Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease

PLoS One. 2017 Jan 19;12(1):e0169826. doi: 10.1371/journal.pone.0169826. eCollection 2017.


Objectives: Proton-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.

Methods: We 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.

Results: Patients 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.

Conclusions: In 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.

MeSH terms

  • Acute Coronary Syndrome / chemically induced
  • Acute Coronary Syndrome / etiology
  • Acute Coronary Syndrome / mortality
  • Aged
  • Case-Control Studies
  • Coronary Disease / complications
  • Coronary Disease / drug therapy*
  • Coronary Disease / mortality
  • Female
  • Heart Failure / chemically induced
  • Heart Failure / etiology*
  • Heart Failure / mortality
  • Humans
  • Ischemic Attack, Transient / chemically induced
  • Ischemic Attack, Transient / etiology
  • Ischemic Attack, Transient / mortality
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Risk Factors
  • ST Elevation Myocardial Infarction / chemically induced
  • ST Elevation Myocardial Infarction / etiology
  • ST Elevation Myocardial Infarction / mortality
  • Stroke / chemically induced
  • Stroke / etiology
  • Stroke / mortality


  • Proton Pump Inhibitors

Grant support

This work was supported by grants from Fondo de Investigaciones Sanitarias [grant numbers PI 14/1567, PI13/00047, PIE13/00051], ISCIII-RETIC REDinREN RD12/0021, Comunidad de Madrid [sGEN/0247/2006, S2010/BMD-2378], Spanish Society of Cardiology; Spanish Heart Foundation; RECAVA [grant number RD06/0014/0035]; Instituto de Salud Carlos III FEDER [FJD biobank grant number RD09/0076/00101]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.