Adherence and dosing frequency of common medications for cardiovascular patients.

OBJECTIVES: To compare adherence between once-daily (QD) and twice-daily (BID) dosing with chronic-use prescription medications used by patients with cardiovascular disease. STUDY DESIGN: Retrospective cohort database analysis. METHODS: Analysis consisted of 1,077,474 patients aged >18 years with a prescription index date from January 1 to December 31, 2007, for an antidiabetic, antihyperlipidemic, antiplatelet, or cardiac agent with QD or BID dosing. Adherence (medication possession ratio [MPR]) was the number of days of medication supplied between the first prescription fill date and the subsequent 365 days divided by 365 days. Overall mean MPR and comparisons between dosing frequency groups were assessed with a generalized estimating equation. Covariates included age at index date, gender, Charlson comorbidity index, therapeutic class, dosing frequency, and the interaction between therapeutic class and dosing frequency group. RESULTS: Overall, the adjusted mean MPR ± standard error (SE) value for QD agents was 13.6% greater than BID agents (0.66 ± 0.0006 vs 0.57 ± 0.0016; P <.01). The adjusted mean MPR value for QD agents was 2.9%, 17.5%, and 29.4% greater than BID agents in the antidiabetic, antihyperlipidemic, and antiplatelet therapeutic classes, respectively. For cardiac agents, the adjusted mean MPR value was similar between QD and BID agents. Carvedilol represented approximately 80% of the cardiac agents in the BID group. The adjusted mean MPR ± SE for carvedilol phosphate QD was 0.73 ± 0.0024 and 0.65 ± 0.0027 for carvedilol BID (11% difference; P <.01). CONCLUSIONS: In this large analysis, the QD dosing regimen was related to greater adherence versus a BID regimen.

A comparison of the VerifyNow P2Y12 point-of-care device and light transmission aggregometry to monitor platelet function with prasugrel and clopidogrel: an integrated analysis.

We compared platelet function results obtained with the VerifyNow P2Y12 (VN-P2Y12) point-of-care device and the light transmission aggregometry (5 and 20 microM adenosine diphosphate) method using an integrated database of eight clinical trials with a total of 591 subjects. The study was performed in healthy subjects, patients with coronary artery disease, patients with end-stage renal disease, and patients with acute coronary syndrome after treatment with prasugrel or clopidogrel. Analyses focused on loading doses of 60 mg prasugrel or 600 mg clopidogrel and daily maintenance doses of 10 mg prasugrel or 75 or 150 mg clopidogrel. Similar patterns of platelet inhibition were observed for light transmission aggregometry versus VN-P2Y12 and assay results were well correlated (r approximately 0.7), although a sigmoidal model may more accurately represent the relationship between light transmission aggregometry and VN-P2Y12, because VN-P2Y12 was relatively less sensitive to low and high levels of inhibition. The percentage of poor responders was less with prasugrel compared with clopidogrel by both assays, but the percentages tended to differ between the assays. The VN-P2Y12 "BASE" channel appeared to be susceptible to high levels of P2Y12 blockade, which would underestimate the VN-P2Y12-reported percent inhibition in individuals who respond well to loading doses of thienopyridines. This integrated analysis supports the findings of earlier individual studies comparing these methodologies that assess platelet function.

Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy Chinese and white volunteers: an open-label trial.

