BACKGROUND: Recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk. METHODS AND RESULTS: We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with versus without concurrent use of PPIs in 3 large cohorts of patients > or =65 years of age, treated between 2001 and 2005. All patients had undergone percutaneous coronary intervention or had been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and subsequently had initiated treatment with clopidogrel. We recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. We assessed our primary end point of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. We entered 18 565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results. CONCLUSIONS: Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel-PPI interaction of major clinical relevance. Our data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase.
Pharmacy benefit managers (PBMs) have a unique opportunity to promote health and generate value in the healthcare system. Today, PBMs are largely evaluated on their ability to control costs rather than improve health. Pharmacy benefit managers should be evaluated along 3 dimensions in which they can increase value: (1) use of cost-effective medications, (2) timely initiation of appropriate medication therapy, and (3) adherence to that therapy. Value creation requires the development of integrated data systems, stronger partnerships with patients and physicians, and improved measurement and reporting of results. Incentives for PBMs to promote value should drive innovation and improve health outcomes.
BACKGROUND: Prescription medication labels contain valuable health information, and better labels may enhance patient adherence to chronic medications. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve readability and understanding. OBJECTIVE: We evaluated whether the new Target label influenced patient medication adherence. DESIGN AND PATIENTS: Using claims from two large health plans, we identified patients with one of nine chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. MEASUREMENTS: We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on medication adherence. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. RESULTS: Our sample included 23,745 Target users and 162,368 matched non-Target pharmacy users. We found no significant change in adherence between new users of medications at Target or other community pharmacies (p = 0.644) after implementing the new label. In prevalent users, we found a 0.0069 percent reduction in level of adherence (95% CI -0.0138-0.0; p < 0.001) and a 0.0007 percent increase in the slope in Target users (the monthly rate of change of adherence) after implementation of the new label (95% CI 0.0001-0.0013; p = 0.001). CONCLUSIONS: We found no changes in adherence of chronic medication in new users, and small and likely clinically unimportant changes in prevalent users after implementation of the new label. While adherence may not be improved with better labeling, evaluation of the effect of labeling on safety and adverse effects is needed.
CONTEXT: Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. OBJECTIVE: The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. DESIGN: We conducted a cohort study. PARTICIPANTS: Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. MAIN OUTCOME: We measured the incidence of fracture within the cohort. RESULTS: Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98-1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94-1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. CONCLUSIONS: As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.
BACKGROUND: CYP2C9 and VKORC1 genotyping has been advocated as a means of improving the accuracy of warfarin dosing. However, the effectiveness of genotyping in improving anticoagulation control and reducing major bleeding has not yet been compellingly demonstrated. Genotyping currently costs $400 to $550. METHODS AND RESULTS: We constructed a Markov model to evaluate whether and under what circumstances genetically-guided warfarin dosing could be cost-effective for newly diagnosed atrial fibrillation patients. Estimates of clinical event rates, treatment and adverse event costs, and utilities for health states were derived from the published literature. The cost-effectiveness of genetically-guided dosing was highly dependent on the assumed effectiveness of genotyping in increasing the amount of time patients spend appropriately anticoagulated. If genotyping increases the time spent in the target international normalized ratio range by <5 percentage points, its incremental cost-effectiveness ratio would be greater than $100,000 per quality-adjusted life year. The incremental cost-effectiveness ratio falls below $50,000 per quality-adjusted life year if genotyping increases the time spent in range by 9 percentage points. The results were also sensitive to assumptions about the rate of major bleeding events during treatment initiation and the cost of the test. CONCLUSIONS: Our results suggest that genotyping before warfarin initiation will be cost-effective for patients with atrial fibrillation only if it reduces out-of-range international normalized ratio values by more than 5 to 9 percentage points compared with usual care. Given the current uncertainty surrounding genotyping efficacy, caution should be taken in advocating the widespread adoption of this strategy.
