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In a congressionally mandated effort to improve postmarketing safety surveillance, the FDA is seeking to develop the Sentinel Network to link vast amounts of data on patients, medication use, and adverse events. Dr. Richard Platt and colleagues argue that the best solution is a distributed data network. In 2007, Congress directed the Food and Drug Administration (FDA) to create a new postmarketing surveillance system that will, by 2012, be using electronic health data from 100 million people to prospectively monitor the safety of marketed medical products. 1 This new system is intended to complement existing systems of “spontaneous” adverse-event reporting. In May 2008, the FDA announced the Sentinel Initiative, which would “access the capabilities of multiple, existing data systems (i.e., electronic health record systems, medical claims databases).” 2 The network of data systems is intended both to detect signals (i.e., higher-than-expected rates of adverse outcomes) and to confirm signals, . . .

Background: Many older individuals have concomitant hypertension and dyslipidaemia — two conditions that, together with age, increase the risk of adverse cardiovascular events. Adherence to antihypertensive (AH) and lipid-lowering (LL) therapy is therefore particularly important in older patients with concomitant hypertension and dyslipidaemia. Objective: To determine patterns and predictors of adherence to concomitant AH and LL therapy among an older Medicare-eligible population. Methods: Enrolees (n = 4052) aged ≥65 years who initiated treatment with both AH and LL therapy within a 90-day period were studied in this retrospective cohort study conducted in a US managed care organization. Adherence to AH and LL medications was measured as the proportion of days covered by any AH and/or LL medication in each 3-month interval, from the start of concomitant therapy for up to 36 months (mean follow-up 19.5 months). In each interval, patients were considered ‘adherent’ to AH and LL therapy if they had filled prescriptions sufficient to cover ≥80% of days with both medication classes. A multivariable regression model evaluated potential predictors of adherence to concomitant therapy, including patient demographics, clinical characteristics and health services use patterns at baseline. Results: The percentage of patients adherent to both AH and LL therapy declined rapidly, before stabilizing, with 40.5%, 32.7% and 32.9% adherent at 3, 6 and 12 months, respectively. At each timepoint, an additional 27.8–35.0% of patients were adherent to either AH or LL therapy, but not both. Adherence was on average greater to AH than LL therapy. After adjusting for age, sex and other potential predictors, patients were more likely to be adherent if AH/LL therapies were initiated closer together in time (adjusted odds ratio [AOR] 1.13 for 0–30 days vs 61–90 days, p = 0.0563), had a history of cardiovascular disease (AOR 1.27, p = 0.0004), took fewer additional medications (AOR 0.43 for six or more medications vs zero or one medication, p < 0.0001) or had more outpatient physician visits in the prior year (AOR 1.26 for four to six visits vs zero to one visit, p < 0.0027). Conclusion: Adherence to concomitant AH and LL therapy among older adults is poor. Modifiable factors that may improve adherence in Medicare-eligible patients include initiating therapy concurrently and reducing patients’ overall pill burden.

The American Recovery and Reinvestment Act of 2009 included new funding for developing better evidence about health interventions, with a down payment of$1.1 billion for comparative effectiveness research. Our analysis of funds allocated in the legislation found that nearly 90 percent of the $ 1.1 billion will eventually be spent on two main types of activity: developing and synthesizing comparative effectiveness evidence, and improving the capacity to conduct comparative effectiveness research. Based on our analysis, priorities for the new funding should include greater emphasis on experimental research; evaluation of reforms at the health system level; identification of effects on subgroups of patients; inclusion of understudied groups of patients; and dissemination of results. [PUBLICATION ABSTRACT]

Background: While the results of randomized clinical trials have indicated that statins improve outcomes in patients without cardiovascular disease (CVD), it remains uncertain whether there are differences in efficacy between statins, particularly in clinical practice, where the public health implications could be substantial. Objective: We assessed cardiovascular (CV) outcomes among primary-prevention patients newly initiating therapy with atorvastatin or simvastatin. Methods: Using claims data from 92 US managed care plans, we identified new statin users without CVD who initiated atorvastatin (10 or 20 mg) or simvastatin (20 or 40 mg) from January 2003 to September 2005 and were continuously enrolled in a covered plan for ≥12 months before and ≥1 month after the initiation of statin therapy. The main outcome was the time to the first CV event (hospitalization related to myocardial infarction, angina, or coronary artery disease; stroke; amaurosis fugax; transient ischemic attack; peripheral or central nervous system vascular disease; or revascularization). Persistence with treatment was calculated in terms of the number of days during follow-up that a patient remained on statin treatment, starting from the date of the first prescription fill to the end of the study or the date at which therapy was discontinued. Results: A total of 168,973 patients initiating atorvastatin (mean dose, 13.5 mg) and 50,658 patients initiating simvastatin (mean dose, 28.5 mg) were followed for a median of 1.5 years. Atorvastatin patients were significantly more persistent with treatment than simvastatin patients (median treatment duration, 158 vs 124 days, respectively; P < 0.001). After adjustment for age, sex, type of health plan, payer type, geographic region, calendar year of statin initiation, physician specialty, comorbidities, concomitant therapies, and total direct health care costs in the year before statin initiation, use of atorvastatin was associated with significantly fewer CV events compared with use of simvastatin (hazard ratio = 0.88; 95% CI, 0.83-0.93; P < 0.001). Conclusions: In these patients without CVD, atorvastatin 10 or 20 mg was associated with a significantly lower risk of CV events compared with simvastatin 20 or 40 mg. Further studies are required to determine whether differences in persistence, achieved low-density lipoprotein cholesterol levels, or other factors contribute to these differences in outcomes.

