Metaanalysis of Multivessel vs Culprit Artery Only Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction.

Background: Primary percutaneous coronary intervention (PCI) is the most frequently used treatment modality for patients presenting with ST elevation myocardial infarction (STEMI). Current professional society guidelines recommend culprit artery only PCI. Recent evidence suggests the potential benefit of multivessel PCI among patients with STEMI that is not complicated by cardiogenic shock. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical studies of patients with STEMI, not complicated by cardiogenic shock, who underwent primary PCI between January 1966 and January 2018. We evaluated all-cause and cardiovascular mortality, reinfarction, and repeat revascularization among patients randomized to a multivessel PCI strategy compared to a culprit artery only PCI strategy. Results: Four randomized clinical trials with a total of 1,044 patients met the inclusion criteria. Five hundred and sixty-six patients underwent multivessel PCI, and 478 patients underwent culprit artery only PCI. Multivessel PCI reduced all the studied endpoints: total death, cardiac death, reinfarction, and repeat revascularization (all P values <0.05). Conclusion: To our knowledge, this is the largest metaanalysis of randomized controlled trials studying multivessel PCI vs culprit artery only PCI in STEMI patients without shock, among whom lesion severity was graded by angiography alone. We found that compared to culprit artery only PCI, the multivessel PCI strategy was beneficial in reducing all-cause and cardiovascular mortality, reinfarction, and the need for repeat revascularization.

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis.

BACKGROUND: Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs. METHODS: We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I(2) statistics; p values inferior to 0.10 and I(2) >25% were considered significant for heterogeneity. RESULTS: We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding. CONCLUSIONS: The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.

Cyclooxygenase-2 contributes to functional changes seen on experimental hemorrhagic cystitis induced by ifosfamide in rat urinary bladder.

PURPOSE: Ifosfamide (IFS) is often involved in the occurrence of hemorrhagic cystitis due to direct contact of its metabolite acrolein with uroepithelium. It has been shown that COX-2 is involved in this pathogenesis. Thus, we aimed to study the functional changes on the urinary bladder in the putative modifications induced by IFS, as well as the COX-2 role in this process. MATERIALS AND METHODS: IFS-treated rats were evaluated by cystometrography in absence or presence of COX inhibitors indomethacin or etoricoxib or in the presence of mesna. Experiments with isolated strips of urinary bladder obtained from animals with IFS-induced cystitis, either treated or not treated with COX inhibitors or mesna, were performed. Histological analyses, immunohistochemistry for COX-2, and measurement of plasma PGE(2) were also performed. RESULTS: IFS treatment caused severe inflammation of the bladder tissue. Cystometrography recordings of IFS-treated rats revealed bladder with increased micturition frequency and enhanced filling intravesical pressure. Contractility of the isolated smooth muscle from the rat's bladder with IFS-induced cystitis showed decreased force development in response to KCl and CCh. Almost all effects induced by IFS were ameliorated by the use of COX inhibitors or mesna. Enzyme expression in the urinary bladder tissue was positive, and plasma concentration of PGE(2) was increased in IFS-treated animals and decreased significantly in etoricoxib-treated animals. CONCLUSIONS: IFS causes important changes in the micturition physiology in rats, and the inhibition of the isoenzyme COX-2 could be an important event that could prevent the detrimental effects elicited by IFS-induced hemorrhagic cystitis.