Impact Of Proton Pump Inhibitors Research Articles

Do PPIs Protect Against Upper GI Bleeding in Patients Taking Warfarin

Proton-pump inhibitors (PPIs) reduce the risk for upper gastrointestinal bleeding (UGIB) in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents (APAs). To assess the impact of PPIs on bleeding in patients taking warfarin, investigators performed a retrospective cohort study involving 97,430 patients in the Tennessee Medicaid database and the 5% National Medicare sample who were newly prescribed warfarin. Analysis of 75,720 patient-years of follow-up …

Impact of proton pump inhibitors and dual antiplatelet therapy cessation on outcomes following percutaneous coronary intervention: Results From the PARIS Registry.

Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events. We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed. We also explored associations between PPI use and patterns of 2-year DAPT cessation. The cohort comprised 4635 patients (23% PPI users) with mean age 64.4 ±11.4 years. Two year adjusted risk of MACE (HR: 1.27, 95% CI: 1.04-1.55), NACE (HR: 1.21, 95% CI: 1.01-1.44) and TLR (HR: 1.33, 95% CI: 1.04-1.71) were significantly higher in PPI users vs. non-users, without a difference in bleeding. Although the incidence of 2-year DAPT discontinuation and interruption was similar, DAPT disruption was significantly lower among PPI users vs. non-users (10.0% vs. 14.7%, P <0.0001). Compared to non-PPI users on continued DAPT, disruption was associated with higher MACE in both PPI users (HR: 2.34, 95% CI: 1.38-3.97) and non-users (HR: 1.41, 95% CI: 1.02-1.94) but greater BARC 3,5 bleeding only in non-PPI users (HR: 2.06, 95% CI: 1.21-3.51). In clopidogrel treated PCI patients, the 2-year adjusted risk of MACE and NACE was significantly higher in PPI users driven by higher TLR compared to non-PPI users, without a difference in bleeding. PPI use was associated with lower incidence of DAPT disruption without an increase in disruption related bleeding compared to non-PPI users on DAPT. © 2016 Wiley Periodicals, Inc.

Correction.

HomeCirculation: Cardiovascular Quality and OutcomesVol. 9, No. 5Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published1 Sep 2016https://doi.org/10.1161/HCQ.0000000000000021Circulation: Cardiovascular Quality and Outcomes. 2016;9:614This article corrects the followingConflicting Results Between Randomized Trials and Observational Studies on the Impact of Proton Pump Inhibitors on Cardiovascular Events When Coadministered With Dual Antiplatelet TherapyIn the article by Melloni et al, “Conflicting Results Between Randomized Trials and Observational Studies on the Impact of Proton Pump Inhibitors on Cardiovascular Events When Coadministered With Dual Antiplatelet Therapy: Systematic Review,” which initially published online January 13, 2015 and which appeared in the January 2015 issue of the journal (Circ Cardiovasc Qual Outcomes. 2015;8:47–55. doi: 10.1161/CIRCOUTCOMES.114.001177), a correction to the Disclosures section is needed; additional funding needed to be reported.The original text read:“Dr Jones reports research grants to the Duke Clinical Research Institute from the American Heart Association, AstraZeneca and Bristol-Myers Squibb, and consultant/honoraria from the AmericanPhysician Institute and the American College of Physicians. The other authors report no conflicts.”It should read:“Dr Jones reports research grants to the Duke Clinical Research Institute from the American Heart Association, AstraZeneca and Bristol-Myers Squibb, and consultant/honoraria from the AmericanPhysician Institute and the American College of Physicians. Dr Mayer reports grant funding from NIH T32 grant (NIH 5T32DK007012 Endocrinology and Metabolism Research Training Program).”The correction has been made to the final version of the article, which is available at http://circoutcomes.ahajournals.org/content/8/1/47.The authors regret the error. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesConflicting Results Between Randomized Trials and Observational Studies on the Impact of Proton Pump Inhibitors on Cardiovascular Events When Coadministered With Dual Antiplatelet TherapyChiara Melloni, et al. Circulation: Cardiovascular Quality and Outcomes. 2015;8:47-55 September 2016Vol 9, Issue 5 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/HCQ.0000000000000021PMID: 27650353 Originally publishedSeptember 1, 2016 PDF download Advertisement

