Dataset Information

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies.

ABSTRACT:

Background

Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations.

Methods

Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75-325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles.

Findings

The incidence of GI bleeding with low-dose aspirin was 0.48-3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2-1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0-2.6) and 1.8 (1.1-3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2-1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy.

Conclusions

The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events.

SUBMITTER: Garcia Rodriguez LA

PROVIDER: S-EPMC4973997 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description: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.

Project description:ImportanceLow-dose aspirin use for chemoprevention of lung cancer risk remains controversial.ObjectivesTo investigate the association between low-dose aspirin use and lung cancer risk, and to identify specific subgroups that may derive the most benefit from low-dose aspirin use.Design, setting, and participantsThis nationwide, retrospective, cohort study used data from the Korean National Health Information Database from 2002 to 2015. Data analyses were performed from October 2016 to December 2018. Eligible participants (n = 12 969 400) were people aged 40 to 84 years who had undergone national health screening between 2009 and 2010 and had no history of lung cancer between 2006 and 2010 and no standard-dose aspirin use for 6 months between 2002 and 2010.Main outcomes and measuresThe duration of low-dose aspirin use between January 2002 and December 2010 was calculated for each participant. Lung cancer was defined as the first recorded diagnosis of lung cancer-using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and expanding benefit coverage-between January 2011 and December 2015.ResultsA total of 63 040 participants with a mean (SD) age of 66.4 (9.3) years received a diagnosis of lung cancer. Of these, 45 156 (71.6%) were men. The incidence rate of lung cancer was 98.8 per 100 000 person-years. The duration of low-dose aspirin use was none for 10 987 417 participants (84.7%), 1 to 2 years for 750 992 participants (5.8%), 3 to 4 years for 506 945 participants (3.9%), 5 to 6 years for 371 062 participants (2.9%), 7 to 8 years for 240 528 participants (1.9%), and 9 years for 112 456 participants (0.9%). Compared with no aspirin use, 5 to 6 years (adjusted hazard ratio, 0.96 [95% CI, 0.92-0.99]), 7 to 8 years (adjusted hazard ratio, 0.94 [95% CI, 0.90-0.99]), and 9 years (adjusted hazard ratio, 0.89 [95% CI, 0.84-0.94]) of aspirin use were significantly associated with reduced lung cancer risk. After stratified analysis, a significant reduction of lung cancer risk was observed among people aged 65 years or older and among people without diabetes.Conclusions and relevanceAlthough the use of low-dose aspirin for more than 5 years was associated with decreased risk of lung cancer, particularly among elderly participants and among people without diabetes, the observed effect size was quite modest. Future prospective studies are needed to determine whether there is a causal association.

Project description:BackgroundAspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin.MethodsIn a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin.ResultsEleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43).ConclusionsThe majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.