BACKGROUND: Prasugrel is an oral antiplatelet agent approved for the reduction of atherothrombotic cardiovascular events in patients presenting with acute coronary syndrome and undergoing percutaneous coronary intervention. Although the approved loading dose is 60 mg, earlier studies of prasugrel suggested that active-metabolite exposure and pharmacodynamic response may be higher in Asian subjects than in white subjects. OBJECTIVES: This study compared the pharmacodynamic response to a single 30-mg dose of prasugrel in healthy Chinese and white subjects and the response to a single 30-mg dose of prasugrel and a single 300-mg dose of clopidogrel in healthy Chinese subjects. The pharmacokinetics and tolerability of both drugs were also assessed. METHODS: This was an open-label, single-dose study conducted in Singapore. Chinese subjects were randomly allocated to receive prasugrel 30 mg or clopidogrel 300 mg; after a 14-day washout period, they received the alternative drug. White subjects received only prasugrel 30 mg. Blood samples for pharmaco-dynamic assessments were collected before dosing and at 0.5, 1, 2, 4, and 24 hours after dosing. Three methods were used to measure inhibition of platelet aggregation (IPA)-traditional light transmission aggregometry (LTA), the Verify Now P2Y12 (VN-P2Y12) assay, and a vasodilator-stimulated phosphoprotein (VASP) phosphorylation flow cytometry assay-and their results were compared. Blood samples for pharmacokinetic assessments were collected at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours after dosing. Concentrations of the active metabolite of prasugrel were measured using a validated LC-MS/MS method. RESULTS: The study enrolled 18 Chinese subjects and 14 white subjects. Chinese subjects had a mean (SD) age of 31 (10) years and a mean body weight of 65.2 (8.9) kg; 83% were male. The corresponding values for white subjects were 30 (10) years, 77.2 (12.4) kg, and 86%. Thirty of the 32 enrolled subjects completed the study. Two Chinese men were withdrawn from the study, one due to a low platelet-rich plasma count after receipt of prasugrel 30 mg and the other due to mild, intermittent rectal bleeding after bowel movements that began approximately 2 days after receipt of clopidogrel 300 mg. The mean IPA with prasugrel was significantly higher in Chinese than in white subjects at 0.5, 1, and 2 hours after dosing (P < 0.05), but not at 4 or 24 hours. In Chinese subjects, mean maximal IPA (87%) occurred 1 hour after prasugrel dosing; in white subjects, mean maximal IPA (78%) occurred 2 hours after prasugrel dosing. In Chinese subjects, the mean IPA was significantly higher at all time points after administration of prasugrel 30 mg than after administration of clopidogrel 300 mg (P <0.001). After administration of Clopidogrel 300 mg in Chinese subjects, mean maximal IPA (58%) occurred at 4 hours. The VN-P2Y12 and VASP phosphorylation assays yielded results comparable to those obtained by LTA. Mean exposure to prasugrel's active metabolite was higher in Chinese than in white subjects (geometric least squares mean ratio for AUC(0-t) = 1.47 (90% CI, 1.24-1.73). Both drugs were well tolerated. CONCLUSIONS: In this study, platelet inhibition was significantly higher in Chinese than in white subjects up to 2 hours after a single 30-mg dose of prasugrel. Platelet inhibition was significantly higher in Chinese subjects at all time points after a 30-mg dose of prasugrel than after a 300-mg dose of clopidogrel. Both treatments were generally well tolerated.

The effect of male erectile dysfunction on the psychosocial, relationship, and sexual characteristics of heterosexual women in the United States.

Using Internet-based survey data, this study compared the demographic, psychosocial, relationship, and sexual characteristics of three groups of U.S. women: (a) women whose partners had erectile dysfunction (ED) and were taking medication to treat ED; (b) women whose partners had ED in the previous 3 months and were not taking medication to treat ED; and (c) a control group of women whose partners did not have ED. Results indicate that women are affected by their partners' ED and that ED treatment benefits women's sexual self-efficacy, communication about sexual issues, and sexual and relationship satisfaction.

Through the eyes of women: the partners' perspective on tadalafil.

