December 20, 2017 Edited by: Gregory K. Perry, PharmD, BCPS-AQID

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1 VOLUME THREE; ISSUE 11 December 20, 2017 Edited by: Gregory K. Perry, PharmD, BCPS-AQID

2 InPHARMation Pharmacy and Therapeutics Committee Update December 20 th, 2017 Meeting The Pharmacy and Therapeutics Committee at Hendrick Medical Center is a Medical Staff Committee that meets the fourth Wednesday of each month with five physicians and one pharmacist serving as voting members. P and T is Medical Staff Committee. The current Chair of P and T is Kelly Palmere, M.D. (formerly Sunderland). The P and T meeting held on December 20 th, 2017 did not have any action items. Beginning in January of 2018 Charles W. Fuller, M.D. will assume the position of Chairman for the P and T committee at Hendrick Medical Center. Dr. Fuller will replace the outgoing Chair, Dr. Kelly Palmere. Dr. Palmere served the committee well and we are grateful for her time and service. Antimicrobial Stewardship Committee (AMS) Update: Utilization Reports through November 2017 Inpatient use of antibiotics at Hendrick Medical Center has increased in each of the last three months. Our utilization is now at days of therapy (at least one dose of an anti-infective administered) per 1000 patient days. Table 1 is the Hendrick Medical Center SAAR numbers representing the past 4 months of utilization that is reported to the CDC/NHSN. November correlated with an increase in antimicrobial utilization with significant difference which potentially indicates the overuse of antimicrobials. If you would like to see or discuss the NHSN/CDC numbers in detail please reach out to Greg Perry at gperry@hendrickhealth.org. Always remember the premise of Antimicrobial Stewardship using the three R s. R = Right Drug. R = Right Dose. R = Right Duration of Therapy. Chart One 1

3 Table One: NHSN/CDC Data 2

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7 Antimicrobial Stewardship Education Gregory K. Perry, PharmD, BCPS-AQID Therapeutically Speaking by Kristy Walker, PharmD, Critical Care Pharmacist In a 2013 nationwide report, a little less than 600,000 percutaneous coronary interventions (PCIs) were performed. 1 Additionally, about 10% of patients undergoing a PCI are already diagnosed with atrial fibrillation. 2 Current guidelines recommend treating these patients with triple therapy, which is defined as warfarin and aspirin along with an antiplatelet agent to reduce the risk of complications such as stroke. 3 This recommendation does come with the potential adverse risk of bleeding. The challenge then is to strike a balance between an increased risk for bleeding events and ischemic or thrombotic events. 4 The WOEST trial compared clopidogrel and an anticoagulant to triple therapy and showed removing aspirin did not affect the thrombotic risk but did decrease adverse bleeding events. 5 Similar findings were reported in rivaroxaban studied in PIONEER AF-PCI and clopidogrel monotherapy. 6 The RE-DUAL PCI trial was designed to test whether a dual antithrombotic therapy consisting of removing aspirin and replacing warfarin with dabigatran could safely reduce bleeding events without increasing risk of stroke. 7 This was a randomized, parallel, stratified trial. It was designed and led by an executive steering committee and the sponsor, Boehringer Ingeheim, the manufacturer of dabigatran, in collaboration with an international steering committee. The trial included 2,725 patients across the world with atrial fibrillation who had undergone stenting. Patients included were with stable or unstable coronary artery disease undergoing coronary revascularization and with nonvalvular atrial fibrillation. Major points of exclusion were patients with presence of bioprosthetic or mechanical heart valve, severe renal insufficiency (defined here as CrCl <30 ml/min). Patients were randomized to receive either the triple therapy with warfarin or the dabigatran double therapy, with two regimens tested using either 110 or 150 mg of dabigatran taken twice daily. The reason for varying dosage of dabigatran was patients outside of the United States were not eligible for dabigatran 150 mg dose. A noninferiority margin of 1.38 was used to determine the risk of bleeding and thromboembolic events, the cut-off being derived from literature the Food and Drug Administration used for registration trials of non-vitamin K antagonist anticoagulants. Patients were followed up for a minimum of 6 months. Characteristics of these patients included a mean patient age of 72 years, 26% being female, 37% diagnosed with diabetes, 52% had acute coronary syndrome, and 82% received a drug eluting stent. Approximately 10% received ticagrelor as the ADP receptor antagonist, the remaining patients receiving clopidogrel. Overall, 26.9% of patients on the warfarin triple-therapy experienced bleeding, compared to 15.4% of patients on double therapy with the 110 mg dose of dabigatran (p for noninferiority < 0.001, p for superiority < 0.001). 20.2% of patients on double therapy with the 150 mg dabigatran dose experienced bleeding compared to 25.7% of the corresponding warfarin triple therapy cohort (p for noninferiority < 0.001). This gives number needed to treat (NNT) for the 110 mg dabigatran dose group is 9 (cannot calculate the NNT for the 150 mg group as they did not meet superiority). Stroke and other serious adverse advents did not differ in either group. Other recent studies have also suggested that dropping aspirin from triple therapy may help to decrease bleeding events. RE-DUAL PCI study offers more statistical power than these previous studies. However, some drawbacks include dabigatran cannot be used in patients with severe renal dysfunction or in patients with valvular atrial fibrillation. Some limitations of the trial include patients were titrated with warfarin to a goal of 2-3, but no information was provided on how many patients were in therapeutic range. As a reference, according the data registry from ORBIT-AF, only 59% of the measured INR values were therapeutic (i.e. 2.0 and 3.0). 8 This would have been helpful to include in RE-DUAL PCI, so as to compare to national average of therapeutic warfarin. The 6

