From the AGA Journals

Stopping aspirin after bleeding ulcer raises CV death rate sixfold

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Stopping aspirin after ulcer bleeding: More risk than benefit

When patients with coronary artery disease or cerebrovascular disease develop GI bleeding and undergo endoscopic therapy, a question that most gastroenterologists face is whether aspirin, clopidogrel, or both should be restarted, and if so, when. Many of these patients are at high risk for bleeding-related complications due to advanced age and comorbidities and are also at increased risk for cardiovascular or cerebrovascular complications due to advanced vascular disease.

There are four possible courses of action for the practitioner: Discontinue the aspirin and clopidogrel with no intent to resume them, discontinue aspirin and resume clopidogrel, resume both antiplatelet drugs after endoscopic hemostasis is achieved, or withhold antiplatelet drugs for 7-10 days after endoscopic hemostasis has been achieved.

Although we do not have a complete and valid evidence base to guide our current practice, several important points can be made from recent studies. Ms. Derogar and her colleagues show us that discontinuing aspirin completely is associated with a high rate of death or cardiovascular complications. Rebleeding, on the other hand, was rare patients in whom aspirin was continued. In a recent randomized controlled trial, patients on low-dose aspirin who developed a GI bleed were randomized to continued aspirin or no aspirin after endoscopic hemostasis (Ann. Intern. Med. 2010;152:1-9). Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group. Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%). Other studies have shown that resuming aspirin with a proton pump inhibitor is superior to administering clopidogrel alone.

There is little evidence to guide us as to whether aspirin or clopidogrel should be held for a short period of time or resumed immediately after endoscopic hemostasis is achieved. This decision should probably be individualized based on the magnitude of the bleeding, the severity of the underlying cardiovascular and cerebrovascular disease, and concurrent comorbid illnesses. The available evidence is clear that it is unwise to discontinue aspirin in patients receiving this agent for cardiovascular or cerebrovascular disease due to the high rate of adverse outcomes.

Nimish Vakil, M.D., AGAF, is a clinical professor of medicine at the University of Wisconsin School of Medicine and Public Health, Madison. He is a consultant to AstraZeneca, Takeda, Otsuka, Xenoport, Orexo, Ironwood, and Restech, and has stock options in Orexo and Meridian Bioscience.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Aspirin therapy should be continued at the time of hospital discharge in patients with cardiovascular comorbidities treated for peptic ulcer bleeding, researchers say.

Among patients taking low-dose aspirin therapy who were hospitalized for bleeding of peptic ulcers, those who stopped aspirin altogether were more than six times as likely to die or have a cardiovascular event in the near future as were patients who resumed aspirin therapy after discharge, according to a database analysis. Researcher Maryam Derogar of the Karolinska Institute, Stockholm, and her associates reported their findings in the January issue of Clinical Gastroenterology and Hepatology.

Video Source: American Gastroenterological Association YouTube channel

"Balancing between the cardioprotective effect of aspirin and the increased risk of rebleeding associated with aspirin use requires a careful clinical tradeoff," the investigators wrote (Clin. Gastroenterol. Hepatol. 2013;11:38-42).

They noted that all deaths or acute CV events in the study were among patients at least 64 years old. The study findings indicate that aspirin therapy should not be permanently discontinued in older patients at cardiovascular risk who develop bleeding peptic ulcer, but should resume after the bleeding episode is treated, they wrote.

Given the ulcerogenic properties of aspirin, "concomitant prescription of acid suppressants in the form of proton pump inhibitors is highly recommended," the researchers added.

Only one randomized clinical trial has examined the consequences of discontinuing aspirin therapy in this patient population, and it found a substantially higher risk of short-term mortality in patients who didn’t resume taking aspirin after treatment of the bleeding ulcer (Ann. Intern. Med. 2010;152:1-9). However, that trial had methodological flaws and a short follow-up of only 8 weeks, the investigators said.

They used an administrative database at their hospital to examine this issue, reviewing the medical records of 118 adults treated in 2007-2010 for upper GI bleeding. All the study subjects had endoscopically verified peptic ulcer and were taking low-dose aspirin therapy (75 mg or 160 mg daily) at the time of hospitalization.

Patients who had bleeding from sources other than peptic ulcer, such as esophageal varices or angiodysplasia, were excluded from the study.

Aspirin therapy was permanently discontinued in 40% (47) of the study subjects. Forty percent of patients (48) restarted aspirin therapy immediately after hospital discharge, and the remaining 20% (23) restarted aspirin therapy a median of 1 week later (range, 2 days to 2 months).

During a median follow-up of 2 years, 37% (44) of study subjects either died or had acute cardiovascular events.

The rate of death or acute CV events during the first 6 months of follow-up was more than sixfold higher in patients who discontinued aspirin therapy than in those who resumed aspirin therapy, with a hazard ratio of 6.8, the investigators said. The investigators adjusted the comparison to account for numerous potential confounders, such as alcohol abuse, chronic ischemic heart disease (angina), chronic heart failure, previous MI, atrial fibrillation, previous stroke or TIA, chronic renal failure, diabetes, COPD, and cancer.

Further analysis showed that the rate of mortality and acute CV events during the first 6 months of follow-up rose only in study subjects who had existing cardiovascular comorbidities at hospitalization, and did not rise in those who had no CV comorbidities. This rate was 31% in the 26 such patients who stopped aspirin therapy, compared with only 8% in the 50 who resumed aspirin therapy.

After 6 months of follow-up, the rate of mortality and acute CV events was not significantly different between patients who stopped and patients who resumed aspirin therapy.

Six percent of patients required rehospitalization for recurrent peptic ulcer bleeding during follow-up. No patients died from such rebleeding.

These findings confirm and extend those of the previous randomized clinical trial, which reported an eightfold increase in mortality during 2 months of follow-up for patients who permanently discontinued aspirin therapy, Ms. Derogar and her colleagues said.

No patients in their study who were under age 64 died or developed an acute CV event. "The results are therefore not fully applicable to younger patients and might imply that the elderly are more susceptible to discontinuation of aspirin therapy," they wrote.

Ms. Derogar reported no potential financial conflicts of interest. One of her associates reported receiving a scholarship from the Olle Engkvist Byggmastare Foundation.

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