Context Landmark clinical trials have demonstrated the survival benefits of statins, with benefits usually starting after 1 to 2 years of treatment. Research prior to these trials of older lipid-lowering agents demonstrated low levels of 1-year adherence.Objective To compare 2-year adherence following statin initiation in 3 cohorts of patients: those with recent acute coronary syndrome (ACS), those with chronic coronary artery disease (CAD), and those without coronary disease (primary prevention).Design and Setting Cohort study using linked population-based administrative data from Ontario.Patients All patients aged 66 years or older who received at least 1 statin prescription between January 1994 and December 1998 and who did not have a statin prescription in the prior year were followed up for 2 years from their first statin prescription. There were 22379 patients in the ACS, 36106 in the chronic CAD, and 85020 in the primary prevention cohorts. Main Outcome MeasuresAdherence to statins, defined as a statin being dispensed at least every 120 days after the index prescription for 2 years.Results Two-year adherence rates in the cohorts were only 40.1% for ACS, 36.1% for chronic CAD, and 25.4% for primary prevention. Relative to the ACS cohort, nonadherence was more likely among patients receiving statins in the chronic CAD (relative risk [RR], 1.14; 95% CI, 1.11-1.16) and primary prevention cohorts (RR, 1.92; 95% CI, 1.87-1.96). ConclusionsElderly patients with and without recent ACS have low rates of adherence to statins. This suggests that many patients initiating statin therapy may receive no or limited benefit from statins because of premature discontinuation.

Background-Secondary prevention after acute myocardial infarction (AMI) is achieved primarily through medications. However, patients must take their medications to benefit. Medication adherence research has focused primarily on continuation of medications rather than not filling the first prescription written (primary nonadherence). Our objectives were to characterize, to determine factors of, and to measure outcomes associated with primary nonadherence after AMI. Methods and Results-We conducted a population-based cohort study using an AMI registry linked with administrative data in Ontario, Canada. The primary outcome was 1-year mortality. There were 4591 post-AMI patients Ͼ65 years of age included with 12 832 prescriptions written, of which 73% and 79% were filled within 7 and 120 days, respectively. By 120 days after discharge, more cardiac than noncardiac prescriptions were filled (82% versus 35%, respectively; PϽ0.0001). Only 74% of patients filled all their discharge prescriptions by 120 days after discharge after the exclusion of acetylsalicylic acid, which is also available over the counter in Ontario. Factors associated with filling all compared with filling no discharge prescriptions included younger age, low income, discharge medication counseling, in-hospital attending cardiologist, and fewer medications before AMI. The adjusted 1-year mortality rate was higher in patients who filled some versus all (odds ratio, 1.44; 95% confidence interval, 1.15 to 1.79; Pϭ0.001) and none versus all (odds ratio, 1.80; 95% confidence interval, 1.35 to 2.42; PϽ0.0001) of their discharge medications. Conclusions-Patients fill most of their discharge prescriptions within 1 week after AMI. The 1-year mortality rate was higher for those patients who did not fill all of their discharge medications after AMI. Factors such as discharge medication counseling and postdischarge follow-up may help to increase the filling rate of medications after AMI.

Editorial see p 1190 Clinical Perspective on p 1203CKD is also considered as an independent risk factor for bleeding, and, therefore, warfarin use in patients who have severe CKD could increase the risk for bleeding. 2 Moreover, in patients with AF undergoing hemodialysis, it is routine practice to administer heparin, which could also increase the risk for bleeding. 15Current observational studies on warfarin use and the risk for stroke and bleeding in patients with AF undergoing dialysis present conflicting results. 1,8,16,17 Globally, because of a lack of evidence from randomized, controlled trials, AF Background-Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. Methods and Results-We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78-1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13-1.85) after adjusting for potential confounders. Propensity score-adjusted analyses yielded similar results. Conclusions-Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

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Background Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. Methods We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. Results Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07–1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. Conclusions In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.

Complex associations exist between HDL-C levels and sociodemographic, lifestyle, comorbidity factors, and mortality. HDL-C level is unlikely to represent a CV-specific risk factor given similarities in its associations with non-CV outcomes.

