Cynthia A. Jackevicius

Prevalence, Predictors, and Outcomes of Primary Nonadherence After Acute Myocardial Infarction

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 >65 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; P<0.0001). 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; P=0.001) and none versus all (odds ratio, 1.80; 95% confidence interval, 1.35 to 2.42; P<0.0001) 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.

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis

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.

Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation

CONTEXT Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. OBJECTIVE To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. DESIGN, SETTING, AND PATIENTS Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. MAIN OUTCOME MEASURES Risk of stroke. RESULTS The cohort comprised 39,398 men (47.2%) and 44,115 women (52.8%). At admission, women were older and had a higher CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS(2) score, and warfarin treatment. CONCLUSION Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.

Does Performance-Based Remuneration for Individual Health Care Practitioners Affect Patient Care?: A Systematic Review

BACKGROUND Pay-for-performance (P4P) is increasingly touted as a means to improve health care quality. PURPOSE To evaluate the effect of P4P remuneration targeting individual health care providers. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, OpenSIGLE, Canadian Evaluation Society Unpublished Literature Bank, New York Academy of Medicine Library Grey Literature Collection, and reference lists were searched up until June 2012. STUDY SELECTION Two reviewers independently identified original research papers (randomized, controlled trials; interrupted time series; uncontrolled and controlled before-after studies; and cohort comparisons). DATA EXTRACTION Two reviewers independently extracted the data. DATA SYNTHESIS The literature search identified 4 randomized, controlled trials; 5 interrupted time series; 3 controlled before-after studies; 1 nonrandomized, controlled study; 15 uncontrolled before-after studies; and 2 uncontrolled cohort studies. The variation in study quality, target conditions, and reported outcomes precluded meta-analysis. Uncontrolled studies (15 before-after studies, 2 cohort comparisons) suggested that P4P improves quality of care, but higher-quality studies with contemporaneous controls failed to confirm these findings. Two of the 4 randomized trials were negative, and the 2 statistically significant trials reported small incremental improvements in vaccination rates over usual care (absolute differences, 8.4 and 7.8 percentage points). Of the 5 interrupted time series, 2 did not detect any improvements in processes of care or clinical outcomes after P4P implementation, 1 reported initial statistically significant improvements in guideline adherence that dissipated over time, and 2 reported statistically significant improvements in blood pressure control in patients with diabetes balanced against statistically significant declines in hemoglobin A1c control. LIMITATION Few methodologically robust studies compare P4P with other payment models for individual practitioners; most are small observational studies of variable quality. CONCLUSION The effect of P4P targeting individual practitioners on quality of care and outcomes remains largely uncertain. Implementation of P4P models should be accompanied by robust evaluation plans. PRIMARY FUNDING SOURCE None.

Comparative Effectiveness of Rhythm Control vs Rate Control Drug Treatment Effect on Mortality in Patients With Atrial Fibrillation

BACKGROUND Controversy continues concerning the choice of rhythm control vs rate control treatment strategies for atrial fibrillation (AF). A recent clinical trial showed no difference in 5-year mortality between the 2 treatments. We aimed to determine whether the 2 strategies have similar effectiveness when applied to a general population of patients with AF with longer follow-up. METHODS We used population-based administrative databases from Quebec, Canada, from 1999 to 2007 to select patients 66 years or older hospitalized with an AF diagnosis who did not have AF-related drug prescriptions in the year before the admission but received a prescription within 7 days of discharge. Patients were followed until death or administrative censoring. Mortality was analyzed by multivariable Cox regression. RESULTS Among 26,130 patients followed for a mean (SD) period of 3.1 years (2.3 years), there were 13,237 deaths (49.5%). After adjusting for covariates, we found that the effect of rhythm vs rate control drugs changed over time: after a small increase in mortality for patients treated with rhythm control in the 6 months following treatment initiation (hazard ratio [HR], 1.07; 95% CI, 1.01-1.14), the mortality was similar between the 2 groups until year 4 but decreased steadily in the rhythm control group after year 5 (HR, 0.89; 95% CI, 0.81-0.96; and HR, 0.77; 95% CI, 0.62-0.95, after 5 and 8 years, respectively). CONCLUSIONS In this population-based sample of patients with AF, we found little difference in mortality within 4 years of treatment initiation between patients with AF initiating rhythm control therapy vs those initiating rate control therapy. However, rhythm control therapy seems to be superior in the long-term.

Clinical InvestigationElectrophysiologyAdherence to dabigatran therapy and longitudinal patient outcomes: Insights from the Veterans Health Administration

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.

