Clinicians and patients around the world have been intrigued by the concept of developing an oral anticoagulant with a broad therapeutic window and few drug and dietary interactions that can be administered at fixed doses with no or minimal monitoring. The recently approved oral direct thrombin inhibitor dabigatran, along with the emerging oral anti-factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have been developed to address many of the shortcomings of warfarin therapy. As warfarin is associated with extensive food and drug interactions, there is also a need to consider such interactions with the new oral anticoagulants. While to date few drug and dietary interactions have been reported with the new oral anticoagulants, it is still early in their development and clinical use cycle. Pharmacokinetic and pharmacodynamic profiles will have to be closely accounted for when determining the likelihood of a potential drug interaction prior to therapy initiation. As the list of drugs and supplements that interact with warfarin is continuously expanding, and the knowledge on drug interactions with the novel oral anticoagulants is still in its infancy, clinicians need to be vigilant when initiating any of these agents or when any changes in the patient's medication profile occur and perform a close screening for potential drug and dietary interactions. The objective of this paper is to give an update on drug and dietary interactions with warfarin and the novel oral anticoagulants, dabigatran, rivaroxaban, apixaban, and edoxaban.

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants.

Background: Atrial fibrillation (AF) increases the risk of stroke and direct oral anticoagulants (DOACs) are first-line agents for prevention. Gaps in the literature cause reluctance in prescribing DOACs for patients with renal dysfunction and/or extremes in body weight. Objective: To evaluate the impact body weight and renal function have on major and clinically relevant nonmajor (CRNM) bleeding events and ischemic strokes in AF patients receiving a DOAC. Methods: This retrospective cohort study included adults with nonvalvular atrial fibrillation (NVAF) or atrial flutter (AFL) receiving a DOAC ≥12 months. The primary outcome was a composite of major and CRNM bleeding events. Secondary outcomes included ischemic stroke and risk factors for bleeding events. Results: Of the 233 patients analyzed, 25 patients experienced a bleeding event. Patients who bled weighed 10 kg less ( P = 0.043) than those who did not and had a higher HASBLED score ( P = 0.003). Multivariate logistic regression identified weight ( P = 0.048), serum creatinine (SCr; P = 0.027), and HASBLED score ( P = 0.024) as the significant predictors for experiencing a bleed. Three patients experienced a stroke. Conclusion and Relevance: This study demonstrates an association between higher baseline SCr, elevated HASBLED score, and lower weight, with an increased risk of bleeding in patients with NVAF or AFL receiving a DOAC. These findings add to prescribing considerations when initiating DOACs. Closer monitoring is advised for patients with significant renal dysfunction and/or low body weight, even with renal dose adjustments.

Ivabradine lowers heart rate by inhibiting the hyperpolarization-activated current in pacemaker cells, and its use for the treatment of heart failure (HF) and ischemic heart disease (IHD) is well described. Ivabradine may be an attractive treatment option for other conditions for which a reduction in heart rate is desirable but less is known about its role in these settings. The primary objective was to perform a scoping review summarizing the literature evaluating novel uses for ivabradine other than HF and IHD in adults. PubMed and EMBASE were searched for articles for all dates through September 2019. Search strategies combined terms generic, commercial/trade, and international names for ivabradine. Manual search of references was also performed to identify additional articles. Studies were included if they were published in English, evaluated the efficacy of ivabradine for indications other than HF or IHD in patients aged 18 years or older, and the primary outcome included clinically relevant end points. Articles were screened first by title and abstract followed by full-text screening of the remaining articles. After removal of duplicates, 1807 records were screened for inclusion and 84 studies were included in this scoping review. Novel uses of ivabradine were reported for various tachyarrhythmias, valvular heart disease, premedication for coronary computed tomography angiography, perioperative risk reduction, sepsis with and without multi-organ dysfunction syndrome, cor pulmonale, reactive airway disease, and erectile dysfunction. This scoping review identified several potential novel uses for ivabradine in adults. This review may help to identify existing gaps where further research is needed to elucidate the role of ivabradine for indications beyond HF and IHD. KEY WORDS ivabradine, tachycardia, asthma, CT angiography, perioperative risk reduction, pulmonary hypertension, multi-organ dysfunction syndrome, valvular heart disease.

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tensive (HTN) patients. Methods: The study included adults (18 yrs. or older) HTN patients covered by commercial and Medicare Supplemental insurance in the Truven MarketScan database with an HTN diagnosis between October 2009 and December 2011. At least two filled prescriptions for Exforge HCT or two periods of minimum 15 days of concurrent use of amlodipine, valsartan and hydrochlorothiazide (FC cohort) were required. Patients were continuously enrolled at least 12 months before and 12 month after the index prescription and had valsartan initial dose of 160 or 320 mg/day. Adherence was measured with proportion of days covered (PDC) and medication possession ratio (MPR). Persistence was defined as no treatment gap greater than 30 days. Chi-Square tests and independent sample t-tests were used after adequate propensity score matching (PSM) (absolute standardized differences < 0.1) using demographics, comorbidities, pre-index health care utilization , pre-index costs and valsartan initial dose. Results: Exforge HCT patients (N= 9,221) had better unadjusted outcomes compared to FC patients (N= 1,884): higher MPR (81.6% vs 77.0%), PDC (70.0% vs 60.6%) and persistence (42.7% vs 23.6%) (all p< 0.0001). After risk-adjustment with PSM, Exforge HCT patients also exhibited better outcomes compared to FC patients: higher adherence (85.7% vs 77.0%), higher PDC (73.8% vs 60.6%) and persistence (46.8% vs 23.6%) (all p< 0.0001). More patients had MPR> 80% in the Exforge HCT cohort (72.9% vs 57.5%, p< 0.0001). ConClusions: Real-world data indicate that Exforge HCT is associated with improved adherence and persistence compared to amlodipine/ valsartan/hydrochlorothiazide FC. These data should be considered by stakeholders engaged with optimizing outcomes of HTN patients.objeCtives: Diet and exercise along with the pharmacological treatment are required for an adequate control of blood pressure among hypertensive patients. The aim of this study is to identify the drug treatments prescribed and attitudes and factors associated with the adherence to these indications. Methods: Sociodemographic and drug treatment information of hypertensive patients aged 20 years and older was obtained from an institutional health survey, Encoprevenimss 2010. Statistical relationships between socio-demographic variables and adherence to diet and exercise were tested. Two binary logistic regression models were constructed to measure the impact of personal attitudes and social and demographic variables on the decision of the patient whether to follow these recommendations. Results: Captopril was the leading prescribed drug (31.63%), followed by enalapril (22.45%) and metopropol (13.58%). The main combination of drugs recommended was captopril with metopropol. Additionally to the pharmacological treatment, 32.47% and 23.59% of the patients reported full adherence to the diet and exercise indications respectively, 24.04% and 15.78% partially complied and 11.03% and 16.63% did not comply. At 5% level of significance, statistically significant relationship...

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Dabigatran has demonstrated similar efficacy and safety to enoxaparin for VTE prevention in patients undergoing hip and knee arthroplasty, and to warfarin for the treatment of VTE. Dabigatran (110 mg) is noninferior and dabigatran (150 mg) is superior to warfarin for stroke prevention in patients with nonvalvular AF, with a lower rate of intracranial hemorrhage reported at both doses. Apixaban, rivaroxaban and edoxaban provide alternate anticoagulant options to dabigatran. While there are many similarities, there are also significant differences to consider in agent selection based on patient-specific characteristics.