NEW YORK — Evidence is accumulating that an aldosterone antagonist can be a safe and effective treatment for patients with refractory hypertension that has not responded to one or more agents from the first-line antihypertensive drug classes.
Study results further show that aldosterone antagonists, specifically spironolactone and eplerenone, have a range of beneficial effects for patients with hypertension-related cardiovascular disease, including improved heart failure, reduced left ventricular size, improved endothelial function, reduced proteinuria and preserved renal function, and a reduced stroke risk, Dr. David A. Calhoun said at the annual meeting of the American Society of Hypertension.
“Treatment with either eplerenone or spirolactone leads to a substantial reduction in blood pressure when given as monotherapy. The big question for treating primary hypertension is how to use this class of drugs. They are not first-line agents yet,” said Dr. Calhoun, a physician and hypertension specialist at the University of Alabama, Birmingham. He is a consultant to Pfizer Inc., which markets eplerenone (Inspra). Spironolactone is a generic drug.
Dr. Calhoun said that in his experience, a dangerously elevated serum level of potassium usually does not occur in patients treated with one of these drugs. Hyperkalemia is generally defined as a serum potassium level that reaches or exceeds 5.5 mEq/L.
“As long as patients' renal function is good, they're usually okay,” he said.
The value of an aldosterone antagonist for lowering pressure in patients with refractory hypertension was documented in a poster at the meeting from researchers at Rush University in Chicago. They reported on a series of 27 patients who were treated with either 12.5 or 25 mg/day spironolactone, or 50 mg/day eplerenone. These 27 patients were identified as aldosterone-antagonist recipients from among 1,034 patients who had been treated by a hypertension specialist at Rush. All 27 patients were treated with an aldosterone antagonist because their pressure remained above their goal despite treatment with at least three other medications, and an average of more than five drugs per patient.
When their pressures were measured 3–6 weeks after starting their new regimen (average of 35 days), their systolic pressure had dropped from an average of 151 mm Hg before adding the aldosterone antagonist to an average of 144 mm Hg after, a statistically significant difference, reported Dr. Nitin Khosla, a physician at Rush, and his associates. Diastolic pressure fell by an average of 3 mm Hg, not a statistically significant difference.
None of the 27 patients developed hyperkalemia. Their average serum potassium level was 3.9 mEq/L before the new regimen began and 4.4 mEq/L after.
Results reported in a second poster at the meeting documented the efficacy of aldosterone antagonists for lowering blood pressure in patients with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 30 mL/min.
Medical records were reviewed for 836 patients with chronic kidney disease who were treated by any of 10 nephrologists at St. John Hospital in Detroit beginning in 2004. Sixty-nine of the patients were treated with an aldosterone antagonist as part of their multidrug, blood pressure- lowering regimen. Most patients received three to five antihypertensive drugs. The most commonly used drug class was the loop diuretics, which were prescribed to 535 patients, followed by the β-blockers, used on 513 of the patients.
In an analysis that assessed the prevalence of blood pressure control by each drug class used, aldosterone antagonists were the second-most-effective class; about 58% of patients who received an aldosterone antagonist reached their goal blood pressure, exceeded only by the group that received a diuretic other than a loop or thiazide agent, which was linked with a 70% control rate, reported Dr. Joel M. Topf, a clinical nephrologist at St. John Hospital, and his associates.
Among patients with stage 4 or 5 kidney disease, treatment with an aldosterone antagonist was associated with the highest rate of blood pressure control, in 70% of patients. Treatment with an aldosterone antagonist was associated with a “surprisingly high rate of blood pressure control,” the researchers stated in their poster.
The average serum potassium level in patients treated with an aldosterone antagonist was 4.55 mmol/L. The highest average serum potassium level was in the patients treated with an angiotensin-receptor blocker or an ACE inhibitor. Patients who got one of these drugs had an average serum potassium level of 4.71 mmol/L.