Kidney,Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis

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The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial

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.

Conclusions

In 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.     

Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis

We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion.     

Glucose, insulin, and acute myocardial infarction: reply

Dr Das comments that the association between the failure ofglucose levels to drop during hospitalization and higher mortalityfollowing acute myocardial     

Prognostic and Practical Validation of Current Definitions of Myocardial Infarction Associated With Percutaneous Coronary Intervention

Objectives

In 13,038 patients with non–ST-segment elevation acute coronary syndrome undergoing index percutaneous coronary intervention (PCI) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndrome) and TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trials, the relationship between PCI-related myocardial infarction (MI) and 1-year mortality was assessed.

Spontaneous disappearance of refractory viral warts at distant sites following carbon-dioxide laser treatment.

We report the spontaneous disappearance of distant viral skin lesions following carbon-dioxide laser treatment of refractory viral warts.     

Effect of lead ingestion on functions of vitamin D and its metabolites

A study of the effect of ingestion of lead on the metabolism and function of vitamin D was carried out in rats fed diets varying in calcium and phosphorus content. The ingestion of 0.82% lead as lead acetate suppressed plasma levels of 1,25-dihydroxycholecalciferol in rats fed either a low phosphorus or a low calcium diet while it had no effect on this parameter in rats fet either a high calcium diet or a normal phosphorus diet. Most important, the ingestion of lead totally blocked the intestinal calcium transport response to cholecalciferol, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. On the other hand, the ingestion of lead acetate had no influence on the mobilization of calcium from bone, the elevation of serum inorganic phosphorus and in the mineralization of rachitic bone in the same animals. Thus by the feeding of 0.82% lead on the intestinal responses to vitamin D and its metabolites was greatest in animals fed a low calcium or a low phosphorus diet, it was present with all diets tested.