Stopping Aspirin in CV Patients With Ulcers: Pros and Cons
December 1, 2009 (Hong Kong, China) — A new randomized trial--albeit a small one--suggests that continuing aspirin in patients with cardiovascular disease who develop peptic-ulcer bleeding will, not surprisingly, double their risk of bleeding but may also radically reduce their risk of all-cause mortality [1]. The increased bleeding was seen despite all patients receiving a 72-hour infusion of the proton-pump inhibitor (PPI) pantoprazole, followed by oral pantoprazole, after undergoing endoscopic therapy.
The paper, by Dr Joseph JY Sung and colleagues, is published online December 1, 2009 in the Annals of Internal Medicine and concludes that "early resumption" of low-dose aspirin "should be considered" in patients with bleeding ulcers to minimize the mortality risk of stopping aspirin.
To heartwire , Sung emphasized that the study was not powered to detect a difference in mortality: "Therefore, the possibility that the difference in all-cause mortality is merely [due to] chance cannot be excluded. However, cardiologists and gastroenterologists should be aware that there is a likelihood of increasing risk of cardiovascular death if aspirin is withheld for a prolonged period. A balance of risk and benefit of restarting aspirin should be considered."
To Stop or Not Stop
The study enrolled 156 patients already taking aspirin for secondary prevention of cardiovascular or cerebrovascular events who developed peptic-ulcer bleeding; after diagnosis and treatment (hemostasis achieved) of a bleeding ulcer, patients were randomized to receive low-dose aspirin or placebo for eight weeks. (Of note, patients taking clopidogrel were included in the study, but clopidogrel was stopped until the ulcer was completely healed.) Three patients withdrew during the course of the study.
In an intention-to-treat analysis, recurrent ulcer bleeding at 30 days--the study's primary end point--was nearly twice as high in the aspirin group as the placebo group. For the secondary end point of all-cause mortality, placebo-treated patients had a more than 10-fold increase in events, a statistically significant difference. Aspirin-treated patients also had lower rates of mortality due to cardiovascular, cerebrovascular, or gastrointestinal events.
Bleeding and Mortality Outcomes
| Event | Aspirin (%) | Placebo (%) |
| Recurrent ulcer bleeding, 30 d | 10.3 | 5.4 |
| All-cause mortality, 8 wk | 1.3 | 12.9 |
| Death due to cardiovascular, cerebrovascular, or gastrointestinal complications, 8 wk | 1.3 | 10.3 |
"Among low-dose-aspirin recipients who had peptic-ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates," the authors cautiously conclude. "Larger trials are needed to confirm these findings."
Commenting on the findings for heartwire , Dr Dominick Angiolillo (University of Florida, Jacksonville) emphasized the small size of the study, pointing out that, typically, much larger randomized controlled trials have had "difficulty" showing differences in mortality; as such, the mortality differences seen by Sung et al "need to be taken with a grain of salt."
"Especially since this [mortality finding] is a secondary end point, this needs to be considered with caution," Angiolillo warned. "The other thing to keep in mind is that the study outcomes were evaluated out to eight weeks, and we do know that with bleeding, there can be potential clinical implications even long-term, beyond the eight weeks, which obviously are not reported in this study."
Long-term effects of bleeding include future ischemic events and CV mortality, he added.
"I would not make any definitive statements on what should be done [on the basis of this study]," Angiolillo told heartwire . "What we clearly know is that if you continue patients on aspirin, the patient is likely going to bleed, and the PPI, even given under infusion, is not going to prevent that."
What the study underscores is the need to evaluate patients on a case-by-case basis, he continued. Some patients on antiplatelet medication who develop bleeding may have good indications for continuing on aspirin.
"One indication may be a patient with a recent MI, who got a DES placed in the proximal LAD a week ago." he said. "That's very different from another patient who is on aspirin for a CV event [that took place] two years ago."
An editorial accompanying the study also urges caution in interpreting the study results, pointing to a number of methodological issues with the study [2]. But Drs Alan N Barkun (Montreal General Hospital, QC) and Marc Bardou (Centre Hospitalier Universitaire de Dijon, France) also urge physicians to "reconsider the all-too-common paradigm" of focusing on the gut at the expense of the heart.
"On the basis of all available data, international consensus recommendations (including the results from Sung and colleagues) concluded that patients with upper gastrointestinal bleeding who require secondary cardiovascular prophylaxis should resume low-dose aspirin therapy as soon as the cardiovascular risks outweigh the gastrointestinal risks (usually within seven days)," they note. "Until additional data become available to better guide management, clinicians will need to rely on limited evidence and appropriate use of common sense that considers the patient as a whole without focusing on a specific organ system to the detriment of another."
