The relationship between four health-related quality-of-life indicators and use of mammography and Pap test screening in US women.

PURPOSE: Limited evidence is available to explain the role of four components of health-related quality of life (HRQoL) on breast and cervical cancer screening. The objective of this study was to determine the relationship between four HRQoL aspects and use of mammography and Pap test screening in US women. METHODS: Data were obtained from the 2012 Behavioral Risk Factor Surveillance System (BRFSS). The outcome variables were receiving mammogram <2 versus ≥2 years in women aged 50-74 years, and receiving Pap test <3 versus ≥3 years in women aged 18-64 years. Eight logistic regression models were conducted to test the role of four HRQoL aspects (general health status, physical HRQoL, mental HRQoL, and activity limitation) on the two screening variables, after adjusting for covariates. Statistical analysis accounted for the complex sampling design of the BRFSS, and the a priori alpha error was set at p ≤ 0.05. RESULTS: Among respondents, approximately 74 and 78 % of the women received mammography and Pap test, respectively. Three HRQoL aspects (general health status, physical HRQoL, and activity limitation) were significantly associated with mammography use (all p values < 0.05), whereas two HRQoL aspects (general health status and physical HRQoL) were significantly associated with Pap test (p values ≤ 0.05). All significant relationships demonstrated higher cancer screening rates among individuals with better HRQoL. CONCLUSIONS: HRQoL is an important factor associated with use of mammography and Pap test. Future studies should explore the mechanisms associated with an individual's HRQoL and use HRQoL assessment as an avenue to influence adherence to use of mammography and Pap tests.

Dabigatran-dronedarone interaction in a spontaneous reporting system.

OBJECTIVES: To investigate the risk of bleeding events associated with concurrent administration of dabigatran-dronedarone compared with dabigatran standalone therapy using the Food and Drug Administration Adverse Event Reporting System (FAERS) database and to identify the characteristics of patients with bleeding events associated with concurrent use of dabigatran and dronedarone. DESIGN: Retrospective data mining analysis. SETTING: United States, from the dabigatran approval date (October 19, 2010) through the fourth quarter of 2011. PATIENTS: Cases from FAERS with bleeding events (combined in a single term based on adverse event reports such as hemorrhage and rectal hemorrhage) as the adverse event. INTERVENTION: Cases listing concomitant use of the terms Pradaxa, dabigatran, or dabigatran etexilate with Multaq or dronedarone as the suspect drug from FAERS and cases listing dabigatran and dronedarone as standalone therapies were extracted for analysis. MAIN OUTCOME MEASURE: Risk of bleeding among those using dabigatran-dronedarone concomitantly compared with those using dabigatran standalone therapy. RESULTS: 108 dabigatran-dronedarone interaction reports and 14,913 reports concerning bleeding events were extracted from FAERS. Of 108 dabigatran-dronedarone interaction cases, 51 were associated with bleeding events. The odds ratio (OR) for risk of bleeding in patients using dabigatran and dronedarone concomitantly compared with those using neither of the suspect drugs was 13.80 (95% CI 9.45-20.14). The OR for risk of bleeding in patients using only dabigatran compared with those using neither of the suspect drugs was 16.06 (15.00-17.19). CONCLUSION: The likelihood of reporting bleeding events to FAERS among patients using dabigatran only was similar to that among patients using dabigatran and dronedarone concomitantly.

Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review.

INTRODUCTION: Currently available omega-3 (OM-3) fatty acid products in the US are either nonprescription dietary supplements (e.g., fish oils) or prescription (Rx) medications. As such, we aimed to describe critical therapeutic differences among the OM-3 fatty acids, focusing on differences between fish oil supplements and Rx OM-3s. METHODS: A narrative review of known papers salient to this topic was conducted. RESULTS: Despite the multiple purported clinical benefits, the published evidence for OM-3 dietary supplements is generally insufficient, inconsistent, or negative. Rx OM-3 products are indicated as an adjunct to diet to reduce triglycerides (TG) in adults with severe hypertriglyceridemia (TG ≥ 500 mg/dl). Recently, the Rx eicosapentaenoic acid (EPA)-only OM-3, icosapent ethyl, demonstrated cardiovascular (CV) risk reduction among statin-treated patients at high risk of CV disease in a large CV outcomes trial (CVOT), and is now also indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated TG (≥ 150 mg/dL) and established CVD or diabetes mellitus and ≥ 2 additional risk factors for CVD. In contrast to the rigorous regulatory standards for safety, efficacy, and manufacturing of medications (whether Rx or over the counter), the Food and Drug Administration manages dietary supplements as food. Issues specific to OM-3 dietary supplements include variable content, labeling inconsistencies, and poor product quality/impurity. Given these issues, OM-3 dietary supplements should not be substituted for Rx OM-3 products. The efficacy of the EPA-only Rx OM-3 product in a large CVOT cannot be extrapolated to other OM-3 products. CONCLUSION: Consumers and health care providers need to recognize critical differences between Rx and OM-3 dietary supplements to ensure appropriate use of each OM-3 product.

Practical Insight Into Anticoagulation for an Aging Population.

Anticoagulation is almost always required as a part of treatment for atrial fibrillation, but it is also one of the most potentially dangerous pharmacologic strategies. Recently, a number of guidance documents have been released with respect to anticoagulation. Some elements of the guidelines potentially create conflicting considerations for clinicians charged with selecting the safest and most effective anticoagulation protocol, especially for patients older than 75 years of age.

Antiplatelet therapy in patients with unstable angina and non-ST-segment-elevation myocardial infarction: findings from the CRUSADE national quality improvement initiative.

Evidence-based clinical practice guidelines encapsulate current knowledge to guide health care professionals in the treatment of patients with unstable angina or non-ST-segment-elevation myocardial infarction (NSTEMI), yet adherence to guideline recommendations is suboptimal. Guideline adherence may be improved by quality improvement programs such as the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation?) National Quality Improvement Initiative of the American College of Cardiology-American Heart Association Guidelines. The CRUSADE data have been analyzed to demonstrate that overall guideline adherence is directly associated with mortality and that improvement in guideline adherence saves lives. Also, the CRUSADE data have determined that the real-life mortality risk associated with unstable angina and NSTEMI is greater than suggested by clinical trials. The newer antiplatelet drugs recommended in early intervention and discharge treatment strategies are underused across many segments of the unstable angina-NSTEMI population. Glycoprotein IIb-IIIa inhibitors are underused in high-risk populations, and clopidogrel is markedly underused in patients who are medically managed rather than undergoing percutaneous coronary intervention or coronary artery bypass graft surgery. In addition, often the specialty of the treating physician and the status of the hospital influence the use of antiplatelet therapy. The reasons for underprescribing of antiplatelet drugs by physicians are not entirely clear but may be related to a lack of guideline familiarity and understanding, as well as factors such as drug novelty, safety, and cost. Continued education and data dissemination are therefore vital in promoting the prescription of guideline-recommended drugs, both in the early hospitalization phase and as patients transition to community-based care. The role of the pharmacist is pivotal in ensuring adherence to clinical guidelines by interacting with both the physician and patient.

Commentary: Should Pharmacogenomic Evidence Be Considered in Clinical Decision Making? Focus on Select Cardiovascular Drugs.

Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to use pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether pharmacogenomics is cost-effective. However, the implementation of clinical practice guidelines, such as those from professional organizations, is commonplace and often termed the application of evidence-based medicine. Here, we draw an analogy between the evidence supporting many commonly cited clinical practice guidelines and U.S. Food and Drug Administration-approved labeling recommendations and the evidence supporting recommendations from CPIC. Although many clinical practice guideline recommendations are supported by the results of randomized controlled clinical trials, we cite examples of common clinical practices that are supported by levels and types of evidence similar to the evidence supporting many of the CPIC recommendations. Specifically, we discuss clinical recommendations for guidance related to drug-drug interactions, drug-gene interactions, therapeutic range selection, and dosage adjustments based on patient-specific factors within the context of a select set of cardiovascular therapeutic topics.

Statin safety and drug interactions: clinical implications.

The risks of muscle adverse events related to use of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, increase significantly with the addition of interacting drugs to a patient's therapy. The mechanism for most statin drug interactions involves the cytochrome P-450 system, which provides an indication of which drugs may interact. However, it is difficult to predict the probability of a drug interaction in a given patient because there are individual differences in sensitivity to increased statin drug levels. Drug metabolism studies show simvastatin and lovastatin to be especially sensitive to the inhibiting effects of other drugs on the cytochrome P-450 3A4 (CYP3A4) isoenzyme. Atorvastatin metabolism is less affected by inhibitors of this isoenzyme. Case reports, postmarketing surveillance, and clinical trial data demonstrate the clinical effect of CYP3A4 inhibitors on statins. Also, through possible inhibition of statin biliary excretion and glucuronidation, gemfibrozil given concomitantly with rosuvastatin, lovastatin, and simvastatin significantly increases the risk of myopathy and rhabdomyolysis, a potentially life-threatening consequence of statin drug interactions.

