Silent Gastrointestinal Bleeds Track With Antiplatelet Choice After PCI

The degree of new or worsening gastrointestinal (GI) injury after percutaneous coronary intervention (PCI) depended on what patients took for their antiplatelet therapy, according to serial endoscopy results from the OPT-PEACE trial.

Following standard 6-month dual antiplatelet therapy (DAPT) after angioplasty, people who went on to aspirin monotherapy had the lowest rate of progressive gastric injury by 12 months compared with peers randomized to clopidogrel (Plavix) monotherapy or continued DAPT (37.1% vs 48.5% vs 53.1%, P=0.02).

A similar pattern was observed for progressive small intestinal injury (38.6% vs 49.2% vs 54.6%, P=0.03).

In this cohort who went into PCI without high bleeding risk, there was a significantly lower rate of gastric injury progression between aspirin users and DAPT users (RR 0.70, 95% CI 0.49-0.99), which was echoed for the secondary endpoint of worsening of small intestinal injury (RR 0.71, 95% CI 0.50-0.99), reported Zhuan Liao, MD, of Changhai Hospital of Naval Medical University in China, and colleagues in JAMA Network Open.

“The findings of our study suggest that patients without a high risk of GIB [GI bleeding] treated with continuous antiplatelet therapy may progress to a high-risk phenotype for GIB,” the study authors concluded.

Antiplatelets are a standard secondary prevention therapy to avoid subsequent cardiac events — their main caveat being the increased risk of GI bleeding from long-term use. People with clinically silent gastric or small intestinal injury are predisposed to developing overt GI bleeding, and such bleeds after hospital discharge are a strong predictor of mortality.

“The results of our study suggest that routine [magnetically controlled capsule endoscopy] in patients without a high risk of GIB may identify those with dynamic changes in gastrointestinal tract injury scores during antiplatelet therapy, portending an increased risk of overt GIB. Judicious approaches in such patients may include gastrointestinal prophylaxis or a shortened DAPT course if ischemic risk is low,” Liao’s group suggested.

Proton-pump inhibitors are widely used for GI prophylaxis in patients with a history of peptic ulcer, GI bleeding, and other bleeding risk factors. Given their links to kidney disease, bone fractures, dementia, and other adverse events, however, they are not usually considered for individuals without high GI bleeding risk.

With the present report, Liao’s group argued that these patients may still progress to high GI bleeding risk. “Recognizing gastrointestinal injury progression during continuous antiplatelet therapy is an important first step prior to developing risk stratification tools to adjust treatment during long-term use,” the team wrote.

Guidelines currently recommend DAPT for at least 6 or 12 months after PCI, depending on the indication, for those without high bleeding risk. However, newer evidence suggests that a shorter course of DAPT followed by monotherapy can be good enough for ischemic protection without causing excess bleeding.

For the present study, Liao and colleagues performed a post hoc analysis of the OPT-PEACE trial, a double-blind multicenter trial that included patients who underwent successful PCI with drug-eluting stents and who did not have high GI bleeding risk. All had gone into angioplasty for stable coronary artery disease or acute coronary syndrome (without ST-segment elevation) and had serial endoscopy done with the noninvasive, magnetically controlled capsule system NaviEC-1000.

After 6 months of DAPT, those who still had no evidence of gastrointestinal ulcers or bleeding were randomized to aspirin plus matching placebo (aspirin alone; n=132), clopidogrel plus matching placebo (clopidogrel alone; n=132), or DAPT (n=130) for an additional 6 months.

The main result of OPT-PEACE was that nearly all people on antiplatelets after PCI developed some form of GI injury within a year. However, PCI patients who received DAPT for 6 months and switched to monotherapy thereafter had less GI injury, as assessed with serial noninvasive endoscopy, than peers staying on DAPT the whole time.

Included in this report were 394 patients (mean age 56.9 years, 75% of whom were men) with sufficient serial endoscopy results.

Gastric or small intestinal injury progression was defined as a quantitative increase in erosions or ulcers between 6 and 12 months after PCI.

Liao and co-authors reported no differences in progressive GI injury with clopidogrel vs DAPT or aspirin vs clopidogrel.

Nevertheless, the researchers said their report extends results from prior studies “that reported a higher incidence of small-intestinal injury with DAPT than aspirin monotherapy and that clopidogrel exacerbates aspirin-related small-intestinal injury or prevents healing. However, the mechanism underlying how clopidogrel drives gastrointestinal injury from intact mucosa remains uncertain.”

Liao and colleagues warned that the OPT-PEACE trial had not been designed with a power calculation for this secondary analysis, and that the findings should be validated in a broader range of patients. Additionally, the group urged more research on the effects that consuming alcohol and H. pylori infection may have on GI injury in this patient population.

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