Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines.

BACKGROUND: This study evaluates the differences between women and men in medication use, medication adherence, and prescribing alignment with clinical guidelines. METHODS: We conducted an analysis of pharmacy and medical claims for 29.5 million adults with prescription benefits administered by a pharmacy benefits manager in the United States, age 18 and older, between January 1, 2010, and December 31, 2010. Prevalence and intensity of medication use were evaluated by sex, age group, and medication type (acute vs. chronic). Medication adherence was measured by the percentage of patients with a medication possession ratio (MPR) ≥80%. The percentage of patients receiving guideline-based treatment was measured for diabetes and select cardiovascular conditions. RESULTS: The study population comprised 16.0 million women and 13.5 million men with continuous pharmacy benefit eligibility. Women were significantly more likely than men to use one or more medications during the analysis period (68% vs. 59%, respectively, p<0.001), and women used more unique medications, on average, than men (5.0 vs. 3.7 medications per year, respectively, p<0.001). Differences in drug utilization were observed for all age groups and medication types. For all clinical metrics evaluated, women were less likely than men to be adherent in their use of chronic medications, and they were less likely to receive the medication treatment and monitoring recommended by clinical guidelines. CONCLUSIONS: There are significant disparities between women and men in their intensity of medication use, their adherence to medications, and their likelihood of receiving guideline-based drug therapy. These differences may indicate a need for more personalized drug selection and therapeutic management to improve clinical outcomes.

Relation of statin nonadherence and treatment intensification.

Failure to intensify medication and failure to adhere to medication have been shown to contribute to suboptimal low-density lipoprotein cholesterol goal attainment. To examine whether nonadherence to statins in 126,903 patients on stable statin therapy is associated with subsequent treatment intensification, we conducted a retrospective analysis using an integrated pharmacy and medical claims database. Pharmacy claims were analyzed to determine whether nonadherence, as measured by proportion of days covered on statins <80%, was associated with intensification of statin treatment over a 360-day follow-up. Of 11,361 patients who had treatment intensification, 44% were previously nonadherent to statins. Patients whose treatment was intensified had slightly lower adherence to statin therapy than those without intensification (76% vs 78%, p <0.0001) and were more likely to be nonadherent as defined by proportion of days covered <80% (44% vs 37%, p <0.0001). After controlling for confounding factors, patients nonadherent to statins were 30% more likely to have treatment intensification compared to adherent patients (odds ratio 1.30, 95% confidence interval 1.25 to 1.36). In addition, patients with statin intensification were more likely to be younger, women, and have coronary artery disease, diabetes, hypertension, dyslipidemia, stroke, peripheral arterial disease, heart failure, or depression. Primary care physicians were more likely to escalate therapy than cardiologists. In conclusion, nearly 1/2 of patients with therapy escalation were nonadherent to statins. Clinicians should inquire about adherence and consider adherence before escalating statin therapy.

Lack of uniformity in cardiac assessment during trastuzumab therapy.

Adjuvant therapy with trastuzumab is standard in women with early stage HER-2-positive breast cancer. Following reports of left ventricular (LV) dysfunction with trastuzumab in metastatic disease, trials of adjuvant trastuzumab specified LV monitoring schedules. This study analyzes the pattern of cardiac testing and the incidence of heart failure (HF) in women treated with adjuvant trastuzumab in a real-world setting. De-identified medical and pharmacy claims data for women <65 years of age who began trastuzumab therapy between January 1, 2007 and December 31, 2007 were obtained from an integrated database at Medco Health Solutions, Inc. Patients receiving trastuzumab for ≥90 days were assessed for compliance with standard LV testing, defined as testing at baseline, at 4-month intervals, and at the end of trastuzumab therapy. Cardiac risk factors and HF were identified by ICD-9-CM diagnosis codes, by medical claims, and by pharmacy claims for drugs used to treat diabetes, hypercholesterolemia, or HF. A total of 631 women received trastuzumab ≥30 days, and 585 continued for ≥90 days (median duration 356 days [±1Q = 322-378]). Seventy nine patients had no LV tests. Ninety three were fully compliant with baseline, interval, and final testing. Seven women were identified as having new-onset HF. In this retrospective analysis, clinicians did not routinely follow LV testing protocols used in clinical trials or published recommendations. As breast cancer specific survival rates improve, the long-term contribution of cardiotoxic therapies to cardiac morbidity and mortality in survivors will gain attention. Early efforts to ensure compliance with testing could contribute to use of preventive therapies to mitigate future long-term consequences.

Adherence to statins, subsequent healthcare costs, and cardiovascular hospitalizations.

Statins are the primary agents used to decrease low-density lipoprotein cholesterol. Although adherence to statins improves the clinical outcomes, the affect of statin adherence on healthcare costs has not been well studied. To examine the relation among statin adherence, subsequent hospitalizations, and healthcare costs, we conducted a retrospective cohort study of 381,422 patients, aged 18 to 61 years, using an integrated pharmacy and medical claims database. We measured adherence using the medication possession ratio (MPR) for 12 months and the healthcare costs and cardiovascular disease-related hospitalizations during the subsequent 18 months. Of those studied, 258,013 (67.6%) were adherent (MPR ≥80%), 65,795 (17.3%) had an MPR of 60% to 79%, and 57,614 (15.1%) had an MPR of <60%. The adjusted all-cause total healthcare costs were lowest in the adherent group at $10,198 ± $39.4 (mean ± SE) versus $10,609 ± $77.7 (p <0.001) for an MPR of 60% to 79%, and $11,102 ± $84.3 (p <0.001) for an MPR of <60%. The adherent group had greater statin costs at $838 ± $1.0 versus $664 ± $2.0 (p <0.001) and $488 ± $2.2 (p <0.001). When evaluated by 5 levels of MPR, 0% to 59% and increments of 10% >60%, the adjusted total healthcare costs were lowest for the MPR 90% to 100% group and significantly greater statistically (p <0.001) for each lower level of adherence. Compared to the statin-adherent patients, cardiovascular disease-related hospitalizations were more likely for the patients with an MPR of 60% to 79% (odds ratio 1.12, 95% confidence interval 1.08 to 1.16) and an MPR of 0% to 59% (odds ratio 1.26, 95% confidence interval 1.21 to 1.31). In conclusion, statin adherence is associated with reductions in subsequent total healthcare costs and cardiovascular disease-related hospitalizations.

