Acute promyelocytic leukaemia: population-based study of epidemiology and outcome with ATRA and oral-ATO from 1991 to 2021.

BACKGROUND: The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. METHODS: Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. RESULTS: APL occurred in 374 males and 387 females at a median age of 44 (1-97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 109/L, diagnosis during 1991-2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14-161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 109/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010-2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. CONCLUSIONS: There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).

Network meta-analysis of cardiovascular outcomes in randomized controlled trials of new antidiabetic drugs.

BACKGROUND: Randomized controlled trials (RCTs) directly comparing cardiovascular outcomes of new antidiabetic drugs are lacking. We used network meta-analysis to compare new antidiabetic drug classes with respect to major adverse cardiovascular events (MACE) and mortality. METHODS: We searched MEDLINE, EMBASE, the Cochrane database, and ClinicalTrials.gov up to 30 December 2016 for RCTs involving SGLT-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabetic patients that reported MACE and deaths. Outcomes were compared with frequentist and Bayesian methods using R statistics. RESULTS: Seven RCTs with altogether 62,268 patients were included in the network meta-analysis. The SGLT-2 inhibitor and GLP-1 RAs reduced MACE (OR 0.85, 95%CI 0.73-0.99 and 0.89, 0.82-0.97, respectively) and all-cause mortality (0.67, 0.55-0.81 and 0.89, 0.80-0.99, respectively) compared to placebo. Furthermore, the SGLT-2 inhibitor reduced all-cause mortality compared to GLP-1 RAs (0.76, 0.61-0.94). In contrast, DPP-4 inhibitors did not reduce MACE or mortality compared to placebo and were associated with higher all-cause mortality compared to the SGLT-2 inhibitor (1.53, 1.24-1.89) and GLP-1 RAs (1.16, 1.01-1.33). CONCLUSIONS: All-cause mortality and MACE were reduced by the SGLT-2 inhibitor and GLP-1 RAs, but not DPP-4 inhibitors. The SGLT-2 inhibitor had the most beneficial impact on all-cause mortality. DPP-4 inhibitors showed no cardiovascular benefit and were inferior to the other two drug classes in preventing deaths.

Duration of dual antiplatelet therapy after drug-eluting stent implantation: Meta-analysis of large randomised controlled trials.

Patients receive dual antiplatelet therapy (DAPT) for 6-12 months after drug-eluting stents (DES) implantation. The efficacy and safety of prolonged DAPT has been questioned. Therefore, we performed a meta-analysis on randomised trials comparing different DAPT durations. Literature was searched on trials comparing different DAPT durations. For inclusion, reports must report frequency of cardiovascular and bleeding events. Ten trials were included. Compared to 12 months, DAPT beyond 12 months was associated with fewer myocardial infarctions (OR 0.58 95%CI: 0.40-0.84) and stent thrombosis (OR 0.35 95%CI: 0.20-0.62), but more major bleeds (OR 1.60 95%CI: 1.22-2.11) and all-cause (OR 1.30 95%CI: 1.02-1.66) mortality. There was no significant alteration in risk of stroke (OR 0.93 95%CI: 0.66-1.31) or cardiac (OR 1.12 95%CI: 0.73-1.71) mortality. Compared to less than 12 months DAPT, 12 months DAPT did not reduce risk of myocardial infarction, stent thrombosis, strokes, cardiac or all-cause mortality, but increased the risk of major bleeds (OR 1.60 95%CI: 1.22-2.11). DAPT beyond 12 months reduce risk of myocardial infarction and stent thrombosis, but there is substantial increase in major bleeding risk and all-cause mortality which need to be addressed. DAPT beyond 12 months does not appear to alter the risk of stroke.