OBJECTIVES: To evaluate patient and female partner responses on the efficacy of, and overall satisfaction with, tadalafil to treat erectile dysfunction using sexual encounter profile (SEP) diaries. METHODS: Data were pooled from four double-blind, placebo-controlled, 12-week trials that included 746 couples. Patients were randomized to placebo or tadalafil 10 or 20 mg. Efficacy was evaluated by the mean per-patient/per-partner percentage of "yes" responses to patient SEP questions 1, 2, and 5 and partner SEP questions 1 to 3 (erection achievement, penetration, and overall satisfaction with the sexual experience, respectively) for tadalafil versus placebo. For each SEP question, the number of postbaseline intercourse attempts when each couple agreed on the outcome was tabulated and divided by the total number of postbaseline attempts to calculate the mean percentage of agreement by couple. The overall satisfaction with successful postbaseline intercourse attempts was determined. RESULTS: Tadalafil significantly improved the responses for the patient and partner-evaluated SEP questions (P <0.001, both doses versus placebo). Partners tended to report greater overall satisfaction than patients at baseline and postbaseline. The mean percentage of agreement by couple was approximately 98% for erection achievement and penetration and 85% for overall satisfaction. For successful intercourse attempts, patients and partners treated with tadalafil reported more overall satisfaction than those treated with placebo (P <0.05, tadalafil versus placebo comparisons). CONCLUSIONS: Partners reported significantly improved overall sexual satisfaction and corroborated the man's report of improved erections and penetration ability with tadalafil 10 mg or 20 mg. Men reported improved erection achievement, penetration, and overall satisfaction with the sexual experience after taking tadalafil.

Remission, residual symptoms, and nonresponse in the usual treatment of major depression in managed clinical practice.

BACKGROUND: Although published guidelines recommend the continuation of treatment for depression until full remission of symptoms and restoration of functioning, little is known about how often remission is achieved in usual practice and the precipitants of treatment termination when treatment outcome has not been optimal. METHOD: A naturalistic study design examined 1859 patients receiving treatment for DSM-III-R major depression between 1995 and 1997 in the national provider network of a managed behavioral health organization (MBHO). Symptom and impairment ratings by clinicians were used to group patients into full remission, partial remission, and no response. Claims data were used to characterize treatment and identify comorbid medical conditions. RESULTS: According to clinician ratings, approximately 27% to 39% of patients achieved full remission. Medical and substance use comorbidity and hospital admission were more common in those with a partial response to treatment. Only half of patients without a treatment response received a trial of medication during their treatment. Patient choice was the most common reason for termination of treatment, although nearly 40% of clinicians concurred with patients' decisions even when symptoms had not improved. CONCLUSION: Although rates of full remission were comparable to those in clinical trials of antidepressants, results suggest that clinicians may fail to recommend continuation and maintenance treatment consistent with best practice guidelines and that unsuccessful treatment often does not include antidepressant medication.

American attitudes toward and willingness to use psychiatric medications.

Despite recent advances in treatment, many Americans decline to take prescribed psychiatric medication. This study explores the role of attitudes regarding the effectiveness of and potential problems associated with psychiatric medications on Americans' willingness to use them. Face-to-face interviews of a US household population sample were done with 1387 volunteers. The 1998 General Social Survey's (response rate, 76.4%) included questions about efficacy, problems, and potential use. Most Americans agree that psychiatric medications are effective, and fewer than half had concerns regarding potential problems. However, the majority of respondents would not be willing to take them. Willingness to use is influenced by these attitudes and other factors, including health status and past use of mental health treatments. Although Americans perceive psychiatric medications to be effective, and this influences their willingness to take them, many still are not willing to take them.

Appropriateness of prescribing practices for serotonergic antidepressants.

OBJECTIVE: Data from prescribing physicians were used to assess whether serotonergic antidepressants were used for appropriate indications and at appropriate initial dosages. METHODS: Data were derived from the confidential logs of psychiatrists and primary care physicians who provided prescription information from January 1, 1997, through June 30, 1999, as part of the National Disease and Therapeutic Index physician survey. The survey is not affiliated with a reimbursement system and therefore minimizes bias related to reimbursement. Data on the primary reason for use and the dosage at the time of first use were obtained for prescriptions of citalopram, fluoxetine, paroxetine, sertraline, venlafaxine, and extended-release venlafaxine. RESULTS: Depressive disorders accounted for the majority of the 3,206 prescriptions for the six antidepressants (74 percent to 86.2 percent). The next most common indications for use were anxiety (4.1 percent to 12.6 percent) and obsessive-compulsive disorder (1.3 percent to 3.3 percent). For patients with depressive disorders, psychiatrists prescribed slightly higher antidepressant dosages than primary care physicians. CONCLUSIONS: Serotonergic antidepressants are used primarily for the treatment of depression and depression-related disorders and are prescribed at the recommended starting dosages.