6/21/2016 2015 (and early 2016) How to make this talk…. The Year in Review Areas Searched No conflicts of interest • Medline • ACP Journal Club • Residency Journal Clubs • Faculty Suggestion • Practical, Applicable, Interesting • Whatever is not being covered elsewhere…. Afib, GIB and Warfarin- Topics! dangerous brew 1- Therapeutics A 75 year old woman with hypertension and diabetes arrives a week -Afib, GIB and Warfarin- dangerous brew after being sent home after a three day hospitalization after having a upper GIB from a gastric ulcer. Biopsy pathology was benign and her -PPI’s- well tolerated? H.Pylori testing was negative. She has longstanding atrial fibrillation and was taking warfarin which was stopped upon her admission. She 2- Screening Update feels well and wonders if she should restart her anticoagulation. You recommend which of the following: - The dreaded AAA 57% A. Treat with clopidogrel monotherapy 3- When to refer to ortho B. Treat H. Pylori infection 26% 3a- Meniscal tears C. Restart warfarin for INR of 2-3 15% D. Change to a novel oral anticoagulant 3b- Knee replacements 2% 0% E. Reconsider anticoagulation a month after her bleed n . . . 4- Post-op analgesia o . . . . . i o a . i . . c t t e R l a e l N a u l n f r r I o g g i r a o i o e l o d r f i o v c p l n o t i o y i n n P r a c l a a H . r f r h a o e t t t d i a w w e s i e t g n t r r n a T a o e t a c s h e r e C R T R 1
6/21/2016 Stroke Prevention in A. Fib-Rx Meta-analysis Data – 9874 participants, 16 trials 1. Warfarin vs. Placebo � 62-68% RRR INR 2-3 - Absolute risk bleeding 0.3%/year - Reduction of all cause mortality 26% (ARR 1.6%/Year) 2. Aspirin vs. Placebo � 21-25% RRR ANY Dose - Common disorder, increases with age - Absolute risk bleeding 0.2%/Year - AR% increases dramatically with age - No overall reduction of mortality - Circulation 2010: 103:162-182 - Our patient- 75, DM, HTN WHEN/IF Restart anticoagulation? - CHADS2 = 3 - ~6-8%/year stroke Annals of Int. Medicine Vol. 131, No. 7 October 5, 1999 Mortality after Outcomes: 59% GIB with Afib + 61% -Mortality RRR RRR anticoagulation RRR 61% HR=0.39- Warfarin -Thrombosis (0.76- antiplatelet - Post-d/c cohort RRR 59% alone) - 4600 Danes, X=78yo, 45% women Harms: - f/u started 90 days post discharge -Major Bleed - Two years follow-up RRI 37% 37% 34% - 49% mortality - 2 nd GIB RRI RRI - All-cause mortality RRI 34% -Staerk. BMJ -Staerk. BMJ 2015;351:h5876 2015;351:h5876 2
6/21/2016 Survival analysis showing 1-year mortality Timing of Restarting Anticoagulation stratified by duration of interruption of warfarin -Findings similar 1.18 RRI recurrent GIB P=0.47 33% mortality RRR Mortality Recurrent GIB 29% thrombosis RRR Retrospective Cohort 1329 pts - Increased GIB risk <7days - Southeast Michigan - Increased Death or - 2005-2010 Thromboembolism >30 days - X=76 years - 45% women - Recommend 7-21 days - Anticoag 49% restarted - Controlled for chads/hasbled Thromoboembolism Quereshi et al. AJC, Volume 113, Issue 4, 2014, 662–668 Quereshi et al. AJC, Volume 113, Issue 4, 2014, 662–668 Anticoagulation on Discharge Anticoagulation after UGIB • Mortality Benefit to restarting! • 7-15 days seems to be sweet-spot No Statistical • Some increase to bleeding- carefully Difference- council and ensure INR in range BUT power? • Case resolution: 76 yo woman 10 days post-UGIB. Restart warfarin for INR=2-3 Sengupta, Am J Gastroenterol 2015; 110:328–335 with close follow-up Prospective Cohort restarted on anticoagulation on discharge - 90 day outcomes, 197 patients 3
