Unsuccessfully treated Hypertension

Using the PRA test to guide addition and subtraction of anti-V and anti-R type drugs

The protocol determines whether PRA is high, medium or low and then adjusts medications accordingly. The protocol assumes that 10% of PRA remains unblocked in patients taking an ACEI or ARB (1).

Low PRA (< 0.65 ng/ml/hr). Anti-V treatment is given until BP is controlled, or until PRA rises into the medium range without BP control at which point the patient is treated as having medium PRA. But, if an uncontrolled patient with low PRA is currently taking an anti-R drug type, the anti-R drug type is first stopped (if no compelling indications) and only restarted if its withdrawal causes BP to rise. BP may actually fall.

Medium or high PRA (> 0.65 ng/ml/hr): Anti-R treatment is given until BP is controlled, or until the PRA level is effectively blocked by an ACEI or ARB (PRA < 6.5 ng/ml/hr) or suppressed to < 0.65 ng/ml/hr at which point the patient is treated as an uncontrolled hypertensive with low PRA (except there is no need to test stopping the anti-R drug).

High PRA (> 4.5 ng/ml/hr). If an uncontrolled patient with high PRA is currently taking an anti-V type drug, the anti-V drug is stopped (if no compelling indication) and only restarted if its withdrawal causes BP to rise. BP may actually fall(2).

NOT taking an ACEI or ARB Currently taking an ACEI or ARB
PRA
ng/ml/hr		 Reduce anti-V med Add anti-V med Remove anti-R med Add anti-R med PRA
ng/ml/hr		 Reduce anti-V med Add anti-V med Remove anti-R med Add anti-R med
High > 4.5 Yes If BP not controlled High > 45 Yes If BP not controlled
Medium 0.65 – 4.5 Yes Medium 6.5 – 45 Yes
Low
< 0.65		 Yes Yes* Low 0.65 – 6.5 Yes
Low < 0.65 Yes Yes*
*Beta adrenergic blockers lower BP by suppressing PRA. If BP rises when the beta blocker is subtracted it should be restored.

Visit by visit description

First visit:

Measure PRA.

1-2 weeks later:

  • PRA < 0.65 ng/ml/hr. Anti-R drugs can be stopped, unless there are compelling indications. BP may fall(3). Add an anti-V drug if BP not controlled.
  • PRA < 6.5 ng/ml/hr while taking an ACEI or ARB: PRA is blocked. Add anti-V drug type.
  • PRA 0.65 to 6.5 ng/ml/hr while NOT taking an ACEI or ARB. Add ACEI or ARB.
  • PRA 6.5 to 45 ng/ml/hr while taking an ACEI or ARB. Suppress PRA with a beta blocker.
  • PRA > 45 ng/ml/hr while taking an ACEI or ARB. Such patients are usually taking a natriuretic anti-V drug that has stimulated PRA. Test stopping the anti-V drug before adding a beta blocker to suppress PRA(2). BP may fall.

3-4 weeks later:

  • If BP is controlled, test stopping drugs that may not be necessary such as a beta adrenergic blocker in a low renin patient, or a natriuretic drug in someone with high PRA.
  • If BP is uncontrolled, measure PRA again and increase the last drug added to maximum dose.

3-4 weeks later:

  • For patients who are uncontrolled, use the PRA test and the same reasoning to determine whether the patient may be sodium-volume expanded or has PRA in excess.

  1. Hasler C, Nussberger J, Maillard M, Forclaz A, Brunner HR, Burnier M. Sustained 24-hour blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor. Clin Pharmacol Ther. 2005;78(5):501-7.
  2. Egan BM, Basile JN, Rehman SU, Davis PB, Grob CH, 3rd, Riehle JF, et al. Plasma Renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial. Am J Hypertens. 2009;22(7):792-801.
  3. Alderman MH, Cohen HW, Sealey JE, Laragh JH. Pressor responses to antihypertensive drug types. Am J Hypertens. 2010;23(9):1031-7.