CONTEXT: Many patients have palpitations and seek advice from general practitioners. Differentiating benign causes from those resulting from clinically significant cardiac arrhythmia can be challenging and the clinical examination may aid in this process. OBJECTIVE: To systematically review the accuracy of historical features, physical examination, and cardiac testing for the diagnosis of cardiac arrhythmia in patients with palpitations. Data Source, Study Selection, and DATA EXTRACTION: MEDLINE (1950 to August 25, 2009) and EMBASE (1947 to August 2009) searches of English-language articles that compared clinical features and diagnostic tests in patients with palpitations with a reference standard for cardiac arrhythmia. Of the 277 studies identified by the search strategy, 7 studies were used for accuracy analysis and 16 studies for diagnostic yield analysis. Two authors independently reviewed articles for study data and quality and a third author resolved disagreements. DATA SYNTHESIS: Most data were obtained from single studies with small sample sizes. A known history of cardiac disease (likelihood ratio [LR], 2.03; 95% confidence interval [CI], 1.33-3.11), having palpitations affected by sleeping (LR, 2.29; 95% CI, 1.33-3.94), or while the patient is at work (LR, 2.17; 95% CI, 1.19-3.96) slightly increase the likelihood of a cardiac arrhythmia. A known history of panic disorder (LR, 0.26; 95% CI, 0.07-1.01) or having palpitations lasting less than 5 minutes (LR, 0.38; 95% CI, 0.22-0.63) makes the diagnosis of cardiac arrhythmia slightly less likely. The presence of a regular rapid-pounding sensation in the neck (LR, 177; 95% CI, 25-1251) or visible neck pulsations (LR, 2.68; 95% CI, 1.25-5.78) in association with palpitations increases the likelihood of a specific type of arrhythmia (atrioventricular nodal reentry tachycardia). The absence of a regular rapid-pounding sensation in the neck makes detecting the same arrhythmia less likely (LR, 0.07; 95% CI, 0.03-0.19). No other features significantly alter the probability of clinically significant arrhythmia. Diagnostic tests for prolonged periods of electrocardiographic monitoring vary in their yield depending on the modality used, duration of monitoring, and occurrence of typical symptoms during monitoring. Loop monitors have the highest diagnostic yield (34%-84%) for identifying an arrhythmia. CONCLUSIONS: While the presence of a regular rapid-pounding sensation in the neck or visible neck pulsations associated with palpitations makes the diagnosis of atrioventricular nodal reentry tachycardia likely, the reviewed studies suggest that the clinical examination is not sufficiently accurate to exclude clinically significant arrhythmias in most patients. Thus, prolonged electrocardiographic monitoring with demonstration of symptom-rhythm correlation is required to make the diagnosis of a cardiac arrhythmia for most patients with recurrent palpitations.
Drug company-sponsored patient assistance programs (PAPs) provide access to brand-name medications at little or no cost and have been advocated as a safety net for inadequately insured patients. Yet little is known about these programs. We surveyed drug company-sponsored PAPs and found much variability in their structures and application processes. Most cover one or two drugs. Only 4 percent disclosed how many patients they had directly helped, and half would not disclose their income eligibility criteria. A better understanding of PAPs might clarify their role in improving access to medications, the adequacy of existing public programs, and their impact on cost-effective medication use.
BACKGROUND AND OBJECTIVES: In the general population, an early invasive strategy of routine coronary angiography is superior to a conservative strategy of selective angiography in patients who are admitted with unstable angina or non-ST segment elevation myocardial infarction (MI), but the effectiveness of this strategy in individuals with chronic kidney disease (CKD) is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a collaborative meta-analysis with data provided by the main authors of identified trials to estimate the effectiveness of early angiography in patients with CKD. The Cochrane, Medline, and EMBASE databases were searched to identify randomized trials that compared invasive and conservative strategies in patients with unstable angina or non-ST MI. Pooled risks ratios were estimated using data from enrolled patients with estimated GFR <60 ml/min per 1.73 m(2). RESULTS: Five randomized trials that enrolled 1453 patients with CKD were included. An early invasive strategy was associated with nonsignificant reductions in all-cause mortality, nonfatal MI, and a composite of death or nonfatal MI. The invasive strategy significantly reduced rehospitalization. CONCLUSIONS: This collaborative study suggests that the benefits of an early invasive strategy are preserved in patients with CKD and that an early invasive approach reduces the risk for rehospitalization and is associated with trends of reduction in the risk for death and nonfatal re-infarction in patients with CKD. Coronary angiography should be considered for patients who have CKD and are admitted with non-ST elevation acute coronary syndromes.
BACKGROUND: Medication errors represent a major public health concern, and inadequate prescription drug labels have been identified as a root cause of errors. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve health outcomes. OBJECTIVES: To evaluate whether the new Target label influenced patient health services utilization. SUBJECTS: Derived from 2 large health plans. RESEARCH DESIGN AND MEASURES: Using administrative claims, we identified patients with 1 of 9 chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on outpatient, emergency department and inpatient health services use. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. RESULTS: Our sample included 23,745 Target pharmacy users and 162,369 matched non-Target pharmacy users. In the new-user analysis, we found no significant change in rates of both outpatient (event rate ratio: 0.53; 95% CI: 0.15-1.86) and inpatient and emergency department (Event rate ratio: 0.88; 95% CI: 0.62-1.24) health services utilization in Target users after implementation when compared with non-Target users. Similarly, in the prevalent user analysis, we found no change in the level or slope of outpatient or emergency/inpatient services in Target users after implementation of the new label when compared with non-Target users. CONCLUSIONS: We found no statistically significant change in health services use attributable to the implementation of the new prescription drug label at Target pharmacies. These findings highlight the challenge of influencing health outcomes with interventions to improve health literacy.
