Comparing Direct Oral Anticoagulants and Warfarin for Atrial Fibrillation, Venous Thromboembolism, and Mechanical Heart Valves.

OBJECTIVES: To summarize available data for use of direct oral anticoagulants in nonvalvular atrial fibrillation, venous thromboembolism, and mechanical heart valves including dose-response consistency to offer considerations for pharmacotherapeutic decision-making for oral anticoagulants. DATA SOURCES: A Medline search of English-language studies published between 2000 and March 2015 was conducted to identify pertinent papers using combinations of the following words: apixaban, atrial fibrillation, dabigatran, direct oral anticoagulant, edoxaban, factor IIa inhibitors, factor Xa inhibitors, mechanical heart valves, novel oral anticoagulant, rivaroxaban, venous thromboembolism, and warfarin. STUDY SELECTION AND EXTRACTION: Original studies, guidelines, and approved prescribing information were evaluated and included if contributing new or complementary data toward the objective. References for all identified studies were reviewed and entries included if contributory. DATA SYNTHESIS: Randomized controlled trials have established the safety and efficacy of direct oral anticoagulants in atrial fibrillation and venous thromboembolism for most patient groups. Direct oral anticoagulants should not be used in patients with mechanical heart valves until proven safe and effective. There are groups for which questions remain regarding inter-patient dose-response consistency for direct oral anticoagulants. There are postmarketing data suggesting poorer real-world performance of dabigatran relative to clinical trial data. CONCLUSION: Direct oral anticoagulants offer several advantages over warfarin, and large clinical trial data establish the appropriateness of their use in broad populations. There remain groups for whom the relative benefit and risk of these agents relative to warfarin are uncertain. A patient-specific approach in pharmacotherapeutic decision-making is appropriate.

The impact of pioglitazone on bladder cancer and cardiovascular events.

Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI). Pioglitazone does not appear to share this risk. To the contrary, pioglitazone may reduce risk for MI. However, retrospective evaluations have increasingly linked pioglitazone to a higher risk of bladder cancer that appears to be time- and dose-dependent. Pioglitazone remains a medication appropriate for consideration in the management of T2DM; however, clinicians and patients should weigh its risks compared with alternatives, with a regular review of risks.

Patient participation in a clinic-based community pharmacy medication take-back program.

OBJECTIVES: To describe patient interest and involvement in participating in a clinic-based community pharmacy drug take-back program to dispose of unused, unwanted, or expired (UUE) medications and to identify patients' reasons for participating in the program. METHODS: A convenience sample of patients at the University of Oklahoma Family Medicine Pharmacy was recruited to complete a needs assessment survey regarding interest in drug take-back programs and current practices for handling UUE medications. Participants who purchased a postage-paid drug disposal envelope were asked to complete a program survey identifying sources of UUE medications, experience with drug take-back programs, and reasons for participation. These participants were later contacted for a follow-up telephone survey regarding their experience with the program and medications sent back. RESULTS: 62 needs assessment surveys were collected. 61% of patients reported interest in a drug take-back program. 57% reported having no UUE medications at home. Commonly reported UUE handling practices included disposal in the garbage (53.2%) or sewer (29.0%) and home storage (17.7%). 15 disposal envelopes were sold to 10 participants whose most common reasons for participation included concern about the safety of household members, accidental or intentional ingestion, and environmental impact. For 4 patients who returned a median of 9.5 prescriptions, the most common class of returned drugs was antibiotics (19.0%). CONCLUSION: Interest in drug take-back programs exists, but awareness and availability of continuous programs is limited. Programs may be more successful if offered at no cost to patients. Future studies are needed on the types of medications sent back and specific reasons for accumulation.

Incretin-based therapy compared with non-insulin alternatives in elderly patients with type 2 diabetes.

Type 2 diabetes mellitus is an increasingly common threat to the health of elderly Americans. There are a variety of treatment options, each with a unique set of advantages and disadvantages in this population. Discriminating factors between non-insulin drug classes include glucose-lowering effectiveness, weight effects, propensity for hypoglycemia or other adverse events, route of administration, and cost. Metformin offers substantial glucose lowering without weight gain or hypoglycemia at a low cost, but there are several contraindications or warnings for its use. Sulfonylureas offer substantial glucose lowering at low cost, but can cause weight gain and hypoglycemia. Thiazolidinediones provide meaningful glucose lowering, but with weight gain and concern of cardiovascular toxicity and bladder cancer. Incretin agents lower glucose without weight gain and rarely cause hypoglycemia, but are expensive and lower glucose less than alternatives. A patient-specific approach is critical in identification of the optimal medication regimen for elderly patients with diabetes.

