Low-dose antihypertensive combination therapy: its rationale and role in cardiovascular risk management.

Antihypertensive monotherapy, although commonly used, does not address the multifactorial nature of hypertension as a disease with many pathways. Using more than one drug makes more therapeutic sense because combination agents cover more than one pathway, yet the use of drugs in tandem is typically relegated to more problematic patients later in therapy. Many patients with hypertension are not controlled, because the monotherapeutic agent is used at its highest dose, resulting in side effects that lead to noncompliance. As opposed to fixed-dose combinations that merge two drugs at their highest doses, low-dose combination therapy provides more novel coverage of two or more metabolic pathways that contribute to hypertension. Their once-daily dosing encourages compliance. In addition, because the two drugs are combined at low doses, the probability of side effects is decreased and efficacy is often enhanced. The use of low-dose combination antihypertensive agents is a good contemporary strategy for first-line therapy in that patients can take advantage of their cardiovascular benefits and the control these agents offer early in therapy.