OBJECTIVES: To propose standardized methods for measuring concurrent adherence to multiple related medications and to apply these definitions to a cohort of patients with diabetes mellitus. STUDY DESIGN: Retrospective cohort study of 7567 subjects with diabetes prescribed 2 or more classes of oral hypoglycemic agents in 2005. METHODS: For each medication class, adherence for each patient was estimated using prescription-based and interval-based measures of proportion of days covered (PDC) from cohort entry until December 31, 2006. Concurrent adherence was calculated by applying these 2 measures in the following 3 ways: (1) the mean of each patient's average PDC, (2) the proportion of days during which patients had at least 1 of their medications available to them, and (3) the proportion of patients with a PDC of at least 80% for all medication classes. Because patients taking multiple related medications have distinct patterns of use, the analysis was repeated after classifying patients into mutually exclusive groups. RESULTS: Concurrent medication adherence ranged from 35% to 95% depending on the definition applied. Interval-based measures provide lower estimates than prescription-based techniques. Definitions that require the use of at least 1 drug class categorize virtually all patients as adherent. Requiring patients to have a PDC of at least 80% for each of their drugs results in only 30% to 40% of patients being defined as adherent. The variability in adherence is greatest for patients whose treatment regimen changed the most during follow-up. CONCLUSIONS: The variability in adherence estimates derived from different definitions may substantially impact qualitative conclusions about concurrent adherence to related medications. Because the measures we propose have different underlying assumptions, the choice of technique should depend on why adherence is being evaluated.
Insurers and policymakers encourage the use of generic drugs to reduce costs, but generics remain underused. We conducted a national survey of commercially insured adults to evaluate their perceptions about generic drugs. Patients agreed that generics are less expensive and a better value than brand-name drugs, and are just as safe. However, although 56 percent reported that Americans should use more generics, only 37.6 percent prefer to take generics. We discuss perceptions about communicating with practitioners about generics, generic substitution, and policymakers' role in influencing generic use. These findings underscore the challenge that providers, insurers, and policymakers face in stimulating the cost-effective use of medications.
BACKGROUND: Highly effective generic cardiovascular medications are frequently underused, leading to greater overall drug costs and cost-related nonadherence. OBJECTIVE: We sought to assess an intervention to stimulate appropriate generic cardiovascular drug use without creating administrative or financial barriers that may impede essential medication use. TRIAL DESIGN: The SAMPLES (Study Assessing the Effect of Cardiovascular Medications Provided as Low-cost, Evidence-based Generic Samples) trial is a clustered, randomized controlled trial of the effect of providing physicians with free generic samples of hydrochlorothiazide for hypertensive patients and simvastatin for patients with hyperlipidemia. We will randomize 660 primary care physicians in Pennsylvania, clustered by physician practice, to receive free samples for both conditions or to receive no samples. We will use data on filled prescriptions obtained from a state-sponsored prescription drug assistance program to perform an intention-to-treat evaluation of the impact of the intervention on physician prescribing behavior (proportion of prescriptions that are generic) and patient adherence. Secondary outcomes will include physician adherence to established guidelines and overall prescription drug costs. CONCLUSION: This trial will define the potential role of an innovative approach to stimulate clinically appropriate cost-effective prescribing. We will determine whether free generic samples can reduce overall drug costs as well as out-of-pocket costs to the patient without sacrificing efficacy and whether this approach results in improved adherence to essential cardiovascular medications. This intervention may also improve adherence to practice guidelines and improve the quality of care received. If effective, this strategy could be used broadly by private insurers or government payers aiming to stimulate more cost-effective and higher-quality care.
BACKGROUND: Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. OBJECTIVES: To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. RESEARCH DESIGN AND SUBJECTS: We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. MEASURES: We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. RESULTS: The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). CONCLUSIONS: Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use.
BACKGROUND: The clarity of prescription drug instructions is a health literacy and medication safety concern. OBJECTIVE: To assess the variability of pharmacy interpretations of physician prescriptions. DESIGN: Identically written prescriptions for 4 common medications (atorvastatin, alendronate, trimethoprim/sulfamethoxazole, ibuprofen) were filled in 6 pharmacies (2 largest chains, 2 grocery stores, 2 independents) in 4 cities (Boston, Chicago, Los Angeles, Austin). MEASUREMENT: Components of the instruction were coded as dose, frequency, administration route, timing, indication, and auxiliary instructions. RESULTS: In all, 85 labels were evaluated. Dose frequency was omitted on 6% of instructions ("take 1 tablet for cholesterol"). Timing was explicitly stated on 2% of instructions ("in the morning"). All prescriptions included indications; pharmacies transcribed these onto 38% of labels. The prescription for alendronate stated not to lie down for at least 30 minutes after taking; this was transcribed with 50% of instructions. Reading difficulty was above recommended levels for 46% of instructions; with 14% greater than a high school level. CONCLUSIONS: Efforts are needed to ensure patients receive clear, consistent information supporting safe medication use.
