Calcium channel blockers in combination: What we are learning from clinical trials

achieved in Stage 1 hypertensive patients using the age by race construct. In fact, achieving recommended BP goals may require 2, 3 or even more agents, particularly in high-risk hypertensive patients. Major clinical outcome trials, including the HOT (Hypertension Optimal Treatment) study, UKPDS (United Kingdom Prospective Diabetes Study), and ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), have shown that 40% to 50% of patients require multiple agents to achieve BP control. Because of the complexity of medication regimens and the need for more intensive goals for CV risk reduction, it is important to consider therapeutic strategies to simplify the approach to BP control and enhance long-term compliance. The JNC 7 guidelines now recommend initiating antihypertensive therapy with 2 agents, either as separate prescriptions or in fixed-dose combinations, when BP is more than 20 mm Hg above systolic goal or 10 mm Hg above diastolic goal. Combination antihypertensive therapy has been shown to provide greater efficacy and tolerability, compared with high-dose monotherapy. An ideal combination regimen will provide additive or even synergistic BP control, 24-hour BP control, and target-organ protection. An emerging body of evidence in diverse populations suggests that the combination of an angiotensinconverting enzyme inhibitor and a calcium channel blocker is more effective than commonly used monotherapies. The SOLACE (Safety of Lotrel vs Amlodipine in a Comparative Efficacy Trial) trial evaluated the efficacy and safety of initial combination therapy versus monotherapy in patients with Stage 2 hypertension. The major objective of SOLACE was to compare the percentage of subjects treated with combination amlodipine besylate/benazepril HCl and subjects treated with amlodipine besylate monotherapy who achieved reductions in SBP of greater than or equal to 25 mm Hg (if baseline SBP was 180 mm Hg), or a reduction in SBP of greater than or equal to 32 mm Hg (if baseline SBP was greater than or equal to 180 mm Hg). At Week 12, 74% of patients randomized to combination therapy achieved treatment success compared with 54% of those randomized to amlodipine besylate (P 0.0001). Notably, the incidence of peripheral edema was significantly higher in the monotherapy group compared with that in the combination group (23.0% vs 12.6%, respectively; P 0.01). The results from clinical trials support the JNC 7 recommendation for use of initial combination therapy in patients with Stage 2 hypertension or diabetes. Use of a combination agent may be appropriate as initial therapy in patients at high CV risk, such as those with diabetes, CV disease, renal insufficiency, or any combination of these risk factors. Furthermore, because multiple antihypertensive agents are necessary to achieve BP goals in so many patients, the use of combination therapy in addition to, or in replacement of, a failed monotherapy also is a rational option.