Mace

Abstract: The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: 1) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA1c or individualized HbA1c target; 2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and 3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min-1 [1.73 m]-2 or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.

Abstract: Increases in lipid levels and cancers with tofacitinib prompted a trial of major adverse cardiovascular events (MACE) and cancers in patients with rheumatoid arthritis receiving tofacitinib as compared with a tumor necrosis factor (TNF) inhibitor.We conducted a randomized, open-label, noninferiority, postauthorization, safety end-point trial involving patients with active rheumatoid arthritis despite methotrexate treatment who were 50 years of age or older and had at least one additional cardiovascular risk factor. Patients were randomly assigned in a 1:1:1 ratio to receive tofacitinib at a dose of 5 mg or 10 mg twice daily or a TNF inhibitor. The coprimary end points were adjudicated MACE and cancers, excluding nonmelanoma skin cancer. The noninferiority of tofacitinib would be shown if the upper boundary of the two-sided 95% confidence interval for the hazard ratio was less than 1.8 for the combined tofacitinib doses as compared with a TNF inhibitor.A total of 1455 patients received tofacitinib at a dose of 5 mg twice daily, 1456 received tofacitinib at a dose of 10 mg twice daily, and 1451 received a TNF inhibitor. During a median follow-up of 4.0 years, the incidences of MACE and cancer were higher with the combined tofacitinib doses (3.4% [98 patients] and 4.2% [122 patients], respectively) than with a TNF inhibitor (2.5% [37 patients] and 2.9% [42 patients]). The hazard ratios were 1.33 (95% confidence interval [CI], 0.91 to 1.94) for MACE and 1.48 (95% CI, 1.04 to 2.09) for cancers; the noninferiority of tofacitinib was not shown. The incidences of adjudicated opportunistic infections (including herpes zoster and tuberculosis), all herpes zoster (nonserious and serious), and adjudicated nonmelanoma skin cancer were higher with tofacitinib than with a TNF inhibitor. Efficacy was similar in all three groups, with improvements from month 2 that were sustained through trial completion.In this trial comparing the combined tofacitinib doses with a TNF inhibitor in a cardiovascular risk-enriched population, risks of MACE and cancers were higher with tofacitinib and did not meet noninferiority criteria. Several adverse events were more common with tofacitinib. (Funded by Pfizer; ORAL Surveillance ClinicalTrials.gov number, NCT02092467.).