The Effect of Aspirin Alone or Aspirin Plus Additional Antiplatelets Therapy on Upper Gastrointestinal Hemorrhage

Suh Eun Bae; Seong-Eun Kim; Sung-Ae Jung; So Yoon Yoon; Ki-Nam Shim; Hye-Kyung Jung; Tae Hun Kim; Kwon Yoo; Il Hwan Moon

doi:10.4166/kjg.2011.57.4.213

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Bae, Kim, Jung, Yoon, Shim, Jung, Kim, Yoo, and Moon: The Effect of Aspirin Alone or Aspirin Plus Additional Antiplatelets Therapy on Upper Gastrointestinal Hemorrhage

Original Article

Korean J Gastroenterol 2011;57(4):213-220.

Published online: 4 October 2011

DOI: https://doi.org/10.4166/kjg.2011.57.4.213

The Effect of Aspirin Alone or Aspirin Plus Additional Antiplatelets Therapy on Upper Gastrointestinal Hemorrhage

Suh Eun Bae, Seong-Eun Kim, Sung-Ae Jung, So Yoon Yoon, Ki-Nam Shim, Hye-Kyung Jung, Tae Hun Kim, Kwon Yoo, Il Hwan Moon

Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea

Correspondence to: Seong-Eun Kim, Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 911, Mok-dong, Yangchun-gu, Seoul 158-710, Korea. Tel: +82-2-2650-2859, Fax: +82-2-2655-2076, E-mail: kimse@ewha.ac.kr

Received 27 July 2010 Revised 29 January 2011 Accepted 30 January 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

The increasing incidence of cardiovascular disease has led to an increase in the frequency of upper gastrointestinal (GI) hemorrhage due to the use of antiplatelet agents. This study examined the clinical characteristics of patients with upper GI hemorrhage who were administered aspirin alone or a combination treatment of antiplatelet agents.

Methods

A 656 patients who underwent drug-eluting coronary stenting at Ewha Mokdong Hospital in 2008 were divided into three groups according to the antiplatetlet agents used after the intervention; groups of aspirin alone, aspirin plus clopidogrel, and aspirin, and clopidogrel plus another antiplatelet agent, respectively. Patients admitted with GI hemorrhage in the same period without a medication history of antiplatelet or nonsteroidal anti-inflammatory drugs were used as the control hemorrhage group. The medical records were reviewed.

Results

Significant GI symptoms were observed in 21.1% of total patients, of whom 48.2% had ulcers. The upper GI hemorrhage rate was 3.8%. There was no significant difference in the hemorrhage rate between three groups. Compared to the control hemorrhage group, the endoscopic variables of the antiplatelet-related hemorrhage group were not significantly different. However, the Helicobacter pylori infection rate was lower, the admission period was longer, and the mortality rate was higher in the antiplatelet-related hemorrhage group (p＜0.05, respectively). There was no direct association between restarting or dis-continuance of antiplatelets after the hemorrhage event and mortality.

Conclusions

Adding other antiplatelet agents to aspirin did not increase the hemorrhage rate. However, active diagnostic and therapeutic efforts are recommended in patients with GI symptoms during antiplatelet therapy.

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Keywords: Gastrointestinal hemorrhage, Aspirin, Clopidogrel

References

1. Vallurupalli NG, Goldhaber SZ. Gastrointestinal complications of dual antiplatelet therapy. Circulation. 2006; 113:e655–e658.

2. Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation. 2001; 103:1967–1971.

3. Wang F, Stouffer GA, Waxman S, Uretsky BF. Late coronary stent thrombosis: early vs. late stent thrombosis in the stent era. Catheter　Cardiovasc Interv. 2002; 55:142–147.

4. Steinhubl SR, Berger PB, Mann JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002; 288:2411–2420.

5. Patrono C, Bachmann F, Baigent C, et al. Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J. 2004; 25:166–181.

6. Ng FH, Wong SY, Chang CM, et al. High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease. Aliment Pharmacol Ther. 2003; 18:443–449.

7. Moukarbel GV, Signorovitch JE, Pfeffer MA, et al. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J. 2009; 30:2226–2232.

8. Deepak LB, Keith AA, Ch. B, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006; 354:1706–1717.

9. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001; 358:527–533.

10. 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. Circulation. 2008; 118:1894–1909.

11. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008; 51:256–260.

