Factors Associated With Clopidogrel Adherence in Community-Dwelling Patients.

OBJECTIVE: The purpose of this study was to characterize predictors of adherence to clopidogrel therapy focusing on patients' perceptions of clopidogrel and nuisance bleeding. METHODS: This was a cross-sectional study of community-dwelling cardiovascular patients with a self-reported prescription for clopidogrel. Self-report questionnaires assessed depressive symptoms, social support, nuisance bleeding, perceptions of clopidogrel, and adherence to therapy. Low, moderate, and high adherence groups based on the Morisky Medication Adherence Scale were compared and hierarchical multiple linear regression analysis was used to predict adherence. RESULTS: A total of 102 subjects were enrolled, and 55%, 28%, and 16% were classified as having low, moderate, and high adherence, respectively. Greater perceptions of clopidogrel necessity, lower perception of clopidogrel concern, and increased severity of nuisance bleeding were predictors of better adherence. CONCLUSIONS: Data from this cross-sectional study suggest that concerns about clopidogrel and feelings about its necessity play an important role in clopidogrel adherence.

Pharmacogenomics of warfarin dose requirements in Hispanics.

While Hispanics are the largest and most rapidly growing minority population in the United States, they are underrepresented in pharmacogenomic studies with warfarin. We sought to determine the combination of clinical and genetic influences of warfarin dose requirements in Hispanics. In addition, we tested the performance of published warfarin dosing algorithms derived from largely non-Hispanic cohorts in an inner-city U.S. Hispanic population. Genetic samples and clinical data were obtained from 50 Hispanics on a stable dose of warfarin. The contribution of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex-1 (VKORC1) genotypes and clinical factors to warfarin dose requirements was determined. The correlation between the predicted dose using published algorithms and therapeutic dose was also assessed. Compared to the VKORC1-1639 GG genotype, warfarin dose requirements were 30% and 62% lower with the GA and AA genotypes, respectively (p=0.001). The combination of the VKORC1-1639G>A and CYP2C9 genotypes and clinical factors explained 56% of the inter-patient variability in warfarin dose. Warfarin dose predicted using algorithms derived from mostly non-Hispanic cohorts was significantly correlated with the therapeutic dose in our Hispanic cohort (r(2)=0.43 to 0.49; p<0.001); the predicted dose was within 1.0 mg/day of the therapeutic dose for 40% to 50% of patients. Our data suggest that factors influencing warfarin dose requirements in Hispanic Caucasians are similar to those previously described in European Caucasians and that dosing algorithms derived from non-Hispanic Caucasian cohorts are applicable to Hispanics living in the U.S.

Genetic testing for early detection of individuals at risk of coronary heart disease and monitoring response to therapy: challenges and promises.

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient's lifetime, can help guide therapy selection, and may be of utility in family counseling.

Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement.

Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to -1639G>A and 1173CA, and the tightly linked intron1 SNP 1173C>T, predict warfarin dose more accurately than intron 2 SNP 1542G>C in blacks. Increased warfarin dose requirement in blacks was accounted for by lower frequency of the -1639 A allele. Therefore, -1639G>A is a suitable biomarker for warfarin dosing across ethnic populations.

Influence of cyclooxygenase-1 genotype on ex vivo aspirin response in patients at risk for stroke.

BACKGROUND: We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. METHODS: Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the PTGS1 A-707G, PTGS1 P17L, and glycoprotein IIIa (ITGB3)P1(A1/A2) genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B(2) (11-dhTxB(2)) concentrations. The association between PTGS1 A-707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB(2) concentrations, was evaluated by statistical testing and nonlinear mapping. RESULTS: Salicylate concentrations, ITGB3 genotype distribution and 11-dhTxB(2) concentrations were similar among PTGS1 genotype groups. More subjects with the PTGS1 17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the PTGS -707A and 17P alleles, but none with both the PTGS1 -707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the PTGS1 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians. CONCLUSIONS: Our data suggest that the PTGS1 P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between PTGS1 genotype and aspirin response might vary by ethnicity.

Predictors of unstable anticoagulation in African Americans.

