Assuming one dose per day yields a similar estimate of medication adherence in patients with stroke: An exploratory analysis using linked registry data

Purpose: Prescribed daily dose (PDD), the number of doses prescribed to be taken per day, is used to calculate medication adherence using pharmacy claims data. PDD can be substituted by (i) one dose per day (1DD), (ii) an estimate based on the 75th percentile of days taken by patients to refill a script (PDD75) or (iii) the World Health Organization's defined daily dose (DDD). We aimed to compare these approaches for estimating the duration covered by medications and whether this affects calculated 1-year adherence to antihypertensive medications post-stroke. Methods: We conducted a retrospective review of prospective cohort data from the ongoing Australian Stroke Clinical Registry linked with pharmacy claims data. Adherence was calculated as the proportion of days covered (PDC) for 1DD, PDD75 and DDD. Differences were assessed using Wilcoxon rank-sum tests. Results: Among 12 628 eligible patients with stroke, 10 057 (80%) were prescribed antihypertensive medications in the year after hospital discharge (78.2% aged ≥65 years, 45.2% female). Overall, the 75th percentile of patient time until next medication refill was 39 days. The greatest variations in dose regimens, estimated using person- and dose-level refill times, were for beta blockers (11.4% taking two tablets/day). There were comparable levels of adherence between 1DD and the PDD75 (median PDC 91.0% vs 91.2%; P = 0.70), but adherence was slightly higher using DDD (92.3%; both P < 0.001). However, this would represent a clinically nonsignificant difference. Conclusion: Adherence to antihypertensive medications shows similar estimates across standard measures of dosage in patients during the first year after an acute stroke

Patterns of Use and Discontinuation of Secondary Prevention Medications After Stroke

OBJECTIVE: To investigate whether certain patient, acute care, or primary care factors are associated with medication initiation and discontinuation in the community after stroke or TIA. METHODS: This is a retrospective cohort study using prospective data on adult patients with first-ever acute stroke/TIA from the Australian Stroke Clinical Registry (April 2010 to June 2014), linked with nationwide medication dispensing and Medicare claims data. Medication users were those with ≥1 dispensing in the year postdischarge. Discontinuation was assessed among medication users and defined as having no medication supply for ≥90 days in the year postdischarge. Multivariable competing risks regression, accounting for death during the observation period, was conducted to investigate factors associated with time to medication discontinuation. RESULTS: Among 17,980 registry patients with stroke/TIA, 91.4% were linked to administrative datasets. Of these, 9,817 adults with first-ever stroke/TIA were included (45.4% female, 47.6% aged ≥75 years, and 11.4% intracerebral hemorrhage). While most patients received secondary prevention medications (79.3% antihypertensive, 81.8% antithrombotic, and 82.7% lipid-lowering medication), between one-fifth and one-third discontinued treatment over the subsequent year postdischarge (20.9% antihypertensive, 34.1% antithrombotic, and 28.5% lipid-lowering medications). Prescription at hospital discharge (sub-hazard ratio [SHR] 0.70; 95% confidence interval [CI] 0.62-0.79), quarterly contact with a primary care physician (SHR 0.62; 95% CI 0.57-0.67), and prescription by a specialist physician (SHR 0.87; 95% CI 0.77-0.98) were all inversely associated with antihypertensive discontinuation. CONCLUSIONS: Patterns of use of secondary prevention medications after stroke/TIA are not optimal, with many survivors discontinuing treatment within 1 year postdischarge. Improving postdischarge care for patients with stroke/TIA is needed to minimize unwarranted discontinuation

Treatment with Multiple Therapeutic Classes of Medication Is Associated with Survival after Stroke

Introduction: Treatment with several therapeutic classes of medication is recommended for secondary prevention of stroke. We analyzed the associations between the number of classes of prevention medications supplied within 90 days after discharge for ischemic stroke (IS)/transient ischemic attack (TIA) and survival. Methods: This is a retrospective cohort study of adults with first-ever IS/TIA (2010&ndash;2014) from the Australian Stroke Clinical Registry individually linked with data from national pharmaceutical and Medicare claims. Exposure was the number of classes of recommended medications, i.e., blood pressure-lowering, antithrombotic, or lipid-lowering agents, supplied to patients within 90 days after discharge for IS/TIA. The longitudinal association between the number of classes of medications and survival was evaluated with Cox proportional hazards regression models using the landmark approach. A landmark date of 90 days after hospital discharge was used to separate exposure and outcome periods, and only patients who survived until this date were included. Results: Of 8,429 patients (43% female, median age 74 years, 80% IS), 607 (7%) died in the year following 90 days after discharge. Overall, 56% of patients were supplied all 3 classes of medications, 28% 2 classes of medications, 11% 1 class of medications, and 5% no class of medications. Compared to patients supplied all 3 medication classes, adjusted hazard ratios for all-cause mortality ranged from 1.43 (95% confidence interval [CI]: 1.18&ndash;1.72) in those supplied 2 medication classes to 2.04 (95% CI: 1.44&ndash;2.88) in those supplied with no medication class. Discussion/Conclusion: Treatment with all 3 classes of guideline-recommended medications within 90 days after discharge was associated with better survival. Ongoing efforts are required to ensure optimal pharmacological intervention for secondary prevention of stroke. </jats:p

Greater Adherence to Secondary Prevention Medications Improves Survival After Stroke or Transient Ischemic Attack: A Linked Registry Study.

