title: Patient-centered Outcomes with Concomitant Use of Proton Pump Inhibitors and Other Drugs.
abstract: We performed a systematic review of patient-centered outcomes after the concomitant use of proton pump inhibitors (PPIs) and other drugs.
  
  
  
  We searched 4 databases in July 2016 to find studies that reported mortality and morbidity after the concomitant use of PPIs and other drugs. We conducted direct meta-analyses using a random-effects model and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach.
  
  
  
  We included data from 17 systematic reviews and meta-analyses, 16 randomized controlled trials, and 16 observational studies that examined the concomitant use of PPIs with medications from 10 drug classes. Low-quality evidence suggests that the use of PPIs is associated with greater morbidity when administered with antiplatelet drugs, bisphosphonates, antibiotics, anticoagulants, metformin, mycophenolate mofetil, or nelfinavir. Concomitant PPIs reduce drug-induced gastrointestinal bleeding and are associated with greater docetaxel and cisplatin response rates in patients with metastatic breast cancer. For demonstrated statistically significant relative risks and benefits from concomitant PPIs, the magnitudes of the effects are small, with <100 attributable events per 1000 patients treated, and the effects are inconsistent among specific drugs. Among individual PPIs, the concomitant use of pantoprazole or esomeprazole, but not omeprazole or lansoprazole, is associated with an increased risk for all-cause mortality, nonfatal myocardial infarction, or stroke. Clopidogrel is associated with a greater risk for myocardial infarction compared with prasugrel. Conflicting results between randomized controlled trials and observational studies and high risk for bias in the body of evidence lessened our confidence in the results.
  
  
  
  Available evidence suggests a greater risk for adverse patient outcomes after the concomitant use of PPIs and medications from 9 drug classes and warns against inappropriate drug combinations.
authors.affiliation: Evidence-Based Medicine Center, Quality Assurance, Elsevier, Philadelphia, Pennsylvania. Electronic address: t.shamliyan@elsevier.com.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Shamliyan
authors.affiliation: Evidence-Based Medicine Center, Elsevier, Philadelphia, Pennsylvania.
authors.forename: Maria
authors.initials: M
authors.lastname: Middleton
authors.affiliation: Clinical Drug Information, Elsevier, Philadelphia, Pennsylvania.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Borst
mesh_terms: D004347:Drug Interactions; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000453:epidemiology
chemical_list: D054328:Proton Pump Inhibitors
keywords: PPIs; anticoagulants; antiplatelets; cardiovascular disease; combination therapy; drug–drug interactions; hypertension; outcomes; proton pump inhibitors