Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry

Hoedemaker, N.P.G.; Damman, Peter; Ottervanger, Jan Paul; Dambrink, Jan-Henk; Gosselink, A T Marcel; Kedhi, Elvin; Kolkman, Evelien; Winter, Robbert J. de; Hof, Arnoud W J van 't

doi:10.1093/ehjcvp/pvy030

Cited by 18 publications

(26 citation statements)

References 41 publications

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“…ORs reported in this study for the concomitant use of either of the negative control object drugs, ticagrelor and prasugrel, with PPIs also do not show any increased risk of MI compared with non-use of PPIs. Our findings are in agreement with prior observational studies that have assessed clinical endpoints and have reported similar findings among ticagrelor users [30,31] and prasugrel users in a post-hoc analysis of the TRITON-TIMI 38 trial [17]. Goodman et al [28] reported a positive association (adjusted hazard ratio 1.24; 95% CI 1.07-1.45) between PPIs and the composite outcome (cardiovascular death, MI, or stroke) among patients with ACS receiving ticagrelor based on a post-hoc analysis of the PLATO trial.…”

Section: Negative Control Exposure Drugssupporting

confidence: 94%

Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case–Control Study

Farhat

Birkett

Haddad

et al. 2020

Drugs - Real World Outcomes

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Background The clinical implications of potential interactions between proton pump inhibitors (PPIs) and clopidogrel have been debated for over a decade. Objective We assessed the association between combined clopidogrel–PPI treatment and the risk of recurrent myocardial infarction (MI) and three secondary outcomes. Patients and Methods A nested case–control study was conducted within Cerner Corporation’s Health Facts ® database. A retrospective cohort of patients who experienced a first MI and started clopidogrel treatment was created. Within this cohort, patients experiencing a second MI (cases) were matched with up to five controls. Logistic regression was used to estimate adjusted odds ratios (aORs). Findings were compared with those obtained from models with three negative control exposure drugs: H 2 receptor antagonists, prasugrel, and ticagrelor. Results In total, 2890 recurrent MI cases were identified within 12 months following entry into the cohort of clopidogrel users ( N = 52,006). aOR for PPI use versus non-use among clopidogrel users was 1.08 [95% confidence interval (CI) 0.95–1.23]. Similar ORs were obtained for secondary endpoints. A positive association between combined use of clopidogrel/PPIs and increased risk of MI was seen in the group aged 80–89 years (aOR 1.26; 95% CI 1.05–1.51). No associations with MI were observed for (1) H2 receptor antagonist use versus non-use among clopidogrel users or (2) PPI use versus non-use among prasugrel users or among ticagrelor users. Conclusions Overall, our findings do not support a significant adverse clinical impact of concomitant clopidogrel/PPI use by patients with MI. Nonetheless, investigation of the possible association seen in those aged 80–89 years may be warranted. Electronic supplementary material The online version of this article (10.1007/s40801-020-00204-9) contains supplementary material, which is available to authorized users.

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Section: Negative Control Exposure Drugssupporting

confidence: 94%

Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case–Control Study

Farhat

Birkett

Haddad

et al. 2020

Drugs - Real World Outcomes

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“…36 However, the study by Hoedemaker et al indicated that PPI prescription in patients with acute coronary syndrome was associated with reductions in mortality and myocardial infarction risk at 30 days after discharge. 12 The in-hospital mortality rate in our study was 2.9%, which was lower than those in previous studies, probably because we included only CCU patients, and most of them had relatively mild disease severity, as indicated by APACHE-II scores. We observed that PPIs were associated with relatively increased adjusted in-hospital mortality in CCU patients over 75 years old, but prophylactic PPI and H2RA therapy had no apparent impact on cardiac death.…”

Section: Discussioncontrasting

confidence: 67%

The efficacy and safety of acid suppressants for gastrointestinal bleeding prophylaxis in cardiac care unit patients

Chen

Liu

Duan

et al. 2021

J of Gastro and Hepatol

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Background and Aim: Concerns regarding adverse events associated with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) for gastrointestinal bleeding (GIB) prophylaxis in the intensive care unit have increased in recent years. Few studies have focused on acid suppressant use in the cardiac care unit (CCU) setting exclusively. We performed a cohort study to determine the efficacy and safety of acid suppressants for GIB prophylaxis in CCU patients. Methods: This retrospective cohort study included adults who were admitted directly to the CCU for more than 2 days from January 1, 2014, to April 30, 2019. The Crusade score was calculated to evaluate the risk of GIB. The primary outcomes were clinically important gastrointestinal bleeding (CIGIB), hospital-acquired pneumonia (HAP), and in-hospital mortality. Results: Of the 3318 patients enrolled, 2284 (68.8%) patients received PPIs, 515 (15.5%) received H2RAs, and 519 (15.7%) received no acid suppressants. After adjusting for potential confounders, utilization of PPIs (2.69, 95% confidence interval [0.62-11.73]) and H2RAs (1.41, 95% confidence interval [0.19-10.36]) were not associated with a lower risk of CIGIB than the control. Sensitivity analyses revealed that PPI use was an independent risk factor for in-hospital mortality in patients over 75 years old, with an adjusted odds ratio of 4.08 (1.14-14.63). PPIs increased the risk of HAP in patients over 75 years old and in those with heart failure, with adjusted odds ratios of 2.38 (1.06-5.34) and 2.88 (1.34-7.28), respectively. Conclusions: Proton pump inhibitors and H2RAs for GIB prophylaxis in CCU patients were not associated with a lower risk of CIGIB than the controls. PPI therapy is associated with increased risks of HAP and in-hospital mortality in patients over 75 years old. PPIs may increase the risk of HAP in patients with heart failure.

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“…Of 7336 articles, 5,310 were screened after removal of duplicate publications. After screening of the titles and abstracts, the full texts of 86 articles were assessed, of which 22 met the inclusion criteria ( Ng et al, 2008 ; Gao et al, 2009 ; Ho et al, 2009 ; Juurlink et al, 2009 ; O'Donoghue et al, 2009 ; Rassen et al, 2009 ; Bhatt et al, 2010 ; Charlot et al, 2010 ; Kreutz et al, 2010 ; Ray et al, 2010 ; Ren et al, 2011 ; Simon et al, 2011 ; Wu et al, 2011 ; Goodman et al, 2012 ; Schmidt et al, 2012 ; Jiang et al, 2013 ; Hokimoto et al, 2014 ; Yan et al, 2016 ; Jensen et al, 2017 ; Hoedemaker et al, 2019 ; Sehested et al, 2019 and Zhang et al, 2019 ). The lack of data on individual PPIs and only unadjusted outcomes presented were the most common reasons for exclusion.…”

Section: Resultsmentioning

confidence: 99%

Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

Guo

Huang

2021

Front. Pharmacol.

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Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

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Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry

Cited by 18 publications

References 41 publications

Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case–Control Study

Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case–Control Study

The efficacy and safety of acid suppressants for gastrointestinal bleeding prophylaxis in cardiac care unit patients

Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

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