Publications

2014
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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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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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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Berkowitz SA, Seligman HK, Choudhry NK. Treat or eat: food insecurity, cost-related medication underuse, and unmet needs [Internet]. American Journal of Medicine 2014;127(4):303 - 310.e3. WebsiteAbstract

BACKGROUND: Adults with chronic disease are often unable to meet medication and food needs, but no study has examined the relationship between cost-related medication underuse and food insecurity in a nationally representative sample. We examined which groups most commonly face unmet food and medication needs. METHODS:Cross-sectional analysis of data from chronically ill participants (self-report of arthritis, diabetes mellitus, cancer, asthma, chronic obstructive pulmonary disease, stroke, hypertension, coronary heart disease, or presence of a "psychiatric problem") aged ≥20 years, in the 2011 National Health Interview Survey. We fit logistic regression models to identify factors associated with food insecurity, cost-related medication underuse, or both. RESULTS:There were 9696 adult National Health Interview Survey (NHIS) participants who reported chronic illness; 23.4% reported cost-related medication underuse; 18.8% reported food insecurity; and 11% reported both. Adults who reported food insecurity were significantly more likely to report cost-related medication underuse (adjusted odds ratio [aOR] 4.03). Participants with both cost-related medication underuse and food insecurity were more likely to be Hispanic (aOR 1.58), non-Hispanic black (aOR 1.58), and have more chronic conditions (aOR per additional chronic condition 1.56) than patients reporting neither. They also were less likely to have public, non-Medicare insurance (aOR 0.70) and report participation in the Special Supplemental Nutrition Assistance Program for Woman, Infants, and Children (aOR 0.39). CONCLUSIONS: Approximately 1 in 3 chronically ill NHIS participants are unable to afford food, medications, or both. WIC and public health insurance participation are associated with less food insecurity and cost-related medication underuse

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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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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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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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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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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
Desai NR, Canestaro WJ, Kyrychenko P, Chaplin D, Martell LA, Brennan T, Matlin OS, Choudhry NK. Impact of CYP2C19 Genetic Testing on Provider Prescribing Patterns for Antiplatelet Therapy After Acute Coronary Syndromes and Percutaneous Coronary Intervention. Circulation. Cardiovascular Quality and Outcomes 2013;6:694-699.Abstract
BACKGROUND: have an increased risk for adverse cardiovascular events. In 2010, the US Food and Drug Administration issued a boxed warning cautioning against the use of clopidogrel in such patients. We sought to assess the impact of CYP2C19 genetic testing on prescribing patterns for antiplatelet therapy among patients with acute coronary syndrome or percutaneous coronary intervention. METHODS AND RESULTS: testing. Genotype and phenotype results were provided to patients and their physicians, but no specific treatment recommendations were suggested. Patients were categorized based on their genotype (carriers versus noncarriers) and phenotype (extensive, intermediate, and poor metabolizers). The primary outcome was intensification in antiplatelet therapy defined as either dose escalation of clopidogrel or replacement of clopidogrel with prasugrel. Between July 2010 and April 2012, 6032 patients were identified, and 499 (8.3%) underwent CYP2C19 genotyping, of whom 146 (30%) were found to have >/=1 reduced function allele, including 15 (3%) with 2 reduced function alleles. Although reduced function allele carriers were significantly more likely than noncarriers to have an intensification of their antiplatelet therapy, only 20% of poor metabolizers of clopidogrel had their antiplatelet therapy intensified. CONCLUSIONS: allele carriers, but only 20% of poor metabolizers of clopidogrel had an escalation in the dose of clopidogrel or were switched to prasugrel. These prescribing patterns likely reflect the unclear impact and evolving evidence for clopidogrel pharmacogenomics.
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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.CONCLUSTIONS: 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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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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Bateman BT, Bykov K, Choudhry NK, Schneeweiss S, Gagne JJ, Polinski JM, Franklin JM, Doherty M, Fischer MA, Rassen JA. Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ 2013;347:f5416.Abstract

OBJECTIVE: To examine the relation between the type of stress ulcer prophylaxis administered and the risk of postoperative pneumonia in patients undergoing coronary artery bypass grafting. DESIGN: Retrospective cohort study. SETTING: Premier Research Database. PARTICIPANTS: 21,214 patients undergoing coronary artery bypass graft surgery between 2004 and 2010; 9830 (46.3%) started proton pump inhibitors and 11,384 (53.7%) started H2 receptor antagonists in the immediate postoperative period. MAIN OUTCOME MEASURE: Occurrence of postoperative pneumonia, assessed using appropriate diagnostic codes. RESULTS: Overall, 492 (5.0%) of the 9830 patients receiving a proton pump inhibitor and 487 (4.3%) of the 11,384 patients receiving an H2 receptor antagonist developed postoperative pneumonia during the index hospital admission. After propensity score adjustment, an elevated risk of pneumonia associated with treatment with proton pump inhibitors compared with H2 receptor antagonists remained (relative risk 1.19, 95% confidence interval 1.03 to 1.38). In the instrumental variable analysis, use of a proton pump inhibitor (compared with an H2 receptor antagonist) was associated with an increased risk of pneumonia of 8.2 (95% confidence interval 0.5 to 15.9) cases per 1000 patients. CONCLUSIONS: Patients treated with proton pump inhibitors for stress ulcer had a small increase in the risk of postoperative pneumonia compared with patients treated with H2 receptor antagonists; this risk remained after confounding was accounted for using multiple analytic approaches.

