title: Cardiovascular and Renal Outcomes Trials-Is There a Difference?
abstract: There is a general sense that most outcomes trials in patients receiving dialysis failed to yield statistically significant benefits, in contrast to many cardiovascular (CV) trials in the general population. It is unknown whether methodologic reasons caused this discrepancy. We performed a systematic MEDLINE search for randomized trials with mortality end points of the 42 compounds most commonly used for CV indications. In total, 115 trials were selected for review. We further reviewed 9 mortality end point trials in patients receiving dialysis. The CV trials in populations not receiving dialysis enrolled from 66 to 33,357 participants with an average of 4,910; 59% of the trials showed statistically significant results. The average hazard ratio (HR) was 0.77, ranging from 0.10 to 1.65; 10 drugs had ≥5 published trials each. In the population receiving dialysis, most drugs were studied in single trials; the average number of patients was 1,500 with a range of 127 to 3,883. The average HR was 0.77 and ranged from 0.06 to 1.30. Only 22% of the trials showed statistically significant results. The limitations listed in the general population and dialysis studies were similar. In conclusion, no apparent methodologic issues were detected (other than sample size) that could justify the lower frequency of randomized trials with statistically significant results in patients receiving dialysis. The most obvious difference was the paucity of trials with each drug in the dialysis cohorts; this lowers the chances of at least 1 trial being successful.
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: raggi@ualberta.ca.
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.affiliation: Health Economics and Epidemiology, Yucca Valley, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Boer
authors.affiliation: Nephrology, Woodland Hills, California.
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: Division of Nephrology and Hypertension, University of California, Irvine, Irvine, California.
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.affiliation: Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Vasily
authors.initials: V
authors.lastname: Belozeroff
mesh_terms: D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D012107:Research Design
chemical_list: D002317:Cardiovascular Agents