No increased CV, death risk with ticagrelor plus proton pump inhibitor therapy after PCI

AstraZeneca, Biosensor and The Medicines Company supported the GLOBAL LEADERS trial. Serruys reports receiving personal fees from Philips/Volcano, Sino Medical Sciences Technology and Xeltis, outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.

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Concomitant proton pump inhibitor plus ticagrelor monotherapy after PCI does not increase risk for all-cause death or an adverse CV event, in contrast with conventional post-PCI antiplatelet therapy, researchers reported.

In a post hoc analysis of the GLOBAL LEADERS trial, researchers found that patients taking a proton pump inhibitor (PPI) treated with the conventional post-PCI treatment strategy of 12-month dual antiplatelet therapy followed by aspirin monotherapy were more likely to experience all‐cause mortality, MI, stroke or repeat revascularization compared with those not taking a PPI.

Patrick W. Serruys

“In daily clinical practice, PPIs are often prescribed together with antiplatelet agents to prevent upper gastrointestinal bleeding,” Patrick W. Serruys, MD, PhD, professor of medicine at Imperial College London, and colleagues wrote in the study background. “However, previous studies have suggested that PPIs may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to an increase in serious cardiovascular events. Numerous studies have reported conflicting results about the drug interaction between those antiplatelet agents and PPIs. Thus far, a few randomized controlled trials comparing antiplatelet therapy with concomitant PPI in patients with CVD have questioned whether any significant association exists between PPIs and adverse clinical outcomes when used together with clopidogrel or aspirin after PCI; however, there are scarce data on the interaction between PPIs and more potent P2Y12 inhibitors, such as ticagrelor.”

Assessing PPI use

As Healio previously reported, the GLOBAL LEADERS study demonstrated that 1 month of combination ticagrelor (Brilinta, AstraZeneca) and aspirin therapy followed by ticagrelor alone was not superior to 1-year standard DAPT followed by 1-year aspirin monotherapy for reducing deaths or MI over 2 years in patients who undergo PCI.

For the subanalysis, Serruys and colleagues assessed the association between PPIs and clinical outcomes among 15,839 patients assigned to the antiplatelet arm (23‐month ticagrelor monotherapy after 1‐month DAPT) and those assigned to the reference arm (12‐month aspirin monotherapy after 12‐month DAPT) after PCI. Researchers analyzed patient‐oriented composite endpoints, defined as all‐cause mortality, MI, stroke or repeat revascularization) stratified by PPI use.

The findings were published in Catheterization and Cardiovascular Interventions.

Within the cohort, 13.5% of patients experienced a composite endpoint event at 2 years. In both arms, overall PPI use was nearly 50% and did not change over time irrespective of the discontinuation of DAPT according to the assigned treatment.

In the reference arm, the use of PPIs was independently associated with patient‐oriented composite endpoints (HR = 1.27; 95% CI, 1.12-1.44) and its individual components. PPI use was not associated with the composite endpoint in the ticagrelor arm (HR = 1.04; 95% CI, 0.92-1.19; P for interaction = .035).

PPI use ‘may be safe’ with ticagrelor

During the second‐year follow‐up, patients taking aspirin with PPIs had a higher risk for a patient‐oriented composite endpoint compared with those taking aspirin without PPIs (HR = 1.57; 95% CI, 1.27-1.94). Risk did not differ by PPI use for those in the ticagrelor monotherapy group (HR = 1.03; 95% CI, 0.83-1.28; P for interaction = .008).

The researchers noted that PPI use was not randomized in GLOBAL LEADERS and it is possible unmeasured confounders affected the use of PPIs and the outcomes, making any findings hypothesis-generating.

“Among patients treated with the conventional post‐PCI antiplatelet strategy of 12‐month DAPT followed by aspirin monotherapy, the use of PPIs was associated with an increased risk of cardiovascular events,” the researchers wrote. “In contrast, among those with the experimental antiplatelet strategy of 1‐month DAPT followed by 23‐month ticagrelor monotherapy, there were no evidence suggesting that PPIs could increase cardiovascular events. PPI use may be safe in patients with ticagrelor monotherapy, which should be confirmed in further studies.”

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