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Bateman BT, Rassen JA, Schneeweiss S, Bykov K, Franklin JM, Gagne JJ, Polinski JM, Liu J, Kulik A, Fischer MA, Choudhry NK. Adjuvant vancomycin for antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 2013;146:472-8.Abstract

OBJECTIVE: The incidence of hospital-acquired Clostridium difficile infection (CDI) has increased rapidly over the past decade; patients undergoing major surgery, including coronary artery bypass grafting (CABG), are at particular risk. Intravenous vancomycin exposure has been identified as an independent risk factor for CDI, but this is controversial. It is not known whether vancomycin administered for surgical site infection prophylaxis increases the risk of CDI. METHODS: Using data from the Premier Perspective Comparative Database, we assembled a cohort of 69,807 patients undergoing CABG surgery between 2004 and 2010 who received either a cephalosporin alone (65.1%) or a cephalosporin plus vancomycin (34.9%) on the day of surgery. Patients were observed for CDI until discharge from the index hospitalization. In these groups, we evaluated the comparative rate of postoperative CDI with Cox models; confounding was addressed using propensity scores. RESULTS: In all, 77 (0.32%) of the 24,393 patients receiving a cephalosporin plus vancomycin and 179 (0.39%) of the 45,414 patients receiving a cephalosporin alone had postoperative CDI (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.95). After adjusting for confounding variables with either propensity score matching or stratification, there was no meaningful association between adjuvant vancomycin exposure and postoperative CDI (HR, 0.85; 95% CI, 0.61-1.19; and HR, 0.85; 95% CI, 0.63-1.15, respectively). Results of multiple sensitivity analyses were similar to the main findings. CONCLUSIONS: After adjustment for patient and surgical characteristics, a short course of prophylactic vancomycin was not associated with an increased risk of CDI among patients undergoing CABG surgery.

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Ito K, Elkin E, Blinder V, Keating N, Choudhry N. Cost-effectiveness of full coverage of aromatase inhibitors for Medicare beneficiaries with early breast cancer. Cancer 2013;119:2494-502.Abstract

BACKGROUND: Rates of nonadherence to aromatase inhibitors (AIs) among Medicare beneficiaries with hormone receptor-positive early breast cancer are high. Out-of-pocket drug costs appear to be an important contributor to this and may be addressed by eliminating copayments and other forms of patient cost sharing. The authors estimated the incremental cost-effectiveness of providing Medicare beneficiaries with full prescription coverage for AIs compared with usual prescription coverage under the Medicare Part D program. METHODS: A Markov state-transition model was developed to simulate AI use and disease progression in a hypothetical cohort of postmenopausal Medicare beneficiaries with hormone receptor-positive early breast cancer. The analysis was conducted from the societal perspective and considered a lifetime horizon. The main outcome was an incremental cost-effectiveness ratio, which was measured as the cost per quality-adjusted life-year (QALY) gained. RESULTS: For patients receiving usual prescription coverage, average quality-adjusted survival was 11.35 QALYs, and lifetime costs were $83,002. For patients receiving full prescription coverage, average quality-adjusted survival was 11.38 QALYs, and lifetime costs were $82,728. Compared with usual prescription coverage, full prescription coverage would result in greater quality-adjusted survival (0.03 QALYs) and less resource use ($275) per beneficiary. From the perspective of Medicare, full prescription coverage was cost-effective (incremental cost-effectiveness ratio, $15,128 per QALY gained) but not cost saving. CONCLUSIONS: Providing full prescription coverage for AIs to Medicare beneficiaries with hormone receptor-positive early breast cancer would both improve health outcomes and save money from the societal perspective.

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Gagne JJ, Bykov K, Choudhry NK, Toomey TJ, Connolly JG, Avorn J. Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison. BMJ 2013;347 PDF
Lewey J, Shrank WH, Bowry AD, Kilabuk E, Brennan TA, Choudhry NK. Gender and racial disparities in adherence to statin therapy: a meta-analysis. American Heart Journal 2013;165:665-78, 678 e1.Abstract

BACKGROUND: Significant disparities exist in cardiovascular outcomes based on race/ethnicity and gender. Rates of evidence-based medication use and long-term medication adherence also appear to be lower in racial subgroups and women but have been subject to little attention. Our objective was to evaluate the effect of race/ethnicity and gender on adherence to statin therapy for primary or secondary prevention. METHODS AND RESULTS: Studies were identified through a systematic search of MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Database of Systematic Reviews (through April 1, 2010) and manual examination of references in selected articles. Studies reporting on adherence to statins by men and women or patients of white and nonwhite race were included. Information on study design, adherence measurement, duration, geographic location, sample size, and patient demographics was extracted using a standardized protocol. From 3,022 potentially relevant publications, 53 studies were included. Compared with men, women had a 10% greater odds of nonadherence (odds ratio 1.10, 95% confidence interval [CI], 1.07-1.13). Nonwhite race patients had a 53% greater odds of nonadherence than white race patients (odds ratio 1.53, 95% CI 1.25-1.87). There was significant heterogeneity in the pooled estimate for gender (I(2) 0.95, P value for heterogeneity <.001) and race (I(2) 0.98, P value for heterogeneity <.001). The overall results remained unchanged in those subgroups that had significantly less heterogeneity. CONCLUSIONS: Among patients prescribed statins, women and nonwhite patients are at increased risk for nonadherence. Further research is needed to identify interventions best suited to improve adherence in these populations.

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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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