BACKGROUND: Primary medication nonadherence (PMN) occurs when patients do not fill new prescriptions. Interventions to reduce PMN have not been well described. OBJECTIVES: To determine whether 2 pharmacy-based interventions could decrease PMN. DESIGN: Two sequential interventions with a control group were evaluated after completion. The automated intervention began in 2007 and consisted of phone calls to patients on the third and seventh days after a prescription was processed but remained unpurchased. The live intervention began in 2009 and used calls from a pharmacist or technician to patients who still had not picked up their prescriptions after 8 days. SUBJECTS: Patients with newly prescribed cardiovascular medications received at CVS community pharmacies. Patients with randomly selected birthdays served as the control population. MEASURES: Patient abandonment of new prescription, defined as not picking up medications within 30 days of initial processing at the pharmacy. RESULTS: The automated intervention included 852,612 patients and 1.2 million prescriptions, with a control group of 9282 patients and 13,178 prescriptions. The live intervention included 121,155 patients and 139,502 prescriptions with a control group of 2976 patients and 3407 prescriptions. The groups were balanced by age, sex, and patterns of prior prescription use. For the automated intervention, 4.2% of prescriptions were abandoned in the intervention group and 4.5% in the control group (P>0.1), with no significant differences for any individual classes of medications. The live intervention was used in a group that had not purchased prescriptions after 8 days and thus had much higher PMN. In this setting 36.9% of prescriptions were abandoned in the intervention group and 41.7% in the control group, a difference of 4.8% (P<0.0001). The difference in abandoned prescriptions for antihypertensives was 6.9% (P<0.0001) but for antihyperlipidemics was only 1.4% (P>0.1). CONCLUSIONS: Automated reminder calls had no effect on PMN. Live calls from pharmacists decreased antihypertensive PMN significantly, although many patients still abandoned their prescriptions.
Background—With proliferating treatment options for anticoagulant therapy, physicians and patients must choose among them based on their benefits and risks. Using a Discrete Choice Experiment, we elicited patients’ relative preferences for specific benefits and risks of anticoagulant therapy.Methods and Results—We selected a sample of US patients with cardiovascular disease from an online panel and elicited their preferences for benefits and risks of anticoagulant therapy: nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, minor bleeding, major bleeding, bleeding death, and need for monitoring. These attributes were used to design scenarios describing hypothetical treatments that were labeled as new drug, old drug, or no drug. Latent class analysis was used to identify groups of patients with similar preferences. A total of 341 patients completed all Discrete Choice Experiment questions. On average, patients valued a 1% increased risk of a fatal bleeding event the same as a 2% increase in nonfatal myocardial infarction, a 3% increase in nonfatal stroke, a 3% increase in cardiovascular death, a 6% increase in major bleeding, and a 16% increase in minor bleeding. The odds of choosing no drug or old drug versus new drug were 0.72 (95% confidence interval, 0.61–0.84) and 0.86 (95% confidence interval, 0.81–0.93), respectively. Previous stroke or myocardial infarction was associated with membership in the class with larger negative preferences for these outcomes.Conclusions—Patients’ preferences for various outcomes of anticoagulant therapy vary and depend on their previous experiences with myocardial infarction or stroke. Incorporating these preferences into benefit risk calculation and treatment decisions can enhance patient-centered care.
Objectives Evaluation of quality of care across retail clinics in a geographically diverse population has not been undertaken to date. We sought to evaluate and compare the quality of care for otitis media, pharyngitis, and urinary tract infection received in retail medical clinics in CVS pharmacies ("MinuteClinics" [MCs]), ambulatory care facilities (ACFs), and emergency departments (EDs). Methods We used 14 measures constructed from RAND Corporation's Quality Assurance Tools and guidelines from the American Academy of Pediatrics, the American Academy of Family Physicians, and the Infectious Diseases Society of America. Our cohort was drawn from Aetna medical and prescription claims, 2009-2012. Members were matched on visit date, condition, and propensity score. Generalized estimating equations were used to compare quality across clinic type, overall, and by index condition. Results We matched 75,886 episodes of care, of which 20,153 were eligible for at least 1 quality measure. MCs performed better than EDs and ACFs in 7 measures. In a multivariable model, MCs performed better than ACFs and EDs across all quality measures ([OR 0.42; 95% CI, 0.40-0.45; P < .0001; ACF vs MC] [OR 0.29; 95% CI, 0.27-0.31; P < .0001; ED vs MC]). Results for each condition were significant at P < .0001. Conclusions Quality of care for these conditions based on widely accepted objective measures was superior in MinuteClinics compared with ACFs and EDs.
