Publications

2014
Gagne JJ, Choudhry NK, Kesselheim AS, Polinski JM, Hutchins D, Matlin OS, Brennan TA, Avorn J, Shrank WH.

Comparative effectiveness of generic and brand-name statins on patient outcomes: a cohort study

. Annals of Internal Medicine 2014;161:400-7.Abstract
BACKGROUND: Statins are effective in preventing cardiovascular events, but patients do not fully adhere to them. OBJECTIVE: To determine whether patients are more adherent to generic statins versus brand-name statins (lovastatin, pravastatin, or simvastatin) and whether greater adherence improves health outcomes. DESIGN: Observational, propensity score-matched, new-user cohort study. SETTING: Linked electronic data from medical and pharmacy claims. PARTICIPANTS: Medicare beneficiaries aged 65 years or older with prescription drug coverage between 2006 and 2008. INTERVENTION: Initiation of a generic or brand-name statin. MEASUREMENTS: Adherence to statin therapy (measured as the proportion of days covered [PDC] up to 1 year) and a composite outcome comprising hospitalization for an acute coronary syndrome or stroke and all-cause mortality. Hazard ratios (HRs) and absolute rate differences were estimated. RESULTS: A total of 90 111 patients who initiated a statin during the study was identified; 83 731 (93%) initiated a generic drug, and 6380 (7%) initiated a brand-name drug. The mean age of patients was 75.6 years, and most (61%) were female. The average PDC was 77% for patients in the generic group and 71% for those in the brand-name group (P < 0.001). An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group (HR, 0.92 [95% CI, 0.86 to 0.99]). The absolute difference was -1.53 events per 100 person-years (CI, -2.69 to -0.19 events per 100 person-years). LIMITATION: Results may not be generalizable to other populations with different incomes or drug benefit structures. CONCLUSION: Compared with those initiating brand-name statins, patients initiating generic statins were more likely to adhere and had a lower rate of a composite clinical outcome. PRIMARY FUNDING SOURCE: Teva Pharmaceuticals.
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Lewey J, Choudhry NK.

The current state of ethnic and racial disparities in cardiovascular care: lessons from the past and opportunities for the future

. Current Cardiology Reports 2014;16:530.Abstract
Significant racial/ethnic disparities have been documented in cardiovascular care. Although health care quality is improving for many Americans, differences in clinical outcomes have persisted between racial/ethnic minority patients and non-minorities, even when income, education level, and site of care are taken into consideration. Potential causes of disparities are complex and are related to differences in risk factor prevalence and control, use of evidence-based procedures and medications, and social and environmental factors. Minority patients are more likely to receive care from lower-quality health care providers and institutions and experience more barriers to accessing care. Factors such as stereotyping and bias in medicine are hard to quantify, but likely contribute to differences in treatment. Recent trends suggest that some disparities are decreasing. Opportunities for change and improvement exist for patients, providers, and health care systems. Promising interventions, such as health policy changes, quality improvement programs, and culturally targeted community and clinic-based interventions offer hope that high-quality health care in the USA can be provided to all patients.
Desai NR, Krumme AA, Schneeweiss S, Shrank WH, Brill G, Pezalla EJ, Spettell CM, Brennan TA, Matlin OS, Avorn J, Choudhry NK.

Patterns of Initiation of Oral Anticoagulants in Patients with Atrial Fibrillation - Quality and Cost Implications

. The American Journal of Medicine 2014;Abstract
BACKGROUND: Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled-trials on which their approval was based, and how their use has affected health spending for patients and insurers. STUDY DESIGN: We used medical and prescription claims data from a large insurer to identify patients with non-valvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin vs. a novel anticoagulant. RESULTS: 6,893 patients with atrial fibrillation initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (p<0.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant. CONCLUSIONS: This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research.
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Choudhry NK, Bykov K, Shrank WH, Toscano M, Rawlins WS, Reisman L, Brennan TA, Franklin JM.

