A 57-year-old man is evaluated during a routine visit. History is significant for hypertension. Medications are hydrochlorothiazide, 25 mg/d, and amlodipine, 5 mg/d.
On physical examination, blood pressure is 135/86 mm Hg, and pulse rate is 70/min; other vital signs are normal. There is 1+ bilateral ankle edema. The remainder of the examination is normal.
Laboratory studies show a serum creatinine level of 1.0 mg/dL (88.4 µmol/L), a serum potassium level of 3.6 mEq/L (3.6 mmol/L), and an estimated glomerular filtration rate >60 mL/min/1.73 m2.
Which of the following is the most appropriate treatment?
A. Add hydralazine
B. Add losartan
C. Double the amlodipine dose
D. Double the hydrochlorothiazide dose
MKSAP Answer and Critique
The correct answer is B. Add losartan. This content is available to MKSAP 18 subscribers as Question 13 in the Nephrology section. More information about MKSAP is available online.
The addition of losartan is the most appropriate treatment. As antihypertensive agents are titrated or added when there is inadequate blood pressure control, it is important to recognize that there is a nonlinear and diminishing blood pressure–lowering effect when titrating from 50% maximal dose to 100% maximal dose of any agent. A general rule of thumb is that 75% of an agent's blood pressure–lowering effect may be achieved with 50% of its maximal dose. If blood pressure control requires an additional >5–mm Hg reduction, it is unlikely to be achieved by increasing the single agent from 50% to 100% maximal dose. The better strategy is to add a second drug or a third drug to a two-drug regimen, as seen in this patient.
Hydralazine is not the best option because it is a thrice-daily medication and may pose problems with adherence, considering that once-daily medication options have not been exhausted in this patient. In addition, hydralazine is a direct vasodilator and is associated with sodium and water retention and reflex tachycardia; use with a diuretic and a β-blocker is recommended. Hydralazine is typically reserved for patients with resistant hypertension or hypertensive urgencies.
Increasing the amlodipine or hydrochlorothiazide dose is not appropriate because there is diminishing return in blood pressure lowering if the dose is titrated up from 50% to 100% of maximum. Also, it is unlikely that increasing the dose from 50% to 100% of maximum will result in an additional >5–mm Hg reduction to bring this patient's blood pressure to a target of <130/80 mm Hg. In addition, titration to maximum doses may result in manifestation of undesirable side effects and decreased adherence. In this case, the patient already has dependent edema, which may increase with uptitration of the amlodipine dose. His serum potassium is borderline at 3.6 mEq/L (3.6 mmol/L), and increasing the dose of hydrochlorothiazide may further decrease his serum potassium and necessitate a potassium supplement, adding yet another medication to his drug regimen.
- Three strategies can be used for antihypertensive dose adjustment in the treatment of hypertension: 1) maximize the medication dose before adding another; 2) add another class of medication before reaching the maximum dose of the first; and 3) start with two medication classes separately or as fixed-dose combinations.