Referring patients to other physicians is one of the most fundamental and frequently performed tasks in clinical practice. In 2009, referrals to other physicians were made during almost 1 in 10 ambulatory visits in the United States for a total of more than 100 million referrals.1 Despite the routine nature of referrals, there is significant variation in how and when physicians choose to ask for specialist involvement. Rates of referral appear to vary up to 5-fold, with both overreferral and underreferral being common.2 Decisions about whether to refer appear to be influenced by both patient factors, such as illness severity and expectations, as well as physician training and expertise.2 As a consequence, standardizing and optimizing the referral process may affect the cost and quality of care.3
Importance: Although many classes of oral glucose-lowering medications have been approved for use, little comparative effectiveness evidence exists to guide initial selection of therapy for diabetes mellitus. Objective: To determine the effect of initial oral glucose-lowering agent class on subsequent need for treatment intensification and 4 short-term adverse clinical events. Design, Setting, and Participants: This study was a retrospective cohort study of patients who were fully insured members of Aetna (a large national health insurer) who had been prescribed an oral glucose-lowering medication from July 1, 2009, through June 30, 2013. Individuals newly prescribed an oral glucose-lowering agent who filled a second prescription for a medication in the same class and with a dosage at or above the World Health Organization's defined daily dose within 90 days of the end-of-day's supply of the first prescription were studied. Individuals with interim prescriptions for other oral glucose-lowering medications were excluded. Exposures: Initiation of treatment with metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor. Main Outcomes and Measures: Time to addition of a second oral agent or insulin, each component separately, hypoglycemia, other diabetes-related emergency department visits, and cardiovascular events. Results: A total of 15 516 patients met the inclusion criteria, of whom 8964 (57.8%) started therapy with metformin. In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P < .001 for all). In propensity score and multivariable-adjusted Cox proportional hazards models, initiation of therapy with sulfonylureas (hazard ratio [HR], 1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification. Alternatives to metformin were not associated with a reduced risk of hypoglycemia, emergency department visits, or cardiovascular events. Conclusions and Relevance: Despite guidelines, only 57.8% of individuals began diabetes treatment with metformin. Beginning treatment with metformin was associated with reduced subsequent treatment intensification, without differences in rates of hypoglycemia or other adverse clinical events. These findings have significant implications for quality of life and medication costs.
Cigarette smoking can make managing chronic diseases more difficult. For instance, in patients with certain respiratory conditions, smoking increases the risk of acute exacerbation, can worsen disease control, and may limit the effectiveness of inhaled corticosteroids.1 Similarly, by raising blood pressure, smoking can make it challenging to effectively control hypertension and may increase the risk of atherosclerosis and coronary heart disease.2 Smoking can also increase the risk of serious adverse drug events. Oral contraceptive (OC) users older than 35 years who smoke have a 9-fold higher risk of myocardial infarction and venous thromboembolism compared with nonsmokers.3,4
Importance Genetic biomarkers that predict a drug’s efficacy or likelihood of toxicity are assuming increasingly important roles in the personalization of pharmacotherapy, but concern exists that evidence that links use of some biomarkers to clinical benefit is insufficient. Nevertheless, information about the use of biomarkers appears in the labels of many prescription drugs, which may add confusion to the clinical decision-making process.Objective To evaluate the evidence that supports pharmacogenomic biomarker testing in drug labels and how frequently testing is recommended.Data Sources Publicly available US Food and Drug Administration databases.Main Outcomes and Measures We identified drug labels that described the use of a biomarker and evaluated whether the label contained or referenced convincing evidence of its clinical validity (ie, the ability to predict phenotype) and clinical utility (ie, the ability to improve clinical outcomes) using guidelines published by the Evaluation of Genomic Applications in Practice and Prevention Working Group. We graded the completeness of the citation of supporting studies and determined whether the label recommended incorporation of biomarker test results in therapeutic decision making.Results Of the 119 drug-biomarker combinations, only 43 (36.1%) had labels that provided convincing clinical validity evidence, whereas 18 (15.1%) provided convincing evidence of clinical utility. Sixty-one labels (51.3%) made recommendations about how clinical decisions should be based on the results of a biomarker test; 36 (30.3%) of these contained convincing clinical utility data. A full description of supporting studies was included in 13 labels (10.9%).Conclusions and Relevance Fewer than one-sixth of drug labels contained or referenced convincing evidence of clinical utility of biomarker testing, whereas more than half made recommendations based on biomarker test results. It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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
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.
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.
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.