No significant effect of angiotensin II receptor blockade on intermediate cardiovascular end points in hemodialysis patients

Abstract

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

“…Preservation of renal function could improve dialysis care and previous studies in PD patients have suggested a significant effect of renin‐angiotensin‐aldosterone system blockade . However, in the SAFIR study no significant associations were shown between the angiotensin II receptor blocker irbesartan and preservation of renal function or intermediate cardiovascular endpoints …”

“…See modified CONSORT flow chart in Figure . For the original CONSORT flow chart see previous publications . There were no significant differences between patients who completed all three questionnaires and patients who dropped out in terms of HRQOL at baseline.…”

Blood pressure control in conventional hemodialysis

“…The absence of benefit with RAS‐blockers is further supported by the Saving Residual Renal Function among Hemodialysis Patients Receiving Irbesartan Study (SARIF) . This trial showed that among 82 incident hemodialysis patients, 12‐month‐long therapy with the ARB irbesartan was not superior to placebo in causing regression of target‐organ damage, as assessed by measuring Left Ventricular Mass Index (LVMI) and aortic pulse wave velocity (PWV) …”

“…Choice of the appropriate antihypertensive regimen among those on hemodialysis should not rely on extrapolation of evidence derived from the general population or those with earlier stages of chronic kidney disease . To wit, trials that evaluated the efficacy of ACEIs/ARBs suggest that their use as first‐line antihypertensive therapy in hemodialysis patients is not supported by strong evidence of a cardiovascular benefit . By contrast, the BP‐lowering efficacy of atenolol in the HDPAL and its premature termination due to excess risk for serious cardiovascular adverse events in lisinopril‐treated participants support the use of β‐blockers as first therapeutic choice .…”

The Authors Reply

“…Their title was very impressive as previous studies proved the effects of an angiotensin receptor antagonist on hard end points in dialysis patients including our study. 2 Originally, the purpose of central aortic blood pressure measurement was to detect the minute changes in vessels, which would not change the brachial blood pressure. Therefore, measurement of central aortic blood pressure might not be suitable for dialysis patients who show a high value because of aging and advanced arterial calcification.…”