|Year : 2017 | Volume
| Issue : 2 | Page : 92-96
Prevalence of dyspeptic symptoms among patients on low-dose antiplatelet therapy
Uchenna C Okonkwo1, Idongesit O Umoh2, Eshan Henshaw3, Ansa Victor4
1 Department of Internal Medicine, Gastroenterology/Hepatology Unit, University of Calabar, Calabar, Cross River State, Nigeria
2 Department of Internal Medicine, Cardiology Unit, University of Uyo, Akwa Ibom, Nigeria
3 Department of Internal Medicine, Dermatology Unit, University of Calabar, Calabar, Cross River State, Nigeria
4 Department of Internal Medicine, Cardiology Unit, University of Calabar, Calabar, Cross River State, Nigeria
|Date of Web Publication||26-Oct-2017|
Uchenna C Okonkwo
Department of Internal Medicine, Gastroenterology/Hepatology Unit, University of Calabar, P.M.B. 1115, Calabar, Cross River State
Source of Support: None, Conflict of Interest: None
Background: Low-dose antiplatelet therapy is the standard of care for the prevention of primary and secondary cardiovascular events. Dyspeptic symptoms may result in discontinuation of treatment.
Aim: The aim of the study was to determine the prevalence of dyspeptic symptoms among patients on low-dose antiplatelet therapy for primary and secondary prevention of cardiovascular events.
Subjects, Materials, and Methods: This was a cross-sectional descriptive study of 253 adults on low-dose antiplatelet attending the Cardiology Clinic of the University of Calabar Teaching Hospital. Prevalence and clinical impact of dyspepsia were assessed using a structured questionnaire incorporating the gastrointestinal symptom rating scale. Data were analyzed using the Statistical Package for Social Sciences version 20.
Results: A total of 253 patients were recruited for this study. The mean age was 54 ± 12.2 years. The prevalence of dyspeptic symptoms was 47.8%. Epigastric pain was the most common self-reported dyspeptic symptom (33.2%) followed by heartburn (23.7%). Melena and hematemesis were reported by 5.5% and 1.2% of the patients. Treatment duration was longer for those with dyspeptic symptoms (45.8 ± 139.6 vs. 28.3 ± 31 months), but the difference was not statistically significant (P = 0.17). A prior history of peptic ulcer disease was predictive of dyspeptic symptoms (odds radio; 8.62, confidence interval; 2.49–29.83). Majority (71.7%) of the patients reported their symptoms as occasional episodes which mildly impair their daily quality of life. Compliance was impacted in 6.7% of the patients.
Conclusion: Dyspeptic symptoms, mostly epigastric pain, are prevalent among Nigerian patients on low-dose antiplatelets which negatively impact their daily life activities and compliance to treatment.
Keywords: Antiplatelets, dyspepsia, Nigeria
|How to cite this article:|
Okonkwo UC, Umoh IO, Henshaw E, Victor A. Prevalence of dyspeptic symptoms among patients on low-dose antiplatelet therapy. Nig J Cardiol 2017;14:92-6
|How to cite this URL:|
Okonkwo UC, Umoh IO, Henshaw E, Victor A. Prevalence of dyspeptic symptoms among patients on low-dose antiplatelet therapy. Nig J Cardiol [serial online] 2017 [cited 2022 Dec 6];14:92-6. Available from: https://www.nigjcardiol.org/text.asp?2017/14/2/92/217271
| Introduction|| |
Over the past two decades, low-dose antiplatelets, especially low-dose aspirin, have been increasingly recommended for both primary, secondary, and tertiary prevention of adverse cardiovascular events in patients at high risk. Collaborative overview of randomized control trials on antiplatelets has conclusively shown them to be the standard of care for patients at increased risk of atherosclerotic vascular events such as acute coronary syndrome, ischemic stroke including transient ischemic attack, and peripheral vascular disease. Several national and international guidelines recommend long-term use of low-dose antiplatelets for patients with cardiovascular disease and those at risk of adverse cardiovascular events., Aspirin reduces the risk of stroke, myocardial infarction, or death from vascular causes by 25% when compared to placebo. Addition of clopidogrel to aspirin is even more effective, especially in patients undergoing percutaneous coronary artery intervention for acute myocardial infarction reducing the risk of reinfarction by as much as 20%.