6/21/2016 Risk of C. Case #2 Dif with 60 year old woman is concerned about her medications. PPI Use She has heard that her chronic omeprazole that she has taken for several years for her heartburn can cause other medical problems. You say she is right and tell her PPIs • OR = 1.74 are associated with the following complications except: increase in 44% CID with PPI A. Increased risk for C. Dificile infection B. Renal insufficiency 19% C. Drug interaction leading to Clopidogrel 14% • Heterogeneity failure 8% 8% 6% D. Dementia • Consistency E. All of the above Also CAP, B12 deficiency, fracture risk Dementia Increased risk for C. Difici.. Renal insufficiency All of the above A and C only Drug interaction leading .. across studies F. A and C only Kwok et al. Am J. Gastro 2012;107:1011-19 Retrospective cohort study of 8205 VA patients with ACS 5244 on plavix and PPI/2961 without PPI (VA formulary=omeprazole) PPI and Renal Damage? Ho, P. M. et al. JAMA 2009;301:937-944. NNH=11 !! • Chronic kidney disease (CKD) affects approximately 13.6% of adults in United States • Increased risk of death and cardiovascular events • PPIs amongst most commonly used drugs worldwide Re-ACS or death = 29.8% PPI – 40% to 60% no appropriate indication = 20.8% no PPI • Large database study examines relationship • Atherosclerosis Risk in Communities ( ARIC ) prospective cohort study 10,482 participants, 63.0 yo, 56% women • Replication Cohort 248,751 patients with an outpatient eGFR of at least 60 Clopidogrel activated by CYP2C19 – Lazarus et al. JAMA Intern Med. 2016;176(2) Enzyme metabolized/inhibited by omeprazole 4
6/21/2016 Rapid Rise of PPI Use Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease Up to 25% of American adults >55 use PPI’s!!!! Prevalence of Proton Pump Inhibitor (PPI) Ever Use Table Title: Over Time in the Atherosclerosis Risk in Communities Study Lazarus et al. JAMA Intern Med. 2016;176(2). Lazarus et al. JAMA Intern Med. 2016;176(2) Proton Pump Inhibitor Use and the Risk PPI and Dementia of Incident Chronic Kidney Disease • German Study on Aging, Cognition and Dementia in Primary Care Patients • 73K participants free of dementia • X=83 yo, 74% women • Community dwelling at enrollment • q18 month follow up • Memory testing JAMA Intern Med. 2016;176(2). doi:10.1001/jamainternmed.2015.7193 5
6/21/2016 From: Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data From: Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis Analysis JAMA Neurol. 2016;73(4):410-416. doi:10.1001/jamaneurol.2015.4791 hazard ratio 1.44 44% increase risk of dementia with PPI use over 6 years Figure Legend: Table Title: Dementia increase: Gomm et al. JAMA Neurol. 2016;73(4):410-416. 69% RRI 75-79, 49% RRI 80-84, 32% RRI >85 years Bottom Line: – Barrett ’ s or Erosive esophagitis, Hypergastrinemic • Long Term PPI Indications: states, Long term NSAIDS in high risk patients, DAPT – AGA recommends lowest shortest exposure possible • Re-evaluate: • Needs assessment for PPI- frequently • Try protocol Gastroenterol Hepatol (N Y). 2008 May; 4(5): 322–325 Ther Adv Gastroenterol. 2012;5(4):219-232. Anderson and Kotwani- reproduced with permission 6
6/21/2016 Case #3- Abdominal Aortic Aneurysm When talking about Abdominal Aortic Aneurysms • AAA >2.9 cm 6% at 65yo which of the following statements is true? – Increases 6%/decade A. Risk of rupture increases exponentially when – 90% smokers AAA measures >4.5cm 40% – Ehlers Danlos, Marfans 35% B. Smoking is the biggest risk factor for AAA – Familial (30%, 6%) C. Family history of AAA is not a risk factor 20% • Obvious risk=rupture D. Screening for AAA has no impact on disease specific mortality – 90% mortality! 5% E. All of the above are false 0% 9K deaths All of the above are false Risk of rupture increase... Screening for AAA has n... – 2-6% operative mortality Smoking is the biggest ri.. Family history of AAA is ... 1400-2800 deaths Aorta Rupture www.pennhealth.com/ int_rad/health_info/aaa.html When to repair a AAA?? Who to screen for AAA? • Poking a skunk… • Ultrasound Sn=95%, Sp=99% – CT- similar test characteristics, more dye • USPSTF – Male smoker 65-75 years- Grade B (fair data) – Family Hx, Erhlers Danlos, Marfans – AAA mortality screened- OR = 0.57 – Non-smoking Males- Grade C- no rec. – Females 65-75 years- Grade D • OR = 0.98 mortality.. Only one trial Surgical benefit>>Surgical risk when aneurysm is 5.5-6cm • Fleming et al. Ann Intern Med. 2005 Feb 1;142(3):203-11. >1cm expansion/12mos Powell et al. NEJM 348;19, May 8, 2003 7
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