8 number of patients on proton pump inhibitors is not accounted for either in the study groups. Proton pump inhibitors are chosen in patients with triple therapy, especially with a past medical history of bleeding, to prevent major gastrointestinal bleeding events. In conclusion, treatment strategies should be individualized, with consideration of the risk of stroke, the risk and consequences of stent thrombosis, and bleeding risk. Currently, the standard guideline-directed regimen is triple therapy. RE-DUAL PCI trial is the largest trial to date with the most statistical power demonstrating an alternative regimen of removing aspirin and replacing warfarin with dabigatran 150 mg that is no worse than triple therapy. References: 1. Stuntz M, Palak A. Recent Trends in Percutaneous Coronary Intervention Volume in the United States. Value in Health. 2016;19(7):A641. doi: /j.jval Sutton N, Seth M, Ruwende C, Gurm H. Outcomes of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention. Journal of the American College of Cardiology. 2016;68(9): doi: /j.jacc You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e531S-e575S. 4. Fluschnik N, Becher P, Schnabel R, Blankenberg S, Westermann D. Anticoagulation strategies in patients with atrial fibrillation after PCI or with ACS. Herz doi: /s z. 5. Dewilde W, Oirbans T, Verheugt F et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. The Lancet. 2013;381(9872): doi: /s (12) Gibson C, Mehran R, Bode C et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. New England Journal of Medicine. 2016;375(25): doi: /nejmoa Cannon C, Gropper S, Bhatt D et al. Design and Rationale of the RE-DUAL PCI Trial: A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrilla. Clinical Cardiology. 2016;39(10): doi: /clc Pokorney S, Simon D, Thomas L et al. Patients time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry. American Heart Journal. 2015;170(1): e1. doi: /j.ahj Test Your Knowledge: A 6-year-old boy arrives with his mother at the pediatric emergency room complaining of pain in his right hand where a stray cat had bitten him the previous day. The mother had washed the wound with soap and water but noticed the area around the wound was red by that evening. The next morning, the boy awoke crying and complaining of pain in his hand. The physical examination reveals that he has an oral temperature of 39 C. The skin over the wound is erythematous. A serosanguineous drop is expressed from the puncture wound and submitted for a culture and Gram stain. The microbiology laboratory reports abundant growth of gram-negative coccobacilli. The 7

9 organisms were facultatively anaerobic but failed to grow on MacConkey agar. Which organism is most likely responsible for this infection? A. Capnocytophaga B. Eikenella C. Escherichia D. Fusobacterium E. Pasteurella Test Your Knowledge Answer: P. multocida is commonly associated with animal bite wounds, particularly cat bites. Cats can inflict a deep puncture wound that is difficult to clean adequately. P. multocida is a facultative anaerobe that grows on blood and chocolate agars but generally grows poorly or not at all on MacConkey agar. Capnocytophaga organisms, particularly C. canimorsus and C. cynodegmi, are associated with animal bites; however, these bacteria are long, thin gram-negative rods that grow best in a microaerophilic atmosphere. Eikenella is a gram-negative coccobacillus associated with human bite wounds but not animal bites. The Gram stain morphology and poor growth on MacConkey agar are inconsistent with Escherichia. Fusobacterium is a strict anaerobe. 8