Calcium Channel Blockers as Second-Line Therapy in Thiazide-Resistant Hypertension

In Reply.— Whether a diuretic added to a calcium antagonist or calcium antagonist added to diuretic is additive or synergistic is controversial and requires a well-designed study to answer the question.¹Studies with diltiazem,²verapamil,³and nifedipine⁴in which a diuretic was added to a calcium antagonist have shown no additional hypotensive effects. However, two other studies have documented a further decrease in blood pressure with a diuretic.⁵,⁶The acute natriuresis may be dependent on the amount of sodium intake, whereas the antihypertensive effects are present regardless of the sodium intake.⁷The continued natriuretic effect of calcium antagonists⁸may be important in preventing fluid accumulation and reducing the hypotensive effect of an added diuretic. Recently, a multicenter factorial-design trial demonstrated that a slow-release formulation of diltiazem hydrochloride in combination with hydrochlorothiazide is additive.⁹However, we are unaware of studies, other than ours,¹⁰in which a calcium antagonist was added to a diuretic.