OBJECTIVE: We sought to identify contributors to unstable anticoagulation in African Americans. PATIENTS AND METHODS: Sixty African Americans on warfarin were enrolled. Cytochrome P450 2C9 and vitamin K epoxide reductase genotypes and vitamin K intake were assessed, and clinical and dietary data during the 12 months prior to enrollment were collected. Data were compared between stable and unstable patients, classified based on the proportion of international normalized ratio (INR) values outside the therapeutic range. RESULTS: The median proportion of out-of-range INRs among study participants was 44%; 28 patients had a higher proportion of INRs out-of-range and were included in the unstable group, with the remaining constituting the stable group. The median (IQR) number of clinic visits/year was higher among unstable versus stable patients [18 (15-22) vs. 16 (13-19); P = 0.03]. Higher warfarin doses, lower adherence, vomiting or diarrhea, and use of antiinfective agents were more common among unstable patients. Genotype was not associated with anticoagulation stability. After regression analysis, only poor adherence and gastrointestinal illness remained predictive of unstable anticoagulation. In a control group of Caucasians of similar age and sex distribution, poor adherence, but not gastrointestinal illness, was associated with unstable anticoagulation. CONCLUSION: We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

CETP genotype and concentrations of HDL and lipoprotein subclasses in African-American men.

Aim: To assess the association between the CETP Taq1B and I405V polymorphisms with levels of lipoprotein subclasses in African-American (AA) men with and without Type 2 diabetes (T2DM). Patients & methods: AA men, over 30 years of age, with (n = 54) or without T2DM (n = 50), and not receiving lipid-lowering agents, underwent advanced lipid analysis and genotyping. Results & conclusion: In the total patient population Taq1B B2-allele carriers had significantly higher levels of large HDL subclasses (HDL-2b [p = 0.017] and HDL-L [p = 0.019]), lower levels of small-HDL subclasses (HDL-3a [p = 0.004] and HDL-3b [p = 0.031]), and lower levels of LDL subclasses (LDL-IVa [p = 0.012] and LDL-IIIb [p = 0.009]). The only significant genotype-diabetes interaction occurred with the HDL-2a subclass (p = 0.015). No statistically significant associations were seen with I405V genotype. Our observations of lower levels of small-HDL and higher levels of large-HDL suggest that a potentially important HDL subclass-CETP relationship exists.

A qualitative study of nuisance bleeding and medication-related beliefs with dual antiplatelet drug therapy.

OBJECTIVES: The purpose of this qualitative study was to explore perceptions of nuisance bleeding and medication-related beliefs among adults taking dual antiplatelet drug therapy. METHODS: We conducted qualitative telephone interviews with 34 community-dwelling adults with cardiovascular disease. RESULTS: Using qualitative content analysis, we identified 4 dominant themes: nuisance bruising, nuisance bleeding, importance of medication adherence, and duration of therapy. Participants' bruising was frequently more severe than expected given the force of the bump that caused it. Concerns focused on whether increased bleeding tendencies would lead to hemorrhage in the event of a major traumatic injury, confusion about the duration of therapy, and the rationale for when and why therapy should be discontinued. CONCLUSION: Excessive bruising and medication-related concerns about hemorrhage and duration of treatment were salient issues for participants. Effective clinician-patient communication should be used to assist individuals in managing concerns to help assure positive health outcomes with antiplatelet drugs.

A compliance assessment of midpoint formative assessments completed by APPE preceptors.

INTRODUCTION: Experiential pharmacy preceptors should provide formative and summative feedback during a learning experience. Preceptors are required to provide colleges and schools of pharmacy with assessments or evaluations of students' performance. Students and experiential programs value on-time completion of midpoint evaluations by preceptors. The objective of this study was to determine the number of on-time electronically documented formative midpoint evaluations completed by preceptors during advanced pharmacy practice experiences (APPEs). METHODS: Compliance rates of on-time electronically documented formative midpoint evaluations were reviewed by the Office of Experiential Education of a five-member consortium during the two-year study period prior to the adoption of Standards 2016. Pearson chi-square test and generalized linear models were used to determine if statistically significant differences were present. RESULTS: Average midpoint compliance rates for the two-year research period were 40.7% and 41% respectively. No statistical significance was noted comparing compliance rates for year one versus year two. However, statistical significance was present when comparing compliance rates between schools during year two. Feedback from students and preceptors pointed to the need for brief formal midpoint evaluations that require minimal time to complete, user friendly experiential management software, and methods for documenting verbal feedback through student self-reflection. CONCLUSIONS: Additional education and training to both affiliate and faculty preceptors on the importance of written formative feedback at midpoint is critical to remaining in compliance with Standards 2016.

Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.

