Combination therapy as first-line treatment for hypertension.

With the cut-off point between "normal" and "high" blood pressure (BP) being pushed increasingly downward, especially for patients with multiple cardiovascular risk factors, most hypertensives need more than one antihypertensive agent to reach their target BP. In this article, we examine the rationale for combining drugs from different classes that have synergistic or additive effects and properties that might offset one another's adverse hemodynamic and/or metabolic reactions. We suggest circumstances in which the initiation of therapy with a fixed two-drug combination might be preferable to the usual practice of starting with monotherapy followed by upward titration and addition of other agents, and we briefly review the existing fixed drug combinations. We end with the intriguing and provocative notion of the future "polypill," a fixed combination of agents addressing various components of the metabolic syndrome as well as other coexisting common risk factors in both high-risk patients with conditions requiring polypharmacy and in healthy, asymptomatic individuals.