980 Letters JACC VOL. 68, NO.

9, 2016
AUGUST 30, 2016:977–83

a similarly elevated absolute risk of the primary REFERENCES

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In conclusion, in a population of patients with T2D stable ischemic heart disease and diabetes. N Engl J Med 2015;373:610–20.

and stable ischemic heart disease, we found that the 2. Gore MO, Seliger SL, Defilippi CR, et al. Age- and sex-dependent upper
lower concentrations of hsTnT observed in women reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll
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3. Omland T, de Lemos JA, Holmen OL, et al. Impact of sex on the prognostic
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may be appropriate to identify women at elevated
risk of major cardiovascular events. High Risk of
Gastrointestinal Bleeding
*Brendan M. Everett, MD, MPH
Maria Mori Brooks, PhD on Dual Antiplatelet
Helen E.A. Vlachos, MS Treatment
Bernard R. Chaitman, MD
Robert L. Frye, MD
Deepak L. Bhatt, MD, MPH I read with interest the study by Vaduganathan et al.
for the BARI 2D Study Group (1) regarding the protective effect of proton pump
*Division of Preventive Medicine inhibitors compared with placebo on gastrointestinal
Harvard Medical School events in patients using dual antiplatelet therapy.
Brigham and Women’s Hospital One of my concerns about this well-designed study is
900 Commonwealth Avenue the lack of reporting of eradication treatment for
Boston, Massachusetts 02115 Helicobacter pylori infection in the study population
E-mail: beverett@partners.org who were found to be positive for H. pylori. It is well-
http://dx.doi.org/10.1016/j.jacc.2016.06.013 known that the most important risk factor for
Please note: This research was supported by an investigator-initiated research gastrointestinal bleeding under aspirin therapy in-
grant from Roche Diagnostics (Indianapolis, Indiana) to Dr. Everett, as well as by
cludes a history of a gastrointestinal bleeding or ulcer
grants (U01HL061744, U01HL061746, U01HL061748, U01HL063804, and
R21HL121495) from the National Heart, Lung, and Blood Institute and the Na- and H. pylori infection (2). It is also well-known that
tional Institute of Diabetes and Digestive and Kidney Diseases of the National
H. pylori eradication improves peptic ulcer healing
Institutes of Health. The sponsors of the study had no role in the design and
conduct of the study; the collection, management, analysis, or interpretation of and reduces the risk of ulcer bleeding recurrence (3).
the data; the preparation, review, or approval of the manuscript; or the decision
Current European and United States guidelines
to submit the manuscript for publication. Dr. Everett has received investigator-
initiated research awards from Roche Diagnostics and Novartis; and serves as a recommend to test and treat H. pylori infection in
consultant/advisor for Roche Diagnostics and Abbott Diagnostics. Dr. Brooks has
users of low-dose aspirin who are at risk of ulcer
received grant support from Gilead Sciences. Dr. Chaitman has received fees for
serving on clinical events committees from Merck, Eli Lilly, Novo Nordisk, and bleeding (4,5). Notable is the frequency of H. pylori
Roche; and fees for serving on data safety monitoring boards from Pfizer and
antibody positivity (55% and 34%) and gastrointes-
Sanofi. Dr. Bhatt has served on the advisory board for Cardax, Elsevier Practice
Update Cardiology, Medscape Cardiology, Regado Biosciences; served on the tinal bleeding or ulcer (3.8% and 5%) in low- and
board of directors for Boston VA Research Institute, Society of Cardiovascular
high-dose aspirin groups who were under placebo in
Patient Care; has served as a chair for the American Heart Association Quality
Oversight Committee; served on the data monitoring committees for Duke this study. Thus, using double antiplatelet treatment
Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic,
without eradication of H. pylori or concomitant pro-
Population Health Research Institute; has received honoraria from the American
College of Cardiology (Senior Associate Editor, Clinical Trials and News, ton pump inhibitor therapy in such high-risk pop-
ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke
ulations may increase the risk of peptic ulcer
Clinical Research Institute (clinical trial steering committees), Harvard Clinical
Research Institute (clinical trial steering committee), HMP Communications bleeding.
(Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College
of Cardiology (Guest Editor; Associate Editor), Population Health Research
Institute (clinical trial steering committee), Slack Publications (Chief Medical
*Kadri Atay, MD
Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care
*Department of Gastroenterology
(Secretary/Treasurer), WebMD (CME steering committees); has served as Dep-
uty Editor for Clinical Cardiology; Vice-Chair for NCDR-ACTION Registry Steer- Istanbul University
ing Committee; chair for VA CART Research and Publications Committee;
Cerrahpasa School of Medicine
received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers
Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, PB34098
Roche, Sanofi, The Medicines Company; received royalties from Elsevier (Edi-
Fatih, Istanbul, Turkey
tor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease);
has served as a site co-investigator for Biotronik, Boston Scientific, and St. Jude E-mail: dr_kadrii@yahoo.com
Medical; has served as a trustee for the American College of Cardiology; and has
http://dx.doi.org/10.1016/j.jacc.2016.05.079
performed unfunded research for FlowCo, PLx Pharma, and Takeda. Ms. Vla-
chos and Dr. Frye have reported that they have no relationships relevant to the Please note: Dr. Atay has reported that he has no relationships relevant to the
contents of this paper to disclose. contents of this paper to disclose.
JACC VOL. 68, NO. 9, 2016
AUGUST 30, 2016:977–83
REFERENCES
1. Vaduganathan M, Bhatt DL, Cryer BL, et al. Proton-pump inhibitors reduce
