Impact of national valsartan recalls on Veterans' outcomes.

BACKGROUND AND AIMS: Chemical impurities discovered in angiotensin receptor blocker (ARB) products in late 2018-2019 resulted in recalls of various products and has likely had downstream effects for patients and prescribers. The purpose of this study is to determine how the valsartan recall impacted clinical endpoints and prescribing of antihypertensives. METHODS: This was a retrospective, single-center, cohort study including patients receiving recalled valsartan with essential hypertension who were mailed a recall letter on 12 March 2019. Mean blood pressure endpoints were collected 6 months before (pre-recall) and after the recall letter was mailed (post-recall). Antihypertensive medication changes and titrations were also characterized post-recall. RESULTS: A total of 300 patients meeting eligibility criteria were included. There was no statistically significant difference in mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) when pre- and post-recall blood pressures were compared (SBP: 137.2 mmHg versus 135.8 mmHg, p = 0.125; DBP: 78.6 mmHg versus 78.5 mmHg, p = 0.900). In addition, the percentage of patients with controlled blood pressure readings was similar in the pre- and post-recall timeframes (28% versus 27%, p = 0.72). A total of 33 medication changes involving valsartan occurred, with approximately one-third being changed to another ARB (n = 11) or drug class (n = 12). In total, 11 valsartan medication changes were specifically documented to be related to the valsartan recall. CONCLUSION: The results of this study indicate the valsartan recalls that occurred in 2019 did not significantly impact the clinical outcomes of the studied population. PLAIN LANGUAGE SUMMARY: Impact of a medication recall on Veterans' outcomesBackground:: Chemical impurities discovered in a class of blood pressure medications known as angiotensin receptor blockers (ARBs) occurred in late 2018-2019. This resulted in recalls of various products and has likely had downstream effects for patients and prescribers.Objective:: The purpose of this study is to determine how the recall of valsartan, which is a medication in the ARB class, impacted clinical endpoints and prescribing of medications for blood pressure.Methods:: This was a retrospective, single-center, cohort study including patients receiving recalled valsartan with high blood pressure who were mailed a recall letter on 12 March 2019. Blood pressure endpoints were collected 6 months before (pre-recall) and after the recall letter was mailed (post-recall). Medication changes and titrations were also characterized post-recall.Results:: Three hundred patients meeting eligibility criteria were included. There was no difference found in systolic blood pressure (SBP) or diastolic blood pressure (DBP) when pre- and post-recall blood pressures were compared (SBP: 137.2 mmHg versus 135.8 mmHg; DBP: 78.6 mmHg versus 78.5 mmHg). In addition, the percent of patients with controlled blood pressure readings was similar in the pre- and post-recall timeframes (28% versus 27%). A total of 33 medication changes involving valsartan occurred, with approximately one-third being changed to another ARB (n = 11) or drug class (n = 12). Eleven valsartan medication changes were specifically documented to be related to the valsartan recall.Conclusions:: The results of this study indicate the valsartan recalls that occurred in 2019 did not significantly impact the clinical outcomes of the studied population.

Impact of Substance Use Disorder on the Rate of Sustained Virological Response in Veterans With Chronic Hepatitis C Treated With Direct-Acting Antivirals.

BACKGROUND: Substance use disorders (SUDs) are commonly encountered in patients with chronic hepatitis C virus (HCV) infection. It is important to consider the impact of SUDs on HCV treatment. OBJECTIVE: To compare the rate of clinical cure (sustained virological response at least 12 weeks after end of therapy [SVR12]) in veterans with chronic HCV infection treated with direct-acting antivirals (DAAs) with and without ongoing or recent substance use. METHODS: This single-center, retrospective cohort study evaluated 220 HCV patients treated with DAAs based on 2 groups: SUD (ongoing or recent substance use) or non-SUD (without ongoing or recent substance use). The primary end point was SVR12 achievement. Secondary end points included safety, adherence, early discontinuation, SVR12 achievement among SUD subgroups, and enrollment in a SUD treatment program. RESULTS: Most patients were African American men with an average age of 60 years and infected with HCV genotype 1. Almost half of the patients had advanced fibrosis or cirrhosis. There was no difference in SVR12 between groups (SUD: 96.2%; non-SUD: 94.3%; P = 0.54). Overall, 35.5% of patients missed at least 1 dose of DAA therapy, with a significant difference noted between groups (SUD: 44.5%; non-SUD: 26.4%; P = 0.005). Early discontinuation of DAA therapy was similar between groups. SVR12 among SUD subgroups ranged from 92.9% to 100%. In the SUD group, 27.3% of patients were enrolled in a SUD treatment program. Conclusion and Relevance: This study suggests that recent/ongoing substance use does not affect achievement of clinical cure of chronic HCV and reinforces treatment in this patient population.