12. Rao SV, O'Grady K, Pieper KS, et al. Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol. 2005; 96:1200–1206.

13. Twomley KM, Rao SV, Becker RC. Proinflammatory, immunomodulating, and prothrombotic properties of anemia and red blood cell transfusions. J Thromb Thrombolysis. 2006; 21:167–174.

14. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and metaanalysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006; 27:2667–2674.

15. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005; 293:2126–2130.

16. Seddighzadeh A, Wolf AT, Parasuraman S, et al. Gastrointestinal complications after 3 months of dual antiplatelet therapy for drug-eluting stents as assessed by wireless capsule endoscopy. Clin Appl Thromb Hemost. 2009; 15:171–176.

17. O'Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009; 374:989–997.

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Fig. 1.

Study profile. A total of 868 patients who had coronary angiography at Ewha Womans University Mokdong hospital in 2008 were included. One hundred thirty one patients were having aspirin alone therapy, 432 patients having dual therapy (aspirin plus clopidogrel) and 93 patients having triple therapy (aspirin, clopidogrel plus cilostazol or sarpogrelate). CAOD, coronary artery disease.

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Fig. 2.

Incidence of upper gastrointestinal symptoms, ulcer, and hemorrhage in the enrolled patients. Moderate and severe gastrointestinal symptoms were present in 21.1% of the total patients, and 48.2% of those had ulcer. Upper gastrointestinal hemorrhage rate was 3.8%. There was no significant difference of hemorrhage rate among aspirin alone group, double therapy and triple therapy group (3.8%, 3.9% vs. 3.2%).

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Table 1.

Characteristics of the Enrolled Patients

	Aspirin	Aspirin+ Clopidogrel	Aspirin+ Clopidogrel+ Cilostazol or Sarpogrelate
	n=131	n=432	n=93
Male, n (%)	77 (58.8)	287 (66.4)	73 (78.5)
Age (mean±SD)	62±11	63±11	62±10
Drug, %
Antihypertensive agent
ACE inhibitor	6.1	4.2	8.4
Beta blocker	0.8	0.7	1.1
CCB	6.1	5.3	2.1
Nitrates	2.3	2.5	2.1
Dyslipidemic agent	48.1 ^a	73.6	78.9
Thrombolytic agent	0.8	2.1	1.1
NSAID	1.5	1.4	3.2
Steroid	3.1	1.6	2.1
Antisecretory agent, n (%)
Proton pump inhibitor	3 (2.3)	24 (5.5)	5 (5.2)
H2 blocker	10 (7.6)	31 (7.2)	3 (3.2)
Mucoprotectant	28 (21.3)	103 (23.8)	35 (36.8) ^a
Combined disease, %
Hypertension	42.7	50.5	51.6
DM	27.5	30.6	34.7
CRF	6.9	6.0	3.2
CVA	6.1	2.5	8.4
Malignancy	6.1	5.3	2.1
COPD	2.3	2.5	2.1
Rheumatic disease	0.8	0.7	1.1
Liver disease	0	0.2	3.2
Coronary disease, %
1 vessel CAOD	86.3 ^a	55.3	35.8
2 vessels CAOD	6.1 ^a	24.8	38.9
3 vessels CAOD	7.6 ^a	19.9	25.3
Helicobacter pylori infection	15.6	22.5	37.5
Smoking	39.9 ^a	51.3	65.5

ACE inhibitor, angiotensin converting enzyme inhibitor; CCB, calcium channel blocker; NSAID, nonsteroidal anti-inflammatory drug; DM, diabetes mellitus; CRF, chronic renal failure; CVA, cerebral vascular attack; COPD, chronic obstructive pulmonary disease; CAOD, coronary artery occlusive disease.

^a vs other groups, p＜0.05.

Table 2.

Upper Endoscopic Findings according to Antiplatelet Regimen in Patients with Gastrointestinal Symptoms

	Aspirin	Aspirin+ Clopidogrel	Aspirin+ Clopidogrel Cilostazol or Sarpogrelate
	n=35	n=88	n=16
Gastritis, n (%)	13 (37.1)	32 (36.3)	6 (37.5)
Erosion, n (%)	8 (22.8)	11 (12.5)	1 (6.3)
Ulcer, n (%)	14 (40.0)	44 (50.0)	9 (56.2)
Antrum	4	14	3
Body	4	25	4
Duodenum	6	15	2
Large ulcer ≥2 cm, n (%)	1 (2.8)	5 (5.6)	1 (6.3)
Multiple ulcers, n (%)	6 (17.1)	10 (11.2)	8 (50.0)
Active ulcer, n (%)	4 (11.4)	18 (20.4)	3 (18.8)

All p＞0.05, respectively.

Table 3.

Upper Endoscopic Findings according to Antiplatelet Regimen in Patients with Upper Gastrointestinal Hemorrhage

	Aspirin	Aspirin+ Clopidogrel	Aspirin+ Clopidogrel+ Cilostazol or Sarpogrelate	Total
	n=5	n=17	n=3	n=25
Location, n (%)
Stomach	5 (100)	11 (68.7)	3 (100)	19 (79.1)
Antrum	2 (40.0)	3 (17.6)	1 (33.3)	6 (24.0)
Body	3 (60.0)	8 (47.1)	2 (67.6)	13 (52.0)
Duodenum	0	3 (17.6)	0	3 (12.0)
Esophagus	0	2 (11.8)	0	2 (8.0)
Unknown ^a	0	1 (5.9)	0	1 (4.0)
Multiple ulcers, n (%)	2 (40.0)	4 (25.0)	3 (100)	9 (36.0)
Forrest classification,
n (%)
I	0	4 (25.0)	0	4 (16.0)
IIa/IIb	2 (40.0)	3 (17.6)	0	5 (20.0)
IIc	1 (20.0)	2 (11.8)	1 (33.3)	4 (16.0)
Size
≥2 cm	2 (40.0)	1 (5.8)	1 (33.3)	4 (16.0)
＜1 cm	1 (20.0)	8 (47.1)	0	9 (36.0)
H. pylori infection, n (%)	1 (20.0)	3 (21.4)	1 (33.3)	5 (20.0)

All p＞0.05, respectively. H. pylori, Helicobacter pylori.

^a Unkown origin: Levin tube positive patient without endoscopy.

Table 4.

Comparison of Upper Endoscopic Findings between Anti-platelet Related Hemorrhage Group and Control Hemorrhage Group

	Antiplatelet related hemorrhage group (n=25)	Control hemorrhage group (n=25)
Location, n (%)
Stomach	19 (79.1)	25 (100)
Antrum	6 (24.0)	4 (16.0)
Body	13 (52.0)	21 (84.0)
Duodenum	3 (12.0)	0
Esophagus	2 (8.0)	0
Multiple ulcer, n (%)	9 (36.0)	8 (32.0)
Size, n (%)
≥2 cm	4 (16.0)	6 (24.0)
＜1 cm	9 (36.0)	3 (12.0)
H. pylori infection, n (%)	5 (20.0)	15 (65.2) ^a

^a p＜0.05, Control hemorrhage group: patients admitted with gastrointestinal hemorrhage in the same period without a medication history of antiplatelet or nonsteroidal anti-inflammatory drugs, for an age- and gender-matched comparison with the antiplatelet-related hemorrhage group.

Table 5.

Clinical Progress in Patients with Gastrointestinal Hemorrhage

	Aspirin	Aspirin+ Clopidogrel	Aspirin+ Clopidogrel+ Cilostazol or Sarpogrelate	Total	Control hemorrhage group
	n=5	n=17	n=3	n=25	n=25
Medication used in short term (＜1 month), n (%)	1 (20.0)	5 (26.3)	1 (33.3)	7 (28.0)
Admission period, Median days	19	16.46	9	16 ^a	5.92
Mortality, n (%)	2 (40.0)	5 (26.4)	0	7 (28.0) ^a	1 (4.0)
Mortality due to hemorrhage, n (%)	1 (20.0)	0	0	1 (4.0)	1 (4.0)
Endoscopy numbers	2.4	1.5	1.2	1.47	1.32
Rehemorrhage, n (%)	1 (20.0)	0	1 (33.3)	2 (8.0)	4 (16.0)
Transfusion, pint	2.0	1.9	2.0	1.93	2.7
Re-medication, n (%)	1 (20.0)	9 (35.3)	1 (33.3)	11 (44.0)
1 drug, n (median days from hemorrhage)	1 (11ds)	4 (14ds)	0	5
2 drug, n	0	5 (6ds)	1 (9ds)	6
Continuing medication, n (%)	0	3 (17.6)	2 (66.7)	5 (20.0)

^a vs control hemorrhage group, p＜0.05.

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