Eliminating Medication Copayments Reduces Disparities In Cardiovascular Care

[Internet]. Health Affairs 2014;33(5):863-870. Publisher's VersionAbstract
Substantial racial and ethnic disparities in cardiovascular care persist in the United States. For example, African Americans and Hispanics with cardiovascular disease are 10–40 percent less likely than whites to receive secondary prevention therapies, such as aspirin and beta-blockers. Lowering copayments for these therapies improves outcomes among all patients who have had a myocardial infarction, but the impact of lower copayments on health disparities is unknown. Using self-reported race and ethnicity for participants in the Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) trial, we found that rates of medication adherence were significantly lower and rates of adverse clinical outcomes were significantly higher for nonwhite patients than for white patients. Providing full drug coverage increased medication adherence in both groups. Among nonwhite patients, it also reduced the rates of major vascular events or revascularization by 35 percent and reduced total health care spending by 70 percent. Providing full coverage had no effect on clinical outcomes and costs for white patients. We conclude that lowering copayments for medications after myocardial infarctions may reduce racial and ethnic disparities for cardiovascular disease.
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Choudhry NK, Fischer MA, Smith BF, Brill G, Girdish C, Matlin OS, Brennan TA, Avorn J, Shrank WH.

Five features of value-based insurance design plans were associated with higher rates of medication adherence

. Health Affairs 2014;33:493-501.Abstract
Value-based insurance design (VBID) plans selectively lower cost sharing to increase medication adherence. Existing plans have been structured in a variety of ways, and these variations could influence the effectiveness of VBID plans. We evaluated seventy-six plans introduced by a large pharmacy benefit manager during 2007-10. We found that after we adjusted for the other features and baseline trends, VBID plans that were more generous, targeted high-risk patients, offered wellness programs, did not offer disease management programs, and made the benefit available only for medication ordered by mail had a significantly greater impact on adherence than plans without these features. The effects were as large as 4-5 percentage points. These findings can provide guidance for the structure of future VBID plans.
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Gagne JJ, Rassen JA, Choudhry NK, Bohn RL, Patrick AR, Sridhar G, Daniel GW, Liu J, Schneeweiss S.

Near-real-time monitoring of new drugs: an application comparing prasugrel versus clopidogrel

. Drug Safety 2014;37:151-61.Abstract
BACKGROUND: Methods for near-real-time monitoring of new drugs in electronic healthcare data are needed. OBJECTIVE: In a novel application, we prospectively monitored ischemic, bleeding, and mortality outcomes among patients initiating prasugrel versus clopidogrel in routine care during the first 2 years following the approval of prasugrel. METHODS: Using the HealthCore Integrated Research Database, we conducted a prospective cohort study comparing prasugrel and clopidogrel initiators in the 6 months following the introduction of prasugrel and every 2 months thereafter. We identified patients who initiated antiplatelets within 14 days following discharge from hospitalizations for myocardial infarction (MI) or acute coronary syndrome. We matched patients using high-dimensional propensity scores (hd-PSs) and followed them for ischemic (i.e., MI and ischemic stroke) events, bleed (i.e., hemorrhagic stroke and gastrointestinal bleed) events, and all-cause mortality. For each outcome, we applied sequential alerting algorithms. RESULTS: We identified 1,282 eligible new users of prasugrel and 8,263 eligible new users of clopidogrel between September 2009 and August 2011. In hd-PS matched cohorts, the overall MI rate difference (RD) comparing prasugrel with clopidogrel was -23.1 (95 % confidence interval [CI] -62.8-16.7) events per 1,000 person-years and RDs were -0.5 (-12.9-11.9) and -2.8 (-13.2-7.6) for a composite bleed event outcome and death from any cause, respectively. No algorithms generated alerts for any outcomes. CONCLUSIONS: Near-real-time monitoring was feasible and, in contrast to the key pre-marketing trial that demonstrated the efficacy of prasugrel, did not suggest that prasugrel compared with clopidogrel was associated with an increased risk of gastrointestinal and intracranial bleeding.
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Block JP, Choudhry NK, Carpenter DP, Fischer MA, Brennan TA, Tong AY, Matlin OS, Shrank WH.

