Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.

Hybrid simultaneous treatment of thrombosed prosthetic grafts for hemodialysis.

PURPOSE: The aim of the study was to evaluate our experience in the hybrid simultaneous treatment (open and endovascular) of acute thrombosis of prosthetic grafts for hemodialysis. METHODS: Between January 2011 and June 2013, 23 patients with acute thrombosis of a prosthetic graft for hemodialysis were urgently treated with a hybrid simultaneous treatment in order to obtain a prompt restoration of the flow. A new puncture of the graft was scheduled after 24 hours. RESULTS: Intraoperative technical success was 100% with a completion angiography showing the restored patency of the graft. As adjunctive procedures, in 6 patients (26.1%) locoregional thrombolysis was necessary and in all cases further endovascular manoeuvres (angioplasty/stenting) were immediately performed to solve a significant stenosis of the venous anastomosis/first tract of the vein. At 24 hours when the first puncture was done, three grafts were occluded resulting in a primary patency of 87%. During the follow-up (mean duration 5.6 months) four reocclusions occurred. In-stent restenosis occurred in all patients undergone stenting. At 1 year the rates of primary patency, primary assisted patency and secondary patency were 58.7%, 78.3% and 87%, respectively. CONCLUSIONS: In our series the combined simultaneous hybrid approach in urgency maximizes the use of different available techniques, which appeared to improve overall success rate to save a thrombosed graft for hemodialysis. The great difference showed between primary and primary assisted patency demonstrates the necessity of a close follow-up.

Oral anticoagulant therapy in hemodialysis patients: do the benefits outweigh the risks?

Managing oral anticoagulation may be difficult in hemodialysis patients because the antithrombotic effect can be counterbalanced by an increased risk of hemorrhagic complications. There is insufficient evidence to recommend the routine use of warfarin for thrombosis prophylaxis of the vascular access in all patients. If a decision for anticoagulation is made, dosing warfarin to a "therapeutic" level is suggested, although the most appropriate target INR range remains unclear. Many hemodialysis patients with atrial fibrillation have multiple risk factors for stroke and generally benefit from warfarin, with careful and frequent laboratory monitoring. Treatment with standard dose warfarin is also recommended in patients with venous thromboembolism provided that patients do not have contraindications to anticoagulation. For those with such contraindications, placement of an inferior vena cava filter is suggested. These recommendations are limited by the almost complete lack of data in dialysis patients. Sound randomized evidence of efficacy and harm for anticoagulation in these patients will likely never be available. Knowledge of the risk of bleeding and thrombosis in anticoagulated and nonanticoagulated dialysis patients could be provided by feasible, well-designed cohort studies.

Quality of life assessment and instruments in end-stage renal disease.

The main aim of every medical intervention is to improve the "quality of life" of the patients. In recent years, quality of life assessment has become increasingly important as an additional outcome measure in clinical research. The evaluation of quality of life is particularly relevant in patients with end-stage renal disease. The characteristics of the clinical condition in fact--no cure of the pathological state, and the type of the heavy non-stop treatment programs--obviously have an important impact on the patients' quality of life. Mortality, of course, is not an optimal or satisfactory outcome to assess the quality of care provided to these patients. After a general introduction of the current debate on methodological issues in quality of life evaluation, this paper reports several instruments described in the literature to evaluate the quality of life in patients with renal disease. Compared to other medical fields the number of questionnaires available for patients with renal disease is limited. The domains investigated are well defined in terms of generic concepts and disease-specific domains, principal symptoms, and the validity of the questionnaires is generally well documented.

Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study.

BACKGROUND: Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life ( approximately 130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. METHODS: STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within +/- 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29-36). RESULTS: Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (-0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. CONCLUSIONS: Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA.