabetes in an employee health program after discontinuation of management by a clinical pharmacist. METHODS: This was a single-center, retrospective chart review of patients followed by a clinical pharmacist from January 1, 2020, through March 31, 2021. Patients included had type 2 diabetes, were 18 years of age or older, were not pregnant, and were not using an insulin pump. The baseline visit was defined as the last pharmacist visit within the study period. The follow-up visit was defined as the most recent visit upon chart review that occurred at least 5 months after the baseline visit. The primary and secondary endpoints were the mean change in HbA1c and number of antihyperglycemic agents from baseline to follow-up, respectively. Statistical analysis included descriptive statistics for baseline characteristics, a paired t test for the primary endpoint, and a McNemar test for the secondary endpoint. RESULTS: A total of 590 patients were screened, of whom 131 were included in the analysis. For the primary outcome, the mean baseline HbA1c was 7.3% while that at follow-up was 7.41% (mean change of 0.11%; SD, 1.22%; P = 0.326). For the secondary outcome, the baseline number of antihyperglycemic agents was 274 while the follow-up number was 276. There were no statistically significant differences for the primary and secondary outcomes. CONCLUSION: This study highlights a unique patient population with controlled HbA1c at baseline, for whom diabetes control may potentially be influenced by the patients' employment within a healthcare system and improved access to care. The lack of a significant difference in the primary endpoint implies that it may be appropriate to limit or have less frequent pharmacist visits for well-controlled patients. Further research should investigate how to identify patients who would benefit from continued follow-up with a clinical pharmacist vs those who can be managed with minimal resources.

Association between mental health and self-care behavior among older adults with diabetes according to Behavioral Risk Factor Surveillance System 2019.

AIM: To assess the association of mental health burden with diabetes-related self-care behaviors and healthcare utilization among older adults. METHOD: This cross-sectional 2019 Behavioral Risk Factor Surveillance System (BRFSS) study included ≥ 65 years old adults with self-reported diabetes. Three groups were used based on the number of days in the past month affected by mental health: 0 days (no burden), 1-13 days (occasional burden), and 14-30 days (frequent burden). Primary outcome was performing ≥ 3 of 5 diabetes-related self-care behaviors. Secondary outcome was performing ≥ 3 of 5 healthcare utilization behaviors. Multivariable logistic regression was used in Stata/SE 15.1. RESULTS: Of 14,217 included individuals, 10.2 % reported frequent mental health burden. Compared to 'no burden', 'occasional' and 'frequent burden' groups included more female, obese, not married persons with younger age of diabetes diagnosis, and reported more comorbidities, insulin use, cost-related barriers to see doctors, and diabetes-related eye issues (p < 0.05). 'Occasional/frequent burden' groups reported less self-care and healthcare utilization behaviors, except 30 % higher healthcare utilization was observed in the 'occasional burden' group compared to no burden (aOR 1.30, 95 %CI 1.08-1.58, p = 0.006). CONCLUSIONS: Overall, mental health burden was associated with reduced participation in diabetes-related self-care and healthcare utilization behaviors in a stepwise manner, except occasional burden was associated with higher healthcare utilization.

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice.

OBJECTIVE: The objective of this article was to review pharmacology, efficacy, safety, and place in therapy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched through September 7, 2022, using the keyword "tirzepatide." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with available results were included. DATA SYNTHESIS: Seven published phase 3, multicenter, randomized, parallel-group trials investigated efficacy and safety of tirzepatide versus placebo, semaglutide, insulin degludec, and insulin glargine for type 2 diabetes mellitus (T2DM) treatment. Studies included adults with uncontrolled T2DM and body mass index above 23 or 25 kg/m2. Hemoglobin A1c reduction from baseline was greater with tirzepatide across all studies with absolute reductions up to 3.02% and relative reductions ranging 0.44% (vs semaglutide) to 2.11% (vs placebo). Weight loss was significant. Incidence of gastrointestinal adverse effects (AE) was similar to semaglutide, and major cardiovascular events was similar to insulin glargine. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Studies demonstrated greater A1c lowering and weight reduction versus placebo and active comparators with AE similar to semaglutide, suggesting tirzepatide will be a valuable addition to the growing list of antidiabetic medications. Although tirzepatide's effects on major cardiovascular events was not increased when compared with insulin glargine, further evidence is needed to assess long-term implications on cardiovascular outcomes compared with agents with proven cardiovascular benefits. CONCLUSIONS: Tirzepatide has the potential to significantly impact the clinical management of T2DM, and results of ongoing clinical trials will help to fully determine its place in therapy.

Racial and ethnic differences in blood pressure before and after the 2016 United States general election.

OBJECTIVES: The 2016 U.S. presidential election was a major source of stress among many adults. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Little is known regarding the association of macro-level sociopolitical events with BP changes at the population-level. This study sought to characterize population-level changes in BP following the 2016 U.S. presidential election. METHODS: Using 2015-2018 National Health and Nutrition Examination Survey, we included participants aged ≥18 years during the same periods prior to (May to October 2015/2016) and after (May to October 2017/2018) the election. Survey-weighted data were analyzed to compare population-level systolic BP (SBP) and diastolic BP (DBP) pre- and post-election, stratified by race/ethnicity. Sex differences were also investigated. RESULTS: We observed significant increases in SBP among non-Hispanic (NH) Asian participants (+3.4 mmHg; p = .046), but not among other racial/ethnic participants. DBP increased among NH Black participants (+2.3 mmHg; p = .049) and Mexican American participants (+2.9 mmHg; p = .007), but not among other racial/ethnic participants. These changes appeared attributable to differential BP changes by sex. CONCLUSIONS: At the population-level, variable changes in BP were observed by race/ethnicity following the 2016 U.S. presidential election, possibly driven by SBP elevations among women.

Prescribing Patterns of Antihypertensive Agents and Blood Pressure Control Among Patients With Incident Stage 2 Hypertension.

Background: Initiation of appropriate antihypertensive therapy is crucial, particularly among patients with stage 2 hypertension, whom initiation of dual antihypertensive agents is suggested. Little is known regarding real-world prescribing of antihypertensive agents for patients with incident stage 2 hypertension. Objective: The primary objective was to describe prescribing patterns of antihypertensive therapy among patients with incident stage 2 hypertension. The secondary objectives included determining association of blood pressure (BP) control with initial multiple antihypertensive agents. Methods: Retrospective cohort analysis was conducted using electronic medical records from 6 primary care clinics between January 2014 and June 2019. Included patients were ≥18 years with an initial diagnosis of stage 2 hypertension, defined as BP ≥160/100 mm Hg Primary analysis was characterizing prescribing patterns of antihypertensive agents among patients with incident stage 2 hypertension. Investigation of BP control (<140/90 mm Hg) at 3 months of diagnosis was also performed. Results: We identified 261 patients with incident stage 2 hypertension (mean age, 52 years; 53.2% males; mean baseline BP, 162.1/100.1 mm Hg). Approximately 72% of patients were initiated on single antihypertensive agent, with the most common being angiotensin receptor blockers (ARBs; 25.7%) and angiotensin-converting-enzyme (ACE) inhibitors (24.6%). Commonly initiated multiple antihypertensive agents were ACE-inhibitor + thiazide-like diuretic (52.7%), followed by an ARB + thiazide-like diuretic (21.6%). Multiple antihypertensive therapy was associated with improved BP control at 3 months (adjusted odds ratio [OR], 3.54; 95% confidence interval [CI], 1.55-8.06). Conclusion: Majority of patients with incident stage 2 hypertension were prescribed initial single antihypertensive therapy, though better BP control at 3 months was seen among those initiated on multi-antihypertensive therapy.

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management.

OBJECTIVE: To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords "semaglutide" and "obesity," "weight," "high dose," "high-dose," or "2.4." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. DATA SYNTHESIS: Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. CONCLUSIONS: High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

U.S. trends in prescription nonsteroidal anti-inflammatory drug use among patients with cardiovascular disease, 1988-2016.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased risk of adverse cardiovascular events prompting labeling revisions cautioning their use among patients with cardiovascular disease (CVD). However, little is known regarding long-term trends in real-world prescribing of NSAIDs within the CVD population. We aimed to characterize the use of prescription NSAIDs among U.S. adults with CVD from 1988 to 2016. METHODS: We used the National Health and Nutrition Examination Survey cross-sectional data from 1988-1994 and 19992016 to identify participants aged greater than or equal to 18 years with hypertension (defined by self-report, mean blood pressure ≥ 140/90 mm Hg, or antihypertensive medication use), or aged greater than or equal to 20 years with self-reported congestive heart failure (CHF), coronary heart disease (CHD), angina, myocardial infarction (MI), or stroke. Prevalence of prescription NSAID use was analyzed in 6-year examination periods. Weighted logistic regression was performed to test time trends in prescription NSAID use. RESULTS: Overall, prescription NSAID use declined among all CVD populations. The highest prevalence of overall prescription NSAID use was observed during the 1999-2004 examination years, thereafter declining through the 2005-2010 and 2011-2016 examination years: in patients with hypertension (13.9% [1999-2004] to 8.5% [2011-2016]), CHF (14.6%-8.5%), CHD (16.3%-7.4%), angina (17.6%-8.5%), MI (16.1%-9.0%), and stroke (15.7%-7.9%). Decreased use of COX-2-selective inhibitors was observed during the same period; whereas, nonselective NSAID use remained relatively stable. Trends in prescription NSAID use were reflective of the general adult population. CONCLUSIONS: Prescription NSAID use among patients with CVD appears to have declined from 1988 to 2016, primarily due to reduced COX-2-selective inhibitor use. Nonetheless, the prevalence of prescription NSAIDs has persisted among a subset of high-risk CVD populations.

Partnering With Pharmacists to Reduce Cardiovascular Risk in Outpatient Settings.

See Article Martinez-Mardones et al.

Use of Prescription Medications That Potentially Interfere With Blood Pressure Control in New-Onset Hypertension and Treatment-Resistant Hypertension.

BACKGROUND: Withdrawing medications that interfere with blood pressure (BP) is recommended in patients with uncontrolled BP, yet real-world use of such agents is not well characterized among individuals with hypertension. We aimed to evaluate the use of BP-interfering prescription medications among US patients with hypertension. METHODS: This retrospective drug utilization study used medical and prescription claims (January 2008 to December 2014) in the MarketScan commercial claims database. We included adults, aged 18-65 years, with a hypertension diagnosis (International Classification of Diseases, Ninth Revision, code 401) and ≥1 antihypertensive medication fill. Two hypertension cohorts were examined-new antihypertensive drug users (incident hypertension) and patients requiring titration to a fourth antihypertensive (incident treatment-resistant hypertension [TRH]). Patient-level exposure to BP-interfering medications was assessed 6 months before and after the index date, defined as the first prescription fill of an antihypertensive drug or the first occurrence of overlapping use of ≥4 antihypertensive drugs. RESULTS: We identified 521,028 patients with incident hypertension and 131,764 patients with incident TRH. The most prevalent BP-interfering prescription medications were nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophens, and hormones. Overall, 18.3% of the incident hypertension cohort and 17.6% of the incident TRH cohort initiated a BP-interfering medication following antihypertensive titration. Among patients previously taking a BP-interfering medication, 57.6% with incident hypertension and 64.9% with incident TRH refilled that medication after antihypertensive intensification. CONCLUSIONS: The use of prescription BP-interfering medications, especially NSAIDs, is prevalent among patients requiring intensification of their antihypertensive regimen. Greater efforts to limit the use of these medications, where feasible, may be required among patients with uncontrolled hypertension.

Evaluation of SAMe-TT2R2 Score on Predicting Success With Extended-Interval Warfarin Monitoring.

BACKGROUND: In patients with stable international normalized ratios, 12-week extended-interval warfarin monitoring can be considered; however, predictors of success with this strategy are unknown. The previously validated SAMe-TT2R2 score (considering sex, age, medical history, treatment, tobacco, and race) predicts anticoagulation control during standard follow-up (every 4 weeks), with lower scores associated with greater time in therapeutic range. OBJECTIVE: To evaluate the ability of the SAMe-TT2R2 score in predicting success with extended-interval warfarin follow-up in patients with previously stable warfarin doses. METHODS: In this post hoc analysis of a single-arm feasibility study, baseline SAMe-TT2R2 scores were calculated for patients with ≥1 extended-interval follow-up visit. The primary analysis assessed achieved weeks of extended-interval follow-up according to baseline SAMe-TT2R2 scores. RESULTS: A total of 47 patients receiving chronic anticoagulation completed a median of 36 weeks of extended-interval follow-up. The median baseline SAMe-TT2R2 score was 1 (range 0-5). Lower SAMe-TT2R2 scores appeared to be associated with greater duration of extended-interval follow-up achieved, though the differences between scores were not statistically significant. No individual variable of the SAMe-TT2R2 score was associated with achieved weeks of extended-interval follow-up. Analysis of additional patient factors found that longer duration (≥24 weeks) of prior stable treatment was significantly associated with greater weeks of extended-interval follow-up completed ( P = 0.04). Conclusion and Relevance: This pilot study provides limited evidence that the SAMe-TT2R2 score predicts success with extended-interval warfarin follow-up but requires confirmation in a larger study. Further research is also necessary to establish additional predictors of successful extended-interval warfarin follow-up.