The Role of Atomoxetine for Parkinson Disease-Related Executive Dysfunction: A Systematic Review.

BACKGROUND: Atomoxetine selectively inhibits the reuptake of norepinephrine. Given the noradrenergic system's role in executive function, pharmacotherapy options that affect norepinephrine are of particular clinical interest in Parkinson disease-related executive dysfunction. OBJECTIVE: The aim of this study was to assess the efficacy and safety of atomoxetine for Parkinson disease-related executive dysfunction. METHODS: MEDLINE (1946 to May 2018) and EMBASE (1947 to May 2018) were queried using the search term combination: Parkinson's disease, Parkinson disease, inhibition, impulse behavior, impulse control disorder, executive function, executive dysfunction, cognition, cognitive dysfunction, cognitive defect, response inhibition, strategic planning, strategy, or verbal fluency and atomoxetine hydrochloride or atomoxetine. Studies analyzed for relevance evaluated clinical outcomes of patients treated with atomoxetine for Parkinson disease-related executive dysfunction. Studies appropriate to the objective were evaluated, including 1 open-label flexible dose trial, 2 placebo-controlled longitudinal trials, and 4 placebo-controlled crossover single-dose trials. RESULTS: In patients with Parkinson disease, treatment with atomoxetine resulted in improvements in several markers of executive dysfunction including impulsivity, risk taking, and global cognition. Study durations ranged from single-dose trials to 10 weeks and used varying doses of atomoxetine. Atomoxetine was well tolerated in most studies with some reports of gastrointestinal adverse effects and insomnia. CONCLUSIONS: Based on the reviewed literature, atomoxetine continues to be a therapy of interest for the treatment of executive dysfunction in patients with Parkinson disease. Larger long-term trials are necessary to further define the role of atomoxetine for patients with Parkinson disease-related executive dysfunction.

The role of mirtazapine in patients with fibromyalgia: a systematic review.

Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in patients with fibromyalgia. The objective of this systematic review is to assess the efficacy and safety of mirtazapine in the treatment of patients with fibromyalgia. Pubmed (1946-May 2018), Embase (1947-May 2018), CENTRAL, and ClinicalTrials.gov were queried using the search term combination: fibromyalgia, pain, chronic pain, neuralgia, neuropathic pain, chronic widespread pain, or chronic pain syndrome and mirtazapine. Studies appropriate to the objective were evaluated, including three randomized, placebo-controlled trials and one open-label trial, investigating the effect of mirtazapine in patients with fibromyalgia. In patients with fibromyalgia, treatment with mirtazapine resulted in improvements in pain, sleep, and quality of life. Study durations ranged from 6 to 13 weeks and studies used varying dosing strategies for mirtazapine. Minor occurrences of somnolence, weight gain, nasopharyngitis, dry mouth, and increased appetite were reported with mirtazapine use. Based on the reviewed literature, mirtazapine appears to be a promising therapy to improve pain, sleep, and quality of life in patients with fibromyalgia. These benefits were demonstrated in patients that were treatment naïve and those that had failed previous therapies. Additional clinical evidence through larger and longer length trials would be of benefit to further define the role of mirtazapine for patients with fibromyalgia.

Incidence of Drug Interactions Identified by Clinical Pharmacists in Veterans Initiating Treatment for Chronic Hepatitis C Infection.

BACKGROUND: Many direct-acting antivirals (DAAs) have drug-drug interactions (DDIs) with the potential to affect efficacy and safety. OBJECTIVE: To describe the incidence and severity of DDIs with DAAs identified by the hepatitis C virus (HCV) clinical pharmacist within a Veterans Affairs health care system. METHODS: This single-center, retrospective cohort study evaluated patients with HCV treated with DAA therapy. Primary end points included the total number of identified DDIs, percentage of patients with at least 1 DDI, mean number of DDIs per patient, and the number of DDIs by severity category. Additional end points included characterization of interacting drugs, clinical consequence of interaction, intervention recommended, acceptance rate of actionable recommendations, and achievement of sustained virological response 12 weeks after treatment (SVR12). RESULTS: A total of 300 patients were included. There were 554 identified DDIs, and 80.3% of patients had at least 1 DDI, with an average of 1.85 DDIs per patient; 76% of the DDIs identified were categorized as either a potentially clinically significant or critical interaction. The most common DDIs involved acid suppression agents (20%). Patient monitoring was the most commonly recommended intervention (59%), followed by dose modification of the interacting medication (30%). There was no difference in SVR12 between patients with at least 1 DDI compared with those with no DDIs (94.8% vs 95.8%; P = 0.73). There were a total of 227 actionable recommendations, with an acceptance rate of 84.1%. CONCLUSIONS: This study suggests that DDIs are prevalent among patients treated with DAAs for HCV. A HCV clinical pharmacist can help optimize patient care by identifying DDIs and recommending interventions to providers.