Gastrointestinal bleeding associated with myocardial infarction

Gastrointestinal bleeding associated with myocardial infarction: 

Gastrointestinal bleeding associated with myocardial infarction Sarayuth Eiamsa-ard , M.D. October 25 th , 2011

Overview: 

Overview EBM : Antiplatelet use  ↓CV events  ↑GI bleeding (upper or lower) ASA : mucosal break, diminished gastric mucosal blood flow (mediated byTXA2) Thienopyridine : no mucosal break but aggravated mucosal lesion healing & bleeding

Overview: 

Overview Deal with UGIB in AMI, clinical scinario UGIB  AMI AMI  UGIB before/after PCI UGIB without AMI but transient ischemic pattern from ECG

INCIDENCE OF GI BLEEDING IN AMI: 

INCIDENCE OF GI BLEEDING IN AMI Incidence vary from 0.5 - 2.3%

UGIB affect to morbidity & Mortality of AMI?: 

UGIB affect to morbidity & Mortality of AMI?

30 day ischemic event rate: 

30 day ischemic event rate ACUITY trial, Nikolsky et al, JACC 2009; 54(14) : 1293-302 GIB was strongly associated with 30-day all-cause mortality = 4.87 [2.61 -9.08], p 0.0001) cardiac mortality = 5.35 [2.71 -10.59], p 0.0001), composite ischemia = 1.94 [1.14 to 3.30], p 0.014), Multivariates analysis for HR

1 yr ischemic event rate: 

1 yr ischemic event rate ACUITY trial, Nikolsky et al, JACC 2009; 54(14) : 1293-302 Multivariates analysis for HR all-cause mortality = 3.97 [2.64 -5.99], p 0.0001 cardiac mortality = 3.77 [ 2.14 -6.63], p 0.0001 myocardial infarction = 1.74 [ 1.01- 3.02], p 0.047 composite ischemia = 1.90 [1.37 -2.64], p 0.0001 “Patients who experienced GIB had significantly higher rates of stent thrombosis compared with patients without GIB (5.8% vs. 2.4%, p 0.009)”

Anemia from UGIB result in myocardial ischemia?: 

Anemia from UGIB result in myocardial ischemia?

Slide 9: 

Fabio B et al, AJM 2005 ; 118 : 548-51

Sympathetic stimulation: 

Sympathetic stimulation Association between UGIB and Myocardial Ischemia

Antiplatelet Rx in AMI result in UGIB: 

Antiplatelet Rx in AMI result in UGIB

Risk GI complication of ASA alone: 

Risk GI complication of ASA alone The risk of GI bleeding was dose related: OD 2.3 for 75 mg/d 3.2 for 150 mg/d 3.9 for 300 mg/d . as low as 10 mg/d can significantly decrease the gastric mucosal prostaglandin level and cause gastric erosions OD 1.7 for all (low + high dose) ASA dose

Risk GI complication of ASA alone: 

Risk GI complication of ASA alone During 4-year study in UK-TIA -Mild dyspepsia (31%) -Life-threatening bleeding and perforation (3%) Plain , enteric-coated, or buffed aspirin did not differ

Risk GI complication of clopidogrel alone: 

Risk GI complication of clopidogrel alone In a retrospective analysis , the frequency of GI bleeding in a high-risk population with prior peptic ulcer disease was 12 % CAPRIE trial : Clopidogrel 0.5% vs ASA 0.7% P 0.07

Risk GI complication of DAPT: 

Risk GI complication of DAPT Overt GI bleeding 1.3% in first 30 days CURE study, risk of bleeding increases with increasing dose of aspirin with or without clopidogrel . At the highest dose of aspirin (200 mg) given with placebo, bleeding = 3.7% vs 3.0% aspirin in the lowest-dose (100 mg) group GI bleeding risk : DAPT > {ASA ≈ Clopidogrel } Circulation March 28, 2006

Incidence, predictors, and outcomes of gastrointestinal bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel.: 

Incidence, predictors, and outcomes of gastrointestinal bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel . Case-control study, N=1857, at Albert Einstein Medical Center A ll patients who had DES implanted between May 2003 and April 2007. R ate of GI bleeding = 2.7% Mean age70.9yr in Bleeding gr vs 66.5 yr in control gr P<0.05 Multivariate analysis : J Clin Gastroenterol . 2011 ;45(5):410-4.

