By Dr. Geoffrey Modest
A rather common clinical conundrum in patients with/at high risk for cardiovascular disease is whether to reinstate aspirin after a GI bleed. A recent retrospective study from Hong Kong suggested that the benefit outweighs the risk for lower GI bleeds (see doi.10.1053/j.gastro.2016.04.013). They reviewed their data on patients with documented lower GI bleed (melena or hematochezia and absence of upper GI source) from 2001-2008.
Details:
- 295 patients who were on aspirin at the time of the lower GI bleed, followed up to 5 years
- 93% were considered to be of “high cardiovascular risk”, using the Antithrombotic Trialists’ Collaborative definition: history of unstable angina, acute MI, prior MI, stroke, or TIA
- Non-users were defined as taking aspirin <20% of the follow-up period (n=121; 87% actually took aspirin <10% of the follow-up period); users were those with cumulative use >50% of that period (n=174; 84% took aspirin >75% of the follow-up period). Aspirin use was determined by prescription patterns.
- All used <=160mg aspirin, and 88% used only 80 mg/d
- Non-users were older (76.7 vs 73.1 years, p=0.003), fewer smokers (26.4% vs 42.0%, p=0.006), and more needed transfusion of >= 2 units (54.5% vs 39.7%)
- Predefined covariables at baseline: age, sex, alcohol consumption, smoking, severity of comorbidities, history of GI bleeding (upper and lower), blood transfusion, meds (anticoagulants, steroids, non-aspirin antiplatelet drugs) within the 30 days prior to index bleed.
- Outcomes assessed: recurrent lower GI bleed, serious cardiovascular events (nonfatal MI, nonfatal stroke, death from vascular cause), and deaths from other causes
- Results, comparing non-users to users:
- Lower GI bleeding recurred in 18.9% of those on aspirin vs 6.9% of non-users (SHR 2.76; p=0.011) [SHR is subdistribution hazard ratios, which from my understanding is the probability of an event due to aspirin at a moment in time, comparing cause-specific cumulative incidences of different effects]
- Overt bleeding in 6.6% of non-users (n=8) vs 17.8% of users (n=31). both groups were transfused a median of 2 units of blood
- Occult bleeding in 1.7% (n=2) of non-users vs 6.9% of users (n=12)
- Serious cardiovascular events occurred in 22.8% of those on aspirin vs 36.5% of non-users (SHR 0.59; p=0.019)
- 2% of aspirin users died from other causes vs 26.7% of non-users (SHR 0.33; p=0.001): 42 patients overall died, including 22 from sepsis, 10 from cancer, and 6 from renal failure
- Multivariable analysis: aspirin use was an independent predictor of rebleeding but protected against major cardiovascular events and deaths
- Lower GI bleeding recurred in 18.9% of those on aspirin vs 6.9% of non-users (SHR 2.76; p=0.011) [SHR is subdistribution hazard ratios, which from my understanding is the probability of an event due to aspirin at a moment in time, comparing cause-specific cumulative incidences of different effects]
Commentary:
- A large number of people are on aspirin, up to 50% of men >40 yo. The major GI toxicity is upper GI, which can be decreased by concomitant use of a proton pump inhibitor (though that has its concerns: see https://stg-blogs.bmj.com/bmjebmspotlight/2016/02/25/primary-care-corner-with-geoffrey-modest-md-ppi-use-and-dementia/ which comments on a couple of articles on potential PPI-associated dementia and includes references to PPI-associated microbiome changes, MIs in those without prior history of heart disease, chronic kidney disease, pneumonia and a variety of GI infections, decreased bone density, etc.). But there is somewhat more concern about the lower GI bleeding: several observational studies have documented an increase in aspirin-associated lower GI bleeding (where PPIs are unlikely to be protective, so continued aspirin use is more dangerous). And those hospitalized for lower GI bleeding actually have a higher mortality than those with upper GI bleed.
- It is hard to draw clear conclusions from a retrospective study, given that the nonusers were older (which perhaps explains their increase in noncardiovascular deaths), though fewer were smokers. So, the multivariate analysis may have not fully compensated for differences in all risk factors/biases.
- But, I would add a few points:
- This article highlights the very likely conclusion that those with a lower GI bleed but at high cardiovascular risk are more likely to get benefit over harm by continuing aspirin use. The issue with the more common adverse event of aspirin-associated upper GI bleeding is a bit easier given the potential of adding acid suppression therapy to minimize recurrent risk
- I think it is also important to stress that aspirin may have real benefits in preventing cancer (see below). The data on this has been accumulating for many decades (I remember seeing data on aspirin or NSAIDs decreasing colonic adenomas/cancer dates back to the 1970s, with the support of a really large number of suggestive epidemiologic and animal studies), though potential cancer prevention was only recently incorporated into mainstream recommendations (see USPSTF guideline link below).
https://stg-blogs.bmj.com/bmjebmspotlight/2015/09/09/primary-care-corner-with-geoffrey-modest-md-low-dose-aspirin-and-colon-cancer-risk/ looks at the data on colon cancer prevention by low dose aspirin with links to other blogs on ovarian, prostate and other cancers.
http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer?ds=1&s=aspirin is a link to the USPSTF 2016 aspirin recommendations, which highlights using low dose aspirin in the primary prevention of both cardiovascular disease and colorectal cancer (i.e., not just for cardiovascular protection)