The Antiplatelet Effect of Aspirin Is Reduced by Proton Pump Inhibitors in Patients With Coronary Artery Disease

Würtz, Morten; Grove, Erik Lerkevang; Kristensen, Steen Dalby

doi:10.1016/s0735-1097(10)60451-2

Cited by 43 publications

(54 citation statements)

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“…Since aspirin absorption is dependent on low intragastric pH 29) , it is possible that PPIs, which were recommended for patients at high risk for gastrointestinal tract bleeding under antithrombotic therapy 30) , may influence the antiplatelet effect of aspirin 31) . Indeed, some studies have reported that concomitant use of PPIs reduced the platelet response to aspirin in patients with CAD 32) and increased cardiovascular events 33) ; however, in the present study, MARs and the PRP-PATI value were not notably different between patients receiving PPIs or not, suggesting that PPIs did not affect the antiplatelet effect of aspirin in the real clinical setting.…”

Section: Incidence Of Macces In Subgroup Of Patients Aged 70 Years Ancontrasting

confidence: 83%

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Yamane¹,

Ikeda²,

Taniguchi³

et al. 2012

JAT

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Aim:Aspirin is an antiplatelet drug widely used for the prevention of cardiovascular disease; however, it is known to increase bleeding events. A low response to aspirin was reported to correlate with poor prognosis in patients undergoing antiplatelet therapy with aspirin. The aim of this study was to evaluate the impact of the antiplatelet activity of aspirin on cardiovascular and bleeding events in Japanese patients. Methods: We analyzed the clinical course of 239 Japanese patients undergoing antiplatelet therapy with aspirin for a median of 64 months in this study. Their residual platelet reactivity was examined at enrollment and after 2 years. The co-primary endpoints were the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) and bleeding events. Results: The annual incidence of MACCEs and major bleeding events was 3.7% and 0.48%, respectively. With defined criteria, 67 patients (28%) were classified as low responders based on the platelet aggregability measured at enrollment. Low response to aspirin was not associated with increased MACCEs, while it clearly increased MACCEs in patients less than 70 years old (low responders 36.9% vs. responders 14.8%, log rank p=0.008). Five major types of bleeding occurred in the responders, but not in low responders, although the difference was not statistically significant (p = 0.07). Conclusion: Low response to aspirin was not associated with the increase of long-term MACCEs, while it increased MACCEs in patients less than 70 years old; however, it tended to decrease major bleeding events in Japanese patients.

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Section: Incidence Of Macces In Subgroup Of Patients Aged 70 Years Ancontrasting

confidence: 83%

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Yamane¹,

Ikeda²,

Taniguchi³

et al. 2012

JAT

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“…Fourth, there is limited evidence that PPIs may interfere with the response to acetylsalicylic acid. 39,40 Theoretically, this mechanism could account for an increased risk of cardiovascular events associated with the use of PPIs in both the clopidogrel and ticagrelor groups; however, the data are conflicting in regard to this potential. 40 -44 Fifth, our analysis is derived from a clinical trial population that specifically excluded some patients with high bleeding risk and/or comorbidities such that the potential impact of PPIs on clinical outcomes may differ when compared with a more generalized population.…”

Section: Discussionmentioning

confidence: 99%

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor

et al. 2012

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on behalf of the Platelet Inhibition and Patient Outcomes (PLATO) Trial InvestigatorsBackground-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (nϭ6539) compared with those not on a PPI (nϭ12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79 -1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14 -1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00391872. Key Words: acute coronary syndrome Ⅲ clopidogrel Ⅲ mortality Ⅲ myocardial infarction Ⅲ ticagrelor I n patients with both ST-segment and non-ST-segment elevation acute coronary syndromes (ACS), current clinical practice guidelines recommend the use of dual antiplatelet therapy with acetylsalicylic acid and P2Y12 inhibition. 1,2 Conflicting data exist regarding the potential adverse interaction between the effects on clinical events of the P2Y12 inhibitor clopidogrel and proton pump inhibitors (PPIs), whereas the importance of such an interaction with other P2Y12 inhibitors is less investigated. Clinical Perspective on p 986Several pharmacodynamic studies have shown that some PPIs reduce the inhibition of platelet aggregation achieved with clopidogrel treatment. [3][4][5][6][7][8][9][10] This phenomenon seems meContinuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. ). Relevant exclusions to trial participation included an increased risk of bleeding (eg, active bleeding, major surgery Յ30 days), clinically im...

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“…95 However, in a large cohort study event rates among patients discharged on PPIs were increased independently of whether or not they were also discharged on clopidogrel, indicating that drug interaction was not the responsible mechanism. 96 Moreover, the COGENT trial of 3873 patients receiving DAPT and randomised to omeprazole or placebo was reassuring in showing no difference in the primary cardiovascular end point, a composite of death from cardiovascular causes, non-fatal myocardial infarction, revascularisation, or stroke.…”

Section: High Residual Platelet Reactivitymentioning

confidence: 96%

Almanac 2011: stable coronary artery disease. The national society journals present selected research that has driven recent advances in clinical cardiology

Henderson

2011

Revista Portuguesa de Cardiologia

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The Antiplatelet Effect of Aspirin Is Reduced by Proton Pump Inhibitors in Patients With Coronary Artery Disease

Cited by 43 publications

References 0 publications

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor

Almanac 2011: stable coronary artery disease. The national society journals present selected research that has driven recent advances in clinical cardiology

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