Exploring patient expectations for pharmacist-provided literacy-sensitive communication.

BACKGROUND: Limited health literacy is common and associated with adverse health care outcomes. Although pharmacies and pharmacists are accessible to most patients, research has indicated that they do not routinely report efforts to target interventions for patients with suboptimal health literacy. Moreover, little is known about the use and expectation of literacy-based communication techniques in pharmacies from the patient perspective. OBJECTIVE: The intent of this pilot study was to describe the use of health literacy-based communication techniques, expectations for their use, and satisfaction with communication as reported by patients at high risk for medication misadventures who receive care at a clinic-based community pharmacy. METHODS: A cross-sectional telephonic interview of a purposive sample of patients aged 65 years or older who were prescribed at least 8 unique medications was conducted. Patients were recruited from 1 clinic-based pharmacy that serves a predominantly urban low-income population. A telephonic interview guide was derived from previous literature and included 52 questions related to respondent characteristics, perceptions of experiences regarding verbal communications with the pharmacist, expectations for communication with the pharmacist, and satisfaction with current pharmacy communication techniques. Responses were summarized and described. RESULTS: Nineteen patients completed the telephonic interviews. Patients commonly reported that the pharmacist provided the following counseling for new prescriptions: how to take their medication (88.9%), side effects (84.2%), and indication (47.4%). In contrast, only 44.4%, 55.6%, and 33.3% of patients expected the pharmacist to engage in these same counseling behaviors. A minority of patients reported the use of various recommended clear health communication techniques by the pharmacist, and an even smaller percentage expressed expectations for their use. Despite the limited use of literacy-based communication techniques, 73.7% of patients reported being very satisfied with pharmacy counseling, and 94.7% reported good to excellent understanding of their medications. CONCLUSION: Patient-pharmacist interactions consistently met or exceeded patient expectations. However, pharmacists use of literacy-based communication techniques was low as were patient expectations. Future research and training efforts should focus on not only increasing pharmacists' use of literacy-based communication techniques but also raising patients' expectations for performing these activities.

Warfarin versus dabigatran: comparing the old with the new.

Warfarin is an oral anticoagulant for treatment and prevention of venous and arterial thromboembolism. It requires regular monitoring and patient adherence to a variety of lifestyle factors that can influence its effect. Dabigatran is an oral direct thrombin-inhibitor recently approved for stroke prevention in atrial fibrillation. The primary advantages of dabigatran are freedom from monitoring, a short duration of action, and a limited number of factors influencing its effect. Primary disadvantages of dabigatran compared with warfarin are that less is known about its use, cost, and poor gastrointestinal tolerability. Clinical studies have revealed both agents to be effective, with comparable rates for major bleeding. Divergent recommendations have been offered by consensus guidelines. A patient-specific approach involving the perspectives of informed patients is most reasonable.

Identification of barriers to appropriate dietary behavior in low-income patients with type 2 diabetes mellitus.

OBJECTIVE: To identify barriers to appropriate dietary behavior in an urban, low-income population of patients with type 2 diabetes and to examine a new instrument in the identification of these barriers in this population. METHODS: A cross-sectional survey was developed, validated, and anonymously administered to low-income adults with type 2 diabetes in an academic family medicine physician group practice with a pharmacist-operated diabetes education and comanagement service. The survey consisted of three key subscales: determinants of food selection, importance of life challenges, and barriers to appropriate eating. RESULTS: The survey was administered to 98 patients with a mean age of 51.98 years, a mean duration of diabetes of 9.76 years, and a mean hemoglobin A1c of 7.99%. When asked to rate factors most important in food selection, the highest mean responses were taste (3.97 out of 5) and cost (score of 3.94 out of 5). Barriers that the majority of respondents agreed or strongly agreed were important included: stress causing over-eating or unhealthy food choices, difficulty resisting the temptation to eat unhealthy food, and healthy food being too expensive. The Cronbach's Alpha for the subscales of food selection, importance of life challenges, and barrier were 0.673, 0.853, and 0.786, respectively. CONCLUSIONS: In a low-income, urban, predominantly African American and Caucasian diabetic population, cost of healthy food, stress-related inappropriate eating, and the temptation to eat unhealthy food were the most frequently reported barriers to healthy eating. Diabetes education programs serving similar populations should evaluate the presence of these barriers. The survey instrument was a reliable measure of the constructs it purported to measure.

