Retrospective comparison of clinical and angiographic outcomes after primary stenting using sirolimus-eluting and bare-metal stents in nonrandomized consecutive 568 patients with first ST-segment elevated myocardial infarctions

SummaryBackground and purposeThe long-term safety and efficacy of primary stenting using drug-eluting stents (DES) in patients with ST-segment elevation myocardial infarction (STEMI) are not fully understood in Japan. Therefore, we retrospectively examined the midterm clinical and angiographic outcomes in STEMI patients after primary stenting using sirolimus-eluting stents (SES) in a clinical setting through a historical comparison with those of bare-metal stents (BMS).Methods and resultsThe study design was a retrospective, nonrandomized, and single-center study. The clinical outcomes for 568 consecutive patients who presented within 12h of their first STEMI and who were treated with BMS (n=198; 184 STEMIs from June 2003 to August 2004 and 14 STEMIs from September 2004 to May 2007) or SES (n=370; from August 2004 to May 2007) at our medical center in Japan were retrospectively investigated in February 2010. The incidence of post-discharge events (comprising cardiac death and nonfatal recurrent MI) after SES placement (3.9%) was not significantly different from that after BMS placement (6.7%). SES was not related to the risk of post-discharge events (mean follow-up for SES, 1327±415 days; BMS, 1818±681 days) (hazard ratio of 0.369 at 95% CI, 0.119–1.147, p=0.085). The incidence of definite stent thromboses after SES placement (0.54%) was not significantly higher than that after BMS placement (0%). The incidence of binary in-stent restenosis (% diameter stenosis of more than 50% at secondary angiography) after SES placement (8.3%) was significantly lower than that after BMS placement (25.7%; p<0.001).ConclusionsFrom the present historical comparison of SES and BMS, we conclude that primary stenting using SES in a clinical setting has favorable clinical and angiographic outcomes in Japanese STEMI patients

Spesolimab Efficacy and Safety in Patients with Moderate-to-Severe Palmoplantar Pustulosis: A Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase IIb, Dose-Finding Study

Abstract Introduction We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP). Methods This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician’s Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed. Results 152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from − 14.6% (95% confidence interval [CI]: − 31.5%, 2.2%) to − 5.3% (95% CI: − 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference − 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo. Conclusion The primary objective to demonstrate a non-flat dose–response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518)