Blood Pressure Lowering With Olmesartan No Better at Preventing Negative Outcomes in Patients on Hemodialysis

Patients receiving olmesartan fared no better in terms of outcomes or blood pressure lowering than those receiving conventional antihypertensive therapy other than angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors in a recent study. The study looked at the effect of olmesartan in lowering blood pressure to decrease the risk of death and nonfatal cardiovascular (CV) outcomes in hypertensive hemodialysis patients.

Data indicate that hypertensive hemodialysis patients have a better prognosis compared to hemodialysis patients with normal or low blood pressure, but guidelines for treating hypertension in hemodialysis patients do not exist, said lead author Kunitoshi Iseki, MD, of the University Hospital of the Ryukyus in Nishihara, Okinawa, Japan. On the other hand, a meta-analysis showed that survival in hemodialysis patients was better if they received antihypertensive drugs, regardless of their blood pressure, suggesting possible other effects of the drugs.

The Olmesartan Clinical Trial in Okinawa Patients Under Okinawa Dialysis Study (OCTOPUS) was an open-label, prospective, randomized, controlled trial with blinded outcome assessment to determine if an ARB would lower the risk of CV disease and death among hypertensive hemodialysis patients. In an interview with Kidney News at the 49th European Renal Association–European Dialysis and Transplant Association Congress in Paris, Iseki described OCTOPUS and its findings.

Eligible patients had a predialysis blood pressure of 140/90 mm Hg to 200/100 mm Hg and could not have used ACE inhibitors or ARBs in the previous month. The trial’s target was a predialysis blood pressure below 140/90 mm Hg.

The mean age of the patients included in the study was 60 years (range 20–79 years), and they received hemodialysis three times a week. After a 1-month period using other conventional blood pressure medications, during which resistant hypertension was confirmed, patients were randomized to conventional therapy not directed at the renin-angiotensin system (234 patients) or to olmesartan 10 mg/day (235 patients). Doses could be escalated in either group to achieve the target blood pressure.

The groups were well matched at baseline for pre-hemodialysis blood pressure, hemodialysis duration (88 months), and hemodialysis dose (Kt/V, 1.15–1.16), as well as other characteristics. The primary end points were 1) all-cause mortality; and 2) the composite of death or nonfatal CV disease, including stroke, myocardial infarction, unstable angina, and heart failure requiring hospitalization.

After a median follow-up of 3.6 years, “there were no blood pressure differences between the groups,” Iseki said. The blood pressure in both groups had dropped by approximately 7/2 mm Hg compared with baseline.

The olmesartan group had a nonsignificant reduction in systolic blood pressure versus the conventional therapy control group (0.9 mm Hg, p = 0.45). There was no difference in the degree of diastolic blood pressure reduction.

Among the olmesartan patients, 28.9 percent reached the primary composite end point versus 28.6 percent of patients in the control arm (hazard ratio [HR], 1.00, p = 0.99). Similarly, 16.2 percent of patients in the olmesartan group died from any cause versus 16.7 percent in the control group (HR, 0.97, p = 0.91).

Iseki concluded that blood pressure reduction with olmesartan did not alter the risk for major CV events or death among chronic hemodialysis patients with hypertension compared with other drugs to lower blood pressure. Fewer than 20 percent of patients in either treatment group reached the target blood pressure of less than 140/90 mm Hg.

He said the annual incidence of the primary composite end point (9.1 percent) and overall mortality (4.7 percent) were lower than expected. Japanese hemodialysis patients typically experience annual mortality of about 6.5 percent, Iseki noted.

A limitation of the study was that olmesartan was compared with active blood pressure-lowering therapies and not with placebo, so the absolute effect of blood pressure reduction with olmesartan could not be determined. A second and important limitation was that adherence to olmesartan and to the other antihypertensive drugs was marginal.

July 2012 (Vol. 4, Number 7)