Daniele Pastori

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78–0.94) and ischemic stroke (HR 0.68, 95%CI 0.55–0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38–2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43–103) and the NNH to cause major bleeding was 107 (77–193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

Background Midregional‐proAdrenomedullin (MR‐proADM) has been recently proposed as a tool in patients with sepsis and septic shock. Our aim was to evaluate the prognostic role of MR‐proADM in hospitalized patients with sepsis and septic shock. Methods PRISMA guideline was followed. MEDLINE and EMBASE were searched up to June 2023. Primary outcome was mean difference in MR‐proADM among survivors and nonsurvivors, secondary outcome mean difference in MR‐proADM according to infection severity and type. Risk of bias was evaluated using Newcastle–Ottawa scale for observational studies and Cochrane tool for randomized trials. Pooled mean differences (MD) with corresponding 95% confidence intervals (CIs) were calculated in a random‐effects model. Results Twenty‐four studies included 6730 adult patients (1208 nonsurvivors and 5522 survivors) and three studies included 195 paediatric patients (30 nonsurvivors and 165 survivors). A total of 10, 4 and 13 studies included, respectively, patients with sepsis (3602 patients), septic shock (386 patients) and a mixed population (2937 patients). Twenty‐one studies included patients with different source of infection, three with pneumonia and one with a catheter‐related infection. Most studies ( n = 12) had a follow‐up of 28 days. In adult cohort, pooled mean difference between nonsurvivors and survivors of MR‐proADM was 2.55 mmol/L (95% CI: 1.95–3.15) with higher values in patients with septic shock (4.25 mmol/L; 95% CI, 2.23–6.26 mmol/L) than in patients with sepsis (1.77 mmol/L; 95% CI: 1.11–2.44 mmol/L). In paediatric cohort, pooled mean difference was 3.11 mmol/L (95% CI: −0.02‐6.24 mmol/L). Conclusions Higher values of MR‐proADM are detectable in nonsurvivors adult and paediatric‐hospitalized patients with sepsis or septic shock.