By 2030, more than 40% of the adult population of the United States is expected to exhibit one or more forms of cardiovascular disease, which in turn is likely to increase the aggressive use of antiplatelet and anticoagulant therapies to prevent cardiovascular (CV) events. But the benefits of antithrombotic therapies “is offset by the very real risk of gastrointestinal (GI) bleeding, especially in the aging baby boomer population,” Neena S. Abraham, MD, MSc, FACG, said in the David Sun Lecture she delivered at the American College of Gastroenterology (ACG) Virtual 2020 clinical meeting and postgraduate course.

Dr Abraham is a professor of Medicine and the Director of the CardioGI Clinic at the Mayo Clinic in Scottsdale, Arizona.

“It seems fitting in this year of change and unprecedented challenge that we think beyond our usual clinical paradigms,” she said. “Today, I’m going to share my medical passion with you that evolved from an unmet clinical need to a pragmatic field of study that has daily clinical relevance.”

She continued, “My journey started with a patient like this: a 76-year-old man with acute coronary syndrome, who had 3 drug-eluting stents placed and was put on a regimen of high-dose aspirin and clopidogrel. He came back to me with persistent occult GI bleeding and iron deficiency anemia despite iron supplementation. He also had some periodic hematochezia.”

Later, this patient also developed nonvalvular atrial fibrillation, causing their cardiologist to prescribe a third drug. “I had to wonder, what would his risk of GI bleed be with 3 antithrombotic drugs?”

The case motivated her to focus her attention on a new discipline she called cardioGI, which was further spurred by the introduction of another new oral anticoagulant therapy. “I started working closely with cardiologists to close knowledge gaps. Often I had to ask the questions most people don’t, do the studies most people weren’t interested in, had to apply flexibility in thinking outside my clinical training,” she explained.

Today, ACG, the American Heart Association, and the American College of Cardiology have  developed consensus documents on safety of concomitant use of thienopyridines and proton pump inhibitors (PPIs) to provide protection against GI bleeds and balance the needs of both the heart and the gut. However, Dr Abraham said, “There really is no contest. The heart always wins.”

Still, she said, epidemiological data confirm that a doubling of out-of-hospital bleeding was seen from 1995 to 2015, congruent with increase in use of antithrombotic agents. “We know it takes as few as 15 to 23 patients to be treated with triple therapy to incur one additional clinically significant GI bleed,” Dr Abrahams explained. “When you consider 150 million patients worldwide are prescribed an antithrombotic agent, that’s a lot of potential GI bleeding.”

Dr Abraham gave her 3 key pearls of wisdom when dealing with patients who need both protection against GI bleeds and antithrombotic therapy for CV disease. “First, remember that a drug is a poison with one good side effect,” she said. “You must know who the high-risk patient is, first of all. And across all subgroups of CV disease, GI bleeding increases with age, regardless of drug strategy. Bleeds in patients over 75 years of age increase from 10% to 17.5% per year on therapy with multiple antithrombotics.”

“All antithrombotics are bad for the GI tract,” she said, leading to the key question, “What’s the better bad choice? Apixaban is the safest of all the oral antithrombotics, even in very elderly patients.”

The second pearl is “An ounce of prevention is worth a TON of cure.” Preventing GI bleeds can be a matter of working with cardiologists to aggressively manage risk, which is the most impactful strategy, she said. “Always recommend the lowest possible dose of aspirin, and remember, enteric formulas offer NO protection. That is so 1990s!”

Patients should also be checked for Helicobacter pylori and if it is found, it must be eradicated, Dr Abraham said. Combination therapy with antithrombotics is significant risk factor for GI bleeds, but adding a PPI “is low hanging fruit every gastroenterologist should prescribe to reduce risk.”

Finally, Dr Abraham said, “Think beyond the scope. Aggressive risk minimization always yields favorable results. And consider nonpharmacologic options for CV, such as left atrial appendage occlusion devices (LAAO), a proven alternative to drugs for stroke prevention, if patients continue to have GI bleeds. With the LAAO, there have been 72% fewer bleeding incidents shown in one study.”

Eradicating GI bleeds in cardiac patients will require closing significant knowledge gaps through both pharmacogenic studies and endoscopic strategies, Abraham said. “We must embrace intersectional thinking, or what’s called the Medici effect—when you bring together different disciplines to force thinking into new paths.”

--Rebecca Mashaw

Reference:

Abraham NS. David Sun Lecture: Cardiogastroenterology: intersectional thinking to meet new clinical needs. Talk presented at: American College of Gastroenterology Virtual 2020 Clinical Meeting and Postgraduate Course. October 23, 2020.