Objective To describe characteristics of dosing history in patients prescribed a once a day antihypertensive medication. Design Longitudinal database study. Setting Clinical studies archived in database for [1989][1990][1991][1992][1993][1994][1995][1996][1997][1998][1999][2000][2001][2002][2003][2004][2005][2006]. Participants Patients who participated in the studies whose dosing histories were available through electronic monitoring. Main outcome measures Persistence with prescribed antihypertensive treatment and execution of their once a day drug dosing regimens. Results The database contained dosing histories of 4783 patients with hypertension. The data came from 21 phase IV clinical studies, with lengths ranging from 30 to 330 days and involving 43 different antihypertensive drugs, including angiotensin II receptor blockers (n=2088), calcium channel blockers (n=937), angiotensin converting enzyme inhibitors (n=665), β blockers (n=195), and diuretics (n=155). About half of the patients who were prescribed an antihypertensive drug had stopped taking it within one year. On any day, patients who were still engaged with the drug dosing regimen omitted about 10% of the scheduled doses: 42% of these omissions were of a single day's dose, whereas 43% were part of a sequence of several days (three or more days-that is, drug "holidays"). Almost half of the patients had at least one drug holiday a year. The likelihood that a patient would discontinue treatment early was inversely related to the quality of his or her daily execution of the dosing regimen. Conclusions Early discontinuation of treatment and suboptimal daily execution of the prescribed regimens are the most common facets of poor adherence with once a day antihypertensive drug treatments. The shortfalls in drug exposure that these dosing errors create might be a common cause of low rates of blood pressure control and high variability in responses to prescribed antihypertensive drugs. INTRODUCTIONHypertension is a major risk factor for the development of cardiovascular disease.1 2 Effective and well tolerated once a day antihypertensive drugs are now available. Yet poor adherence with prescribed treatment continues to be one of the main causes of unsatisfactory control of blood pressure and might lead to target organ damage and increased cardiovascular risk. 3-5 Although many studies have examined the "adherence issue" over many years, the absence of a common taxonomy and the lack of reliable measurements of ambulatory patients' exposure to prescribed pharmaceuticals have resulted in much confusion, with "adherence rates" ranging from 35% to as high as 97%. One aspect of the problem is that traditional methods (pill counts, questionnaires, patients' diaries, measurements of drug concentration in plasma, etc) have repeatedly been shown to overestimate adherence. 8 9A reliable assessment of the prevalence of poor adherence, including short persistence, can be inferred over long term follow-up from the timing of refills in large prescription databases,...

No abstract

BackgroundNon-adherence to medications is prevalent across all medical conditions that include ambulatory pharmacotherapy and is thus a major barrier to achieving the benefits of otherwise effective medicines.ObjectiveThe objective of this systematic review was to identify and to compare the efficacy of strategies and components thereof that improve implementation of the prescribed drug dosing regimen and maintain long-term persistence, based on quantitative evaluation of effect sizes across the aggregated trials.Data sourcesMEDLINE, EMBASE, CINAHL, the Cochrane Library, and PsycINFO were systematically searched for randomized controlled trials that tested the efficacy of adherence-enhancing strategies with self-administered medications. The searches were limited to papers in the English language and were included from database inception to 31 December 2011.Study selectionOur review included randomized controlled trials in which adherence was assessed by electronically compiled drug dosing histories. Five thousand four hundred studies were screened. Eligibility assessment was performed independently by two reviewers. A structured data collection sheet was developed to extract data from each study.Study appraisal and synthesis methodsThe adherence-enhancing components were classified in eight categories. Quality of the papers was assessed using the criteria of the Cochrane Handbook for Systematic Reviews of Interventions guidelines to assess potential bias. A combined adherence outcome was derived from the different adherence variables available in the studies by extracting from each paper the available adherence summary variables in a pre-defined order (correct dosing, taking adherence, timing adherence, percentage of adherent patients). To study the association between the adherence-enhancing components and their effect on adherence, a linear meta-regression model, based on mean adherence point estimates, and a meta-analysis were conducted.ResultsSeventy-nine clinical trials published between 1995 and December 2011 were included in the review. Patients randomized to an intervention group had an average combined adherence outcome of 74.3 %, which was 14.1 % higher than in patients randomized to the control group (60.2 %). The linear meta-regression analysis with stepwise variable selection estimated an 8.8 % increase in adherence when the intervention included feedback to the patients of their recent dosing history (EM-feedback) (p < 0.01) and a 5.0 % increase in adherence when the intervention included a cognitive-educational component (p = 0.02). In addition, the effect of interventions on adherence decreased by 1.1 % each month. Sensitivity analysis by selecting only high-quality papers confirmed the robustness of the model. The random effects model in the meta-analysis, conducted on 48 studies, confirmed the above findings and showed that the improvement in adherence was 19.8 % (95 % CI 10.7–28.9 %) among patients receiving EM-feedback, almost double the improvement in adherence for studies that did not inclu...

Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen. There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification. Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management.

Our intervention was efficacious in improving adherence and sustainable. Further research should investigate clinical impact, cost-effectiveness, and scalability.