Cost-effectiveness analysis of allopurinol versus febuxostat in chronic gout patients: a U.S. payer perspective.

BACKGROUND: Gout is a chronic inflammatory condition associated with poor urate metabolism. Xanthine oxidase inhibitors such as allopurinol and febuxostat are recommended to reduce uric acid levels and to prevent gout attacks in adult patients. Under budget-driven constraints, health care payers are faced with the broader challenge of assessing the economic value of these agents for formulary placement. However, the economic value of allopurinol versus febuxostat has not be assessed in patients with gout over a 5-year time period in the United States. OBJECTIVE: To evaluate the cost-effectiveness of allopurinol versus febuxostat in adult patients with gout over a 5-year time period from a U.S. health care payer's perspective. METHODS: A Markov model was developed to compare the total direct costs and success of serum uric acid (sUA) level reduction associated with allopurinol and febuxostat. Treatment success was defined as patient achievement of a sUA level less than 6 mg/dL (0.36 mmol/L) at 6 months. Event probabilities were based on published phase III randomized clinical trials and included long-term sequelae from open-label extension studies. A hypothetical cohort of 1,000 adult gout patients with sUA levels of ≥ 8 mg/dL (0.48 mmol/L) who had received either allopurinol 300 mg or febuxostat 80 mg at model entry transitioned among the 4 health states defined by treatment success, treatment failure and switch, treatment dropout, and death. The length of each Markov cycle was 6 months. Costs were gathered from the RED BOOK, Medicare fee schedules, Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, and for a limited number of inputs, expert consultation. Direct costs included treatment drug costs, costs for prophylaxis drugs, diagnostic laboratory tests, and the treatment and management of acute gout flare. Resource utilization was based on clinical evidence and expert consultation. All costs were inflated to 2014 U.S. dollars and were discounted at 3% in the base case. One-way sensitivity analysis and probabilistic sensitivity analyses (PSAs) were performed to assess the robustness of the results. RESULTS: The total per patient cost incurred over 5 years was $50,295 for febuxostat and $48,413 for allopurinol, with an incremental total cost of $1,882. The expected percentage of treatment success during the 5-year period was 72 for febuxostat and 42 for allopurinol, resulting in an incremental percentage of treatment success of 30. The estimated incremental cost-effectiveness ratio for febuxostat compared with allopurinol was $6,322 per treatment success over a 5-year time period. The one-way sensitivity analysis indicated that the results were sensitive to probability of treatment success for allopurinol, probability of treatment dropouts for both allopurinol and febuxostat, and the probability of failure and switch to allopurinol. PSAs demonstrated that at a willingness-to-pay threshold of $50,000 per treatment success, febuxostat was cost-effective compared with allopurinol. CONCLUSIONS: Febuxostat was found to be a cost-effective option compared with allopurinol based on a U.S. payer perspective.

Combination antiplatelet therapy: implications for pharmacists.

OBJECTIVES: To present two case reports of patients who received suboptimal oral antiplatelet therapy and to review recent changes in national guidelines for management of acute coronary syndromes. DATA SOURCES: Personal observation by the authors, and clinical practice guidelines and related clinical trials of the American Heart Association and the American College of Cardiology. SUMMARY: The American College of Cardiology and the American Heart Association revised the guidelines for administration of antiplatelet and anticoagulant therapy in patients with unstable angina and non-ST-segment elevation myocardial infarction in March 2002. Two cases observed by the authors illustrate the consequences of suboptimal antiplatelet therapy when a combination of two antiplatelet drugs should have been administered. CONCLUSION: Evidence from recent randomized controlled trials led to changes in the national guidelines for administration of oral antiplatelet therapy in patients with acute coronary syndromes. Pharmacists should be aware of these changes and counsel patients about appropriate administration of antiplatelet drugs.

Underidentification and undertreatment issues.

