Atenolol Demonstrates Superior Safety Profile in Comparative Effectiveness Trial

Results of a late-breaking clinical trial presented at Kidney Week 2013 show that atenolol-based antihypertensive therapy may be superior to lisinopril-based therapy in preventing cardiovascular morbidity and all-cause hospitalizations among maintenance dialysis patients. The trial was terminated early in September by the data safety monitoring committee when it became clear that lisinopril was associated with an increased risk for cardiovascular events.

“The results suggest that atenolol-based antihypertensive therapy among hypertensive hemodialysis patients with left ventricular hypertrophy may reduce cardiovascular events,” said lead author Rajiv Agarwal, MD, MBBS, FASN, of the Indiana University School of Medicine and the VA Medical Center in Indianapolis.

The HDPAL (Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril) trial was designed to evaluate the comparative efficacy and safety of antihypertensive therapy using either an angiotensin-converting enzyme (ACE) inhibitor or a beta blocker. Agarwal conducted a randomized, open-label, parallel-group, single-center trial of 200 maintenance hemodialysis patients who were diagnosed with echocardiographic left-ventricular hypertrophy and hypertension. One hundred patients each were randomized to receive either lisinopril or atenolol 3 times weekly after dialysis, with a primary outcome of change in left ventricular mass index.

Both antihypertensives were effective in controlling blood pressure and left ventricular mass index with no statistically significant difference observed. However, there were significantly more serious cardiovascular events in the lisinopril group (40 events in 26 subjects) than the atenolol group (18 events in 14 subjects). Patients receiving lisinopril also had significantly higher rates of combined serious adverse events (myocardial infarction, stroke, hospitalization for heart failure or cardiovascular death), hospitalizations for heart failure, and all-cause hospitalizations

“Most physicians who take care of dialysis patients and have used atenolol are aware that it can lower blood pressure effectively and more so than ACE inhibitors, so the results are not entirely surprising. But we were certainly surprised by the magnitude of the difference,” said Agarwal.

“Nothing really surprises me about dialysis patients anymore,” said Frank Brosius, MD, of the University of Michigan Health System, and who was not associated with the study. “They have so many different responses than the general population that we really cannot extrapolate from studies of other populations, even from studies of chronic kidney disease patients. That’s why these sorts of clinical trials are so important to help make sure we give our maintenance dialysis patients optimal care.”

Although these results need to be confirmed in other larger multicenter studies, they strongly suggest that interdialytic hypertension might be best managed with a beta blocker instead of ACE inhibitors,” Brosius said. “This is a bit surprising given the cardiovascular protective effects of ACE inhibitors in other populations, but again cardiovascular disease in dialysis patients is clearly different.”

Brosius pointed out that administering the antihypertensive just after dialysis is probably a different management practice than that used in most dialysis units. “There was not a comparison of the same/similar treatments given daily at home which is probably more common practice. Nonetheless the postdialysis treatment has multiple advantages,” he said.

“A small study such as ours comparing two inexpensive and commonly used drugs in a randomized trial design suggests that we should stop extrapolating from studies from CKD or in the general population and start performing randomized trials,” Agarwal said. “Observational studies can only go so far, but for real answers we need randomized trials.”

Reference

1. 

Agarwal R, et al. Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL): A Randomized Controlled Trial. J Am Soc Nephrol 2013; 24 (Suppl):1B (Abstract)