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Study Highlights Cardiovascular Benefits, Lower GI Risks of Low-dose Aspirin

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Key clinical point: Resuming low-dose aspirin after a lower gastrointestinal bleed increased the risk of recurrence but protected against cardiovascular events.

Major finding: At 5 years, the cumulative incidence of recurrent lower GI bleeding was 19% for patients who stayed on aspirin and 7% for patients who largely stopped it (P = .01). The cumulative incidence of serious cardiovascular events was 25% for users and 37% for nonusers (P = .02).

Data source: A single-center 5-year retrospective cohort study of 295 patients with aspirin-associated melena or hematochezia and no upper gastrointestinal bleeding.

Disclosures: The Chinese University of Hong Kong funded the study. Dr. Chan reported financial ties to Pfizer, Eisai, Takeda, Otsuka, and Astrazeneca.

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'The message is clear'

Going back to low-dose aspirin after an index lower-gastrointestinal (LGI) bleed significantly increased recurrences of LGI bleeding while reducing rates of serious cardiovascular (CV) events and deaths, in a single-center, retrospective study of 295 patients from Hong Kong. Specifically, the 5-year cumulative risks of recurrent LGI bleeding were 19% in aspirin users vs. 7% for nonusers (P = .01), severe CV events (myocardial infarction or cerebrovascular accident) were 25% in aspirin users vs. 37% in nonusers (P = .02), and all-cause mortality rates for aspirin users vs. nonusers were 8.2% vs. 26.7% (P = .001).

This study complements what this research group previously published about resuming aspirin early in high-risk patients after severe ulcer hemorrhage to reduce the risk of fatal CV events (Ann Intern Med. 2010;151:1-9). Recurrent ulcer bleeding was more common in those who resumed aspirin, but fewer died of CV causes within 30 days. Until the investigators’ current publication, no reports on LGI hemorrhage were available to help clinicians weigh the risks and benefits of resuming aspirin. Despite some limitations of the current study, the message is clear about the benefits of aspirin even in the face of recurrent, nonfatal bleeding.

It seems wise to restart low-dose aspirin in patients who have a documented risk for CV events. Meanwhile, gastroenterologists can take care of the rebleeding and further study this problem.

Dennis Jensen, MD, is a digestive diseases specialist in the departments of medicine and gastroenterology at Ronald Reagan UCLA Medical Center, Los Angeles.


 

FROM GASTROENTEROLOGY

References

Resuming low-dose aspirin after an initial lower gastrointestinal bleed significantly increased the chances of recurrence but protected against serious cardiovascular events, based on a single-center retrospective study published in the August issue of Gastroenterology.

In contrast, “we did not find concomitant use of anticoagulants, antiplatelets, and steroids as a predictor of recurrent lower GI bleeding,” said Dr. Francis Chan of the Prince of Wales Hospital in Hong Kong and his associates. “This may be due to the low percentage of concomitant drug use in both groups. Multicenter studies with a large number of patients will be required to identify additional risk factors for recurrent lower GI bleeding with aspirin use.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Low-dose aspirin has long been known to help prevent coronary artery and cerebrovascular disease, and more recently has been found to potentially reduce the risk of several types of cancer, the researchers noted. Aspirin is well known to increase the risk of upper GI bleeding, but some studies have also linked it to lower GI bleeding. However, “patients with underlying cardiovascular diseases often require lifelong aspirin,” they added. The risks and benefits of stopping or remaining on aspirin after an initial lower GI bleed are unclear (Gastroenterology 2016 Apr 26. doi: 10.1053/j.gastro.2016.04.013).

Accordingly, the researchers retrospectively studied 295 patients who had an initial aspirin-associated lower GI bleed, defined as 325 mg aspirin a day within a week of bleeding onset. All patients had melena or hematochezia documented by an attending physician and had no endoscopic evidence of upper GI bleeding.

For patients who continued using aspirin at least half the time, the 5-year cumulative incidence of recurrent lower GI bleeding was 19% (95% confidence interval [CI], 13%-25%) – more than double the rate among patients who used aspirin 20% or less of the time (5-year cumulative incidence, 7%; 95% CI, 3%-13%; P = .01). However, the 5-year cumulative incidence of serious cardiovascular events among nonusers was 37% (95% CI, 27%-46%), while the rate among aspirin users was 23% (95% CI, 17%-30%; P = .02). Mortality from noncardiovascular causes was also higher among nonusers (27%) than users (8%; P less than .001), probably because nonusers of aspirin tended to be older than users, but perhaps also because aspirin had a “nonvascular protective effect,” the researchers said.

A multivariate analysis confirmed these findings, linking lower GI bleeding to aspirin but not to use of steroids, anticoagulants, or antiplatelet drugs, or to age, sex, alcohol consumption, smoking, comorbidities, or cardiovascular risks. Indeed, continued aspirin use nearly tripled the chances of a recurrent lower GI bleed (hazard ratio, 2.76; 95% CI, 1.3-6.0; P = .01), but cut the risk of serious cardiovascular events by about 40% (HR, 0.59; 95% CI, 0.4-0.9; P = .02).

Deciding whether to resume aspirin after a severe lower GI bleed “presents a management dilemma for physicians, patients, and their families, particularly in the absence of risk-mitigating therapies and a lack of data on the risks and benefits of resuming aspirin,” the investigators emphasized. Their findings highlight the importance of weighing the cardiovascular benefits of aspirin against GI toxicity, they said. “Since there is substantial risk of recurrent bleeding, physicians should critically evaluate individual patients’ cardiovascular risk before resuming aspirin therapy. Our findings also suggest a need for a composite endpoint to evaluate clinically significant events throughout the GI tract in patients receiving antiplatelet drugs.”

The Chinese University of Hong Kong funded the study. Dr. Chan reported financial ties to Pfizer, Eisai, Takeda, Otsuka, and Astrazeneca.

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