Despite the Adult Treatment Panel (ATP) guidelines and strong evidence that reduction of blood cholesterol levels favorably decreases the morbidity and mortality associated with coronary heart disease (CHD), a significant number of patients remain undiagnosed and untreated. With the aggressive detection and evaluation methods ATP III advocates, more than 65 million Americans are now eligible for lipid modification through lifestyle changes and/or drug therapy. Recent data suggest, however, that as many as 50% of all patients do not have their cholesterol assessed and less than 45% receive lipid-modifying therapy. Additionally, more than 75% of patients who receive therapy fail to achieve their National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol goal. Persistence with therapy is another challenge, as less than 30% of patients continue with therapy beyond one year. If a realistic attempt is to be made to reduce the CHD risk among Americans, diagnosis of dyslipidemia and treatment to therapeutic targets must be improved.

Quality improvement in the continuum of care: impact of atherothrombosis in managed care pharmacy.

OBJECTIVE: To review the clinical and economic impact of atherothrombosis, the use of antiplatelet therapy for patients with atherothrombosis, and the impact of disease management programs on quality improvement and health care costs. SUMMARY: Atherothrombosis is a new term that describes the formation of a thrombus on an existing atherosclerotic plaque. While simple, this pathophysiologic mechanism underlies a vast array of vascular diseases, including myocardial infarction, ischemia, peripheral arterial disease, vascular death, and many forms of stroke. In fact, atherothrombosis is the leading cause of death worldwide. Treatment approaches include lifestyle modification and the use of pharmacologic agents such as lipid-lowering therapy, antihypertensive agents, hypoglycemic therapy, ACE inhibitors, and beta-blockers. Despite these treatments, studies have indicated that not all patients receive recommended therapies. The continuing upward spiral in health care costs in the United States has spurred numerous initiatives aimed at improving the quality of care while maintaining or reducing costs. Among these approaches to quality improvement are programs that promote adherence to evidence-based clinical data, including published guidelines, and improve the appropriate use of pharmaceuticals. Although expenditures for prescription drugs are rising, they remain a minority of overall health care expenditures, and evidence suggests that improved usage of medications can reduce other direct costs, such as hospitalizations and inpatient care, which may account for a far greater proportion of total costs. CONCLUSION: The utilization of quality improvement techniques and disease management tools can be used to improve the quality of care of patients with atherothrombosis. A key component of this strategy is pharmacologic therapy. The appropriate use of prescription drugs involves several key factors, including the proper selection of the agent based on available clinical evidence, choosing regimens that enhance patient compliance, and sound methodologies to evaluate outcomes. Improvements in the quality of care for patients with atherothrombosis can have a significant impact on the overall quality of health care as well as total costs.

Investigation of pegloticase-associated adverse events from a nationwide reporting system database.

PURPOSE: Pegloticase-associated adverse events reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database in the United States were evaluated. METHODS: Retrospective data-mining analysis of FAERS case reports listing Krystexxa or pegloticase as the suspect drug and specific adverse events (cardiovascular events, infusion-related reactions, gout flares, and anaphylaxis) was conducted from the drug's approval date (September 14, 2010) through August 27, 2012. Initial and follow-up reports with the same primary linked identification number were identified as unique to each patient case. When multiple reports for the same patient were identified with a common case number, the report with the most recent date was used to eliminate duplicate reports. Bayesian confidence propagation neural network methodology was used to identify signals of drug-associated adverse events. A potential signal for drug-adverse event reports is generated when the lower limit of the 95% two-sided confidence interval of the information component is greater than 0. RESULTS: A total of 118 unique cases of adverse events involving pegloticase in the United States were identified during the study period. Fourteen reports were related to pegloticase-associated cardiovascular events, and 35 were related to pegloticase-associated infusion-related reactions. Twenty-six reports were related to pegloticase-associated gout, and 11 were reports of pegloticase-associated anaphylaxis. Bayesian statistics identified potential signals for all pegloticase-associated adverse events (cardiovascular events, infusion reactions, gout flares, and anaphylaxis). CONCLUSION: Analysis of pegloticase-associated adverse events submitted to the FAERS database found that cardiovascular events, infusion-related reactions, gout flares, and anaphylaxis occurred more frequently than was statistically expected.

Educational outcomes necessary to enter pharmacy residency training.