BACKGROUND AND PURPOSE: Although a target of 80% medication adherence is commonly cited, it is unclear whether greater adherence improves survival after stroke or transient ischemic attack (TIA). We investigated associations between medication adherence during the first year postdischarge, and mortality up to 3 years, to provide evidence-based targets for medication adherence. METHODS: Retrospective cohort study of 1-year survivors of first-ever stroke or TIA, aged ≥18 years, from the Australian Stroke Clinical Registry (July 2010-June 2014) linked with nationwide prescription refill and mortality data (until August 2017). Adherence to antihypertensive agents, statins, and nonaspirin antithrombotic medications was based on the proportion of days covered from discharge until 1 year. Cox regression with restricted cubic splines was used to investigate nonlinear relationships between medication adherence and all-cause mortality (to 3 years postdischarge). Models were adjusted for age, sex, socioeconomic position, stroke factors, primary care factors, and concomitant medication use. RESULTS: Among 8363 one-year survivors of first-ever stroke or TIA (44% aged ≥75 years, 44% female, 18% TIA), 75% were supplied antihypertensive agents. In patients without intracerebral hemorrhage (N=7446), 84% were supplied statins, and 65% were supplied nonaspirin antithrombotic medications. Median adherence was ≈90% for each medication group. Between 1% and 100% adherence, greater adherence to statins or antihypertensive agents, but not nonaspirin antithrombotic agents, was associated with improved survival. When restricted to linear regions above 60% adherence, each 10% increase in adherence was associated with a reduction in all-cause mortality of 13% for antihypertensive agents (hazard ratio, 0.87 [95% CI, 0.81-0.95]), 13% for statins (hazard ratio, 0.87 [95% CI, 0.80-0.95]), and 15% for nonaspirin antithrombotic agents (hazard ratio, 0.85 [95% CI, 0.79-0.93]). CONCLUSIONS: Greater levels of medication adherence after stroke or TIA are associated with improved survival, even among patients with near-perfect adherence. Interventions to improve medication adherence are needed to maximize survival poststroke

Towards better reporting of the proportion of days covered method in cardiovascular medication adherence: A scoping review and new tool TEN-SPIDERS

Although medication adherence is commonly measured in electronic datasets using the proportion of days covered (PDC), no standardized approach is used to calculate and report this measure. We conducted a scoping review to understand the approaches taken to calculate and report the PDC for cardiovascular medicines to develop improved guidance for researchers using this measure. After prespecifying methods in a registered protocol, we searched Ovid Medline, Embase, Scopus, CINAHL Plus and grey literature (1 July 2012 to 14 December 2020) for articles containing the terms “proportion of days covered” and “cardiovascular medicine”, or synonyms and subject headings. Of the 523 articles identified, 316 were reviewed in full and 76 were included (93% observational studies; 47% from the USA; 2 grey literature articles). In 45 articles (59%), the PDC was measured from the first dispensing/claim date. Good adherence was defined as 80% PDC in 61 articles, 56% of which contained a rationale for selecting this threshold. The following parameters, important for deriving the PDC, were often not reported/unclear: switching (53%), early refills (45%), in-hospital supplies (45%), presupply (28%) and survival (7%). Of the 46 articles where dosing information was unavailable, 59% reported how doses were imputed. To improve the transparent and systematic reporting of the PDC, we propose the TEN-SPIDERS tool, covering the following PDC parameters: Threshold, Eligibility criteria, Numerator and denominator, Survival, Presupply, In-hospital supplies, Dosing, Early Refills, and Switching. Use of this tool will standardize reporting of the PDC to facilitate reliable comparisons of medication adherence estimates between studies

The role of extracellular vesicles when innate meets adaptive

Innate immune cells are recognized for their rapid and critical contribution to the body's first line of defense against invading pathogens and harmful agents. These actions can be further amplified by specific adaptive immune responses adapted to the activating stimulus. Recently, the awareness has grown that virtually all innate immune cells, i.e., mast cells, neutrophils, macrophages, eosinophils, basophils, and NK cells, are able to communicate with dendritic cells (DCs) and/or T and B cells, and thereby significantly contribute to the orchestration of adaptive immune responses. The means of communication that are thus far primarily associated with this function are cell-cell contacts and the release of a broad range of soluble mediators. Moreover, the possible contribution of innate immune cell-derived extracellular vesicles (EVs) to the modulation of adaptive immunity will be outlined in this review. EVs are submicron particles composed of a lipid bilayer, proteins, and nucleic acids released by cells in a regulated fashion. EVs are involved in intercellular communication between multiple cell types, including those of the immune system. A good understanding of the mechanisms by which innate immune cell-derived EVs influence adaptive immune responses, or vice versa, may reveal novel insights in the regulation of the immune system and can open up new possibilities for EVs (or their components) in controlling immune responses, either as a therapy, target, or as an adjuvant in future immune modulating treatments