The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

/pdf/the-2018-european-heart-rhythm-association-practical-guide-4iood3iocz.pdf

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

The current manuscript is an update of the original Practical Guide, published in June 2013[Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-51; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-106]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group defined what needs to be considered as 'non-valvular AF' and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 15 topics are (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring adherence of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (xi) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; and (xv) NOACs vs. VKAs in AF patients with a malignancy. Additional information and downloads of the text and anticoagulation cards in >16 languages can be found on an European Heart Rhythm Association web site (www.NOACforAF.eu).

https://www.anmco.it/uploads/u_cms/media/2015/9/9b148683e3980189a9acab2c9a0ea6dd.pdf

Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.

New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients will have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group listed 15 topics of concrete clinical scenarios and formulated as practical answers as possible based on available evidence. The 15 topics are: (1) Practical start-up and follow-up scheme for patients on NOACs; (2) How to measure the anticoagulant effect of NOACs; (3) Drug–drug interactions and pharmacokinetics of NOACs; (4) Switching between anticoagulant regimens; (5) Ensuring compliance of NOAC intake; (6) How to deal with dosing errors; (7) Patients with chronic kidney disease; (8) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding? (9) Management of bleeding complications; (10) Patients undergoing a planned surgical intervention or ablation; (11) Patients undergoing an urgent surgical intervention; (12) Patients with AF and coronary artery disease; (13) Cardioversion in a NOAC-treated patient; (14) Patients presenting with acute stroke while on NOACs; (15) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming available at a rapid pace, an EHRA Web site with the latest updated information accompanies this text ([www.NOACforAF.eu][1]).

 [1]: http://www.NOACforAF.eu

/pdf/european-heart-rhythm-association-practical-guide-on-the-use-58ts9ic39r.pdf

European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation

Pd32-09 socioeconomic predictors of receiving a vaginal hysterectomy compared to open and laparoscopic/robotic approaches for treatment of apical prolapse: an analysis of over 38,000 women in the healthcare cost and utilization project (hcup)

Importance Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic kidney disease (CKD). Objective To quantify the association between PPI use and incident CKD in a population-based cohort. Design, Setting, and Participants In total, 10 482 participants in the Atherosclerosis Risk in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m 2 were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analyzed from May 2015 to October 2015. The findings were replicated in an administrative cohort of 248 751 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m 2 from the Geisinger Health System. Exposures Self-reported PPI use in the Atherosclerosis Risk in Communities study or an outpatient PPI prescription in the Geisinger Health System replication cohort. Histamine 2 (H 2 ) receptor antagonist use was considered a negative control and active comparator. Main Outcomes and Measures Incident CKD was defined using diagnostic codes at hospital discharge or death in the Atherosclerosis Risk in Communities Study, and by a sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m 2 in the Geisinger Health System replication cohort. Results Among 10 482 participants in the Atherosclerosis Risk in Communities study, the mean (SD) age was 63.0 (5.6) years, and 43.9% were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication. Proton pump inhibitor use was associated with incident CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% CI, 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55). The association persisted when baseline PPI users were compared directly with H 2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score–matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21). Conclusions and Relevance Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.

/pdf/proton-pump-inhibitor-use-and-the-risk-of-chronic-kidney-3xjboez5n4.pdf

Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease

Comprehensive Medication Therapy Management: Identifying and Resolving Drug-Related Issues in a Community Pharmacy

Proton pump inhibitors (PPI) are a widely-used class of drugs for the treatment of gastro-esophageal reflux disease and other acid-related disorders of the gastrointestinal tract. As a class, PPIs have demonstrated a favorable safety profile. However, case reports have suggested that this class of drugs may be linked to acute kidney injury, which may in turn lead to chronic injury or failure. The objective of this study was to determine if an association between PPIs and kidney failure exists and to estimate an effect size for the relationship between PPI use and renal disease. A nested case–control study was conducted in a privately insured population in a single Midwestern state including a total of 184,480 patients aged 18 years or older who were continuously enrolled with the insurer for at least 24 months between September 2002 and November 2005. Of the patients eligible for the study, 854 cases were identified as having at least two claims for an acute renal disease diagnosis. Cases were randomly matched with up to four controls (n = 3,289) based on age, gender, county of residence, and date of entry into the cohort. Patient demographic data, PPI use, illnesses, and medications associated with renal disease and a proxy for health status using pre-existing patient comorbidities were collected from inpatient, professional, and prescription claims data. Conditional logistic regression models were used to evaluate the association between renal disease and PPI use. Renal disease was positively associated with PPI use (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.27, 2.32, p < 0.001) even after controlling for potential confounding conditions. After removing patients with potential confounding disease states from the study population, the number of cases (195 of the 854) and controls (607) was lower, but the relationship between renal disease and PPI use remained consistent (OR 2.25, CI 1.09-4.62, p < 0.001). Patients with a renal disease diagnosis were twice as likely to have used a previous prescription for a PPI. Therefore, it is necessary for physicians to increase recognition of patient complaints or clinical manifestations of this potentially harmful event in order to prevent further injury.

