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OBJECTIVES: To conduct a systematic review and meta-analysis of studies examining the impact of periprocedural intravenous morphine on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: Morphine analgesia may reduce the absorption of co-prescribed P2Y12 antagonists attenuating platelet inhibition. The impact of periprocedural intravenous morphine on clinical outcomes in patients undergoing PCI for STEMI is not well defined. METHODS: Analysis of the electronic databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science and ClinicalTrials.gov for association of peri-PCI intravenous morphine use with in-hospital or 30-day myocardial infarction (MI) (primary outcome) and in-hospital or 30-day mortality. RESULTS: A total of 11 studies were included for systematic review. One study was a randomized controlled trial, 10 were observational studies. Five studies including 3,748 patients were included in meta-analysis of in-hospital or 30-day MI. Within this group, patients were treated concurrently with ticagrelor (n = 2,239), clopidogrel (n = 1,256) and prasugrel (n = 253). There was no significant association of in-hospital or 30-day MI with intravenous morphine (odds ratio 1.88; 95% confidence interval [CI] 0.87-4.09; I2 0%). Across seven studies and 5,800 patients, no increased risk of mortality at the same composite time endpoint was evident (odds ratio 0.70; 95% CI 0.40-1.23; I2 19%). CONCLUSIONS: Periprocedural intravenous morphine administration was not associated with adverse short-term clinical outcomes in patients undergoing primary PCI for STEMI. Further randomized trial data are needed to evaluate the pharmacologic interaction between morphine and P2Y12 antagonists with clinical outcomes.

BACKGROUND: Clopidogrel's anti-platelet effects may be attenuated by a pharmacokinetic interaction with co-prescribed proton pump inhibitors, which inhibit oxidative pathways that convert clopidogrel into its active metabolites. Despite this, the impact of PPIs on cardiovascular risk in the absence of clopidogrel is not well defined. AIM: To report on a systematic review and meta-analysis of the association between PPIs and cardiovascular risk, independent of clopidogrel. METHODS: The databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were systematically searched in October 2017. The primary outcome was association between PPI monotherapy and any adverse cardiovascular event. The secondary outcome was association between proton pump inhibitor monotherapy and acute myocardial infarction. Studies were excluded if they reported or did not adjust for concomitant anti-platelet therapy or involved participants aged less than 18 years. RESULTS: A total of 22 studies were included in the systematic review. Data from 16 studies were included in the meta-analysis (involving 447 408 participants). Of these, eight were randomised controlled trials, seven were observational studies and one was a retrospective analysis of a randomised controlled trial. An increased risk of any adverse cardiovascular event with PPI monotherapy was observed using pooled data from observational studies (risk ratio 1.25, 95% CI 1.11-1.42, I2 81%, P < 0.001), but not from randomised controlled trials (risk ratio 0.89, 95% CI 0.34-2.33, I2 0%, P = 0.85). CONCLUSION: There is no clear evidence of an association between PPI monotherapy and increased cardiovascular risk.

BACKGROUND AND AIM: Proton pump inhibitors (PPIs) are among the most widely used medications worldwide. Dementia is an increasingly common cause of disability in older populations. Recent studies have suggested an increased risk of cognitive impairment and dementia diagnosis among people who consume PPIs. This systematic review explores dementia, cognitive impairment, and the use of PPIs. METHODS: Systematic searches were conducted in the databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PSYCinfo, Scopus, Web of Science, and ClinicalTrials.gov for articles published from inception to June 30, 2016. Primary outcomes of interest were the use of PPIs and diagnosis of dementia or acute cognitive impairment. Studies conducted on people aged less than 18 years old were excluded. All study designs were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from included studies. RESULTS: The systematic search strategy and screening process yielded 11 studies for inclusion in the systematic review. Four studies explored PPI use and dementia, and seven studies explored PPI use and acute cognitive impairment. Three of the four studies exploring dementia identified a positive association with PPI use. A positive association was also observed in the majority of studies exploring acute cognitive impairment. CONCLUSIONS: Based on the current published literature, this systematic review has identified that the reported association between PPI use and dementia is limited by methodological issues and conflicting results. Further longitudinal studies with robust bias limitation are required to explore the use of PPIs and dementia or acute cognitive impairment, and to ascertain the existence of any causal relationships.