Medication reconciliation in a community pharmacy setting.

OBJECTIVES: To describe the types and frequencies of medication discrepancies identified through medication reconciliation in a community pharmacy setting, to identify potential correlations between a patient's electronic medical record (EMR) and pharmacy medication list, and to determine the relationship between patients who use prescribers and/or pharmacies outside of the Family Medicine Center (FMC) and the occurrence of medication discrepancies. METHODS: Cross-sectional comparison of patients' EMR medication lists and pharmacy medication fill history for a sample of patients presenting to the Family Medicine Pharmacy (FMP), which is located in the FMC on the University of Oklahoma Health Sciences Center campus in Oklahoma City. Discrepancies identified were classified according to one of six categories that included therapeutic duplication, medication exclusion, medications that should be designated inactive in the EMR medication list, and differences in medication strength, dosage form, or dosing regimen. RESULTS: A total of 100 patients were included. Most patients reported having all of their medications dispensed from FMP (89%), and most patients had prescriptions prescribed by FMC physicians only (57%). Each patient had an average of six medication discrepancies. Most discrepancies belonged to the inactive medication category (41%). The correlation between patients' FMP medication lists and their EMR medication lists was 0.73. Patients with one or more non-FMC prescribers had a greater number of medication discrepancies than patients with FMC prescribers only, but this relationship was not identified for those who used pharmacies outside of FMP (P = 0.0264 and 0.2580, respectively). CONCLUSION: A variety of medication discrepancies were observed, signaling a need for medication reconciliation in the outpatient setting. Future research on this topic should focus on the implications of such discrepancies in the outpatient setting, interventions to reduce the number of discrepancies, and identifying patients at high risk for such discrepancies.

Extended therapy for primary and secondary prevention of venous thromboembolism.

Clinical practice guidelines currently suggest extended anticoagulation therapy for primary and secondary prevention of venous thromboembolism (VTE). The optimal duration of anticoagulation has been an active area of clinical investigation for patients undergoing orthopedic surgeries and those diagnosed with a first episode of unprovoked VTE. Practice guidelines, VTE incidence, clinical predictors/mediators, and clinical trial evidence is reviewed to help pharmacists and other health care providers make an informed, patient-specific decision on the optimal duration of anticoagulation therapy. Extended anticoagulation up to 5 weeks following orthopedic surgery for primary VTE prevention and indefinitely following a first episode of unprovoked VTE for secondary VTE prevention should be considered only if the risk of bleeding is not high and the cost and burden of anticoagulation is acceptable to the patient. The optimal duration of anticoagulation therapy for primary or secondary prevention of VTE should include the health care provider and patient making a decision based on evaluation of individual benefits, risks, and preferences.

Warfarin versus aspirin: using CHADS2 to guide therapy for stroke prevention in nonvalvular atrial fibrillation.

Atrial fibrillation (AF) results in nearly a quarter of the strokes suffered in patients 80 to 89 years of age. Aspirin and warfarin are primary choices for preventing these ischemic strokes. CHADS2 (Congestive heart failure, Hypertention, Age, Diabetes, Stroke) is a validated assessment tool for cardioembolic stroke in AF. Ischemic stroke rates increase from 1.9 to 18.2 events per 100 patient-years with CHADS2 scores of 0 and 6, respectively. Warfarin is more effective than aspirin at preventing stroke in AF, but is associated with more hemorrhagic events. The American College of Chest Physicians recommends the use of warfarin in patients with a CHADS2 score of 2 or higher and suggests warfarin be used in patients with a score of 1. We recommend a patient-specific approach to therapy in which warfarin is offered to patients with a CHADS2 score of 1 or higher unless the patient is at high risk for a hemorrhagic event or cannot attain regular warfarin monitoring.

Aldosterone antagonists in the treatment of heart failure.