ABSTRACT Background: In clinical practice, persistence with statin therapy is poor. While little is known about relative persistence to specific statins, previous studies have observed greater persistence in patients who achieve greater degrees of lipid lowering. Identification of statin therapies which improve patient persistence has the potential to improve the quality of patient care and clinical outcomes. Therefore, we assessed patient persistence with atorvastatin and simvastatin in primary and secondary prevention patients enrolled in managed care. Methods: New statin users aged ≥18 years, both with and without prior cardiovascular (CV) events within the 12 month pre-treatment period, were identified from a large national database of managed care patients. Patients initiated atorvastatin or simvastatin therapy from January 1, 2003 to September 30, 2005 and were continuously enrolled in a covered plan for at least 12 months before and after initiation of statin therapy. Subanalyses of patients ≥65 years were also conducted. Measures of interest included demographic and clinical characteristics of the study samples and persistence of statin utilization over the 1-year follow-up period. Persistence was defined as the number of days a patient remained on treatment in the first year following their index date, measured from the date of first fill to study end or the date of discontinuation. Results: A total of 129 764 atorvastatin users and 45 558 simvastatin users without prior CV events were included in the study. For those patients with prior CV events, a total of 6888 atorvastatin users and 4443 simvastatin users were included in the study. Median persistence in patients without prior CV events was 50 days longer for patients initiating therapy with atorvastatin than simvastatin (207 vs. 157 days, p < 0.0001) and after adjusting for confounding factors, those treated with atorvastatin were 15% less likely to discontinue therapy during the first year than those treated with simvastatin (HR = 0.85; 95% CI 0.84, 0.86; p < 0.001). In secondary prevention patients median persistence was 85 days longer in atorvastatin patients than simvastatin patients (266 vs. 181 days, p < 0.0001) and atorvastatin patients were 22% less likely to discontinue therapy (HR = 0.78; 95% CI 0.75, 0.82; p < 0.001). Persistence was worse in the elderly patients, but the relative difference between atorvastatin and simvastatin was similar to the overall patient population. Conclusions: In patients with and without prior CV disease, persistence is generally poor, even worse in the elderly, but significantly better for atorvastatin patients than simvastatin patients (p < 0.001). Further studies are required to determine whether this is due to differences in cost, effectiveness, side-effects, or other attributes of the statins. Study limitations: Differences in persistence could be, in part, due to unmeasured confounders although all available variables were adjusted in multivariate analyses. Additionally, the claims database lacks some clinical data such as lipid levels, limiting assessments of statin efficacy, and does not include any reasons for discontinuation of therapy.

Background: Nonadherence with highly active antiretroviral therapy (HAART) is common in typical human immunodeficiency virus (HIV) patient care settings, but the consequences have not been well described. This study aimed to quantify the clinical and economic effects of nonadherence and estimate the cost-effectiveness of improving adherence in treatment-naive HIV patients. Methods: A Markov model was developed to project quality-adjusted life expectancy and direct medical costs for patients on an initial once-daily regimen of efavirenz, lamivudine, and stavudine XR. The model compared 2 adherence scenarios: \"ideal\" (based on clinical trials) and \"typical\" (based on observational studies in actual practice). Disease progression was a function of viral load, CD4 count, and adherence. Data on HIV natural history, treatment benefits, costs, and utilities were derived from the literature. Results: With typical adherence, patients lose 1.2 quality-adjusted life years (QALYs) that could be gained with ideal adherence. Improving adherence to ideal levels is cost-effective at $29,400/QALY gained. As much as $1600/y per patient could be spent on an intervention to improve adherence to ideal levels, and the incremental cost-effectiveness would remain less than $50,000/QALY gained. A cost-effectiveness ratio of $50,000/QALY is a commonly accepted minimum standard for cost-effective medical interventions in the United States, although many experts believe this standard has drifted upwards over time. Conclusions: Typical adherence with HAART reduces quality-adjusted life expectancy by 12% compared with ideal adherence. Interventions to improve adherence appear to be a highly costeffective use of resources.