In spite of these benefits, upper gastrointestinal symptoms ranging from minor events such as dyspepsia and gastroduodenal erosions, to life-threatening gastroduodenal ulceration, bleeding, and perforation are major side effects of antiplatelet medications. This is not unexpected as aspirin acts by irreversibly inhibiting the enzyme cyclooxygenase (COX), the rate limiting enzyme in prostaglandin synthesis resulting in the loss of a major protective mechanism against mucosal injury in the gastrointestinal tract. Clopidogrel, a thienopyridine derivative, inhibits platelet aggregation by irreversibly inhibiting the binding of adenosine-5-diphosphate, to the platelet P2Y12 receptor. This interaction amplifies the platelet aggregation process. It does not inhibit COX and therefore acts independently of aspirin.
Long-term aspirin therapy even at low doses is associated with increased risk of upper gastrointestinal symptoms. The United Kingdom transient ischemic attack aspirin trial documented a prevalence rate of 31% for dyspepsia and 3.1% for upper gastrointestinal bleeding over a 4-year period. Advancing age, previous peptic ulcer disease (PUD), Helicobacter pylori infection, and concomitant use of more than one antiplatelet agent increases the risk of aspirin-related side effects.,, The clopidogrel versus aspirin in patients at risk of ischemic events trial showed that clopidogrel was associated with fewer upper gastrointestinal adverse events when compared to aspirin (0.97% vs. 1.22%, P < 0.05).
There is paucity of data on the prevalence of dyspepsia among Nigerian patients on low-dose antiplatelets for either primary or secondary prevention of adverse cardiovascular events. A study in a rural community in North-eastern Nigeria found the prevalence of dyspepsia in the general population to be 26% and was associated with older age. This study was designed to assess the prevalence and pattern of upper gastrointestinal symptoms in patients on low-dose antiplatelets attending the cardiology clinic of a tertiary health facility in Calabar.
Aims and objectives
The aim of this study was to determine the prevalence and pattern of dyspeptic symptoms among patients on low-dose antiplatelet therapy for primary and secondary prevention of cardiovascular events.
| Subjects, Materials, and Methods|| |
This was a cross-sectional descriptive study. Consecutive adult patients attending the Cardiology Clinic of the University of Calabar Teaching Hospital were recruited over a 6-month period from February to July 2013. Dyspepsia for this study was defined as the presence of one or more of the following symptoms, namely, epigastric pain, heartburn, regurgitation, excessive belching, easy satiety, bloating, and nausea/vomiting. A structured questionnaire incorporating the gastrointestinal symptom rating scale and pretested for reliability and validity was researcher administered to the patients after obtaining a written informed consent. Sociodemographic data such as age, gender, body mass index, and other risk factors for dyspepsia were also obtained. Duration and type of antiplatelet prescribed, concurrent use of medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), antacids, and proton pump inhibitors was also documented. Questionnaires without adequate information were excluded from the analysis. All stable patients on antiplatelet medication for primary or secondary prevention of cardiovascular disease who gave a written informed consent were included in the study. Patients who were not on antiplatelets and those who were too ill to respond to the questionnaire such as patients with symptomatic heart failure were excluded from the study.
Sample size calculation
The minimum sample size for this study was 295, which was calculated using the formula n = z 2p(1-p)/d 2 where Z = confidence interval (CI) of 95%, P = prevalence of dyspepsia in a Nigerian population taken as 26%, and d is the desired precision which was 5%.
Data generated from the study were analyzed using the Statistical Package for Social Sciences version 20 (SPSS Inc., IL, Chicago, USA). Continuous variables were presented as means and standard deviation while categorical variables were presented as percentages. Odds ratio (OR) (95% CI) was used to test for association between variables. Statistical significance was established as P < 0.05.
Ethical clearance was obtained from the University of Calabar Health Research Ethics Committee with reference number - UCTH/HREC/33/48. All information was treated as anonymous and confidential. Questionnaires were destroyed at the end of the study.
| Results|| |
A total of 295 patients were recruited while 253 patients were included in the final analyses giving a response rate of 85.7%. Forty-two were excluded due to inaccurate data. Some patients claimed they were on antiplatelets. However, when we cross-checked in their folders, they were not on antiplatelets and so were excluded from the final analysis. They were 110 males and 143 females with a M:F ratio of 1:1.3. Their ages ranged from 21 to 90 years with a mean age of 54 ± 12.2 years. The mean age of males was 55.98 ± 12.45 years and the mean age of females was 52.59 ± 11.98 years. The difference was statistically significant (P = 0.031). Majority (54.2%) were within the age group of 41–60 years. Hypertension/hypertensive heart disease was the most common indication for prescription of low-dose antiplatelet (62.8%). The frequency of antiplatelets prescribed was low-dose aspirin (79.4%), clopidogrel (15.4%), aspirin/clopidogrel (3.6%), and dipyridamole (1.2%). [Table 1] shows further characteristics of the study population.
The prevalence of dyspeptic symptoms was 47.8%. Epigastric pain was the most common self-reported dyspeptic symptom (33.2%) followed by heartburn (23.7%). [Table 2] shows frequency of other reported dyspeptic symptoms.
The mean treatment duration for patients with dyspeptic symptoms was longer than that for those without dyspeptic symptoms (45.8 ± 139.6 vs. 28.3 ± 31 months), but the difference was not statistically significant (P = 0.17). Majority (71.7%) of the patients reported their symptoms as occasional episodes of short duration which mildly impaired their daily quality of life. Of those with dyspeptic symptoms, 57% reported their symptoms to the doctor, 24% resorted to self-medication, and 6.7% stopped their medications. Passage of melena stool and hematemesis was reported by 5.5% and 1.2% of the patients. A prior history of PUD and concomitant use of NSAID were predictive of dyspeptic symptoms (OR; 8.62, CI; 2.49–29.83 and OR; 2.83, CI: 1.52–5.25), respectively [Table 3]. Patients with dyspeptic symptoms were more likely to use antacids or proton pump inhibitors (P < 0.001).
|Table 3: Association between presence of dyspeptic symptoms and other risk factors for dyspepsia|
Click here to view
| Discussion|| |
Low-dose antiplatelet therapy prescribed for patients with cardiovascular diseases for secondary prevention of adverse cardiovascular events is shown to be cost-effective., However, the prevalence of gastrointestinal toxicity has been scarcely reported among Nigerian patients. Our study showed a high prevalence of dyspeptic symptoms among patients on low-dose antiplatelets. This was higher than the 26% and 29% reported among the general population in Northern and Western Nigeria but comparable to the 20%–40% reported by similar studies in Europe.,,,, Low-dose aspirin was the most common antiplatelet prescribed, and hypertension/hypertensive heart disease was the most common indication for its prescription. Epigastric pain was the most common form of dyspeptic symptom in our study and is similar to what was reported by Hameed et al. in Western Nigeria. This was followed by heartburn and bloating. Regurgitation was less common. Focks et al. had reported gastroesophageal reflux symptoms of heartburn and regurgitation as the most common symptoms among their patients on low-dose aspirin. This may be due to differences in the population demographics. Gastroesophageal reflux disease is thought to be more common in Europeans than Africans. Dyspeptic symptoms were reported to occur occasionally and for short duration with mild impairment of daily quality of life in majority of the patients. Cayla et al. in the study of the prevalence and clinical impact of upper gastrointestinal symptoms in cases treated with low-dose aspirin noted that dyspeptic symptoms occurred at least once a week in their cohort and most reported mild-moderate impairment in quality of life. The use of low-dose aspirin was shown to be associated with a slight but significant risk of upper gastrointestinal bleeding and is in keeping with findings from other studies , In a meta-analysis, low doses of aspirin increased the risk for gastrointestinal bleeding; risk increased with accompanying use of clopidogrel and anticoagulant therapies.
A prior history of PUD and concomitant use of NSAIDs were predictive of dyspeptic symptoms in patients on low-dose antiplatelet and were similar to previous reports. The effect of NSAIDs in the gastrointestinal tract is synergistic to that of aspirin as both inhibit the COX pathway. Patients with a history of PUD already have impaired gastroprotective mechanism which potentiates aspirin toxicity. Combined use of clopidogrel/aspirin does not appear to worsen dyspeptic symptoms unlike what was reported in other studies., This may be because of the small number of patients on concomitant use of aspirin/clopidogrel in this study. Again, clopidogrel exerts its antiplatelet effect independent of vasoprin and may not enhance its gastric toxicity. Obesity, alcohol use, and cigarette smoking did not have a significant association with occurrence of dyspeptic symptoms and are similar to findings from other studies in Europe.,
However, alcohol and kola nut consumption was reported to have a significant association with dyspepsia in a rural community in Northern Nigeria. The reason may be due to the high concentration of ethanol in local brews of alcohol consumed in that rural region. Kola nut consumption was not assessed in our study.
Dyspeptic symptoms were the reason for noncompliance to medications in a small percentage of our patients when compared to findings from other studies. This is likely due to the high prevalence of self-medication with antacids and proton pump inhibitors among our study participants. Proton pump inhibitors have been shown to be effective in reducing upper gastrointestinal symptoms associated with the use of low-dose aspirin.
| Conclusion|| |
A high proportion of patients treated with low-dose antiplatelets for primary or secondary prevention of cardiovascular events suffer dyspeptic symptoms mostly “epigastric pain” which negatively affects their daily life activities and compliance to treatment.