Prevalence of Medication-Related Risks for Falls and Osteoporosis at a Hospital Network: A Post-hoc Analysis

AIM : PRO-OSTEO Extend 1was an osteoporosis management study at a Victorian Healthcare service. This post-hoc analysis examined comorbidities and drug-related risks for falls and osteoporosis, and analysed the accuracy of the medication subcomponent of the falls risk assessment tool used at the service. The secondary aim of this analysis was to evaluate the impact of proton pump inhibitors on the success of anti-osteoporosis therapies. Material and Methods : This analysis was part of a two year retrospective cohort study. The falls risk assessment tool medication subsection results, completed by nursing staff, were compared to scores given by the data collection pharmacist based on medical history notes using Mann-Whitney U test. The impact of proton pump inhibitors use on active osteoporosis therapy in patients admitted after a fall was analysed using the Fisher Exact test. Prevalence of medical and medication-related risk factors for osteoporosis and falls was compared between patients with fractures without osteoporosis treatment at admission and patient who were excluded from the primary study due to active osteoporosis therapy, or admission after a fall without a fracture. RESULTS : The falls risk assessment tool completion rate was approximately 80%, with accuracy below 50% P < 0.001. Medications which increase osteoporosis and falls risk were prevalent, with high use of benzodiazepines, opioids, serotonin reuptake inhibitors antidepressants and proton pump inhibitors. The impact of proton pump inhibitors carried a 14% increased relative risk of a fracture in this cohort (P = 0.218). There was also high prevalence of pre-existing fractures, pulmonary disease, heart failure and strokes in the study population. CONCLUSION : Falls risk assessment in relation to medication use is frequently inaccurate and is not done at all for a significant proportion of patients. The use proton pump inhibitors and medication-related risks for falls and osteoporosis treatment can be improved with potential for hospital pharmacists to contribute to the risk reduction strategies.

Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial

Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.

Prevalence of Medication-Related Risks for Falls and Osteoporosis at a Hospital Network: A Post-hoc Analysis

AIM : PRO-OSTEO Extend 1was an osteoporosis management study at a Victorian Healthcare service. This post-hoc analysis examined comorbidities and drug-related risks for falls and osteoporosis, and analysed the accuracy of the medication subcomponent of the falls risk assessment tool used at the service. The secondary aim of this analysis was to evaluate the impact of proton pump inhibitors on the success of anti-osteoporosis therapies. Material and Methods : This analysis was part of a two year retrospective cohort study. The falls risk assessment tool medication subsection results, completed by nursing staff, were compared to scores given by the data collection pharmacist based on medical history notes using Mann-Whitney U test. The impact of proton pump inhibitors use on active osteoporosis therapy in patients admitted after a fall was analysed using the Fisher Exact test. Prevalence of medical and medication-related risk factors for osteoporosis and falls was compared between patients with fractures without osteoporosis treatment at admission and patient who were excluded from the primary study due to active osteoporosis therapy, or admission after a fall without a fracture. RESULTS : The falls risk assessment tool completion rate was approximately 80%, with accuracy below 50% P &lt; 0.001. Medications which increase osteoporosis and falls risk were prevalent, with high use of benzodiazepines, opioids, serotonin reuptake inhibitors antidepressants and proton pump inhibitors. The impact of proton pump inhibitors carried a 14% increased relative risk of a fracture in this cohort (P = 0.218). There was also high prevalence of pre-existing fractures, pulmonary disease, heart failure and strokes in the study population. CONCLUSION : Falls risk assessment in relation to medication use is frequently inaccurate and is not done at all for a significant proportion of patients. The use proton pump inhibitors and medication-related risks for falls and osteoporosis treatment can be improved with potential for hospital pharmacists to contribute to the risk reduction strategies.

TCTAP A-095 Impact of Proton Pump Inhibitor on One-Year Clinical Outcomes in Patients Underwent Percutaneous Coronary Intervention According to Dual Versus Triple Antiplatelet Agents

It is controversial that proton pump inhibitor (PPI) might affect clopidogrel platelet response and can be associated with major adverse cardiovascular events (MACEs) in patients (pts) undergoing percutaneous coronary intervention (PCI). Particularly impact of PPI on pts with triple antiplatelets (

Impact of proton pump inhibitors on clinical outcomes in patients receiving clopidogrel and possible mechanisms

Impact of proton pump inhibitors on clinical outcomes in patients receiving clopidogrel and possible mechanisms

Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted.

Proton pump inhibitor intake neither predisposes to spontaneous bacterial peritonitis or other infections nor increases mortality in patients with cirrhosis and ascites.

Background and AimThe aim of this study was to assess the impact of proton pump inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis (SBP) or other infections, as well as on mortality, in a thoroughly documented cohort of patients with cirrhosis and ascites.Patients and MethodsWe performed a retrospective analysis of follow-up data from 607 consecutive patients with cirrhosis undergoing their first paracentesis at a tertiary center. A binary logistic regression model investigating the association between PPI intake and SBP at the first paracentesis was calculated. Competing risk analyses and Cox models were used to investigate the effect of PPIs on the cumulative incidence of SBP or other infections and transplant-free survival, respectively. Adjustments were made for age, hepatocellular carcinoma, history of variceal bleeding, varices and model of end-stage liver disease score.ResultsEighty-six percent of patients were receiving PPIs. After adjusting for potential confounding factors, PPI intake was neither associated with increased SBP prevalence at the first paracentesis (odds ratio (OR):1.11,95% confidence interval (95%CI):0.6–2.06; P = 0.731) nor cumulative incidence of SBP (subdistribution hazard ratio (SHR): 1.38; 95%CI:0.63–3.01; P = 0.42) and SBP or other infections (SHR:1.71; 95%CI:0.85–3.44; P = 0.13) during follow-up. Moreover, PPI intake had no impact on transplant-free survival in both the overall cohort (hazard ratio (HR):0.973,95%CI:0.719–1.317; P = 0.859) as well as in the subgroups of patients without SBP (HR:1.01,95%CI:0.72–1.42; P = 0.971) and without SBP or other infections at the first paracentesis (HR:0.944,95%CI:0.668–1.334; P = 0.742).ConclusionsThe proportion of cirrhotic patients with PPI intake was higher than in previous reports, suggesting that PPI indications were interpreted liberally. In our cohort with a particularly high prevalence of PPI intake, we observed no association between PPIs and SBP or other infections, as well as mortality. Thus, the severity of liver disease and other factors, rather than PPI treatment per se may predispose for infectious complications.

Letter: PPI‐responsive oesophageal eosinophilia – from initial skepticism to consistent prospective data; authors' reply

We appreciate and thank Drs Molina-Infante and Gisbert for their interest in our paper.1, 2 Their thoughtful comments and valuable appraisal of the literature on the impact of proton pump inhibitor (PPI) therapy on oesophageal eosinophilic infiltration (≥15 eosinophils/HPF) helps to put our study findings in perspective. Current thinking suggests that eosinophilic oesophagitis is an immune-mediated, antigen-driven disorder;3 thus, diet elimination and/or corticosteroid therapy would seem the fitting therapeutic strategy.4 There is now, however, confirmatory evidence available, including our study2 and their data,5, 6 as well as other studies,7-15 that symptomatic patients with oesophageal eosinophilic infiltration, which is phenotypically indistinguishable from eosinophilic oesophagitis, respond to PPI therapy. In further support of Drs. Molina-Infante and Gisbert's comments, we would like to offer the following observations. Studies validating these findings come from geographically diverse centres across both sides of the Atlantic2, 5, 9 and Asia.10 The benefits are noted in both children7, 8, 12 and adult populations.2, 5 The magnitude of the response rates is robust (at least 33%, and as much as 75%).2, 5-7, 15 The improvement seems unrelated to the type of PPI used (at least two PPIs have been examined, namely omeprazole and rabeprazole).2, 5 Finally, higher PPI dose does not necessarily result in superior response rates,6 although only one study has examined the concept of higher doses. Taken together, these findings highlight the existence of an oesophageal esosinophilia PPI-responsive population that is clinically and endoscopically indistinguishable from eosinophilic oesophagitis.16 They also reiterate the need to treat these patients with a trial of PPI prior to initiating dietary therapy or immunotherapy.3, 4 The authors' declaration of personal and financial interests are unchanged from those in the original article.2

