Hypertension
Conditions
Keywords
resistant hypertensions, spironolactone, amiloride, ambulatory blood pressure monitoring
Brief summary
Joint National Committee 7 (JNC-7) defines resistant hypertension as a persistent elevation of blood pressure (BP) above goal - ≥ 140/90 mm Hg for the general hypertensive population or ≥ 130/80 mm Hg for persons with diabetes mellitus or chronic kidney disease - for at least three months despite treatment with three or more optimally dosed antihypertensive agents, including a diuretic. The exact prevalence of resistant hypertension is uncertain but may include 5-20% of hypertensive persons in primary care settings and 15-35% of the older, higher cardiovascular risk hypertensive patients incorporated into recent clinical trials of antihypertensive therapy. Observational studies demonstrate that patients with resistant hypertension experience a higher rate of cardiovascular and renal target organ damage such as left ventricular hypertrophy, microalbuminuria, and renal insufficiency and more cardiovascular disease (CVD) events than patients whose hypertension is well-controlled. Additionally, resistant hypertension patients may be subjected to the considerable expense of multiple office visits, diagnostic testing for secondary causes of hypertension, and referral to hypertension specialists. Because multiple factors can contribute to resistant hypertension, an explicit, sequential approach to evaluation and management is essential to optimize blood pressure, reduce cardiorenal morbidity and mortality, and avoid unnecessary expense. A number of observational studies have suggested the potential efficacy of both spironolactone and amiloride when added to a 3 drug antihypertensive regimen, but to date no randomized study has directly compared the two agents. The goal of this study is to determine whether spironolactone or amiloride is the more effective fourth agent to add to a three drug regimen in patients with resistant hypertension.
Detailed description
m/a
Interventions
DRUGspironolactone
tablet form. doses used range from 12.5-50mg po QDAY. Total duration would be until completion or study or medication intolerance.
DRUGamiloride
amiloride 2.5-10 mg po QDAY. Duration until completion of study or until tolerance
Sponsors
VA Salt Lake City Health Care System
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants will be selected from a broad range of medical clinics at the Salt Lake City VA Medical Center and surrounding community based outpatient clinics (CBOCs). * The participants will be referred to a resistant hypertension clinic by either their primary care provider or by a subspecialist. The referrals are made via a computerized system that is used in the Veterans Affairs Medical Center (VA) called Computerized Patient Record System (CPRS). * Patients are referred if their blood pressure is above goal as defined by JNC 7 and they are on 3 antihypertensive medications with one of the agents being a diuretic. * All patients age 18 -80 years old.
Exclusion criteria
* Patients that will be excluded from the study if they have had a documented adverse reaction to either spironolactone or amiloride. * diagnosis of primary hyperaldosteronism * inability to adhere to frequent laboratory monitoring * estimated glomerular filtration rate (GFR) \< 45 ml/min/1.73m2 * baseline serum potassium above 5.0 mEq/L * type 4 renal tubular acidosis * pregnancy * heart failure that meets criteria for using either eplerenone or spironolactone * current unstable renal function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose titration of spironolactone and amiloride will cease once the ABPM study reveals a goal 24 hour mean BP below 130/80 in the general hypertensive patients or below 120/70 in patients with diabetes mellitus or chronic kidney disease (eGFR < 60) | 2-6 months |
Countries
United States
Outcome results
None listed