Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study

Zhai, Yinghong; Ye, Xiaofei; Hu, Fangyuan; Xu, Jinfang; Guo, Xiaojing; Lin, Zhen; Zhou, Xiang; Guo, Zhigang; Cao, Yang; He, Jia

doi:10.3389/fcvm.2022.767987

Cited by 16 publications

(18 citation statements)

References 43 publications

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“…29 , 30 Baxer and colleagues performed a large‐scale case control study to analyse for an association between SSNHL and vaccinations. 21 The odds ratios for vaccination to SSNHL were 0.965 (95% CI, 0.61–1.50) for influenza vaccine, 0.842 (95% CI 0.39–1.62) for tetanus, and 0.454 (95% CI 0.08–1.53) for zoster vaccine, demonstrating no association between these vaccination and the rate of SSNHL. Given the fact that influenza vaccine has been deemed acceptably safe since they have undergone thorough safety evaluations in the form of continued population‐based post‐market surveillance, 31 , 32 we set it as the control group to compare the disproportionality pattern.…”

Section: Discussionmentioning

confidence: 93%

“…Long before COVID‐19 vaccine, anecdotal case reports of SSNHL following other vaccines have led to a speculation that vaccination might be the cause of hearing loss in some cases 29,30 . Baxer and colleagues performed a large‐scale case control study to analyse for an association between SSNHL and vaccinations 21 . The odds ratios for vaccination to SSNHL were 0.965 (95% CI, 0.61–1.50) for influenza vaccine, 0.842 (95% CI 0.39–1.62) for tetanus, and 0.454 (95% CI 0.08–1.53) for zoster vaccine, demonstrating no association between these vaccination and the rate of SSNHL.…”

Section: Discussionmentioning

confidence: 99%

“…The ROR = (ad/cb) 20 . A signal emerged if the lower limits of the 95% confidence intervals (95% CI) of ROR exceeded 1 in at least three records 21 …”

Section: Methodsmentioning

confidence: 99%

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Hearing disorder following COVID ‐19 vaccination: A pharmacovigilance analysis using the Vaccine Adverse Event Reporting System

Chen

Ding

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective Evidence on whether the coronavirus disease 2019 (COVID‐19) vaccination could cause hearing‐related adverse events is still conflicting. This study aims to access the association between COVID‐19 vaccine and hearing disorder. Methods The Vaccine Adverse Event Reporting System (VAERS) was queried between January 2020 to November 2021. The disproportionality pattern for hearing impairment of COVID‐19 vaccine was accessed by calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR). A further subgroup analysis based on the type of COVID‐19 vaccine and the doses administered was performed. In addition, the disproportionalities for hearing dysfunction between COVID‐19 and influenza vaccines were compared. Results and discussion A total of 14,956 reports of hearing‐related adverse events were identified with COVID‐19 vaccination and 151 with influenza vaccine during the analytic period in VAERS. The incidence of hearing disorder following COVID‐19 vaccination was 6.66 per 100,000. The results of disproportionality analysis revealed that the adverse events of hearing impairment, after administration of COVID‐19 vaccine, was significantly highly reported (ROR 2.38, 95% confidence interval [CI] 2.20–2.56; PRR: 2.35, χ 2 537.58), for both mRNA (ROR 2.37, 95% CI 2.20–2.55; PRR 2.34, χ 2 529.75) and virus vector vaccines (ROR 2.50, 95% CI 2.28–2.73; PRR 2.56, χ 2 418.57). While the disproportional level for hearing dysfunction was quite lower in influenza vaccine (ROR 0.36, 95% CI 0.30–0.42; PRR 0.36, χ 2 172.24). What is new and conclusion This study identified increased risk for hearing disorder following administration of both mRNA and virus vector COVID‐19 vaccines compared to influenza vaccination in real‐world settings.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Hearing disorder following COVID ‐19 vaccination: A pharmacovigilance analysis using the Vaccine Adverse Event Reporting System

Chen

Ding

et al. 2022

Clinical Pharmacy Therapeu

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“…Independent of clopidogrel use, Dahal et al [ 41 ] demonstrated that PPI use alone was not at increased risk for cardiovascular mortality, all-cause mortality, myocardial infarction, or stroke in a meta-analysis of nine RCTs including patients taking aspirin for the prevention of cardiovascular diseases and stroke. Zhai et al [ 42 ] sought to examine the safety of PPIs for cardiac and vascular health using the Food and Drug Administration Adverse Event Reporting System (FAERS). PPIs were not associated with more cardiac and vascular events compared with the whole database.…”

Section: Discussionmentioning

confidence: 99%

The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis

Jeridi

Pellat

Ginestet

et al. 2022

JCM

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Introduction: Proton pump inhibitors (PPIs) are one of the most prescribed classes of drugs worldwide as a first-line treatment of acid-related disorders. Although adverse effects are rare and rapidly reversible after a short exposure, concerns have been recently raised about a greater toxicity on cardiovascular health after a longer exposure, especially when combined with clopidogrel. We aimed to evaluate the safety of long-term PPI use on cardiovascular health in patients with known atheromatous cardiovascular disease. Methods: A literature search was conducted in the PubMed, Embase, and Cochrane Library databases and grey literature in April 2022. Articles published between 2014 and 2022 were considered relevant if they were designed as randomized controlled trials (RCTs) that included post hoc analyses or prospective observational studies and if they investigated clinical cardiovascular outcomes associated with PPI use for 6 months or more in patients suffering from cardiovascular disease requiring antiplatelet agent therapy and/or coronary angioplasty. Statistical analyses were performed using RevMan 5.4 software (Computer program, the Cochrane Collaboration, 2020, London, UK). The risk of bias was assessed using the Cochrane risk-of-bias tool for the RCTs and the Newcastle–Ottawa scale for the observational studies. Results: A total of 10 full-text articles involving 53,302 patients were included. Substantial heterogeneity was found among the 10 included studies. The primary analysis showed no significant differences between the PPI group and the control group for the risks of major adverse cardiovascular events (MACEs), all-cause death (ACD), or target vessel revascularization (TVR) using a random-effects model (OR 1.15, 95% CI 0.98–1.35, p = 0.08, I2 = 73%; OR 1.24, 95% CI 0.94–1.65, p = 0.13, I2 = 63%; and OR 1.19, 95% CI 0.76–1.87, p = 0.45, I2 = 61%, respectively). The primary analysis yielded similar results for the risks of myocardial infarction (MI), stroke, and cardiovascular death (CVD) using a fixed-effects model (OR 0.98, 95% CI 0.88–1.09, p = 0.66, I2 = 0%; OR 1.02, 95% CI 0.90–1.17, p = 0.73, I2 = 0%; and OR 1.04, 95% CI 0.94–1.16, p = 0.44, I2 = 35%, respectively). Likewise, a subgroup analysis based on eight randomized controlled trials failed to identify any association between PPI use and the risks of MACEs, MI, stroke, TVR, ACD, or CVD using a fixed-effects model (overall pooled OR 1.01, 95% CI 0.96–1.06; p = 0.66; I2 = 0%). The pulled data from the two included observational studies (OS) demonstrated a significantly increased risk of MACEs in the PPI group (OR 1.42, 95% CI [1.29–1.57], p <0.001; I2 = 0%). In another subgroup analysis, no evidence of an increased risk of adverse cardiovascular events in the co-therapy PPI/clopidogrel versus clopidogrel alone groups was found with the exception of the risk of ACD (OR 1.50, 95% CI 1.23–1.82, p = 0.001, I2 = 0%). Nevertheless, after performing a sensitivity analysis reaching heterogeneity I2 = 0%, the co-prescription of PPIs and clopidogrel was at increased risk of MACEs (p < 0.001), CVD (p = 0.008), and TVR (p < 0.001) but remained statistically non-significant for the risk of MI (p = 0.11). Conclusions: The overall results of this meta-analysis showed that long-term PPI use was not associated with an increased risk of adverse cardiovascular events. However, inconsistent results were found for combined PPI/clopidogrel therapy. These results should be considered with caution in light of the significant heterogeneity, the limited number of included studies, and the lack of adjustment for potential confounders.

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“…PPIs are also metabolized by CYP enzymes and thus could inhibit the conversion of clopidogrel into its active metabolite ( Furuta et al, 2017 ). Furthermore, mounting clinical data have shown that long-term intake of PPIs increases the susceptibility of patients to serious adverse events, including cardiovascular events and damage to the lower GI tract ( Lue and Lanas, 2016 ; Xie et al, 2019 ; Marlicz et al, 2022 ; Zhai et al, 2022 ). However, the existing clinical studies of the association between cardiovascular events and the concomitant use of PPIs with aspirin-clopidogrel DAPT in CHD have been conflicting ( Ben Ghezala et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis

Luo

et al. 2023

Front. Pharmacol.

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Background: Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD).Method: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195).Results: A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 post hoc analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06–1.26, p = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30–0.64, p < .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups.Conclusion: In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.

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Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study

Cited by 16 publications

References 43 publications

Hearing disorder following COVID ‐19 vaccination: A pharmacovigilance analysis using the Vaccine Adverse Event Reporting System

Hearing disorder following COVID ‐19 vaccination: A pharmacovigilance analysis using the Vaccine Adverse Event Reporting System

The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis

Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis

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