Wednesday, May 14, 10:00 AM-12:00 PM-Achieving Blood Pressure Goals: Is Fixed-Dose Combination Therapy the Answer?: Who should be considered for initial therapy with combination antihypertensive agents?

Recent trends in hypertension research and treatment guidelines have emphasized stratification of the hypertensive population by risk level to provide greater specification in therapeutic strategies. This increased focus on special populations reflects a greater recognition of the heterogeneous nature of hypertension; the strong correlations of high blood pressure (BP) with increased risks for cardiovascular (CV) and renal morbidity and mortality; and the need for hypertension treatment to help reduce these associated disease risks by providing target-organ protection beyond BP reduction. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) established 3 risk categories, the highest of which is Risk Group C, including patients with target-organ damage, clinical CV disease, and/or diabetes. The JNC VI report sets a BP goal of <130/85 mm Hg for Risk Group C patients, a level lower than the <140/90 mm Hg goal for patients with uncomplicated hypertension.

This goal, however, is very difficult to attain in high-risk patients, whose BP is difficult to control due to their advanced disease and associated conditions. Angiotensin-converting enzyme (ACE) inhibitors are widely recommended as preferred antihypertensive therapy for patients with diabetes, especially type 1 diabetes. Along with diuretics, ACE inhibitors are also recommended for use in patients with heart failure. These recommendations are based on substantial research data demonstrating that ACE inhibitors can significantly retard the progression of renal disease and reduce the risk of CV events in high-risk patients. Major clinical outcome trials, including HOT (Hypertension Optimal Treatment), 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. Moreover, the SHIELD (Study of Hypertension and the Efficacy of Lotrel in Diabetes) study has demonstrated that starting with combination therapy will achieve goal BP faster, compared with the monotherapy approach.

For these reasons, a fixed, low-dose combination agent that includes an ACE inhibitor may be appropriate initial therapy in high-risk patients. The combination of a calcium channel blocker (CCB) or diuretic with an ACE inhibitor can provide additive effects, thus lowering BP more quickly and effectively than would occur with monotherapy. The combination of an ACE inhibitor with either a CCB or diuretic would also help bring the benefits of target-organ protection provided by ACE inhibitors to African Americans, who are at disproportionately high risk for CV and renal morbidity and mortality. Data from AASK (African American Study of Kidney Disease and Hypertension) have clearly indicated that ACE inhibitors are associated with better renal outcomes, compared with conventional drugs, in African Americans with hypertension and mild renal insufficiency.

The LOGIC (Lotrel: Gauging Improved Control) trial, a large, open-label study (n=6000) of patients whose BP was uncontrolled with amlodipine monotherapy, found that switching patients to a combination of a CCB with an ACE inhibitor produced an additional mean reduction in BP of 15.6/11.5 mm Hg (P<0.001 vs amlodipine monotherapy) and a significant reduction of amlodipine-associated pedal edema. An analysis of the African-American cohort of this study (n=1423) found results similar to those in the overall group: with the switch from amlodipine monotherapy to combination therapy, adding the ACE inhibitor produced an additional mean reduction in BP of 13.9/10.4 mm Hg (P<0.001 vs amlodipine monotherapy). Therefore, fixed, low-dose combination therapy may be considered for initial antihypertensive treatment in all high-risk patients, including African Americans.