Cardiovascular events associated with rofecoxib : final analysis of the APPROVe trial

Background: Selective inhibition of cyclo-oxygenase-2 has been associated with an increased risk of cardiovascular events in several clinical trials. The Adenomatous Polyp Prevention on Vioxx (APPROVe) study assessed the effect of 3-year treatment with a cyclo-oxygenase-2 inhibitor, rofecoxib (25 mg), on recurrence of neoplastic polyps of the large bowel. We report the cardiovascular outcomes of a long-term follow-up of participants in the trial. Methods: The APPROVe study is a multicentre, randomised, placebo-controlled, double-blind trial. 2587 patients with a history of colorectal adenomas were recruited at 108 centres worldwide during 2000 and 2001. Participants were followed for adverse events while on treatment and during the following 14 days. However, after early termination of treatment because of cardiovascular toxicity, we attempted to follow up all randomised patients for at least 1 year after stopping study treatment. External committees blindly assessed potential serious cardiovascular events. The focus of the analysis was the combined incidence of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and unknown causes (Antiplatelet Trialists' Collaboration [APTC] combined endpoint). We used Cox proportional hazards regression to calculate endpoint hazard ratios. The study is registered with ClinicalTrials.gov, number NCT0282386. Findings: We obtained extended post-treatment cardiovascular follow-up data from 84% of participants, and extended mortality follow-up from 95%. In total, 59 individuals had an APTC endpoint in the rofecoxib group and 34 in the placebo group (hazard ratio 1.79, 95% CI 1.17-2.73; p=0.006). In the first year after cessation of treatment, there was a non-significant increase in the risks of APTC endpoints. The APTC hazard ratio did not substantially change over time. Interpretation: Use of rofecoxib is associated with increased rates of APTC events. Study data are compatible with an early increase in risk that persists for one year after stopping treatment

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien\u2013Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9\ub72 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4\u20137) and 7 (6\u20138) days respectively (P < 0\ub7001). There were no significant differences in rates of readmission between these groups (6\ub76 versus 8\ub70 per cent; P = 0\ub7499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0\ub790, 95 per cent c.i. 0\ub755 to 1\ub746; P = 0\ub7659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34\ub77 versus 39\ub75 per cent; major 3\ub73 versus 3\ub74 per cent; P = 0\ub7110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients