Beyond the usual strategies for blood pressure reduction: therapeutic considerations and combination therapies.

Rapidly accumulating clinical data have repeatedly demonstrated not only the critical importance of even small increases in blood pressure as a pathophysiologic factor in the development of cardiovascular disease, particularly in individuals with diabetes mellitus, but also the therapeutic necessity of more aggressive blood pressure reduction and the achievement of progressively lower blood pressure targets in reducing cardiovascular event rates. JNC VI has defined optimal blood pressure as <or=120/80 mm Hg, and Stage 1 hypertension as >or=140/80 mm Hg. Target blood pressures are now <or=130/80 mm Hg in patients with diabetes and <125/75 mm Hg for patients with hypertensive renal disease with proteinuria of >1 gm/24 hours. Achieving such target pressures is increasingly difficult, particularly in diabetic patients with chronic renal disease, who require complex multidrug antihypertensive regimens. This review attempts to provide some suggestions for constructing such antihypertensive regimens, and provides considerations for the appropriate use of diuretics and the most effective drug combinations. Factors potentially contributing to drug resistant hypertension include such problems as failure to maximize drug dosing, suboptimal diuretic use, noncompliance, and possible confounding effects of such concomitant medications as nonsteroidal and anti-inflammatory drugs or decongestants. The issues underlying drug-resistant hypertension are listed, together with strategies for overcoming this problem.