Comprehensive Meta-Analysis of Safety and Efficacy of Bivalirudin Versus Heparin With or Without Routine Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Coronary Syndrome

AbstractObjectivesThe aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS).BackgroundBivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear.MethodsA total of 13 randomized, controlled trials involving 24,605 patients were included.ResultsThere was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (≤24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly.ConclusionsOverall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI

Results of Polish Adult Leukemia Study Group (PALG) project assessing TP53 mutations with next-generation sequencing technology in relapsed and refractory chronic lymphocytic leukemia patients — an 18-month update

Indtroduction and methods: In chronic lymphocytic leukemia (CLL), molecular and cytogenetic diagnostics are crucial for the determination of accurate prognosis and treatment choice. Among different genetic aberrations, del(17p13) or TP53 mutations constitute high-risk factors, and early identification of such defects is a high priority for CLL patients. While cytogenetic diagnostics is well-established and accessible for the majority of CLL patients in Poland, molecular diagnostics of TP53 mutations is performed only in a few ERIC-certified centers (eight as of September 2020), and only two of these employ next-generation sequencing (NGS) for routine analysis of TP53 status in CLL patients. Here we report the interim results of a project assessing TP53 mutations with NGS technology in relapsed or refractory CLL patients with confirmed negative del(17p13) status. 249 patients from 32 clinical centers were included in the study. Results: NGS analysis revealed TP53 mutations in 42/249 (17%) patients, half of whom (21/249, 8.5%) had subclonal mutations (VAF ≤10%). These results are in line with published data in relapsed/refractory CLL patients. Conclusions: The results of the project demonstrated the feasibility and accuracy of NGS testing in CLL patients despite several initial logistical and technical obstacles. Our study also proved that, with appropriate funding, CLL patients from any hematological center in Poland can have access to state-of-the-art molecular diagnostic