It is the position of the American College of Clinical Pharmacy (ACCP) that formal postgraduate residency training, or equivalent experience, is required to enter direct patient care practice. Therefore, it is important to align professional degree educational outcomes with the knowledge, skills, and attitudes needed to enter residency training. This position statement addresses the outcomes necessary in the professional degree program curriculum to ensure the ability of pharmacy graduates to transition effectively into postgraduate year one residency training. Five key outcome areas are identified: communication, direct patient care, professionalism, research, and practice management. The position statement examines how performance in each of the five outcome areas should be addressed by professional degree programs. The ACCP believes that for the student to achieve the clinical proficiency necessary to enter residency training, the professional degree program should emphasize, assess, and provide adequate opportunities for students to practice: communication with patients, caregivers, and members of the health care team in direct patient care environments; provision of direct patient care in a wide variety of practice settings, especially those involving patient-centered, team-based care; professionalism under the supervision and guidance of faculty and preceptors who model and teach the traits of a health care professional; application of principles of research that engender an appreciation for the role of research and scholarship in one's professional development; and application of practice management, including documentation of direct patient care activities that affect drug-related outcomes.

Cardiovascular thromboembolic events associated with febuxostat: investigation of cases from the FDA adverse event reporting system database.

OBJECTIVE: Uloric (Febuxostat) has been linked with cardiovascular thromboembolic events in gout patients. However, no post-marketing data analysis has investigated these drug-associated adverse event reports. The study objective was to identify febuxostat-associated cardiovascular thromboembolic event reports in the US using the Food and Drug Administration adverse event reporting system (AERS) database. METHODS: Reports listing uloric and febuxostat as the suspect drug and cardiovascular thromboembolic events (combined in a single term based on adverse event reports of myocardial infarction, stroke, among others) as the adverse event were extracted from the drug's approval date through the fourth quarter of 2011. Bayesian statistics within the neural network architecture was implemented to identify potential signals of febuxostat-associated cardiovascular thromboembolic events. A potential signal for the drug-adverse event combination reports is generated when the lower limit of the 95% two-sided confidence interval of the information component (IC), denoted by IC025 is greater than zero. RESULTS: Twenty-one combination reports of febuxostat-associated cardiovascular thromboembolic events were identified in gout patients in the US. The mean age of combination cases was 64 years. Potential signals (IC025 = 4.09) was generated for combination reports of febuxostat-associated cardiovascular thromboembolic events. CONCLUSION: AERS indicated potential signals of febuxostat-associated cardiovascular thromboembolic events. AERS is not capable of establishing the causal link and detecting the true frequency of an adverse event associated with a drug. The positive IC value found in this study merits continued surveillance and assessment of cardiovascular thromboembolic events associated with Febuxostat.

Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database.

STUDY OBJECTIVE: To investigate reports of thrombotic events associated with the use of C1 esterase inhibitor products in patients with hereditary angioedema in the United States. DESIGN: Retrospective data mining analysis. SOURCE: The United States Food and Drug Administration (FDA) adverse event reporting system (AERS) database. MEASUREMENTS AND MAIN RESULTS: Case reports of C1 esterase inhibitor products, thrombotic events, and C1 esterase inhibitor product-associated thrombotic events (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a drug-associated adverse event. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC025 , is greater than zero. This suggests that the particular drug-associated adverse event was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze) were identified in patients with hereditary angioedema. A potential signal demonstrated by an IC025 value greater than zero (IC025 = 2.91) was generated for these combination cases. CONCLUSION: The extracted cases from the AERS indicate continuing reports of thrombotic events associated with the use of one C1 esterase inhibitor product among patients with hereditary angioedema. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of C1 esterase inhibitor product-associated thrombotic events among patients with hereditary angioedema were identified in the extracted combination cases.

Combination antiplatelet therapy: implications for pharmacists.

OBJECTIVES: To present two case reports of patients who received suboptimal oral antiplatelet therapy and to review recent changes in national guidelines for management of acute coronary syndromes. DATA SOURCES: Personal observation by the authors, and clinical practice guidelines and related clinical trials of the American Heart Association and the American College of Cardiology. SUMMARY: The American College of Cardiology and the American Heart Association revised the guidelines for administration of antiplatelet and anticoagulant therapy in patients with unstable angina and non-ST-segment elevation myocardial infarction in March 2002. Two cases observed by the authors illustrate the consequences of suboptimal antiplatelet therapy when a combination of two antiplatelet drugs should have been administered. CONCLUSION: Evidence from recent randomized, controlled trials led to changes in the national guidelines for administration of oral antiplatelet therapy in patients with acute coronary syndromes. Pharmacists should be aware of these changes and counsel patients about appropriate administration of antiplatelet drugs.