The limitations of this study include the lack of a control group. This limits the usefulness of establishing a causal relationship between low-dose antiplatelets and dyspepsia.
The authors acknowledge the effort and cooperation of the staff of the Records Department, University of Calabar Teaching Hospital, Calabar.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348:1329-39.
Collaborative overview of randomised trials of antiplatelet therapy – I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ 1994;308:81-106.
Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al
. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task force on practice guidelines. Circulation 2004;110:e82-92.
Bassand JP, Hamm CW, Ardissino D. Guidelines for the diagnosis and treatment of non-ST segment elevation acute coronary syndromes. The task Force for the Diagnosis and Treatment of non-ST segment elevation acute coronary syndrome of the European society of cardiology. Eur Heart J 2007;28:1598-660.
Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al.
Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N
Engl J Med 2006;354:1706-17.
Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med 2011;124:426-33.
Farrell B, Godwin J, Richards S, Warlow C. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: Final results. J Neurol Neurosurg Psychiatry 1991;54:1044-54.
Okada K, Inamori M, Imajo K, Chiba H, Nonaka T, Shiba T, et al.
Clinical study of upper gastrointestinal bleeding associated with low-dose aspirin in Japanese patients. Hepatogastroenterology 2009;56:1665-9.
Fletcher EH, Johnston DE, Fisher CR, Koerner RJ, Newton JL, Gray CS. Systematic review: Helicobacter pylori
and the risk of upper gastrointestinal bleeding risk in patients taking aspirin. Aliment Pharmacol Ther 2010;32:831-9.
Marcum ZA, Hanlon JT. Recognizing the risks of chronic nonsteroidal anti-inflammatory drug use in older adults. Ann Longterm Care 2010;18:24-7.
Holcombe C, Omotara BA, Padonu MK, Bassi AP. The prevalence of symptoms of dyspepsia in North Eastern Nigeria. A random community based survey. Trop Geogr Med 1991;43:209-14.
Hameed L, Onyekwere CA, Otegbayo JA, Abdulkareem FB. A clinicopathological study of dyspeptic subjects in Lagos. Gastroenterology Insights. 2012;4: e11;39-42.
Yeomans ND, Lanas AI, Talley NJ, Thomson AB, Daneshjoo R, Eriksson B, et al.
Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther 2005;22:795-801.
Pratt S, Thompson VJ, Elkin EP, Næsdal J, Sörstadius E. The impact of upper gastrointestinal symptoms on nonadherence to, and discontinuation of, low-dose acetylsalicylic acid in patients with cardiovascular risk. Am J Cardiovasc Drugs 2010;10:281-8.
Tournoij E, Peters RJ, Langenberg M, Kanhai KJ, Moll FL. The prevalence of intolerance for low-dose acetylsalicylacid in the secondary prevention of atherothrombosis. Eur J Vasc Endovasc Surg 2009;37:597-603.
Jaspers Focks J, Tielemans MM, van Rossum LG, Eikendal T, Brouwer MA, Jansen JB, et al.
Gastrointestinal symptoms in low-dose aspirin users: A comparison between plain and buffered aspirin. Neth Heart J 2014;22:107-12.
Segal I. The gastro-oesophageal reflux disease complex in sub-Saharan Africa. Eur J Cancer Prev 2001;10:209-12.
Cayla G, Collet JP, Silvain J, Thiefin G, Woimant F, Montalescot G. Prevalence and clinical impact of Upper Gastrointestinal Symptoms in subjects treated with low dose aspirin: The UGLA survey. Int J Cardiol 2012;156:69-75.
Valkhoff VE, Sturkenboom MC, Kuipers EJ. Risk factors for gastrointestinal bleeding associated with low-dose aspirin. Best Pract Res Clin Gastroenterol 2012;26:125-40.
Negovan A, Iancu M, Moldovan V, Voidazan S, Bataga S, Pantea M, et al.
Clinical risk factors for gastroduodenal ulcer in Romanian low-dose aspirin consumers. Gastroenterol Res Pract 2016;2016:7230626.
Lanas A, Wu P, Medin J, Mills EJ. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol 2011;9:762-8.e6.
Okeke EN, Malu AO, Obafunwa JO, Nwana EJ. Aetiological significance of alcohol in liver cirrhosis on the Jos Plateau. West Afr J Med 2002;21:12-4.
Mo C, Sun G, Wang YZ, Lu ML, Yang YS. PPI versus Histamine H2 receptor antagonists for prevention of upper gastrointestinal injury associated with low-dose aspirin: Systematic review and meta-analysis. PLoS One 2015;10:e0131558.
[Table 1], [Table 2], [Table 3]