Impact of Proton Pump Inhibitors on Disease Progression in Autoimmune Myasthenia Gravis Patients Treated with Mycophenolate Mofetil (P02.190)

Impact of Proton Pump Inhibitors on Disease Progression in Autoimmune Myasthenia Gravis Patients Treated with Mycophenolate Mofetil (P02.190)

Clinical Significance of the Clopidogrel–Proton Pump Inhibitor Interaction After Peripheral Endovascular Intervention for Claudication

Despite numerous studies in the cardiology literature, the clinical impact of proton pump inhibitor (PPI) administration on the antiplatelet effect of clopidogrel remains controversial. The objective of this study is to evaluate the effects of concurrent PPI and clopidogrel administration on outcomes after percutaneous transluminal angioplasty and stenting (PTA&S) of the superficial femoral artery (SFA) for claudication. Retrospective review of a prospectively maintained database (2004-2010) identified patients undergoing PTA&S of the SFA for lifestyle-limiting claudication (Rutherford Class III). Statistical analysis included univariate comparison (Wilcoxon, chi-square) of demographics, lesion characteristics, complication rates, and outcome measures. Patency comparisons were made with Cox-PH multivariable models and Kaplan-Meier survival analysis. Totally, 109 limbs were treated in 103 patients. All were prescribed clopidogrel for 1 month; concurrent PPI use (+PPI) was identified after 42 (38.5%) interventions. There were no statistically significant differences in demographics, comorbidity prevalence, lesion length, degree of stenosis, or runoff associated with PPI use. There were no cases of early thrombosis in either group. There were more instances of patency loss (28 [50%] vs 21 [42%]; P = .40) in patients with +PPI, and a trend toward reduced primary patency that did not achieve statistical significance (P = .5). By multivariate analysis only TransAtlantic Inter-Society Consensus (TASC) D lesions were independent predictors of primary (hazards ratio [HR] = 4.366; [95% confidence interval (CI): 1.291-14.764; P = .018) and assisted patency loss (HR = 6.815 [1.181-39.327]; P = .032). The clinical significance of the clopidogrel-PPI interaction is a controversial topic that has been the subject of numerous studies in the cardiology literature. This is the first report to examine this medication interaction after peripheral intervention. While there is no apparent association between PPI coadministration with clopidogrel in this series, the high prevalence of PPI use among patients prescribed clopidogrel following peripheral intervention warrants ongoing attention to this purported medication interaction.

Impact of proton pump inhibitors or famotidine on the antiplatelet actions during dual-antiplatelet therapy in Japanese patients

It has been reported that the antiplatelet action becomes attenuated when a proton pump inhibitor is used in combination with clopidogrel. The effect of an antacid causing platelet aggregation during the administration of clopidogrel was investigated. The subjects consisted of 265 patients with coronary artery disease. Platelet aggregation function testing (light transmittance aggregometry) was conducted while aspirin and clopidogrel 75mg were taken orally and the minimum concentration of aggregation induction platelet aggregation threshold index was measured. The ADP-PATI, measured with ADP as the inducing substance, was compared and investigated according to the type of concomitantly used antacid. The results of the ADP-PATI were: control group: 3.47±0.95μM (N=67), famotidine group: 3.80±0.52μM (N=32), rabeprazole group: 3.43±0.93μM (N=87), lansoprazole group: 3.28±1.04μM (N=63) and omeprazole group: 3.33±0.81μM (N=16). No statistically significant difference was observed regarding the ADP-PATI of respective groups compared to the control group. The concomitant use of famotidine, rabeprazole, lansoprazole, and omeprazole did not affect the antiplatelet action of clopidogrel in Japanese patients.

Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia

The impact of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) on the efficacy of nilotinib was evaluated. Retrospective analyses were performed in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP; N=492) and in patients with imatinib-resistant or imatinib-intolerant Ph+ CML-CP (N=256) treated with nilotinib. In the newly diagnosed population, 87 (17.7%) and 49 (10.0%) patients received PPIs and H2 blockers, respectively. Major molecular response at 12months was achieved by 59 (49.6%) patients who received at least one PPI or H2 blocker (n=119) and 153 (41.0%) patients who did not receive any comedication (n=373; P=0.13). PPIs and H2 blockers were used by 77 (30.1%) and 17 (6.6%) patients with imatinib-resistant or imatinib-intolerant CML-CP, respectively. Major cytogenetic response by 12months was achieved by 55 (64.0%) patients who received at least one PPI or H2 blocker (n=86) versus 98 (57.6%) patients who did not receive any comedication (n=170; P=0.40); 39 (45.3%) versus 65 (38.2%), respectively, achieved complete cytogenetic response by 12months (P=0.34). Similar findings were observed in patients who received comedication for >50% of the time on nilotinib therapy. Nilotinib steady-state trough concentration was not affected by the presence of PPIs or H2 blockers. Concurrent use of PPIs or H2 blockers did not affect the pharmacokinetics and efficacy of nilotinib in patients with Ph+ CML-CP.

Clinical Significance of the Clopidogrel-Proton Pump Inhibitor Interaction After Peripheral Endovascular Intervention

The impact of proton pump inhibitor (PPI) administration on the antiplatelet effect of clopidogrel remains controversial. Studies suggest that mechanistic interactions between these medications may lead to higher rates of adverse cardiac events after myocardial infarction or coronary intervention. The objective of this study is to evaluate the effects of concurrent PPI and clopidogrel administration on outcomes after peripheral endovascular interventions.

Inter-patient variability and impact of proton pump inhibitors on platelet reactivity after prasugrel

Although there is considerable variability of platelet reactivity among patients treated with clopidogrel, little is known about inter-individual differences and possible role of proton pump inhibitors (PPIs) after prasugrel. We defined the extent of inter-patient variability, and evaluated the impact of PPI interaction in prasugrel-treated patients with acute coronary syndrome (ACS). Between January 2010 and May 2011, 104 prospective, high-risk patients with ACS were recruited into this multicentre, prospective, observational study. Twelve to 24 hours after receiving 60 mg loading dose of prasugrel, light transmission aggregometry (LTA) and whole blood impedance aggregometry (Multiplate) were used to assess platelet activity. Platelet function measurements were repeated during maintenance phase on reduced (5 mg) or on conventional (10 mg) doses of prasugrel. High platelet reactivity (HPR) was defined according to the consensus document of the Working Group on High On-Treatment Platelet Reactivity (LTA:>46%; Multiplate:>47U). Compared to maintenance doses, 60 mg loading dose of prasugrel provided significantly greater platelet reactivity inhibition (p<0.05). There were no significant differences between the conventional and reduced maintenance doses. Notably, a remarkable inter-patient variability was present in platelet reactivity after all doses of prasugrel, and the prevalence of HPR was significantly higher during the maintenance doses (p<0.05). Although median platelet reactivity values were consistently higher when prasugrel was used in combination with PPIs, these differences were not significant (p≥0.17). Despite potent platelet inhibition, inter-patient variability is present after all tested doses of prasugrel. The 60 mg loading dose is superior to conventional and reduced maintenance doses in terms of platelet reactivity inhibition and regarding the prevention of HPR.