The benefits of physician-pharmacist collaboration.

Over the past decade, physician-pharmacist collaborative practices have gained traction in primary care as a way to implement team-based-care models. And there is evidence pointing to the effectiveness of this multidisciplinary heath care team approach, in which pharmacists are typically responsible for such things as obtaining medication histories, identifying barriers to adherence, and adjusting medication regimens. Several studies have shown the significant impact that physician-pharmacist collaborative management (PPCM) can have on blood pressure control among patients with hypertension. Additionally, PPCM may have positive effects on HbA1c reduction and diabetes control, suggesting that benefits may extend to other chronic diseases, too.

Resistant Hypertension: Mechanisms and Treatment.

PURPOSE OF REVIEW: Emerging evidence suggests that multiple mechanisms may be responsible for the development of treatment-resistant hypertension (TRH). This review aims to summarize recent data on potential mechanisms of resistance and discuss current pharmacotherapeutic options available in the management of TRH. RECENT FINDINGS: Excess sodium and fluid retention, increased activation of the renin-angiotensin-aldosterone system, and heightened activity of the sympathetic nervous system appear to play an important role in development of TRH. Emerging evidence also suggests a role for arterial stiffness and, potentially, gut dysbiosis. Therapeutic approaches for TRH should include diuretic optimization and the addition of aldosterone antagonists as the preferred fourth agent in most patients. Further therapeutic approaches may be guided by the suspected underlying mechanism of TRH in conjunction with other patient-specific factors. The pathophysiology of TRH is multifaceted; however, increasing evidence supports several mechanisms that may be targeted to improve blood pressure control among patients with TRH. Further studies are needed to determine whether such approaches may be more effective than usual care.

Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know.

The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half-lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient-clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and anti-factor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC-treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1-3 months after initiation and then at least every 6 months, with more frequent follow-up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient-specific monitoring plans.

Trends in Antihypertensive Medication Use Among US Patients With Resistant Hypertension, 2008 to 2014.

Little is known of US trends in antihypertensive drug use for patients with treatment-resistant hypertension (TRH). We analyzed antihypertensive use among patients with TRH (treated with ≥4 antihypertensive drugs concurrently) from July 2008 through December 2014 using Marketscan administrative data. We included adults aged 18 to 65 years, with ≥6 months of continuous enrollment, a hypertension diagnosis, and ≥1 episode of overlapping use of ≥4 antihypertensive drugs; patients with heart failure were excluded. We identified 411 652 unique TRH episodes from 261 652 patients with a mean age of 55.9 years. From 2008 to 2014, we observed an increased prevalence, among TRH episodes, of ß-blockers (+6.8% [79% to 85.8%]) and dihydropyridine calcium antagonists (+8.1% [69.1% to 77.2%]), and a decreased prevalence of angiotensin-converting enzyme inhibitors (-12.5% [60.4% to 47.9%]) and nondihydropyridine calcium antagonists (-5.0% [15% to 10%]). The prevalence of most other classes changed by <5% from 2008 to 2014. Thiazide diuretic use was largely unchanged from 2008 to 2014, with hydrochlorothiazide being by far the most prevalent thiazide diuretic; chlorthalidone use increased only modestly (+2.6% [3.8% to 6.4%]). Aldosterone antagonist use increased only modestly (+2.9% [7.3% to 10.2%]). Use of optimal regimens increased steadily (+13.8% [50.8% to 64.6%]) during the study period, whereas combined angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use declined (-11.4% [17.7% to 6.3%]). Our results highlight the persistent infrequent use of recommended therapies in TRH, including spironolactone and chlorthalidone, and suggest a need for better efforts to increase the use of such approaches in light of recent evidence demonstrating their efficacy.