OBJECTIVE: To determine whether retail prices for prescription drugs are higher in poorer areas. DATA SOURCES: The MyFloridarx.com website, which provides retail prescription prices at Florida pharmacies, and median ZIP code income from the 2000 Census. STUDY DESIGN: We compared mean pharmacy prices for each of the four study drugs across ZIP code income groups. Pharmacies were classified as either chain pharmacies or independent pharmacies. DATA COLLECTION: Prices were downloaded in November 2006. PRINCIPAL FINDINGS: Across the four study drugs, mean prices were highest in the poorest ZIP codes: 9 percent above the statewide average. Independent pharmacies in the poorest ZIP codes charged the highest mean prices. CONCLUSIONS: Retail prescription prices appear to be higher in poorer ZIP codes of Florida.
In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.
BACKGROUND: Medication nonadherence is a major public health problem, especially for patients with coronary artery disease. The cost of prescription drugs is a central reason for nonadherence, even for patients with drug insurance. Removing patient out-of-pocket drug costs may increase adherence, improve clinical outcomes, and even reduce overall health costs for high-risk patients. The existing data are inadequate to assess whether this strategy is effective. TRIAL DESIGN: The Post-Myocardial Infarction Free Rx and Economic Evaluation (Post-MI FREEE) trial aims to evaluate the effect of providing full prescription drug coverage (ie, no copays, coinsurance, or deductibles) for statins, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers to patients after being recently discharged from the hospital. Potentially eligible patients will be those individuals who receive their health and pharmacy benefits through Aetna, Inc. Patients enrolled in a Health Savings Account plan, who are > or =65 years of age, whose plan sponsor (ie, the employer, union, government, or association that sponsors the particular benefits package) has opted out of participating in the study, and who do not receive both medical services and pharmacy coverage through Aetna will be excluded. The plan sponsor of each eligible patient will be block randomized to either full drug coverage or current levels of pharmacy benefit, and all subsequently eligible patients of that same plan sponsor will be assigned to the same benefits group. The primary outcome of the trial is a composite clinical outcome of readmission for acute MI, unstable angina, stroke, congestive heart failure, revascularization, or inhospital cardiovascular death. Secondary outcomes include medication adherence and health care costs. All patients will be followed up for a minimum of 1 year. CONCLUSION: The Post-MI FREEE trial will be the first randomized study to evaluate the impact of reducing cost-sharing for essential cardiac medications in high-risk patients on clinical and economic outcomes.
BACKGROUND: Effective therapies for the secondary prevention of coronary heart disease-related events are significantly underused, and attempts to improve adherence have often yielded disappointing results. Elimination of patient out-of-pocket costs may be an effective strategy to enhance medication use. We sought to estimate the incremental cost-effectiveness of providing full coverage for aspirin, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins (combination pharmacotherapy) to individuals enrolled in the Medicare drug benefit program after acute myocardial infarction. METHODS AND RESULTS: We created a Markov cost-effectiveness model to estimate the incremental cost-effectiveness of providing Medicare beneficiaries with full coverage for combination pharmacotherapy compared with current coverage under the Medicare Part D program. Our analysis was conducted from the societal perspective and considered a lifetime time horizon. In a sensitivity analysis, we repeated our analysis from the perspective of Medicare. In the model, post-myocardial infarction Medicare beneficiaries who received usual prescription drug coverage under the Part D program lived an average of 8.21 quality-adjusted life-years after their initial event, incurring coronary heart disease-related medical costs of $114,000. Those who received prescription drug coverage without deductibles or copayments lived an average of 8.56 quality-adjusted life-years and incurred $111,600 in coronary heart disease-related costs. Compared with current prescription drug coverage, full coverage for post-myocardial infarction secondary prevention therapies would result in greater functional life expectancy (0.35 quality-adjusted life-year) and less resource use ($2500). From the perspective of Medicare, full drug coverage was highly cost-effective ($7182/quality-adjusted life-year) but not cost saving. CONCLUSIONS: Our analysis suggests that providing full coverage for combination therapy to post-myocardial infarction Medicare beneficiaries would save both lives and money from the societal perspective.