Washington DC - Proton-pump inhibitors (PPIs) should be the mainstay of treatment and prevention of gastrointestinal ulcers and bleeding in patients on antiplatelet therapy who are at increased risk for the GI complications, according to an "expert consensus document" developed by the American College of Cardiology, American Heart Association, and American College of Gastroenterology and published online October 3, 2008 [1].

The report supplements evidence-based guidelines in an area for which there is little clinical-trial-quality data for guidance: how to manage the two-edged sword of prostaglandin suppression by aspirin (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors, in patients taking antiplatelets. These agents are anti-inflammatory and, ASA in particular, can reduce vascular thrombotic risk, but they also can promote GI ulcer formation and bleeding. Other antiplatelets like clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) can worsen GI bleeding.

"Given the high prevalence of antiplatelet therapy in clinical practice, coupled with an increased emphasis on [its] extended use, especially after implantation of a drug-eluting stent, it is imperative that physicians know the potential benefits and the associated risks of antiplatelet therapy for primary or secondary prevention of cardiac ischemic events when combined with NSAID agents," states the report. Its writing committee was cochaired by cardiologist Dr Deepak L Bhatt (Brigham and Women's Hospital and VA Boston Healthcare System, Boston, MA) and gastroenterologist Dr James M Scheiman (University of Michigan, Ann Arbor).

The expert consensus document represents a collaborative effort between cardiologists and gastroenterologists aimed at putting both groups on the same page regarding safety issues that straddle both specialties, Bhatt told heartwire. It identifies several groups of patients on antiplatelet therapy in whom the GI risk is particularly pronounced and who, therefore, would benefit from taking a PPI. The high-risk groups, according to the report, include patients with a history of ulcer disease, GI bleeding, a need for dual antiplatelet therapy, or an indication for warfarin or other anticoagulants.

When to recommend gastroprotection with a PPI "was something that the cardiology and gastroenterology experts discussed quite a bit," Bhatt said. The cardiologists, used to basing recommendations on randomized, controlled trials, wrestled somewhat with what to recommend given the limited evidence base, Bhatt observed. But, "the gastroenterologists were unanimous in their opinion that in a patient at high risk of GI bleeding, a proton pump inhibitor would be indicated prophylactically. Their feeling was, other than issues of cost, there really wasn't much reason to give that a second thought."

Other points and recommendations made in the document:

• All NSAIDs, including COX-2 inhibitors, raise the risk of GI ulcers and bleeding when combined with ASA taken chronically for cardioprotection.
• Even on its own, chronic ASA for cardioprotection increases the risk of upper-GI events and should generally be limited to 81 mg/day.
• Patients at increased GI bleeding risk should go on a PPI; those with a history of ulcers should be evaluated and, as appropriate, treated for Helicobacter pylori infection before starting antiplatelet therapy.
• Substituting clopidogrel for ASA doesn't cut the risk of GI bleeding and isn't as effective as the combination of ASA and a PPI.
• PPIs such as lansoprazole and omeprazole are preferred over misoprostol, sucralfate, or H2-receptor antagonists for both the prevention and treatment of gastroduodenal lesions associated with ASA and other NSAIDs.
• "Communication between cardiologists, gastroenterologists, and primary-care physicians is critical to weigh the ischemic and bleeding risks in an individual patient who needs antiplatelet therapy but who is at risk for or develops significant GI bleeding."

Bhatt acknowledged that consideration of H pylori infection might be something new for many cardiologists. "I must say that before getting involved with this, it wasn't at the top of my thinking, either," the writing committee cochair said. "But I hope what this document does is broaden cardiologists' thinking, such that if they are prescribing antiplatelets and anticoagulants, which of course they will be prescribing all the time, they will at least consider the gastrointestinal risks and either take steps themselves to modify that risk or refer to other physicians who handle gastrointestinal risk."