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

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.

The Association Between Proton Pump Inhibitors and Incident Asthma in Patients with Coronary Artery Disease: A Population-Based Cohort Study

“…Daily low-dose aspirin is recommended for the prevention of cardiovascular events in patients with CAD, and PPI is recommended to prevent or treat aspirin-associated gastrointestinal injury [16][17][18] . Previous studies have reported that low-dose aspirin therapy protects against incident asthma [27][28][29] .…”

“…Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population 15 . Daily low-dose aspirin is recommended for the prevention of cardiovascular events in patients with CAD, and PPI is recommended to prevent or treat aspirin-associated gastrointestinal injury [16][17][18] . However, the association between PPIs use and incident asthma in patients with CAD remains unclear till now.…”

Use of proton pump inhibitors is associated with lower rates of first‐time ischemic stroke in community‐dwelling elderly

“…Dai et al 24 and others 25,26 suggested that the tendency of physicians to prescribe certain medications to patients with more severe illnesses, termed the ‘channeling bias’, is responsible for the association between PPI consumption and cardiovascular risk. This practice creates the false impression that the drugs are predisposing patients to illness because patients with certain diseases are more likely to be taking them.…”

Hypochlorhydria reduces mortality in heart failure caused byKcne2gene deletion

“…68 In contrast, in a study of 42902 PPI initiators vs 3296 histamine H 2 receptor antagonist (H2RA) initiators, H2RA use was associated with lower mortality in HF patients than was PPI use. 69 In a study of 706 patients, PPI use was associated with increased HF incidence and mortality 70 ; in a study of all-cause mortality associated with taking PPIs conducted in more than 200 000 US veterans, PPI use was associated with a "small excess" of cause-specific mortality including deaths from cardiovascular disease. 71 If the positive effects we observe in mice are repeated in a large animal model, the possibility of assessing the worth of altering the gut microbiome for HF patients could be considered, perhaps with dietary modifications or fecal transplantation rather than with PPIs, given the potential health concerns.…”