Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial

Abstract

Background: The purpose of this study was to determine among maintenance hemodialysis patients with echocardiographic left ventricular hypertrophy and hypertension whether in comparison with a β-blocker-based antihypertensive therapy, an angiotensin converting enzyme-inhibitor-based antihypertensive therapy causes a greater regression of left ventricular hypertrophy.

Methods: Subjects were randomly assigned to either open-label lisinopril (n = 100) or atenolol (n = 100) each administered three times per week after dialysis. Monthly monitored home blood pressure (BP) was controlled to <140/90 mmHg with medications, dry weight adjustment and sodium restriction. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to 12 months.

Results: At baseline, 44-h ambulatory BP was similar in the atenolol (151.5/87.1 mmHg) and lisinopril groups, and improved similarly over time in both groups. However, monthly measured home BP was consistently higher in the lisinopril group despite the need for both a greater number of antihypertensive agents and a greater reduction in dry weight. An independent data safety monitoring board recommended termination because of cardiovascular safety. Serious cardiovascular events in the atenolol group occurred in 16 subjects, who had 20 events, and in the lisinopril group in 28 subjects, who had 43 events {incidence rate ratio (IRR) 2.36 [95% confidence interval (95% CI) 1.36-4.23, P = 0.001]}. Combined serious adverse events of myocardial infarction, stroke and hospitalization for heart failure or cardiovascular death in the atenolol group occurred in 10 subjects, who had 11 events and in the lisinopril group in 17 subjects, who had 23 events (IRR 2.29, P = 0.021). Hospitalizations for heart failure were worse in the lisinopril group (IRR 3.13, P = 0.021). All-cause hospitalizations were higher in the lisinopril group [IRR 1.61 (95% CI 1.18-2.19, P = 0.002)]. LVMI improved with time; no difference between drugs was noted.

Conclusions: Among maintenance dialysis patients with hypertension and left ventricular hypertrophy, atenolol-based antihypertensive therapy may be superior to lisinopril-based therapy in preventing cardiovascular morbidity and all-cause hospitalizations. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number: NCT00582114).

Keywords: hemodialysis; hypertension; randomized trial.

Figures

FIGURE 1:

BP profiles at baseline and over time. BP obtained in the interdialytic period (Left panel) and self-measured by the patients at home (right panel) are shown. Ambulatory BP monitoring was performed in the interdialytic period over 44 h at baseline, 3, 6 and 12 months. Solid line shows the atenolol group and the dotted line the lisinopril group; vertical bars represent standard error of mean. The table at the bottom of each graph shows the number of patients in each drug [atenolol (n), lisinopril (n)]; the change from baseline (CFB) and between group comparisons of the changes (lisinopril–atenolol CFB). The declines in both systolic and diastolic blood pressure were numerically greater with atenolol but no statistical difference was present between drugs. Home BP monitoring was performed at baseline and at every month for the entire duration of the trial; the mean reduction in BP overall was reduced more with atenolol therapy (linear rate of change for atenolol was −1.5 mmHg systolic/month and that for lisinopril was 0.47 mmHg flatter (P = 0.037). The square root transformation of time had a between group difference of slope with a P value of 0.012. Both these analyses were post hoc).

FIGURE 2:

Time course of change in postdialysis weight and antihypertensive drug number. Whereas atenolol group gained weight, on average the lisinopril group experienced a mean 1.5 kg reduction in weight. The between group changes in weight was statistically significant. Despite the reduction in weight the lisinopril group required greater number of antihypertensive drugs to achieve a similar degree of BP control. The notations in the table appearing below each graph are explained in the legend for Figure 1.

FIGURE 3:

Time course of change in echocardiographic LVMI. At 12 months, each group had an improvement in LVMI (P = 0.015 for lisinopril and P