gastrointestinal events regardless of aspirin dose in patients requiring dual
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2. Lanas A, Fuentes J, Benito R, Serrano P, Bajador E, Sainz R. Helicobacter
pylori increases the risk of upper gastrointestinal bleeding in patients taking
low-dose aspirin. Aliment Pharmacol Ther 2002;16:779–86.
3. Leodolter A, Kulig M, Brasch H, Meyer-Sabellek W, Willich SN,
Malfertheiner P. A meta-analysis comparing eradication, healing and relapse
rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer.
Aliment Pharmacol Ther 2001;15:1949–58.
4. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert
consensus document on reducing the gastrointestinal risks of antiplatelet
therapy and NSAID use: a report of the American College of Cardiology
Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll
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5. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Heli-
cobacter pylori infection: the Maastricht IV/Florence Consensus Report. Gut
2012;61:646–64.
REPLY: High Risk of Gastrointestinal
Bleeding on Dual Antiplatelet Treatment
We thank Dr. Atay for his interest in our work (1).
The COGENT (Clopidogrel and the Optimization of
Gastrointestinal Events Trial; NCT00557921) trial
demonstrated that omeprazole safely attenuated
major gastrointestinal (GI) events at 180 days
compared with placebo in patients with coronary
artery disease requiring dual antiplatelet therapy
(DAPT) (2). Randomization in COGENT was stratified
by serologic positivity for Helicobacter pylori. A
similar proportion of patients had positive or inter-
mediate H. pylori results on screening in the omep-
razole and placebo arms (47.8% vs. 48.3%) (2).
Although treatment eradication of H. pylori was not
confirmed in COGENT, there was no heterogeneity
observed in gastroprotective benefits of omeprazole
by H. pylori serologic status (p ¼ 0.47 for interaction)
(2). Consistent with current expert consensus docu-
ments (3,4), proton pump inhibitor gastroprotection
should be strongly considered in appropriately
selected patients deemed high risk for GI bleeding on
DAPT. Factors that may influence clinician decision-
making regarding use of proton pump inhibitor
prophylaxis during DAPT include H. pylori serologic
status, older age, select concomitant medications
(anticoagulants, nonsteroidal anti-inflammatory
drugs, or corticosteroids), history of alcoholism,
and recent upper GI bleeding or peptic ulcer disease.
In addition to pharmacologic gastroprotective stra-
tegies, physicians should be aware of and attempt to
minimize other alternative sources of GI bleeding in
DAPT candidates. We agree with Dr. Atay that
H. pylori detection and its eradication (as appro-
priate) represents an important adjunct to reducing
Letters 981
upper GI bleeding risk in this population. However,
we acknowledge the diagnostic complexity, prag-
matic barriers to delaying potentially urgent DAPT,
and practical challenges with patient adherence to
multidrug treatment of H. pylori. As such, it is
important to recognize that short-term prophylactic
administration of proton pump inhibitor therapy
in appropriately selected patients represents a sim-
ple, effective, and safe approach to reducing GI
complications on DAPT, irrespective of H. pylori
status.
Muthiah Vaduganathan, MD, MPH
*Deepak L. Bhatt, MD, MPH
Byron L. Cryer, MD
Yuyin Liu, MS
Wen-Hua Hsieh, PhD
Gheorghe Doros, PhD
Marc Cohen, MD
Angel Lanas, MD, DSc
Thomas J. Schnitzer, MD, PhD
Thomas L. Shook, MD
Pablo Lapuerta, MD
Mark A. Goldsmith, MD, PhD
Loren Laine, MD
Christopher P. Cannon, MD
on behalf of the COGENT Investigators
*Brigham and Women’s Hospital
Heart & Vascular Center
75 Francis Street
Boston, Massachusetts 02115
E-mail: dlbhattmd@post.harvard.edu
http://dx.doi.org/10.1016/j.jacc.2016.06.008
Please note: The COGENT trial was funded by Cogentus Pharmaceuticals. The
study investigators had full access to the trial database and retained complete
control on the decision to pursue publication. The sponsor did not have the
right to review or approve this letter. A full list of the COGENT investigators
can be found in Bhatt DL et al. N Engl J Med 2010;363:1909-1917. Dr. Bhatt is on
the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape
Cardiology, and Regado Biosciences; the board of directors of Boston VA
Research Institute and Society of Cardiovascular Patient Care; is chair of the
American Heart Association Quality Oversight Committee; is on the data
monitoring committees of Duke Clinical Research Institute, Harvard Clinical
Research Institute, Mayo Clinic, and Population Health Research Institute; has
received honoraria from the American College of Cardiology (Senior Associate
Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief,
Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering
committees), Harvard Clinical Research Institute (clinical trial steering com-
mittee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology),
Journal of the American College of Cardiology (Guest Editor; Associate Editor),
Population Health Research Institute (clinical trial steering committee), Slack
Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of
Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering
committees); has a relationship with Clinical Cardiology (Deputy Editor),
NCDR-ACTION Registry Steering Committee (Vice-Chair), and VA CART
Research and Publications Committee (Chair); has received research funding
from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest
Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines
Company; has received royalties from Elsevier (Editor, Cardiovascular Inter-
vention: A Companion to Braunwald’s Heart Disease); is site co-investigator for
Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American
College of Cardiology; and has performed unfunded research for Cogentus
(Chair of COGENT), FlowCo, PLx Pharma, and Takeda. Dr. Cryer has served as a