Abstract

ObjectivesProton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD.MethodsWe followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death.ResultsPatients on PPIs were older [62.0 (53.0–73.0) vs. 58.0 (50.0–70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244–4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628–20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results.ConclusionsIn patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings.

Highlights

  • The efficacy of proton-pump inhibitors (PPIs) in suppressing gastric acid secretion has led them to be preferred over other drugs such as histamine H2 receptor antagonists [1].In patients with coronary artery disease (CAD), aspirin is used to decrease the incidence of cardiovascular events, and in patients who have undergone stent placement or have suffered an acute coronary syndrome, a P2Y12 receptor blocker such as clopidogrel is added

  • PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244–4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use

  • In patients with CAD, PPI use is independently associated with an increased incidence of heart failure (HF) and death but not with a high rate of acute ischaemic events

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Summary

Introduction

In patients with coronary artery disease (CAD), aspirin is used to decrease the incidence of cardiovascular events, and in patients who have undergone stent placement or have suffered an acute coronary syndrome, a P2Y12 receptor blocker such as clopidogrel is added. These antiplatelet agents, may favour the development of gastrointestinal (GI) complications. It has been suggested that PPIs may increase the incidence of cardiovascular events in CAD patients by decreasing the effect of aspirin—and, mainly, clopidogrel—on platelet aggregation [7,8,9,10,11]. Several pharmacodynamic studies have suggested an interaction between PPIs and antiplatelet drugs [12], clinical studies have shown divergent results [13,14]

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