Use of Ezetimibe in the United States and Canada

BACKGROUND Ezetimibe lowers low-density lipoprotein cholesterol, but current lipid-lowering guidelines in the United States and Canada do not recommend it as a first option for either primary or secondary prevention. We sought to describe the adoption of ezetimibe relative to that of other lipid-lowering agents and compare its use in the two countries. METHODS We conducted a population-level, cohort study using data from January 2002 to December 2006, provided by IMS Health, to describe prescribing practices and expenditures for lipid-lowering agents and ezetimibe in the United States and Canada. RESULTS From 2002 to 2006, the monthly number of prescriptions for lipid-lowering agents rose from 3719 to 7401 per 100,000 population in Canada and from 3927 to 6827 per 100,000 population in the United States. Of these prescriptions, the proportion for ezetimibe rose from 0.2% in 2003 to 3.4% in 2006 in Canada and from 0.1% in 2002 to 15.2% in 2006 in the United States. Statin use was relatively constant between 2002 and 2006 in Canada, whereas the proportion of statin prescriptions decreased from 86.5 to 80.8% in the United States. In 2006, the ratio of prescriptions for statins to those for ezetimibe was 26:1 in Canada and 5:1 in the United States. In 2006, expenditures for ezetimibe per 100,000 population were higher in the United States than in Canada by a factor of more than 4. CONCLUSIONS Distinct patterns of use of ezetimibe emerged in the United States and Canada from 2002 to 2006, a difference that markedly altered the approach to the treatment of hyperlipidemia in the United States. The U.S. pattern increased overall costs, but the effect on clinical outcomes is uncertain.

Rhythm Versus Rate Control Therapy and Subsequent Stroke or Transient Ischemic Attack in Patients With Atrial Fibrillation

Background— Stroke is a debilitating condition with an increased risk in patients with atrial fibrillation. Although data from clinical trials suggest that both rate and rhythm control are acceptable approaches with comparable rates of mortality in the short term, it is unclear whether stroke rates differ between patients who filled prescriptions for rhythm or rate control therapy. Methods and Results— We conducted a population-based observational study of Quebec patients ≥65 years with a diagnosis of atrial fibrillation during the period 1999 to 2007 with the use of linked administrative data from hospital discharge and prescription drug claims databases. We compared rates of stroke or transient ischemic attack (TIA) among patients using rhythm (class Ia, Ic, and III antiarrhythmics), versus rate control (&bgr;-blockers, calcium channel blockers, and digoxin) treatment strategies (either current or new users). The cohort consisted of 16 325 patients who filled a prescription for rhythm control therapy (with or without rate control therapy) and 41 193 patients who filled a prescription for rate control therapy, with a mean follow-up of 2.8 years (maximum 8.2 years). A lower proportion of patients on rhythm control therapy than on rate control therapy had a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or TIA) score of ≥2 (58.1% versus 67.0%, P<0.001). Treatment with any antithrombotic drug was comparable in the 2 groups (76.8% in rhythm control versus 77.8% in rate control group). Crude stroke/TIA incidence rate was lower in patients treated with rhythm control in comparison with rate control therapy (1.74 versus 2.49, per 100 person-years, P<0.001). This association was more marked in patients in the moderate- and high-risk groups for stroke according to the CHADS2 risk score. In multivariable Cox regression analysis, rhythm control therapy was associated with a lower risk of stroke/TIA in comparison with rate control therapy (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87). The lower stroke/TIA rate was confirmed in a propensity score–matched cohort. Conclusions— In comparison with rate control therapy, the use of rhythm control therapy was associated with lower rates of stroke/TIA among patients with atrial fibrillation, in particular, among those with moderate and high risk of stroke.

Site-Level Variation in and Practices Associated With Dabigatran Adherence

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.

Use of Fibrates in the United States and Canada

CONTEXT Interest in the role of fibrates intensified after the publication of the negative results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which assessed therapy with fenofibrate plus statins. The evidence for clinical benefit in outcomes with the use of fibrates is heavily weighted on the use of the older fibrates such as gemfibrozil and clofibrate. OBJECTIVES To examine trends in the current use of fibrates and to examine the relationship between differences in the availability and use of brand-name vs generic formulations of fenofibrate and the economic implications in the United States compared with Canada. DESIGN, SETTING, AND PATIENTS Population-level, observational cohort study using IMS Health data from the United States and Canada of patients prescribed fibrates between January 2002 and December 2009. MAIN OUTCOME MEASURES Fibrate prescriptions dispensed and expenditures. RESULTS In the United States, fibrate prescriptions dispensed increased from 336 prescriptions/100,000 population in January 2002 to 730 prescriptions/100,000 population in December 2009, an increase of 117.1% (95% confidence interval [CI], 116.0%-117.9%), whereas in Canada, fibrate prescriptions increased from 402 prescriptions/100,000 population in January 2002 to 474 prescriptions/100,000 population in December 2009, an increase of 18.1% (95% CI, 17.9%-18.3%) (P <.001). In the United States, fenofibrate prescriptions dispensed increased from 150 prescriptions/100,000 population in January 2002 to 440 prescriptions/100,000 population in December 2009, an increase of 159.3% (95% CI, 157.7%-161.0%), comprising 47.9% of total fibrate prescriptions in 2002 and 65.2% in 2009. In Canada, fenofibrate prescriptions increased from 321 prescriptions/100,000 population in January 2002 to 429 prescriptions/100,000 population in December 2009. The annual ratio of generic to brand-name fenofibrate use in the United States ranged from 0:1 to 0.09:1 between 2002 and 2008, while the ratio in Canada steadily increased from 0.51:1 to 1.89:1 between 2005 and 2008. In the United States, crude fenofibrate expenditures increased from