Antihypertensive medication adherence and subsequent healthcare utilization and costs.

OBJECTIVES: To evaluate the relationship between adherence to antihypertensive medications (AHMs) and subsequent hospitalizations, emergency department (ED) visits, and costs of care. STUDY DESIGN: Retrospective analysis of a national pharmacy benefits database of deidentified pharmacy and medical claims among patients with a diagnosis of hypertension. Adherence was estimated using the medication possession ratio (MPR). METHODS: Multivariate logistic and 2-part general linear models were estimated to study the relationship between adherence level (estimated by the MPR) and subsequent association with healthcare costs and cardiovascular (CV)-related hospitalizations and ED visits. RESULTS: We identified 625,620 patients with at least 2 claims for AHMs and divided them into 3 cohorts based on year 1 MPR of less than 60% (62,388 patients with low adherence), 60% to 79% (96,226 patients with moderate adherence), and 80% or higher (467,006 patients with high adherence). Patients with high adherence to AHMs were more likely to be older and male, have higher chronic disease scores and lower AHM copayments, and fill a greater percentage of prescriptions by mail order. Year 2 total mean (SD) adjusted healthcare costs were significantly lower for patients with an MPR of 80% or higher ($7182 [$27]) vs 60% to 79% ($7560 [$59]) or less than 60% ($7995 [$73]) (P <.001 for both). In addition, patients with low or moderate adherence had higher age- and sex-adjusted odds of CV-related hospitalizations (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.25-1.41) and ED visits (OR, 1.45; 95% CI, 1.33-1.58) (P <.001 for both). CONCLUSION: Adherence to AHMs is associated with significantly lower total healthcare costs and with significantly lower odds of CV-related hospitalizations and ED visits.

Tolerability of atorvastatin in a population aged > or =65 years: a retrospective pooled analysis of results from fifty randomized clinical trials.

OBJECTIVE: The aim of this study was to compare the safety profile of atorvastatin calcium at 4 doses with that of placebo in elderly patients (age, > or =65 years). METHODS: A single pooled database (Pfizer Atorvastatin Clinical Program Database) of 50 published and unpublished completed clinical trials was analyzed retrospectively. Tolerability data from male and female study participants aged > or =65 years at the time of study enrollment were extracted from this database and grouped based on treatment: atorvastatin 10, 20, 40, or 80 mg/d, or placebo. Analyses included comparisons of treatment-related and serious adverse events (AEs) of the musculoskeletal, hepatic, and renal systems. Descriptive statistics were employed. No inferential statistical analyses were performed. RESULTS: A total of 5924 patients were included in the pooled analysis (range of mean age, 71-74 years; white race, 5437 [91.8%]; female sex, 2506 [42.3%]; treatment with atorvastatin 10 mg/d, n = 2042; atorvastatin 20 mg/d, n = 667; atorvastatin 40 mg/d, n = 522; atorvastatin 80 mg/d, n = 1698; and placebo, n = 995). The overall AE profiles appeared similar with all atorvastatin doses and placebo. The proportions of patients experiencing at least 1 treatment-related AE were 16.1%, 10.2%, 11.3%, 15.0%, and 15.3% in the atorvastatin 10-, 20-, 40-, and 80-mg/d, and placebo groups, respectively. The rates of discontinuation due to treatment-associated AEs appeared comparable between all doses of atorvastatin and placebo (2.1% vs 1.7%). Serious AEs were rare (< or =1.0%) and seldom led to withdrawal. The prevalence of treatment-associated myalgia was low in all treatment groups (< or =1.8%). None of the patients experienced persistent creatine kinase elevations >10-fold the upper limit of normal (x ULN), and no cases of myopathy or rhabdomyolysis were reported. The rates of patients with persistent elevation >3 x ULN) of hepatic aminotransferases were 0.1%, 0%, 0.2%, 0.5%, and 0.2% in the atorvastatin 10-, 20-, 40-, and 80-mg/d, and placebo groups, respectively. Although the prevalences of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations appeared slightly higher in the 80-mg/d group (3.2% vs < or =0.9% in all other groups), specific musculoskeletal and hepatic AEs were rare (< or =3.0%). CONCLUSIONS: This pooled analysis of 50 published and unpublished studies in elderly patients found that the overall prevalences of AEs did not appear to increase with dose and appeared comparable to that observed with placebo. Although the prevalences of ALT/AST elevations appeared slightly higher in the 80-mg/d group (3.2% vs < or =0.9% in all other groups), specific musculoskeletal and hepatic AEs were rare (< or =3.0%). The rates of discontinuation appeared comparable between all 4 doses of atorvastatin and placebo. The results of this analysis support the favorable safety profile of atorvastatin across the full dose range in patients aged > or =65 years.