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Proton pump inhibitors increase 2-year MACE risk in patients treated with clopidogrel, PCI
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In clopidogrel-treated patients who undergo PCI, the use of proton pump inhibitors is associated with significantly higher 2-year adjusted risk for MACE and net adverse CV events, according to results from the PARIS registry.
In the prospective observational study conducted between July 2009 and December 2010, Jaya Chandrasekhar, MBBS, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues evaluated 4,635 patients (mean age, 64 years) who underwent PCI in 15 U.S. and European centers. According to the researchers, all of the patients underwent PCI with a minimum of one stent implantation and were discharged on a regimen of aspirin and clopidogrel; 1,062 (23%) patients were discharged from the hospital on proton pump inhibitors (PPIs) after index PCI.
Patients were followed up by telephone at 30 days, and 6, 12 and 24 months. The researchers acquired source documents for all patients who reported adverse events. Formal adjudication of all adverse events, as well as episodes of dual antiplatelet therapy cessation, were conducted by an independent, masked clinical events committee, the researchers wrote.
The study’s primary ischemic endpoint was 2-year MACE, defined as the composite of cardiac death, definite or probable stent thrombosis, spontaneous MI or clinically indicated target lesion revascularization, according to the researchers. The Bleeding Academic Research Consortium (BARC) and TIMI risk score criteria were used to define the bleeding endpoints, with major bleeding classified as BARC types 3 or 5.
Secondary endpoints included net adverse CV events, defined as a composite of MACE or BARC types 3 or 5 bleeding. DAPT cessation was assessed as a composite of discontinuation, interruption or disruption, and analyzed for associations with PPI use, the researchers wrote.
They found that PPI users had the following baseline characteristics vs. non-PPI users: older age (65 years vs. 64 years; P = .0015), higher prevalence of women (30.5% vs. 24.7%; P = .0002), lower prevalence of current smoking (16.9% vs. 20.2%), higher prevalence of previous MI (27.1% vs. 23.1%; P = .0074) and higher prevalence of previous PCI (40.2% vs. 35.1%; P = .0025).
PPI and MACE
MACE at 2 years was higher in PPI users (13.8% vs. 10.2%; adjusted HR = 1.27; 95% CI, 1.04-1.55), due to higher rates of TLR (9.1% vs. 6.3%; adjusted HR = 1.33; 95% CI, 1.04-1.71) in PPI users. There were no differences in death (5.6% vs. 4.3%), stent thrombosis (1.9% vs. 1.2%) or MI (3.9% vs. 3.5%) in PPI users vs. non-PPI users, according to the data.
Likewise, no difference was seen in the incidence of BARC types 3 or 5 (4% vs. 4.1%), TIMI major (1.9% vs. 2.2%) or TIMI minor bleeding (1.5% vs. 1.5%) between groups. However, net adverse CV events were more prevalent in PPI users (16.3% vs. 13%; adjusted HR = 1.21; 95% CI, 1.01-1.44).
Adjustment for potential confounders revealed a persistent higher risk for MACE (HR = 1.28; 95% CI, 1.05-1.56) in PPI users vs. non-PPI users.
DAPT disruption
Although the two groups had comparable rates of 2-year DAPT discontinuation and interruption, PPI users had lower rates of DAPT disruption vs. non-PPI users (10% vs. 14.7%; P < .0001). Physician nonrecommended disruption of DAPT was linked to higher rates of MACE in PPI users (HR = 2.34; 95% CI, 1.38-3.97) and nonusers (HR = 1.41; 95% CI, 1.02-1.94), but was associated with higher risk for BARC types 3 or 5 bleeding only in non-PPI users (HR = 2.06; 95% CI, 1.21-3.51).
“Clopidogrel-treated PCI patients discharged on PPI represent a higher-risk group with a significantly greater adjusted 2-year risk of MACE and [net adverse CV event] outcomes driven by higher TLR compared to non-PPI users, without a difference in bleeding,” the researchers wrote. “PPI use is associated with lower rates of DAPT disruption without an increase in disruption-related major bleeding compared to non-PPI users on DAPT.” – by Jennifer Byrne
Disclosure: Chandrasekhar reports no relevant financial disclosures. Please see the full study for a list of the other researchers’ relevant financial disclosures.
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