Study highlights cardiovascular benefits, lower GI risks of low-dose aspirin

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.”

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.

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.”

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.

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.”

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.