Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.
ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.
Both oxygen consumption index (VO2-index) and simplified acute physiology score (SAPS) are reported to be reliable predictors of the ultimate outcome in critically ill patients. The purpose of this study was to verify whether survivors and nonsurvivors have different VO2-indices and whether the prognostic potency of SAPS can be improved by addition of VO2-index as a supplemental physiological variable. In 50 mechanically ventilated surgical ICU patients with heterogeneous underlying diseases, SAPS was calculated and VO2-index was determined by continuous 24-h measurement of oxygen consumption. The VO2-indices of survivors and nonsurvivors were not significantly different (p greater than 0.05), which is in contrast to the results of earlier studies. This contrast may be explained by a difference both in methods of VO2-measurement and in study populations. SAPS was significantly lower in survivors than in nonsurvivors (p less than 0.005) and was able to classify the patients correctly into groups of increasing probability of death. However, SAPS failed to be a helpful prognosticator in the individual patient. The addition of VO2-index to SAPS as a supplemental physiological variable did not substantially improve the prognostic potency. Because a higher VO2-index did not necessarily indicate a better survival chance, there is no argument for therapeutic interventions aimed exclusively at increasing VO2-index, as suggested previously.
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