STUDY OBJECTIVE: To determine whether beta-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure. DESIGN: Prospective clinical study. SETTING: Two heart failure centers. PATIENTS: Eighty-eight spironolactone-naïve patients with heart failure who were taking beta-blockers. INTERVENTION: In a subset of 29 patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to 25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (> or = 50% of recommended target dose) of beta-blockers. Patients receiving low-dose beta-blockers had higher mean +/- SD PIIINP concentrations (6.6 +/- 3.5 vs 4.9 +/- 2.6 microg/L, p=0.03) and tended to have higher PINP concentrations (74.0 +/- 44.1 vs 57.1 +/- 28.6 microg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low-dose (9 patients) and high-dose (20 patients) beta-blocker groups. Low beta-blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] -14.3 microg/L [-9.8 to -19.3 microg/L] vs -2.5 microg/L [5.9 to -9.8 microg/L], p=0.02) and PIIINP (-1.4 microg/L [-0.9 to -2.4 microg/L] vs 0.1 microg/L [0.9 to -1.3 microg/L], p=0.045) with spironolactone therapy than high beta-blocker doses. In addition, 100% of the patients in this subset taking low-dose beta-blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis. CONCLUSION: Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of beta-blocker dosages, at least in terms of its effects on cardiac remodeling.

Markers of cardiac collagen turnover are similar in patients with mild and more severe symptoms of heart failure.

Cardiac fibrosis plays an important role in the pathophysiology of heart failure. The authors sought to determine whether biomarkers of cardiac fibrosis for milder clinical degrees of heart failure are comparable to those of more advanced disease. Procollagen types I and III amino-terminal peptides (PINP and PIIINP) and type I collagen telopeptide (ICTP) were compared between aldosterone-antagonistnaive patients with heart failure and New York Heart Association class I or II (n=22/23) and class III or IV (n=42/3) symptoms. Median (interquartile) range concentrations of PINP (63.3 [44.2-88.8] vs 48.6 [37.8-74.9] microg/L), ICTP (7.0 [5.4-16.8] vs 6.5 [4.7-12.7] microg/L), and PIIINP (4.7 [3.2-7.0] vs 4.7 [2.9-7.3] microg/L) were comparable between patients with mild and moderate to severe disease, respectively. These data suggest that patients with mild heart failure may have similar degrees of cardiac fibrosis to patients with more severe disease and support the examination of antifibrotic therapy, including aldosterone antagonists, in milder degrees of heart failure.

Student pharmacists' preparedness to evaluate primary literature pre- and post-Advanced Pharmacy Practice Experiences.

BACKGROUND AND PURPOSE: The primary objective of this study was to assess the effect of formal primary literature evaluation (PLE) during advanced pharmacy practice experiences (APPEs) on student pharmacists' preparedness and knowledge related to literature evaluation. EDUCATIONAL ACTIVITY AND SETTING: A perception of preparedness survey and knowledge assessment was given to student pharmacists pre- and post-APPEs. Student pharmacists were also asked to characterize their opportunities for formal PLE during APPEs. Literature evaluation experiences, knowledge base and preparedness data were compared between student pharmacists who completed two or more PLE on APPE and those who did not. FINDINGS: A total of 211 student pharmacists completed 529 formal PLE during their APPE experiences. Quiz grades and average perception of preparedness increased significantly from pre- to post-APPE regardless of whether student pharmacists had the opportunity for formal PLE on APPE. Student pharmacists who completed two or more PLE on APPE stated they felt more confident in evaluating primary literature after APPE, had greater post-APPE preparedness scores and a trend towards higher post-APPE quiz scores. DISCUSSION AND CONCLUSION: APPEs provide an important opportunity for student pharmacists to improve their PLE knowledge.

Antibiotic drug interactions.

Drug-drug interactions in the field of infectious diseases continue to expand as new drugs are approved, metabolic enzymes and transporters are identified, and recommendations for co-administration of drugs are revised. This article provides an overview of the principles and mechanisms of drug-drug interactions and describes pharmacokinetic-pharmacodynamic interactions commonly associated with antibacterial therapy, antiviral agents (non-retroviral), and drugs for tuberculosis.

Racial differences in potassium response to spironolactone in heart failure.

Evidence of racial differences in aldosterone concentrations and K+ disposition suggests that response to aldosterone antagonism might vary by race. The authors sought to determine whether K+ response to spironolactone differs between African Americans and Caucasians with heart failure. Heart failure patients of African-American (n = 34) or Caucasian (n = 17) race were started on spironolactone 12.5 mg/d, with up-titration as tolerated. Laboratory values and drug therapy were similar between racial groups at baseline. Spironolactone was titrated to a median dose of 25 mg/d in both groups. Neither concomitant medications nor serum creatinine changed significantly in either group during spironolactone dose titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, -0.7 to 1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, -0.8 to 0.9 mEq/L) in African Americans; p < 0.01. These data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone.

Simulated Order Verification and Medication Reconciliation during an Introductory Pharmacy Practice Experience.