Time series analyses of the effect of FDA communications on use of prescription weight loss medications

. Obesity 2014;22:943-9.Abstract
OBJECTIVE: To determine the impact of FDA safety communications regarding the weight loss medications sibutramine and orlistat. METHODS: The 2008 to 2011 pharmacy claims data from CVS Caremark were used to determine the effect of the relevant FDA warnings on (1) use of sibutramine and orlistat, (2) their rates of discontinuation, and (3) substitution to an alternate weight loss medication in the 3-month period following discontinuation. RESULTS: The use of sibutramine, orlistat, or phentermine declined from 45 users per 100,000 Caremark enrollees in May 2008 to 24 users per 100,000 enrollees in December 2010. In the time series analyses of overall use of medications, a very small decline in the trend of use of sibutramine after the FDA communication (0.000002% per month decline after the communication; P < 0.001) was found. However, rates of discontinuation of sibutramine and orlistat were similar before and after relevant FDA communications (all P values >0.1 for both level and trend changes post-warning). Patients discontinuing sibutramine post-communication increased use of phentermine at a rate of 0.004% per month after discontinuation (P = 0.01). CONCLUSION: From 2008 to 2010, use of prescription weight loss medications was low and declined over time. FDA communications regarding the safety of these medications had limited effect on use.
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Moss AC, Lillis Y, Edwards George JB, Choudhry NK, Berg AH, Cheifetz AS, Horowitz G, Leffler DA.

Attitudes to Mesalamine Questionnaire: A Novel Tool to Predict Mesalamine Nonadherence in Patients with IBD

. American Journal of Gastroenterology 2014;Abstract
OBJECTIVES:Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence.METHODS:A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8).RESULTS:From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5).CONCLUSIONS:Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).Am J Gastroenterol advance online publication, 10 June 2014; doi:10.1038/ajg.2014.158.
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Franklin JM, Choudhry NK, Uscher-Pines L, Brill G, Matlin OS, Fischer MA, Schneeweiss S, Avorn J, Brennan TA, Shrank WH.

Equity in the receipt of oseltamivir in the United States during the H1N1 pandemic

. American Journal of Public Health 2014;104:1052-8.Abstract
OBJECTIVES: We assessed the relationship between individual characteristics and receipt of oseltamivir (Tamiflu) in the United States during the H1N1 pandemic and other flu seasons. METHODS: In a cohort of individuals enrolled in pharmacy benefit plans, we used a multivariate logistic regression model to measure associations between subscriber characteristics and filling a prescription for oseltamivir during 3 flu seasons (October 2006-May 2007, October 2007-May 2008, and October 2008-May 2010). In 19 states with county-level influenza rates reported, we controlled for disease burden. RESULTS: Approximately 56 million subscribers throughout the United States were included in 1 or more study periods. During pandemic flu, beneficiaries in the highest income category had 97% greater odds of receiving oseltamivir than those in the lowest category (P < .001). After we controlled for disease burden, subscribers in the 2 highest income categories had 2.18 and 1.72 times the odds of receiving oseltamivir compared with those in the lowest category (P < .001 for both). CONCLUSIONS: Income was a stronger predictor of oseltamivir receipt than prevalence of influenza. These findings corroborate concerns about equity of treatment in pandemics, and they call for improved approaches to distributing potentially life-saving treatments.
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Choudhry NK, Dugani S, Shrank WH, Polinski JM, Stark CE, Gupta R, Prabhakaran D, Brill G, Jha P. Despite increased use and sales of statins in India, per capita prescription rates remain far below high-income countries . Health Affairs 2014;33:273-282.Abstract
Statin use has increased substantially in North America and Europe, with resultant reductions in cardiovascular mortality. However, little is known about statin use in lower-income countries. India is of interest because of its burden of cardiovascular disease, the unique nature of its prescription drug market, and the growing globalization of drug sales. We conducted an observational study using IMS Health data for the period February 2006–January 2010. During the period, monthly statin prescriptions increased from 45.8 to 84.1 per 1,000 patients with coronary heart disease—an increase of 0.80 prescriptions per month. The proportion of the Indian population receiving a defined daily statin dose increased from 3.35 percent to 7.78 percent. Nevertheless, only a fraction of those eligible for a statin appeared to receive the therapy, even though there were 259 distinct statin products available to Indian consumers in January 2010. Low rates of statin use in India may reflect problems with access to health care, affordability, underdiagnosis, and cultural beliefs. Because of the growing burden of cardiovascular disease in lower-income countries such as India, there is an urgent need to increase statin use and ensure access to safe products whose use is based on evidence. Policies are needed to expand insurance, increase medications’ affordability, educate physicians and patients, and improve regulatory oversight.
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Patrick AR, Fischer MA, Choudhry NK, Shrank WH, Seeger JD, Liu J, Avorn J, Polinski JM.

