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August 1990

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

Arch Intern Med. 1990;150(8):1758-1760. doi:10.1001/archinte.1990.00040031758033

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.1 Studies with diltiazem,2 verapamil,3 and nifedipine4 in 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.5,6 The acute natriuresis may be dependent on the amount of sodium intake, whereas the antihypertensive effects are present regardless of the sodium intake.7 The continued natriuretic effect of calcium antagonists8 may 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.9 However, we are unaware of studies, other than ours,10 in which a calcium antagonist was added to a diuretic.