Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial)

BACKGROUND: Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial. METHODS: We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890. RESULTS: 2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364). No significant differences were reported in the safety variables nor in the rate of adverse events. INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke

Patients with prior coronary artery bypass grafting have a poor outcome after myocardial infarction: an analysis of the VALsartan in acute myocardial iNfarcTion trial (VALIANT)

The number of patients presenting with an acute myocardial infarction (MI) and prior coronary artery bypass grafting (CABG) is increasing. We compared the baseline characteristics, treatment, and clinical outcomes of patients with and without prior CABG in the VALIANT trial. Of the 14 703 patients with heart failure (HF), left ventricular systolic dysfunction, or both enrolled in VALIANT, 1026 (7%) had prior CABG. Prior CABG patients were older [mean age (SD): 67 (10) vs. 65 (12) years; P less than 0.0001], had more comorbidity, and more frequent non-Q wave MI (66 vs. 30%; P less than 0.0001). At hospital presentation, prior CABG patients received less aspirin (82 vs. 90%; P less than 0.0001) and thrombolysis (21 vs. 36%; P less than 0.0001), but had a similar rate of primary percutaneous coronary intervention (14 vs. 15%; P = 0.2). Prior CABG patients were more likely to experience the composite outcome of cardiovascular death, MI, HF, resuscitated cardiac arrest, or stroke; 3 year Kaplan-Meier rate, 64 vs. 39% (adjusted hazard ratio 1.29, 95% confidence interval 1.17-1.43; P less than 0.0001). Patients with prior CABG had a worse clinical profile and experienced more fatal and non-fatal outcomes. Greater recognition is necessary for these high-risk patients including optimization of evidence-based secondary preventive therapy