Bleeding Prevention in an Era of Expanding Combination Antithrombotic Therapies

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1 Bleeding Prevention in an Era of Expanding Combination Antithrombotic Therapies Muthiah Vaduganathan, MD MPH Cardiovascular Medicine Brigham and Women s Hospital December 8 th, 2017

2 Disclosures None

3 Key Points Attenuating bleeding is an important (adjunctive) treatment goal in the management of contemporary antithrombotic therapy Limited-duration PPI therapy decreases upper GI bleeding risk with select antithrombotic regimens Lowest doses for the shortest duration clinically indicated should be maintained

4 Changing Landscape of Antithrombotic Therapies GARFIELD-AF ~40,000 pts with newly-diagnosed AF Prospectively enrolled from 2010 to 2015 Non-VKA OACs 4% to 37% AP Monotherapy 30% to 17% Camm AJ et al. Heart 2016

5 Intensity of Antithrombotic Therapy: Bleeding Denmark ~120,000 patients discharged after first hospitalization for AF >10% fatal or nonfatal bleeding over 3.3 years Hansen ML Arch Intern Med 2010

6 Bleeding Linked to Excess Mortality 30-Day Mortality after Bleeding (%) GUSTO TIMI ACUITY BARC Transfusion CHAMPION Trials >25,000 patients undergoing PCI 4 validated different scales Major bleeding within 48h (range <0.5% to >3.5%) Vaduganathan M EuroIntervention 2017

7 Prevention of Bleeding is Worthwhile Gibson CM N Engl J Med 2016

8 Prevention of Bleeding is Worthwhile Gibson CM Circulation 2016 Bhatt DL Circulation 2016 (editorial)

9 COGENT: Effect of PPI on Composite GI Events Probability of Freedom from Primary GI Endpoint HR=0.34, 95% CI= P<0.001 Omeprazole Placebo No. at Risk Time (Days) Placebo Omeprazole Bhatt DL N Engl J Med 2010

10 COGENT: Effect of PPI on Composite CV Events Probability of Freedom from Primary Cardiovascular Endpoint HR=0.99, 95% CI= P=0.98 Omeprazole Placebo No. at Risk Time (Days) Placebo Omeprazole Bhatt DL N Engl J Med 2010

11 Do PPIs Work with Oral Anticoagulation? Flack KF Clin Gastroenterol Hepatol 2017 Vaduganathan M and Bhatt DL Clin Gastroenterol Hepatol 2017 (editorial)

12 COMPASS: Ongoing PPI Randomization Partial Factorial Design (n=17,598) Bosch J Can J Cardiol 2017

13 COMPASS: Ongoing PPI Randomization Specific Collection of Safety Endpoints Gastric atrophy Pneumonia Clostridium difficile infections Other enteric infections Bone fractures New diagnosis since randomization of: Chronic kidney disease Diabetes Chronic obstructive lung disease Dementia Bosch J Can J Cardiol 2017

14 Time Course of Bleeding After Acute MI or PCI Denmark National Registries ~11,000 patients with AF admitted for MI or PCI Lamberts M Circulation 2012

15 Clinical Prediction Rules to Guide Ongoing Need for Gastroprotection Yeh RW JAMA 2016

16 Algorithm to Assess GI Risk With Antithrombotic Therapy Test for H pylori; treat if infected Yes History of ulcer complication History of ulcer disease (nonbleeding) Prior GI bleeding Dual antiplatelet therapy Concomitant anticoagulant More than one risk factor: Aged 60 years or more Corticosteroid use Dyspepsia or GERD symptoms Yes No Yes PPI Bhatt DL Circulation 2008

17 Dose Matters: Low-Dose Aspirin CURRENT-OASIS 7 NEJM 2010

18 Dose Matters: Low-Dose Aspirin Target Enrollment 20,000 Jones WS JACC 2016

19 COGENT: PPI Benefit Even with Low-Dose Aspirin 34% >100mg daily 66% 100mg daily Composite Upper GI Events at 6mo: 1.2% (PPI) vs. 3.1% (placebo) Number Needed to Treat is 52 Vaduganathan M JACC 2016

20 Gastroprotective Strategies Use of PPIs for at least 6 months appears to be safe and effective with DAPT in reducing major upper GI bleeding COMPASS is evaluating the utility of PPIs in the setting of OAC Limit NSAIDs Maintain the lowest doses for the shortest duration clinically indicated

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22 Flack KF Clin Gastroenterol Hepatol 2017 Vaduganathan M and Bhatt DL Clin Gastroenterol Hepatol 2017 (editorial) Important of Endoscopic Interrogation after GI Bleeding RE-LY trial Source documents of initial endoscopic interrogation of all major GI bleeding events were re-examined (n=595) 8% were related to GI malignancies (80% colorectal cancer) Bleeding in these patients occurred sooner after anticoagulant exposure, persisted for a longer duration

23 Can We Omit Aspirin in Secondary Prevention Regimens? n=601,527; Swedish Nationwide, Population-Based Sundstrom J Circulation 2017