Trends in insulin initiation and treatment intensification among patients with type 2 diabetes

. Journal of General Internal Medicine 2014;29:320-7.Abstract
BACKGROUND: Many patients with type 2 diabetes eventually require insulin, yet little is known about the patterns and quality of pharmacologic care received following insulin initiation. Guidelines from the American Diabetes Association and the European Association for the Study of Diabetes recommend that insulin secretagogues such as sulfonylureas be discontinued at the time of insulin initiation to reduce the risk of hypoglycemia, and that treatment be intensified if HbA1c levels remain above-target 3 months after insulin initiation. OBJECTIVE: To describe pharmacologic treatment patterns over time among adults initiating insulin and/or intensifying insulin treatment. DESIGN: Observational study. SUBJECTS: A large commercially insured population of adult patients without recorded type 1 diabetes who initiated insulin. MAIN MEASURES: We evaluated changes in non-insulin antidiabetic medication use during the 120 days immediately following insulin initiation, rates of increase in insulin dose and/or dosing frequency during the 270 days following an insulin initiation treatment period of 90 days, and rates of insulin discontinuation. KEY RESULTS: Seven thousand, nine hundred and thirty-two patients initiated insulin during 2003-2008, with the majority (61 %) initiating basal insulin only. Metformin (55 %), sulfonylureas (39 %), and thiazolidinediones (30 %) were commonly used prior to insulin initiation. Metformin was continued by 64 % of patients following mixed or mealtime insulin initiation; the continuation rate was nearly as high for sulfonylureas (58 %). Insulin dose and/or dosing frequency increased among 22.9 % of patients. Insulin was discontinued by 27 % of patients. CONCLUSIONS: We found evidence of substantial departures from guideline-recommended pharmacotherapy. Insulin secretagogues were frequently co-prescribed with insulin. The majority of patients had no evidence of treatment intensification following insulin initiation, although this finding is difficult to interpret without HbA1c levels. While each patient's care should be individualized, our data suggest that the quality of care following insulin initiation can be improved.
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Berkowitz SA, Seligman HK, Choudhry NK.

Treat or eat: food insecurity, cost-related medication underuse, and unmet needs

[Internet]. 2014;127(4):303 - 310.e3. Website PDF
Kesselheim AS, Bykov K, Avorn J, Tong A, Doherty M, Choudhry NK.

Burden of Changes in Pill Appearance for Patients Receiving Generic Cardiovascular Medications After Myocardial Infarction: Cohort and Nested Case–Control Studies

. Annals of Internal Medicine 2014;161:96-103.Abstract
Background: Generic prescription drugs made by different manufacturers may vary in color or shape, and switching among these drug products may interrupt medication use.Objective: To determine whether nonpersistent use of generic drugs among patients with cardiovascular disease after myocardial infarction (MI) is associated with inconsistent appearance of their medications. Design: Cohort and nested case–control studies.Setting: Claims from a commercial health insurance database in the United States. Patients: Patients discharged after hospitalization for MI between 2006 and 2011 who initiated treatment with a generic β-blocker, angiotensin-converting enzyme inhibitor, angiotensin II–receptor blocker, or statin. Case patients discontinued their index medication for at least 1 month; control patients continued treatment. Control patients were matched to case patients on therapeutic class, number of dispensings before nonpersistence, sex, and age. Measurements: Rates of changes in pill color and shape during the year after MI were calculated. Next, 2 refills preceding nonpersistence were evaluated to determine whether pill color or shape had changed. Odds of discordance among case and control patients were compared using conditional logistic regression. Results: A total of 29% of patients (3286 of 11 513) had a change in pill shape or color during the study. Statins had the most changes in appearance, whereas β-blockers had the fewest. A total of 4573 episodes of nonpersistence was matched to 19 881 control episodes. The odds of nonpersistence in case patients increased by 34% after a change in pill color (adjusted odds ratio, 1.34 [95% CI, 1.12 to 1.59]) and 66% after a change in pill shape (adjusted odds ratio, 1.66 [CI, 1.43 to 1.94]). Limitation: Only 3 categories of drugs indicated after MI were evaluated, and clinical outcomes were not addressed. Conclusion: Variation in the appearance of generic pills is associated with nonpersistent use of these essential drugs after MI among patients with cardiovascular disease. Primary Funding Source: Agency for Healthcare Research and Quality and the Harvard Program in Therapeutic Science.
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Sanfélix-Gimeno G, Franklin JM, Shrank WH, Carlo M, Tong AY, Reisman L, Matlin OS, Brennan TA, Choudhry NK.

