Adverse Cardiovascular Effects of Concomitant Use of Proton Pump Inhibitors and Clopidogrel in Patients with Coronary Artery Disease: A Systematic Review and Meta-Analysis

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
Archives of medical research (Impact Factor: 2.41). 05/2012; 43(3):212-24. DOI: 10.1016/j.arcmed.2012.04.004
Source: PubMed

ABSTRACT Conclusions from clinical studies and previous meta-analyses were inconsistent regarding the cardiovascular effects of concomitant use of proton pump inhibitors (PPIs) and clopidogrel. As new studies are constantly emerging, we performed this meta-analysis to further assess the cardiovascular effects of concomitant use of PPIs and clopidogrel with a focus on individual PPIs.
A systematic electronic literature search was conducted in EMBASE, MEDLINE, PubMed and Chinese Biomedical Literature Database (CBM) to identify the studies reporting on the association of concomitant use of PPIs and clopidogrel with adverse cardiovascular outcomes. A hand search of reference lists was performed to identify further studies. Only studies published in English or Chinese were included in this review.
Twenty seven full-text articles and five abstracts with 159,998 patients were included in meta-analysis. Concomitant use of PPIs and clopidogrel is associated with an increased risk of major cardiovascular events (MACE) (HR 1.40, 95% CI 1.19-1.64; OR 1.27, 95% CI 1.13-1.42) and acute coronary syndrome (HR 1.42, 95% CI 1.14-1.77; OR 1.42, 95% CI 1.08-1.87) but not with all-cause mortality (HR 1.30, 95% CI 0.91-1.86; OR 0.92, 95% CI 0.82-1.04), cardiovascular death (HR 1.21, 95% CI 0.60-2.43) and stent thrombosis (HR 1.52, 95% CI 0.87-2.65). In the analyses of individual PPIs, none of the PPIs is associated with an increased MACE risk except for pantoprazole (HR 1.52, 95% CI 1.18-1.94).
Concomitant use of PPIs and clopidogrel in patients with coronary artery disease is associated with an increased risk of MACE or acute coronary syndrome, but there is insufficient evidence to conclude that there is an interaction between individual PPIs and clopidogrel.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Emerging evidences have shown that the Glu504Lys variant in ALDH2 gene may greatly reduce the ability of ALDH2 to metabolize acetaldehyde, which could increase the risk of coronary artery disease (CAD) and myocardial infarction (MI). However, the reported results are still conflicting. To investigate the association between ALDH2 Glu504Lys polymorphism and the risk of CAD and MI in Asians, we analyzed all available studies in a meta-analysis. A literature search of PubMed, Embase, Web of Science and Chinese BioMedical (CBM) databases was conducted for articles published before March 1, 2013. The principal outcome measure was the crude odds ratios (ORs) with their corresponding confidence intervals (95% CIs) for evaluating the strength of the association. Meta-analysis showed that carriers of ALDH2*504lys allele were associated with increased risks of both CAD and MI (CAD: OR = 1.28, 95% CI: 1.10-1.48, p = 0.001; MI: OR = 1.58, 95% CI: 1.15-2.19, p = 0.005). Subgroup analysis by country showed significant correlations between mutant genotypes (Glu/Lys + Lys/Lys) and increased risk to MI among Chinese and Korean populations (Chinese: OR = 1.89, 95% CI: 1.16-3.09, p = 0.011; Korean: OR = 1.69, 95%CI: 1.12-2.55, p = 0.013), whereas similar associations were not observed among Japanese populations. The current meta-analysis provides strong evidence that ALDH2 Glu504Lys polymorphism may be associated with increased risk of CAD and MI in East Asians, especially among Chinese and Korean populations. However, more detailed and well-designed studies are still warranted to confirm these findings.
    Archives of medical research 12/2013; DOI:10.1016/j.arcmed.2013.10.002 · 2.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There have been mounting safety concerns over increasing prescription rates for proton pump inhibitors (PPIs). Trends in PPI use have not been studied in emergency departments (EDs). We characterize trends in PPI use in US EDs. We used data from the National Hospital Ambulatory Care Survey, from 2001 to 2010, focusing on encounters with a reason for visit with a potential indication for a PPI, histamine receptor (H2) blocker, or antacid. Patient, provider, visit, and hospital-level factors associated with increases in PPI use were evaluated. Among included visits, ED PPI prescribing more than doubled from 3.0 (95% confidence interval [CI]: 2.4-3.8) to 7.2% (95% CI: 6.3-8.3) from 2001 to 2010. Histamine receptor blocker use decreased from 6.8% (95% CI: 6.0-7.7) to 5.7% (95% CI: 4.9-6.7) and antacids from 7.2% (95% CI: 6.3-8.2) to 5.5% (95% CI: 4.8-6.3). Proton pump inhibitor prescribing was higher in males and whites yet increased across all demographics, including in adults aged 65 years and older. Proton pump inhibitor prescribing increased significantly in all US regions and across all hospital and payer types. Pantoprazole was the agent with the largest increase in use. Over the past decade, there have been considerable increases in PPI prescribing in US EDs. This trend occurred despite rising safety concerns, even in populations at higher risk for adverse events such as older adults. More education may be needed to ensure that ED providers are familiar with indications for PPIs.
    The American journal of emergency medicine 03/2014; 32(6). DOI:10.1016/j.ajem.2014.03.019 · 1.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: CYP2C19 is involved in the metabolism of clinically relevant drugs, including the antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19 genotyping. The CYP2C19∗4B allele is defined by both gain-of-function [c.−806C>T (∗17)] and loss-of-function [c.1A>G (∗4)] variants on the same haplotype; however, current genotyping and sequencing assays are unable to determine the phase of these variants. Thus, the aim of this study was to develop an assay that could rapidly detect and discriminate the related ∗4A, ∗4B, and ∗17 alleles. An allele-specific PCR assay, composed of four unique primer mixes that specifically interrogate the defining ∗17 and ∗4 variants, was developed by using samples (n = 20) with known genotypes, including the ∗4A, ∗4B, and/or ∗17 alleles. The assay was validated by testing 135 blinded samples, and the results were correlated with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly, among the six ∗4 carriers in the validation cohort, after allele-specific PCR testing both samples with a ∗1/∗4 genotype were reclassified to ∗1/∗4A, all three samples with a ∗4/∗17 genotype were reclassified to ∗1/∗4B, and a sample with a ∗4/∗17/∗17 genotype was reclassified to ∗4B/∗17. In conclusion, this rapid and robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer phenotype classification by determining the phase of the defining ∗17 and ∗4 variants, which may have utility when testing CYP2C19 for clopidogrel response.