Background: Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual study estimates of DOAC adherence/persistence rates have been discordant. Our aims were to characterize real-world observational evidence for DOAC adherence/persistence and evaluate associated clinical outcomes in patients with AF. Methods and Results: PubMed, EMBASE, and CINAHL were searched from inception to June 2018. Observational studies that reported real-world DOAC adherence/persistence in patients with AF were included. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Outcomes included DOAC mean proportion of days covered or medication possession ratio, proportion of good adherence (proportion of days covered/medication possession ratio ≥80%), persistence, DOAC versus vitamin K antagonists persistence, and clinical outcomes associated with nonadherence/nonpersistence. Forty-eight observational studies with 594 784 unique patients with AF (59% male; mean age 71 years) were included. The overall pooled mean proportion of days covered/medication possession ratio was 77% (95% CI, 75%–80%), proportion of patients with good adherence was 66% (95% CI, 63%–70%), and proportion persistent was 69% (95% CI, 65%–72%). The pooled proportion of patients with good adherence was 71% (95% CI, 64%–78%) for apixaban, 60% (95% CI, 52%–68%) for dabigatran, and 70% (95% CI, 64%–75%) for rivaroxaban. Similar patterns were found for pooled persistence by agent. The pooled persistence was higher with DOACs than vitamin K antagonists (odds ratio, 1.44 [95% CI, 1.12–.86]). DOAC nonadherence was associated with an increased risk of stroke (hazard ratio, 1.39 [95% CI, 1.06–1.81]). Conclusions: Suboptimal adherence and persistence to DOACs was common in patients with AF, with 1 in 3 patients adhering to their DOAC <80% of the time, which was associated with poor clinical outcomes in nonadherent patients. Although it is convenient that DOACs do not require laboratory monitoring, greater effort in monitoring for and interventions to prevent nonadherence may be necessary to optimize stroke prevention. Increased clinician awareness of DOAC nonadherence may help identify at-risk patients.

IMPORTANCE Unlike warfarin, which requires routine laboratory testing and dose adjustment, target-specific oral anticoagulants like dabigatran do not. However, optimal follow-up infrastructure and modifiable site-level factors associated with improved adherence to dabigatran are unknown. OBJECTIVES To assess site-level variation in dabigatran adherence and to identify site-level practices associated with higher dabigatran adherence. DESIGN, SETTING, AND PARTICIPANTS Mixed-methods study involving retrospective quantitative and cross-sectional qualitative data. A total of 67 Veterans Health Administration sites with 20 or more patients filling dabigatran prescriptions between 2010 and 2012 for nonvalvular atrial fibrillation were sampled (4863 total patients; median, 51 patients per site). Forty-seven pharmacists from 41 eligible sites participated in the qualitative inquiry. EXPOSURE Site-level practices identified included appropriate patient selection, pharmacist-driven patient education, and pharmacist-led adverse event and adherence monitoring. MAIN OUTCOMES AND MEASURES Dabigatran adherence (intensity of drug use during therapy) defined by proportion of days covered (ratio of days supplied by prescription to follow-up duration) of 80% or more. RESULTS The median proportion of patients adherent to dabigatran was 74% (interquartile range [IQR], 66%-80%). After multivariable adjustment, dabigatran adherence across sites varied by a median odds ratio of 1.57. Review of practices across participating sites showed that appropriate patient selection was performed at 31 sites, pharmacist-led education was provided at 30 sites, and pharmacist-led monitoring at 28 sites. The proportion of adherent patients was higher at sites performing appropriate selection (75% vs 69%), education (76% vs 66%), and monitoring (77% vs 65%). Following multivariable adjustment, association between pharmacist-led education and dabigatran adherence was not statistically significant (relative risk [RR], 0.94; 95% CI, 0.83-1.06). Appropriate patient selection (RR, 1.14; 95% CI, 1.05-1.25), and provision of pharmacist-led monitoring (RR, 1.25; 95% CI, 1.11-1.41) were associated with better patient adherence. Additionally, longer duration of monitoring and providing more intensive care to nonadherent patients in collaboration with the clinician improved adherence. CONCLUSIONS AND RELEVANCE Among nonvalvular atrial fibrillation patients treated with dabigatran, there was variability in patient medication adherence across Veterans Health Administration sites. Specific pharmacist-based activities were associated with greater patient adherence to dabigatran.