Some Do’s and Don’ts for Tough-to-Treat Hypertensives

At the annual ASH meeting, 2 difficult therapeutic scenarios in hypertension were updated. The treatment of resistant hypertensives and the management of ACEI/ARB-induced hyperkalemia were reviewed. Important innovations are summarized here:

1. Resistant hypertension (a blood pressure not at target despite a 3-drug regimen that includes a diuretic) is on the rise. From 1988 through 1994, 8.8% of all hypertensives were resistant. That number increased to 14.5% (1999-2004) and finally to 20.7% (2005-2008).

2. To make an accurate diagnosis of resistant hypertension, white coat hypertension must be considered. One study referenced at the ASH meeting discovered that in 38% of white coat hypertensives by ambulatory monitoring of blood pressure, a 3-drug regimen failed. Later on follow-up, half of the white coat cohort progressed to true resistance. Identifying someone as a white coat hypertensive does not mean that the person should not be followed.

3. Spironolactone is the magic bullet for resistant hypertension. It can decrease systolic and diastolic blood pressures in resistant hypertensives an average of 25 mm Hg and 12 mm Hg, respectively.

4. One would suspect that an elevated aldosterone/renin ratio would predict a better response to spironolactone. The systolic/diastolic declines in blood pressure were the same in patients with resistant hypertension-regardless of whether they had an elevated ratio. Talk about the “real deal” for resistant persons, and spironolactone fills the bill. 

5. We tend to ignore salt intake in this cohort to everyone’s detriment. A study in similar patients compared blood pressures on 50 mEq/d salt intake versus 250 mEq/d. Low salt intake accomplished a 23 mm Hg and 9 mm Hg reduction, respectively, in systolic and diastolic blood pressures.

6. What if titration of an antihypertensive fails to reach target after 3 drugs (an ACEI or ARB + a calcium channel blocker + a diuretic appropriate for glomerular filtration rate [GFR]) and the addition of spironolactone? The presenter, Dr David A. Calhoun, adds medications sequentially to reach target blood pressure as follows: labetalol or carvedilol; then guanfacine (not clonidine); and finally minoxidil.

7. ACEIs and ARBs are critical medications to prescribe and titrate to maximum dose in patients with renal disease and proteinuria. Unfortunately, these agents are either witheld or not titrated to therapeutic levels because of hyperkalemia. Only 40% of patients who need these important drugs are at an appropriate dose. This is bad for our patients. Every effort should be made to continue the ACEI/ARB and mitigate the hyperkalemia. Diet is often inappropriately ignored. Diet is important.

8. Patients at high risk for hyperkalemia have identifying characteristics:
A. A potassium level of 4.5 mEq despite diuretic therapy
B. A GFR less than 45 mL/min
C. Proteinuria (more than 1 g)
D. A BMI of less than 25

Certain interventions can help, such as using a potassium-wasting diuretic, such as furosemide or chlorthalidone. Occasionally, kayexelate may be necessary, but it should not be used long-term.

Patients with resistant hypertension and hypertensive patients prone to hyperkalemia are on the rise. They are not easy to care for, but certain “tricks of the trade” can help.