To determine the degree to which swallowing valproate (VP) tablets is an issue, the proportion of patients who would prefer an alternative formulation, and the predictors of preference. A quantitative telephone survey of eligible adults (n = 400, >/=18 years old) who currently take (n = 236) or previously took (n = 164) VP tablets within the past 6 months was conducted. More than half of the patients indicated that VP tablets were 'uncomfortable to swallow' (68.5%, n = 274) and were 'very interested' (65.8%, n = 263) in medications that were easier to swallow. When choosing conceptually between taking VP tablet once/day or an equally safe and effective but significantly smaller soft gel capsule twice per day, the 82.8%, (n = 331) preferred the soft gel capsule. In the multivariate regression analysis, perceiving soft gel capsules to be easier to swallow (OR = 73.54; 95% CI = 15.01 to 360.40) and taking VP more frequently (OR = 2.02; 95% CI = 1.13 to 3.61) were significant predictors of soft gel capsule treatment preference. VP users would prefer a formulation that is easier to swallow, even if it is needed to be taken twice per day. When choosing between medications with similar efficacy and safety, physicians can consider patient preferences to optimize conditions for medication adherence.

A previous study in 4703 patients suggested that a single-pill combination of amlodipine and atorvastatin is associated with greater adherence to therapy than a two-pill calcium channel antagonist (calcium channel blocker [CCB]) and HMG-CoA reductase inhibitor (statin) regimen. However, the impact of prior medication use on the potential adherence benefits of single-pill amlodipine/atorvastatin has not been studied. To compare adherence to single-pill amlodipine/atorvastatin versus two-pill CCB + statin regimens in a large managed care population, stratified according to prior CCB and statin use. This retrospective study was conducted among managed care enrolees in the US. Patients included in the analysis had to have a pharmacy claim for single-pill amlodipine/atorvastatin or claims for both a CCB and a statin within any 30-day window between April 2004 and April 2005. Adherence was measured over 6 months following the index date (the date of the first single-pill amlodipine/atorvastatin claim or of the claim for the second medication class for any two-pill CCB + statin regimen) as the proportion of days covered (PDC) by both CCB and statin therapy; patients were considered 'adherent' if PDC was > or =80%. Patients were divided into four cohorts based on pre-index CCB and statin use: (i) naive (CCB)/naive (statin); (ii) experienced (CCB)/naive (statin); (iii) naive (CCB)/experienced (statin); and (iv) experienced (CCB)/experienced (statin). Within each cohort, adherence was compared for patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin or other two-pill CCB + statin regimens (including amlodipine or atorvastatin but not both) at index. Multivariable logistic regression with propensity score weighting was used to adjust for covariates, including age, sex and co-morbidities. In total, 35,430 patients were included in the analysis. At month 6 (after adjusting for covariates), patients in the experienced (CCB)/naive (statin) cohort receiving single-pill amlodipine/atorvastatin were more than twice as likely to be adherent as those receiving two-pill amlodipine + atorvastatin (odds ratio [OR] 2.20; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.75; p < 0.0001). Similarly, patients in the naive (CCB)/experienced (statin) cohort receiving single-pill amlodipine/atorvastatin were more likely to be adherent than those receiving two-pill amlodipine + atorvastatin (OR 1.72; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.81; p < 0.0001). In contrast, in the naive (CCB)/naive (statin) cohort there was no significant difference in adherence between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.00), although patients receiving single-pill amlodipine/atorvastatin were slightly more likely to be adherent than those receiving other two-pill CCB + statin regimens (OR 1.29; p < 0.01). In the experienced (CCB)/experienced (statin) cohort there was also no significant difference between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.08), and only a slightly greater likelihood of achieving adherence to single-pill amlodipine/atorvastatin versus other two-pill CCB + statin regimens (OR 1.19; p < 0.01). This large retrospective study confirms previous observations that single-pill amlodipine/atorvastatin can help improve adherence versus two-pill CCB + statin regimens. However, greater improvements in adherence are likely to be observed in patients with prior experience of either CCB or statin therapy than in those either naive to, or experienced with, both therapies.

Despite published guidelines and availability of many effective lipid-altering therapies, dyslipidemia in the United States remains largely underdiagnosed and undertreated. This study used data from the 1999-2000 National Health and Nutrition Examination Survey to assess the current state of dyslipidemia management in the US adult population compared with guidelines issued by the Third Adult Treatment Panel of the National Cholesterol Education Program. Percentages were weighted to reflect population estimates, computed using SUDAAN (Research Triangle Institution, Cary, NC). Among 1425 respondents aged ≥20 years with complete data, 29.5% were eligible for therapeutic lifestyle changes (TLCs, 16.0%) or lipid-lowering drug therapy (LDT, 13.4%). Among high-risk adults, 79.3% were eligible for either TLC (35.7%) or LDT (43.6%). Only 43.7% of treatment-eligible adults reported ever being diagnosed with dyslipidemia. Of those diagnosed, 77.4% reported being told to undertake TLC, and 34.2% reported being told to take LDT. Of adults eligible for drug therapy, the average percentage reduction in low-density lipoprotein cholesterol (LDL-C) required to reach goal was 28.0% (standard error [SE] 1.1), and 41.9% required a reduction of >30% in LDL-C to reach goal. Of high-risk adults eligible for drug therapy, the average required reduction was 36.9% (SE 1.4), and 76.3% required a reduction of >30% in LDL-C. Despite advances in dyslipidemia therapy and changes in guidelines over the last decade, LDL-C continues to be inadequately managed among US adults. Of particular concern is the undertreatment of high-risk patients and failure of many treated patients to achieve LDL-C goal.