alvimopan-anhydrous and Cardiovascular-Diseases

Alvimopan is used in abdominal surgery to reduce postoperative ileus in patients undergoing small bowel resections with primary anastomosis. The role and efficacy of alvimopan in patients undergoing radical cystectomy with urinary diversion is not well understood.. To assess the effects of alvimopan in the context of enhanced recovery pathways compared to enhanced recovery pathways alone for perioperative bowel dysfunction in patients undergoing radical cystectomy.. The terms alvimopan and cystectomy were used to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We also reviewed abstracts from the past four years (2013 to 2016) of the American Urologic Association, Society of Urologic Oncology, and American Society of Clinical Oncology Genitourinary Cancers.. We searched for randomized controlled trials that compared alvimopan to placebo.. This study was based on a published protocol. We performed a comprehensive search of multiple databases including CENTRAL in the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, Scopus and Biosis, which we last updated on 6 February 2017. We also searched abstract proceedings for major relevant meetings (2013 to 2016), databases of the grey literature, trial registries, citations of relevant reviews and contacted clinical experts and the drug manufacturer.Two independent reviewers screened the literature in two stages (title and abstract, full-text) using Covidence software. Two independent reviewers assessed the risk of bias on a 'per outcome' basis using the Cochrane 'Risk of bias; tool and rated the quality of evidence according to GRADE. Results of the single eligible trial were reported in a 'Summary of findings' table based on an intention-to-treat analysis.. Based on a single trial and moderate-quality evidence, alvimopan reduced the time to reach a composite endpoint of tolerance of solid food and documented bowel movements (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.41 to 2.23). This represents 165 more patients (109 more to 207 more) per 1000 meeting this endpoint within 10 days of surgery. Based on moderate-quality evidence, alvimopan reduced the time to hospital discharge (HR 1.67, 95% CI 1.38 to 2.01). This represents 138 more patients (82 more to 198 more) per 1000 being discharged within 10 days of surgery. Also based on moderate-quality evidence, alvimopan was associated with a reduced risk of major adverse events (risk ratio (RR) 0.28, 95% CI 0.18 to 0.44) representing 355 fewer patients (404 fewer to 276 fewer) with major adverse events per 1000. We downgraded this outcome for indirectness as it included adverse events that we did not consider major.In terms of secondary outcomes, alvimopan did not appear to alter the rate of readmission (RR 0.89, 95% CI 0.59 to 1.33), change the rate of any cardiovascular event (RR 0.54, 95% CI 0.27 to 1.05) or alter the mean narcotic pain medication use (mean difference 0, 95% CI 14.08 fewer to 14.08 more morphine equivalents). The quality of evidence was moderate for all three outcomes. Based on high-quality evidence, alvimopan reduced the rate of nasogastric tube replacement (RR 0.31, 95% CI 0.16 to 0.59). We did not find evidence for the drug's impact on rates of parenteral nutrition. All outcomes were short term and limited to a 30-day time horizon.Based on the existence of only one trial, we were unable to perform any subgroup or sensitivity analyses.. In patients undergoing radical cystectomy and urinary diversion, the use of alvimopan administered as part of an enhanced recovery pathway for a limited duration (up to 15 doses for up to seven days) probably reduces the time to tolerance of solid food, time to hospital discharge and rates of major adverse events. Readmission rates, rates of cardiovascular events and narcotic pain requirements are probably similar. The need for reinsertion of nasogastric tubes is reduced. We found no evidence for the impact on rates of parenteral nutrition within 30 postoperative days.

Topics: Cardiovascular Diseases; Cystectomy; Defecation; Eating; Gastrointestinal Agents; Humans; Ileus; Patient Discharge; Patient Readmission; Piperidines; Postoperative Complications; Randomized Controlled Trials as Topic; Recovery of Function; Time Factors; Urinary Diversion

Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).. To assess the efficacy of alvimopan to accelerate GI recovery after RC.. We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.. Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo.. The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed.. Patients were randomized to alvimopan (n=143) or placebo (n=137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p<0.0001), shorter mean LOS (7.4 vs 10.1 d; p=0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p<0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p=0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy.. Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo.. This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety.. ClinicalTrials.gov identifier NCT00708201.

Topics: Aged; Analgesics, Opioid; Cardiovascular Diseases; Cystectomy; Defecation; Double-Blind Method; Eating; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Length of Stay; Male; Middle Aged; Piperidines; Postoperative Care; Prospective Studies; Recovery of Function; Time Factors