Did HEDIS Get it Right? Evaluating the Quality of a Quality Measure: Adherence to β-Blockers and Cardiovascular Outcomes After Myocardial Infarction

. Medical Care 2014;52:669-676.Abstract
Background:As an example of the process that could be used to evaluate and optimize the performance of quality measures in routine practice, we evaluated whether the Healthcare Effectiveness Data and Information Set (HEDIS) measure assessing the “persistence of β-blocker treatment after a heart attack” correlates with post-myocardial infarction (MI) outcomes and whether or not there are alternative specifications of this construct which are better predictors and/or may be more easily applied. Research Design:The study included a retrospective cohort of 8672 post-MI patients 18 years old and above. We assessed the strength of the association between the different adherence measures and the composite clinical outcome using multivariable Cox models. We compared the predictive capacity of each adherence definition model to one that did not contain adherence by computing the change in C-statistics and the continuous net reclassification improvement indices (NRIs). Results:Adherence was associated with clinical outcome reductions, with hazard ratios ranging from 0.48 (95% CI, 0.27–0.85) to 0.81 (95% CI, 0.67–0.99). None of the adherence measures, including the HEDIS definition, significantly changed the C-statistic relative to a model that did not include adherence. However, the short-term adherence measure (having 72 d covered during the first 90 d postdischarge) showed a large change in NRI (correctly reclassifying 12% of cases and 16% of noncases; NRI: 28%; 95% CI, 22%–38%), although did not significantly differ from the change in NRI with the HEDIS measure. Conclusions:We identified an adherence measure that showed a predictive ability as good as that of the HEDIS definition to measure β-blocker use after MI, halving the time of assessment required, and thus, allowing for the implementation of quality improvement interventions in a more timely manner.
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Lieberman DA, Polinski JM, Choudhry NK, Avorn J, Fischer MA.

Unintended Consequences of a Medicaid Prescription Copayment Policy

[Internet]. Medical Care 2014;52(5):10.1097/MLR.0000000000000119. Publisher's VersionAbstract
Background and Objectives:Medication copayments can influence patient choices. We evaluated 2 copayment policies implemented by Massachusetts Medicaid incentivizing the use of selected generic medications.Research Design and Measures:In 2009, Massachusetts Medicaid copayments were $1 for generics and $3 for brands. On February 1, 2009, copayments for generic antihypertensives, antihyperlipidemics, and hypoglycemics (target medications) remained at $1, whereas copayments for all nontarget generics increased to $2 (policy #1) and $3 on July 1, 2010 (policy #2). Using state-level, aggregate prescription data, we developed interrupted time-series models with controls to evaluate the impact of these policies on use of target generics, target brands, and nontarget essential medications (defined as medications required for ongoing treatment of serious medical conditions).
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Choudhry NK, Glynn RJ, Avorn J, Lee JL, Brennan TA, Reisman L, Toscano M, Levin R, Matlin OS, Antman EM, Shrank WH. Untangling the relationship between medication adherence and post–myocardial infarction outcomes: Medication adherence and clinical outcomes [Internet]. American Heart Journal 2014;167:51-58. Publisher's VersionAbstract
Background Patients who adhere to medications experience better outcomes than their nonadherent counterparts. However, these observations may be confounded by patient behaviors. The level of adherence necessary for patients to derive benefit and whether adherence to all agents is important for diseases that require multiple drugs remain unclear. This study quantifies the relationship between medication adherence and post–myocardial infarction (MI) adverse coronary events. Methods This is a secondary analysis of the randomized \{MI\} \{FREEE\} trial. Patients who received full prescription coverage were classified as adherent (proportion of days covered ≥80%) or not based upon achieved adherence in the 6 months after randomization. First major vascular event or revascularization rates were compared using multivariable Cox models adjusting for comorbidity and health-seeking behavior. Results Compared with patients randomized to usual care, full coverage patients adherent to statin, β-blocker, or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were significantly less likely to experience the study's primary outcome (hazard ratio [HR] range 0.64-0.81). In contrast, nonadherent patients derived no benefit (HR range 0.98-1.04, P ≤ .01 for the difference in \{HRs\} between adherent and nonadherent patients). Partially adherent patients had no reduction in clinical outcomes for any of the drugs evaluated, although their achieved adherence was higher than that among controls. Conclusion Achieving high levels of adherence to each and all guideline-recommended post-MI secondary prevention medication is associated with improved event-free survival. Lower levels of adherence appear less protective.
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2013
Kulik A, Desai NR, Shrank WH, Antman EM, Glynn RJ, Levin R, Reisman L, Brennan T, Choudhry NK. Full prescription coverage versus usual prescription coverage after coronary artery bypass graft surgery: analysis from the post-myocardial infarction free Rx event and economic evaluation (FREEE) randomized trial . Circulation 2013;128:S219-25.Abstract
BACKGROUND: Eliminating out-of-pocket costs for patients after myocardial infarction (MI) improves adherence to preventive therapies and reduces clinical events. Because adherence to medical therapy is low among patients treated with coronary artery bypass graft surgery (CABG), we evaluated the impact of providing full prescription coverage to this patient subgroup. METHODS AND RESULTS: The MI Free Rx Event and Economic Evaluation (FREEE) trial randomly assigned 5855 patients with MI to full prescription coverage or usual formulary coverage for all statins, beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. We assessed the impact of full prescription coverage on adherence, clinical outcomes, and healthcare costs using adjusted models among the 1052 patients who underwent CABG at the index hospitalization and 4803 who did not. CABG patients were older and had more comorbid illness (P<0.01). After MI, CABG patients were significantly more likely to receive beta-blockers and statins but were less likely to receive angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy (P<0.01). Receiving full drug coverage increased rates of adherence to all preventative medications after CABG (all P<0.05). Full coverage was also associated with nonsignificant reductions in the rate of major vascular events or revascularization for patients treated with CABG (hazard ratio, 0.91; 95% confidence interval, 0.66-1.25) or without CABG (hazard ratio, 0.93; 95% confidence interval, 0.82-1.06), with no interaction noted (Pint=NS). After CABG, full prescription coverage significantly reduced patient out-of-pocket spending for drugs (P=0.001) without increasing overall health expenditures (P=NS). CONCLUSIONS: Eliminating drug copayments after MI provides consistent benefits to patients treated with or without CABG, leading to increased medication adherence, trends toward improved clinical outcomes, and reduced patient out-of-pocket expenses.
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Gagne JJ, Polinski JM, Kesselheim AS, Choudhry NK, Hutchins D, Matlin OS, Tong A, Shrank WH. Patterns and predictors of generic narrow therapeutic index drug use among older adults . Journal of the American Geriatrics Society 2013;61:1586-91.Abstract
OBJECTIVES: To ascertain predictors of initiation of brand-name versus generic narrow therapeutic index (NTI) drugs. DESIGN: Retrospective cohort study. SETTING: Data from CVS Caremark were linked to Medicare claims and to U.S. census data. PARTICIPANTS: Individuals aged 65 and older who initiated an NTI drug in 2006 and 2007 (N = 36,832). MEASUREMENTS: Demographic, health service utilization, and geographic predictors of whether participants initiated a generic or brand-name version of their NTI drug were identified using logistic regression. RESULTS: Overall, 30,014 (81.5%) participants started on a generic version of their NTI drug. The most commonly initiated NTI drugs were warfarin (n = 17,790; 48%), levothyroxine (n = 10,779; 29%), and digoxin (n = 6,414; 17%). Older age (odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.02-1.22 comparing aged >/=85 with 65-74), higher burden of comorbidity (OR = 1.05, 95% CI = 1.04-1.07 for each 1-point increase in comorbidity score), and prior use of any generic drug (OR = 1.55, 95% CI = 1.29-1.87) were positively associated with generic drug initiation. Independent of other predictors, residing in the census block group with the highest generic use was positively associated with greater odds of generic NTI drug initiation (OR = 1.24, 95% CI = 1.14-1.35 compared with the lowest quintile). CONCLUSION: Demographic, health service utilization, and geographic characteristics are important determinants of whether individuals initiate treatment with a brand-name or generic NTI drug. These factors may contribute to disparities in care and highlight potential targets for educational campaigns.
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Franklin JM, Shrank WH, Pakes J, Sanfelix-Gimeno G, Matlin OS, Brennan TA, Choudhry NK.

