Mortality reduction by post-dilution online-haemodiafiltration : A cause-specific analysis

Background. From an individual participant data (IPD) meta-analysis from four randomized controlled trials comparing haemodialysis (HD) with post-dilution online-haemodiafiltration (ol-HDF), previously it appeared that HDF decreases all-cause mortality by 14% (95% confidence interval 25; 1) and fatal cardiovascular disease (CVD) by 23% (39; 3). Significant differences were not found for fatal infections and sudden death. So far, it is unclear, however, whether the reduced mortality risk of HDF is only due to a decrease in CVD events and if so, which CVD in particular is prevented, if compared with HD. Methods. The IPD base was used for the present study. Hazard ratios and 95% confidence intervals for cause-specific mortality overall and in thirds of the convection volume were calculated using the Cox proportional hazard regression models. Annualized mortality and numbers needed to treat (NNT) were calculated as well. Results. Besides 554 patients dying from CVD, fatal infections and sudden death, 215 participants died from 'other causes', such as withdrawal from treatment and malignancies. In this group, the mortality risk was comparable between HD and ol-HDF patients, both overall and in thirds of the convection volume. Subdivision of CVD mortality in fatal cardiac, non-cardiac and unclassified CVD showed that ol-HDF was only associated with a lower risk of cardiac casualties [0.64 (0.61; 0.90)]. Annual mortality rates also suggest that the reduction in CVD death is mainly due to a decrease in cardiac fatalities, including both ischaemic heart disease and congestion. Overall, 32 and 75 patients, respectively, need to be treated by high-volume HDF (HV-HDF) to prevent one all-cause and one CVD death, respectively, per year. Conclusion. The beneficial effect of ol-HDF on all-cause and CVD mortality appears to be mainly due to a reduction in fatal cardiac events, including ischaemic heart disease as well as congestion. In HV-HDF, the NNT to prevent one CVD death is 75 per year

Mortality reduction by post-dilution online-haemodiafiltration : A cause-specific analysis

Background. From an individual participant data (IPD) meta-analysis from four randomized controlled trials comparing haemodialysis (HD) with post-dilution online-haemodiafiltration (ol-HDF), previously it appeared that HDF decreases all-cause mortality by 14% (95% confidence interval 25; 1) and fatal cardiovascular disease (CVD) by 23% (39; 3). Significant differences were not found for fatal infections and sudden death. So far, it is unclear, however, whether the reduced mortality risk of HDF is only due to a decrease in CVD events and if so, which CVD in particular is prevented, if compared with HD. Methods. The IPD base was used for the present study. Hazard ratios and 95% confidence intervals for cause-specific mortality overall and in thirds of the convection volume were calculated using the Cox proportional hazard regression models. Annualized mortality and numbers needed to treat (NNT) were calculated as well. Results. Besides 554 patients dying from CVD, fatal infections and sudden death, 215 participants died from 'other causes', such as withdrawal from treatment and malignancies. In this group, the mortality risk was comparable between HD and ol-HDF patients, both overall and in thirds of the convection volume. Subdivision of CVD mortality in fatal cardiac, non-cardiac and unclassified CVD showed that ol-HDF was only associated with a lower risk of cardiac casualties [0.64 (0.61; 0.90)]. Annual mortality rates also suggest that the reduction in CVD death is mainly due to a decrease in cardiac fatalities, including both ischaemic heart disease and congestion. Overall, 32 and 75 patients, respectively, need to be treated by high-volume HDF (HV-HDF) to prevent one all-cause and one CVD death, respectively, per year. Conclusion. The beneficial effect of ol-HDF on all-cause and CVD mortality appears to be mainly due to a reduction in fatal cardiac events, including ischaemic heart disease as well as congestion. In HV-HDF, the NNT to prevent one CVD death is 75 per year

Cardiorenal end points in a trial of aliskiren for type 2 diabetes.

Background This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 dia- betes and chronic kidney disease, cardiovascular disease, or both. Methods In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting\u2013enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. Results The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pres- sures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, 656 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). Conclusions The addition of aliskiren to standard therapy with renin\u2013angiotensin system block- ade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful

Cardiorenal end points in a trial of aliskiren for type 2 diabetes.

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, 656 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful