Abstract
BackgroundOvert bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, although this is known to occur in healthy volunteers. LDA is used increasingly in primary and secondary prevention of a number of medical conditions, many of which are common in older people, as is anemia. Anemia in older people is associated with adverse outcomes including disability, morbidity and mortality. The purpose of this study was to review the evidence that LDA might cause anemia without overt bleeding.MethodsAn extensive narrative review was carried out. Electronic searching (including database links) and reference lists of reports were used to identify studies reporting on use of aspirin ≤325 mg/day and anemia or change in hemoglobin (Hb) without overt bleeding. Data were extracted from reports of trials, adverse drug reactions (ADRs) and prevalence studies of adults aged ≥18 years, published since 1980.ResultsThere are few relevant data, with considerable heterogeneity among trial designs, duration, and patient characteristics in studies of LDA. In five randomised trials (n = 5879) in (mostly secondary) prevention, the majority of patients were men without peptic ulcer disease aged 50-70 years and no consistent association between LDA and change in Hb was found. In two smaller studies (n = 609) of primary prevention in healthy patients aged ≥70 years, there was a small but statistically significant fall in Hb with LDA. Observational studies, and data from trials in which use of LDA was not a primary focus of the study, were inconclusive.ConclusionsIt is not clear whether there is an association between LDA and anemia in the absence of overt bleeding, but there may be an association between LDA and fall in Hb in (a subset of) older patients. The available evidence has significant limitations, which are discussed; studies including more older patients, and publication of individual patient data, would help clarify this important matter.
Highlights
Overt bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, this is known to occur in healthy volunteers
Evidence from randomized trials in which change in Hb or anemia was reported as an adverse event (ADR) occurring in patients treated with LDA
The current position of LDA in secondary prevention in cardio- and cerebrovascular disease mean that it is unlikely that in future, trials will be run with LDA compared to placebo, but there might be opportunities in studies in primary prevention or where LDA is used for other conditions. It is not clear whether there is a clinically significant effect of LDA on Hb in adults in the absence of overt bleeding, but the limited evidence available at present cannot rule this out and suggests that it may be a problem in older people, or a subset of them
Summary
Overt bleeding associated with low dose aspirin (LDA) is well-recognized, little attention is given to the possibility of association between LDA and occult bleeding, this is known to occur in healthy volunteers. Low dose aspirin (LDA) is taken by an increasing number of people for prophylaxis in a widening variety of medical conditions, including cardio- and cerebrovascular disease, dementia, and some malignancies. Many of these conditions are common, in older people, and changes in demographics (with increasing life expectancy and higher numbers of older people) mean that there is potential for many more older people to take LDA. There have been many studies reporting on overt gastrointestinal bleeding as a primary or secondary outcome of interest [1,2], little attention has been given to the possibility that LDA use may be complicated by occult bleeding, possibly leading to anemia. Even mildly low Hb levels (above the WHO criteria for anemia, Hb < 130 g/L in men and
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