Following Up Angiotensin‐Converting Enzyme Inhibitor Monotherapy

When health care prescribers choose to use an angiotensin-converting enzyme (ACE) inhibitor as the initial agent in an uncomplicated patient with hypertension, do they increase the ACE inhibitor dose or add hydrochlorothiazide (HCTZ) next if the blood pressure (BP) remains uncontrolled at follow-up? This question has multiple answers, depending on the initial dose of the ACE inhibitor and depending on the patient's current BP. This question is particularly important given the overall poor control rate of hypertension (around 34%)1 and the subsequent failure, despite poor BP control, to adjust therapy when patients return for follow-up visits.2 ACE inhibitors are commonly used in the treatment of hypertension. About 50%–60% of white patients will have a good response to monotherapy—a response rate similar to that seen with other antihypertensive drugs used as initial therapy.3,4 Compared with white patients, black patients are less sensitive to ACE inhibitors as monotherapy for hypertension in usual doses.5 The addition of even a low dose of a thiazide diuretic to an ACE inhibitor leads to a decrease in BP that is comparable to that seen in white patients.6 The effectiveness of ACE inhibitors with diuretics is not limited to black patients, since these drugs have an additive effect, attaining goal BP in up to 50%–85% of patients with mild hypertension. The antihypertensive response to diuretics may be limited by the hypovolemia-induced increase in renin release and subsequent angiotensin II production; this effect is prevented by ACE inhibition, leading to a more pronounced reduction in BP. Even very low doses of HCTZ, such as 6.25 mg/d, may be effective in patients already treated with an ACE inhibitor. For similar reasons, dietary sodium restriction can also enhance the response to an ACE inhibitor. ACE inhibitor use will typically result in a 10–12-mm Hg decrease in systolic BP and 6–8-mm Hg decrease in diastolic BP when used at about 50% of the maximum recommended dose. For example, the peak effect with enalapril is usually seen at 10–15 mg/d, with little further response noted at higher doses.7 Increasing to the maximum dose, there may only be an additional 2–4 mm Hg in additional BP lowering. When a diuretic such as HCTZ is added to an ACE inhibitor, it usually has an additive effect, and one can expect an additional 10 (or more)-mm Hg lowering of systolic BP. In considering various scenarios, we would suggest the following: If the patient is on, for example, 5 mg of enalapril and the follow-up office BP measurement is 142/92 mm Hg, we would suggest increasing the dose of the ACE inhibitor to 10 mg/d. This could result in an additional 4–6-mm Hg lowering in systolic BP and bring the patient to goal BP without increasing side effects. However, if the follow-up BP is 156/98 mm Hg, a better BP response would be obtained by titrating the enalapril dose up to 10 mg and adding a diuretic such as HCTZ at 12.5 mg/d. The addition of HCTZ and ACE inhibitor titration should result in an approximately 10–20-mm Hg reduction in systolic BP and about a 10–12-mm Hg reduction in diastolic BP. This would achieve goal BP in many patients. A final comment: when therapy is started for someone with a BP >160 mm Hg systolic and/or >100 mm Hg diastolic, treatment with a combination tablet (such as an ACE inhibitor/diuretic) is appropriate. This is consistent with recent recommendations of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)8 and the International Society for Hypertension In Blacks (ISHIB).9