A Meta-Analysis of Impact of Proton Pump Inhibitors on Antiplatelet Effect of Clopidogrel

. [1] evaluatingthe impact of proton pump inhibitors (PPIs) on antiplatelet effectof clopidogrel by conducting a meta-analysis of comparative con-comitant use of clopidogrel with PPIs versus clopidogrel withoutPPIs, with the endpoint being cardiovascular events. The authorsconducted a comprehensive search using multiple databases.Thirteenarticleswereincludedintheirarticleandonlysevenwereanalyzed in the final module. Heterogeneity was found across thestudy and they concluded that there is an obvious discrepancy be-tween the randomized control trials (RCTs) and the observationaltrials studied, and recommended large-scale RCTs to ascertain thetrue effects of PPIs on clopidogrel with respect to cardiovascularevents.Careful review of this interesting article reveals many weak-nesses and flaws.1. Search criteria and articles included in their final analysis: Noobvious inclusion and exclusion criteria were described in thestudy. It is unclear why they evaluated only seven articles outof the 13 articles they found through their search. A re-cent meta-analysis conducted by Siller-Matula

Impact of proton pump inhibitors on efficacy of clopidogrel: Review of evidence

Clopidogrel is a prodrug which requires cytochrome P450 2C19 (CYP 2C19) enzyme for its conversion to an active thiol metabolite. Proton pump inhibitors (PPIs) inhibits enzyme CYP 2C19 interfering with the conversion of clopidogrel into its active metabolite. Studies document the possible interaction of clopidogrel and PPIs leading to a decrease in the antiplatelet efficacy of clopidogrel. A PubMed/MEDLINE database literature search was carried out and the bibliographies of found articles were checked for other relevant literature. Most retrospective cohort studies and studies using platelet markers found a significant association between PPI use especially omeprazole and decreased efficacy of clopidogrel while few comparative trials using clinical outcomes found no association between the same. Pantoprazole was not associated with the decrease in the antiplatelet efficacy of clopidogrel. Patients on dual antiplatelet therapy and/or with a history of gastrointestinal bleed will require gastroprotection in the form of PPIs. In such cases, pantoprazole should be the preferred PPI. Rabeprazole can be used as an alternative.

Impact of Proton Pump Inhibitors on the Effectiveness of Clopidogrel After Coronary Stent Placement: The Clopidogrel Medco Outcomes Study

To investigate the potential impact of proton pump inhibitors (PPIs) on the effectiveness of clopidogrel in preventing recurrent ischemic events after percutaneous coronary intervention (PCI) with stent placement. Population-based, retrospective cohort study. National medical and pharmacy benefit claims database comprising approximately 19 million members. A total of 16,690 patients who had undergone PCI with stent placement and who were highly adherent to clopidogrel therapy alone (9862 patients) or to clopidogrel with a PPI (6828 patients) between October 1, 2005, and September 30, 2006. The primary end point was the occurrence of a major adverse cardiovascular event during the 12 months after stent placement. These events were defined as hospitalization for a cerebrovascular event (stroke or transient ischemic attack), an acute coronary syndrome (myocardial infarction or unstable angina), coronary revascularization (PCI or coronary artery bypass graft), or cardiovascular death. A composite event rate was compared between patients who received clopidogrel alone and those who received concomitant clopidogrel-PPI therapy. Baseline differences in covariates were adjusted by using Cox proportional hazards models. In the 9862 patients receiving clopidogrel alone, 1766 (17.9%) experienced a major adverse cardiovascular event compared with 1710 patients (25.0%) who received concomitant clopidogrel-PPI therapy (adjusted hazard ratio 1.51, 95% confidence interval 1.39-1.64, p<0.0001). Similar associations of increased risk were observed for each PPI studied (omeprazole, esomeprazole, pantoprazole, and lansoprazole). Concomitant use of a PPI and clopidogrel compared with clopidogrel alone was associated with a higher rate of major adverse cardiovascular events within 1 year after coronary stent placement.