PMID- 27459657 OWN - NLM STAT- MEDLINE DCOM- 20170427 LR - 20220330 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 22 IP - 8 DP - 2016 Aug TI - Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis. PG - 939-47 LID - 10.18553/jmcp.2016.22.8.939 [doi] AB - BACKGROUND: Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. OBJECTIVE: To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. METHODS: We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. RESULTS: We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95% CI = 1.15-1.86). However, concomitant therapy had no statistically significant effect on stent thrombosis, mortality measured by all-cause or cardiovascular death, or major bleeding before or after the grouping of studies that reported a major or minor bleed outcome. Only 1 study reported on gastrointestinal bleed, and pooled analysis could not be conducted. Statistical testing suggested heterogeneity among studies, but subgroup analysis did not reveal a clear source. CONCLUSIONS: Based on the results from this meta-analysis of retrospective analyses of randomized controlled trials and observational studies, concomitant clopidogrel-PPI therapy following PCI appears to be significantly associated with adverse cardiovascular events. Further research on the effect of individual PPIs is needed. DISCLOSURES: Serbin, Guzauskas, and Veenstra were supported by the NIH Common Fund and NIA (1U01AG047109-01, Veenstra, PI) via the Personalized Medicine Economics Research (PriMER) project. The authors do not report any conflicting interests. All authors contributed to the study concept and design. Serbin took the lead in data collection; data interpretation was performed primarily by Serbin, with assistance from the other authors. The manuscript was written primarily by Serbin, along with Guzauskas, and revised by Guzauskas and Veenstra, with assistance from Serbin. FAU - Serbin, Michael A AU - Serbin MA AD - 1 Department of Pharmacy, University of Washington, Seattle. FAU - Guzauskas, Gregory F AU - Guzauskas GF AD - 1 Department of Pharmacy, University of Washington, Seattle. FAU - Veenstra, David L AU - Veenstra DL AD - 1 Department of Pharmacy, University of Washington, Seattle. LA - eng GR - U01 AG047109/AG/NIA NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Proton Pump Inhibitors) RN - A74586SNO7 (Clopidogrel) RN - OM90ZUW7M1 (Ticlopidine) SB - IM MH - Acute Coronary Syndrome/epidemiology/metabolism/*therapy MH - Clopidogrel MH - Combined Modality Therapy/adverse effects MH - *Drug Interactions/physiology MH - Humans MH - Percutaneous Coronary Intervention/*adverse effects MH - Proton Pump Inhibitors/*adverse effects/metabolism MH - Randomized Controlled Trials as Topic/methods MH - Risk Factors MH - Ticlopidine/adverse effects/*analogs & derivatives/metabolism MH - Treatment Outcome PMC - PMC6141192 MID - NIHMS987487 COIS- Serbin, Guzauskas, and Veenstra were supported by the NIH Common Fund and NIA (1U01AG047109-01, Veenstra, PI) via the Personalized Medicine Economics Research (PriMER) project. The authors do not report any conflicting interests. All authors contributed to the study concept and design. Serbin took the lead in data collection; data interpretation was performed primarily by Serbin, with assistance from the other authors. The manuscript was written primarily by Serbin, along with Guzauskas, and revised by Guzauskas and Veenstra, with assistance from Serbin. EDAT- 2016/07/28 06:00 MHDA- 2017/04/28 06:00 PMCR- 2016/08/01 CRDT- 2016/07/27 06:00 PHST- 2016/07/27 06:00 [entrez] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/04/28 06:00 [medline] PHST- 2016/08/01 00:00 [pmc-release] AID - 10.18553/jmcp.2016.22.8.939 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2016 Aug;22(8):939-47. doi: 10.18553/jmcp.2016.22.8.939.