/pdf/proton-pump-inhibitors-and-acute-kidney-injury-a-nested-case-xeau6gpyh9.pdf

Proton pump inhibitors and acute kidney injury: a nested case–control study

Study Objective. To evaluate the effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on mortality in patients with severe sepsis.



Design. Retrospective cohort study.



Setting. Intensive care unit (ICU) of an academic medical center.



Patients. One hundred eighty-eight patients aged 40 years or older with a diagnosis of severe sepsis and an ICU stay between January 1, 2005, and December 31, 2006.



Measurements and Main Results. Patient demographic data, statin use, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the time of sepsis diagnosis were collected from the patient database. We used a multivariable logistic regression model to evaluate the association between statin use and in-hospital all-cause mortality after controlling for age, sex, and severity of illness. Of the 188 patients who met our inclusion criteria, 60 (32%) had statin exposure. Patients receiving statins were similar in age, sex, and APACHE II scores to those not receiving statins. In the univariable comparison, the statin group had a 35% relative reduction in mortality compared with the nonstatin group (mortality rate 31.7% vs 48.4%, p=0.040). Most of the mortality reduction attributed to statins occurred in patients with APACHE II scores higher than 24 (mortality rate 32.3% vs 57.5%, p=0.031), with a minimal mortality difference in patients with APACHE II scores of 24 or lower (31% vs 36.4%, p=0.810). In the multivariable regression model, statin use had a protective effect (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.21-0.84, p=0.014), whereas increasing age (OR 1.03, 95% CI 1.01-1.06, p=0.013) and higher APACHE II score (OR 1.11, 95% CI 1.05-1.18, p=0.001) were associated with increased mortality.



Conclusion. The use of statins was associated with a protective effect in patients with severe sepsis, as demonstrated by a significant reduction in mortality compared with patients not receiving statins.

Reduction in mortality associated with statin therapy in patients with severe sepsis.

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.

Adherence and dosing frequency of common medications for cardiovascular patients

Objectives To examine the effectiveness of collaborative physician–community pharmacist programs to treat influenza-like illness (ILI) with respect to clinical outcomes and health care utilization. Design Prospective multicenter cohort study. Setting Fifty-five pharmacies in Michigan, Minnesota, and Nebraska. Patients Adult patients presenting to the pharmacy with ILI during the 2013–14 influenza season (October 1, 2013 to May 30, 2014). Intervention Pharmacists screened adult patients presenting with ILI, completed a brief physical assessment, performed a point-of-care rapid influenza diagnostic test (RIDT), and provided appropriate referral or treatment per an established collaborative practice agreement (CPA) with a licensed prescriber. Pharmacists followed-up with patients 24 to 48 hours after the encounter to assess patient status and possible need for further intervention. Main outcome measures Number of patients screened, tested, and treated for influenza. Results Of the 121 patients screened, 45 (37%) were excluded and referred to their primary care provider or an urgent care facility for management. Of the 75 patients (62%) eligible for participation, 8 (11%) had a positive RIDT and were managed according to the CPA. Of the patients tested, 34.6% had no primary care physician and 38.7% visited the pharmacy outside of normal office hours. Only 3% of patients reported feeling worse at follow-up. Conclusion This study describes a physician-pharmacist collaborative model for treating ILI. Using an evidence-based CPA, pharmacists were able to provide timely treatment to patients with and without influenza.

https://www.japha.org/article/S1544-3191(15)00009-6/pdf

Donald G. Klepser

Papers

Comprehensive Medication Therapy Management: Identifying and Resolving Drug-Related Issues in a Community Pharmacy

Proton pump inhibitors and acute kidney injury: a nested case–control study

Reduction in mortality associated with statin therapy in patients with severe sepsis.

Adherence and dosing frequency of common medications for cardiovascular patients

Effectiveness of a pharmacist-physician collaborative program to manage influenza-like illness