Incidence, predictors, and outcomes of gastrointestinal bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel.: 

Incidence, predictors, and outcomes of gastrointestinal bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel . Multivariate analysis : - Hx prior GI bleeding : ↑ risk - Statin use : protective, ↓ risk 30-day MR in the GI bleeding and control groups was 3.7% vs 0% (P<0.01) 1 year the MR was 18.9% and 0%, (P<0.001). J Clin Gastroenterol . 2011 ;45(5):410-4.

Predictors of inc. risk of GIB: 

Predictors of inc. risk of GIB VALLIANT study

Rockall risk scoring system: 

Rockall risk scoring system <3 good prognosis >8 high mortality risk Gut 1996 ; 38 (3): 316–21.

EGD before cardiac catheterization in AMI? : 

EGD before cardiac catheterization in AMI ?

Upper Endoscopy in Patients with Acute Myocardial Infarction and Upper Gastrointestinal Bleeding: Results of a Decision Analysis : 

Upper Endoscopy in Patients with Acute Myocardial Infarction and Upper Gastrointestinal Bleeding: Results of a Decision Analysis EGD prior to CAG (EGD strategy) vs CAG without EGD (CATH strategy) ========================================================= Overt UGIB : Death in the EGD << CATH strategy (97 deaths vs 600 deaths/10,000) ↓non-fatal complications in the EGD >> CATH strategy (EGD 1,271 vs CATH 6,000/10,000 patients) Occult blood loss Death in the EGD >> CATH strategy (59 deaths vs 16 deaths per 10,000) ↑non-fatal complications in the EGD >> CATH strategy (EGD 888 vs CATH 160 per 10,000) ========================================================= Patrick Y et al, Dig Dis Sci. 2009 April ; 54(4): 701–711

UGIB Rx result in poor CVs outcomes?: 

UGIB Rx result in poor CVs outcomes? PPI vs H2RA?

Clopidogrel: 

Clopidogrel CYPs : 2C19 & 3A4 CYPs : 2C19 & 3A4 Esterase SR26334 = inactive form = active form PPI

PPIs vs Theinopyridine: 

PPIs vs Theinopyridine All PPIs are metabolized by 2C19, some by 3A4 Omeprazole : highest affinity for 2C19 Pantoprazole : lowest affinity for 2C19 “ Poor metabolizer ” => 2C19*2,*3,*4 (1/2 Asian, ¼ caucasian , ¼ African american ) ↓Platelet inhibition but ↑acid suppression & serum gastrin level

Pharmacodynamic evidence : PPIs vs Clopidogrel: 

Pharmacodynamic evidence : PPIs vs Clopidogrel OCLA study,

Pharmacodynamic evidence : PPIs vs Clopidogrel: 

Pharmacodynamic evidence : PPIs vs Clopidogrel PACA study, Cuisset T et al, JACC 2009; 54 : 1149-53

Clinical evidence of Clopidogrel vs PPIs: 

Clinical evidence of Clopidogrel vs PPIs COGENT trial, NEJM 2010

Clinical evidence of Clopidogrel vs PPIs: 

Clinical evidence of Clopidogrel vs PPIs COGENT trial, NEJM 2010

Clinical evidence of Clopidogrel vs PPIs: 

Clinical evidence of Clopidogrel vs PPIs COGENT trial, NEJM 2010

AHA 2010 focused update: 

AHA 2010 focused update Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both CV and GI complications

AHA 2010 focused update: 

AHA 2010 focused update Patients with prior GI bleeding are at highest risk for recurrent bleeding on antiplatelet therapy. Other clinical characteristics that increase the risk of GI bleeding include advanced age ; concurrent use of anticoagulants, steroids, or NSAIDs including aspirin ; and Helicobacter pylori infection.

AHA 2010 focused update: 

AHA 2010 focused update Use of a PPI or histamine H2 receptor antagonist (H2RA) reduces the risk of upper GI bleeding compared with no therapy. PPIs reduce upper GI bleeding to a greater degree than do H2RAs PPIs are appropriate in patients with multiple risk factors for GI bleeding who require antiplatelet therapy

AHA 2010 focused update: 

AHA 2010 focused update Routine use of either a PPI or an H2RA is not recommended for patients at lower risk of upper GI bleeding, who have much less potential to benefit from prophylactic therapy.

AHA 2010 focused update: 

AHA 2010 focused update The role of either pharmacogenomic testing or platelet function testing in managing therapy with thienopyridines and PPIs has not yet been established

Slide 36: 

……….Thank you……….