Objective. To create, implement, and assess a simulated medication reconciliation and an order verification activity using hospital training software. Design. A simulated patient with medication orders and home medications was built into existing hospital training software. Students in an institutional introductory pharmacy practice experience (IPPE) reconciled the patient's medications and determined whether or not to verify the inpatient orders based on his medical history and laboratory data. After reconciliation, students identified medication discrepancies and documented their rationale for rejecting inpatient orders. Assessment. For a 3-year period, the majority of students agreed the simulation enhanced their learning, taught valuable clinical decision-making skills, integrated material from previous courses, and stimulated their interest in institutional pharmacy. Overall feedback from student evaluations about the IPPE also was favorable. Conclusion. Use of existing hospital training software can affordably simulate the pharmacist's role in order verification and medication reconciliation, as well as improve clinical decision-making.

A patient with HIV and tuberculosis with diminished clopidogrel response.

Patients with HIV are at an increased risk for cardiovascular disease, both as a result of treatment with protease inhibitors and from the disease itself. The medication regimens of patients with HIV and cardiovascular comorbidities are complex and require careful assessment for potentially serious drug-drug interactions. We report a case of clopidogrel non-responsiveness in a patient with HIV, latent tuberculosis and cardiovascular disease with a history of myocardial infarction. To our knowledge, this is the first report of significant drug interactions between clopidogrel, isoniazid and ritonavir. This case underscores the importance of a detailed drug interaction screening in infectious disease patients taking complex medication regimens, including clopidogrel.

Impact of abbreviated lecture with interactive mini-cases vs traditional lecture on student performance in the large classroom.

OBJECTIVE: To compare the impact of 2 different teaching and learning methods on student mastery of learning objectives in a pharmacotherapy module in the large classroom setting. DESIGN: Two teaching and learning methods were implemented and compared in a required pharmacotherapy module for 2 years. The first year, multiple interactive mini-cases with inclass individual assessment and an abbreviated lecture were used to teach osteoarthritis; a traditional lecture with 1 inclass case discussion was used to teach gout. In the second year, the same topics were used but the methods were flipped. Student performance on pre/post individual readiness assessment tests (iRATs), case questions, and subsequent examinations were compared each year by the teaching and learning method and then between years by topic for each method. Students also voluntarily completed a 20-item evaluation of the teaching and learning methods. ASSESSMENT: Postpresentation iRATs were significantly higher than prepresentation iRATs for each topic each year with the interactive mini-cases; there was no significant difference in iRATs before and after traditional lecture. For osteoarthritis, postpresentation iRATs after interactive mini-cases in year 1 were significantly higher than postpresentation iRATs after traditional lecture in year 2; the difference in iRATs for gout per learning method was not significant. The difference between examination performance for osteoarthritis and gout was not significant when the teaching and learning methods were compared. On the student evaluations, 2 items were significant both years when answers were compared by teaching and learning method. Each year, students ranked their class participation higher with interactive cases than with traditional lecture, but both years they reported enjoying the traditional lecture format more. CONCLUSION: Multiple interactive mini-cases with an abbreviated lecture improved immediate mastery of learning objectives compared to a traditional lecture format, regardless of therapeutic topic, but did not improve student performance on subsequent examinations.

A comparison of students' self-assessments with faculty evaluations of their communication skills.

OBJECTIVE: To compare students' self-assessment of their communication skills with faculty members' formal evaluation of their skills in a therapeutics course. METHODS: Over a 3-year period, faculty members evaluated second-year pharmacy students' communication skills as part of a requirement in a therapeutics course. Immediately following an individual oral assessment and again following a group oral assessment, students self-assessed their communication skills using the same rubric the faculty members had used. Students' self-assessments were then compared with faculty members' evaluation of students' communication skills. RESULTS: Four hundred one (97.3%) students consented to participate in this study. Faculty evaluation scores of students for both the individual and group oral assessments were significantly higher than students' self-assessment scores. Students' self-assessment scores of their communication skills increased from the individual to the group oral assessment. CONCLUSION: Students' self-assessments of communication skills were consistently lower than faculty members' evaluations. Greater use of oral assessments throughout the pharmacy curriculum may help to improve students' confidence in and self-assessment of their communication skills.

Statins personalized.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor medications, commonly referred to as statins, are among the most widely prescribed medications. Variation in individual response to statins concerning low-density lipoprotein cholesterol reduction, clinical event benefit, and side effects has been observed. Some of this variability is attributed to demographic and environmental issues, chief of which is compliance. A large portion of the individual response to statin therapy is attributed to single nucleotide polymorphisms that have recently been elucidated, several of which seem to have clinical utility.