PURPOSE: The clinical benefits, adverse effects, pharmacokinetics, and recommendations for the appropriate use of the aldosterone antagonists spironolactone and eplerenone in patients with heart failure are reviewed. SUMMARY: Heart failure is a clinical syndrome characterized by the functional inability of the ventricle to meet the metabolic demands of the body. Renal hypoperfusion occurs as a result of reduced cardiac output, resulting in the activation of the renin-angiotensin-aldosterone system, which compensates for the hypoperfusion. However, this contributes to the pathology of the disease by, among other actions, increasing the release of aldosterone. Aldosterone has been shown to cause coronary inflammation, cardiac hypertrophy, myocardial fibrosis, ventricular arrhythmias, and ischemic and necrotic lesions. There are currently two aldosterone antagonists commercially available in the United States, spironolactone and eplerenone. Spironolactone is a nonselective aldosterone antagonist, and eplerenone is selective to the aldosterone receptor. Although numerous clinical trials have evaluated the efficacy of each drug, no studies have directly compared spironolactone and eplerenone. Both have been shown to improve morbidity and mortality in patients with advanced heart failure. Adverse effects of both spironolactone and eplerenone include potentially life-threatening hyperkalemia, which can be induced by renal insufficiency, diabetes mellitus, advanced heart failure, advanced age, and concurrent drug therapy. CONCLUSION: Spironolactone and eplerenone are life-saving agents in patients with advanced heart failure and may benefit patients with mild heart failure. Potassium and renal function must be routinely assessed to minimize the risk of life-threatening hyperkalemia.

Antidepressant-induced sweating.

OBJECTIVE: To report a case of excessive sweating probably caused by paroxetine, review the literature on antidepressant-induced sweating, and provide recommendations for the management of antidepressant-induced sweating. CASE SUMMARY: A 59-year-old white female presented to a pharmacist-staffed pharmacotherapy clinic with episodes of excessive sweating. The episodes occurred primarily on her head and back of the neck. Other etiologies were ruled out and paroxetine was discontinued. Paroxetine had been initiated at least 7 months prior to the reporting of symptoms. Sweating symptoms gradually improved until resolution 5 weeks following discontinuation of paroxetine. The Naranjo probability scale indicated a causal relationship is probable. DISCUSSION: Excessive sweating has been associated with antidepressants including tricyclic antidepressants, selective serotonin-reuptake inhibitors, and venlafaxine. In some patients, these symptoms require therapeutic intervention such as dose reduction, antidepressant substitution, antidepressant discontinuation, or addition of an agent to control sweating. Agents that have been reported successful in controlling the sweating include benztropine and cyproheptadine. CONCLUSIONS: We recommend a patient-specific approach for the management of antidepressant-induced sweating. First, consider dose reduction or a trial off antidepressant medication. In patients in whom this is inappropriate or ineffective, substitution of another antidepressant should be considered. If episodes of excessive sweating persist, consider treatment of sweating symptoms with benztropine or cyproheptadine in the absence of contraindications.

Second-generation thiazolidinediones and hepatotoxicity.

OBJECTIVE: To report a case of hepatotoxicity probably caused by pioglitazone, summarize case reports of hepatotoxicity induced by rosiglitazone or pioglitazone, and make recommendations regarding routine liver enzyme measurement in patients taking these agents. CASE SUMMARY: A 39-year-old black woman with type 2 diabetes mellitus, hypertension, and congestive heart failure presented to a pharmacist-staffed diabetes comanagement service. She reported fatigue, dark brown urine, nausea, itching, and loss of appetite. Pioglitazone was promptly discontinued because her symptoms were consistent with those of hepatic dysfunction and pioglitazone was identified as a potential cause. The patient was referred to her physician. Liver enzyme levels were checked 13 days after initial presentation and found to be abnormal: alanine aminotransferase 490 U/L, aspartate aminotransferase 360 U/L, alkaline phosphatase 851 U/L, total bilirubin 3.1 mg/dL, direct bilirubin 2.0 mg/dL, and indirect bilirubin 1.1 mg/dL. Within 2(1/2) months of discontinuing pioglitazone, the patient's symptoms resolved and liver enzyme levels returned to normal. DISCUSSION: Troglitazone, a thiazolidinedione (TZD), was removed from the market because of hepatotoxicity. Reported cases involving the newer TZDs, rosiglitazone and pioglitazone, have been few in number and less severe in consequence. Six cases of rosiglitazone-induced hepatotoxicity and 5 of pioglitazone-induced hepatotoxicity have been reported. Most patients improved symptomatically 2-4 weeks following discontinuation of the offending TZD, with normalization of liver enzyme levels in 2 weeks to 6 months following TZD discontinuation. CONCLUSIONS: Although the timeline and extent of liver enzyme elevation in this case are unclear, the Naranjo probability scale suggests that a causal relationship between pioglitazone and liver disease is probable. Patients with previous TZD-induced hepatotoxicity should not be rechallenged. Cases of hepatotoxicity with second generation TZDs, although clearly linked, have been few in number and less severe in consequence when compared to troglitazone. We agree with current package labeling that requires baseline and then periodic measurement of liver enzymes in patients taking pioglitazone or rosiglitazone.