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Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies
Luis A García Rodríguez1, Mar Martín-Pérez1, Charles H Hennekens2
1Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain.
Insights
Low-dose aspirin use for cardiovascular prevention increases gastrointestinal bleeding and intracranial hemorrhage risks. These real-world bleeding risks are comparable to those found in clinical trials, aiding clinical decision-making.
Area of Science:
- Cardiology
- Gastroenterology
- Pharmacology
Background:
- Low-dose aspirin is effective for cardiovascular event prevention but carries bleeding risks.
- Assessing the benefit-risk balance for primary prevention requires data from general populations, which is currently limited.
Purpose of the Study:
- To systematically review observational studies on the risks of gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH) associated with long-term, low-dose aspirin use.
- To provide pooled estimates of the relative risk (RR) for bleeding events with low-dose aspirin compared to non-use.
Main Methods:
- Systematic literature searches of Medline and Embase (1946-March 2015).
- Inclusion of observational studies reporting GI bleeding or ICH risks with low-dose aspirin (75-325 mg/day).
- Calculation of pooled RRs using random-effects models based on data from 39 articles.
Main Results:
- Low-dose aspirin was associated with an overall RR of 1.4 for GI bleeding (0.48-3.64 cases/1000 person-years) and 1.4 for ICH.
- Specific RRs for upper and lower GI bleeding were 2.3 and 1.8, respectively.
- Concomitant use of NSAIDs, clopidogrel, or SSRIs increased bleeding risks, while PPIs decreased upper GI bleeding risk.
Conclusions:
- The real-world risks of major bleeding with low-dose aspirin are similar in magnitude to those reported in randomized trials.
- These findings are crucial for informing clinical judgments on the use of low-dose aspirin for cardiovascular event prevention.
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.