Group-based trajectory models: a new approach to classifying and predicting long-term medication adherence

. Medical Care 2013;51:789-96.Abstract
BACKGROUND: Classifying medication adherence is important for efficiently targeting adherence improvement interventions. The purpose of this study was to evaluate the use of a novel method, group-based trajectory models, for classifying patients by their long-term adherence. RESEARCH DESIGN: We identified patients who initiated a statin between June 1, 2006 and May 30, 2007 in prescription claims from CVS Caremark and evaluated adherence over the subsequent 15 months. We compared several adherence summary measures, including proportion of days covered (PDC) and trajectory models with 2-6 groups, with the observed adherence pattern, defined by monthly indicators of full adherence (defined as having >/=24 d covered of 30). We also compared the accuracy of adherence prediction based on patient characteristics when adherence was defined by either a trajectory model or PDC. RESULTS: In 264,789 statin initiators, the 6-group trajectory model summarized long-term adherence best (C=0.938), whereas PDC summarized less well (C=0.881). The accuracy of adherence predictions was similar whether adherence was classified by PDC or by trajectory model. CONCLUSIONS: Trajectory models summarized adherence patterns better than traditional approaches and were similarly predicted by covariates. Group-based trajectory models may facilitate targeting of interventions and may be useful to adjust for confounding by health-seeking behavior.
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Canestaro WJ, Patrick AR, Avorn J, Ito K, Matlin OS, Brennan TA, Shrank WH, Choudhry NK. Cost-Effectiveness of Oral Anticoagulants for Treatment of Atrial Fibrillation . Circulation: Cardiovascular Quality and Outcomes 2013;6:724-731.Abstract
Background—New anticoagulants may improve health outcomes in patients with atrial fibrillation, but it is unclear whether their use is cost-effective.Methods and Results—A Markov state transition was created to compare 4 therapies: dabigatran 150 mg BID, apixaban 5 mg BID, rivaroxaban 20 mg QD, and warfarin therapy. The population included those with newly diagnosed atrial fibrillation who were eligible for treatment with warfarin. Compared with warfarin, apixaban, rivaroxaban, and dabigatran, costs were $93 063, $111 465, and $140 557 per additional quality-adjusted life year gained, respectively. At a threshold of $100 000 per quality-adjusted life year, apixaban provided the greatest absolute benefit while still being cost-effective, although warfarin would be superior if apixaban was 2% less effective than expected. Although apixaban was the optimal strategy in our base case, in probabilistic sensitivity analysis, warfarin was optimal in an equal number of iterations at a cost-effectiveness threshold of $100 000 per quality-adjusted life year.Conclusions—While at a standard cost-effectiveness threshold of $100 000 per quality-adjusted life year, apixaban seems to be the optimal anticoagulation strategy; this finding is sensitive to assumptions about its efficacy and cost. In sensitivity analysis, warfarin seems to be the optimal choice in an equal number of simulations. As a result, although all the novel oral anticoagulants produce greater quality-adjusted life expectancy than warfarin, they may not represent good value for money.
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