Combination Antihypertensive Therapy is Crucial for High-Risk Groups

A strong offense is the best defense when selecting initial drug therapy for certain populations at increased risk of heart or kidney disease, according to George L. Bakris,MD.

"Aggressive blood pressure [BP] control is needed in patients with diabetes and proteinuria as well as in African Americans to decrease hypertension-related renal morbidity and cardiovascular events," Dr. Bakris said. Such patients are especially suitable candidates for combination therapy that includes an angiotensin- converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), which can protect target organs, and either a diuretic or a calcium-channel blocker (CCB), which provides a valuable extra antihypertensive "kick," he noted.

Increased risk for different types of targetorgan damage represents compelling indications for certain drug choices, according to the new guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (Chobanian AV, et al. JAMA. 2003;289:2560-2571).The clinical trial evidence base suggests, for example, that ACE inhibitors or ARBs are appropriate for patients with chronic kidney disease. Similarly, diuretics, beta blockers, ACE inhibitors, and CCBs can be useful in patients with coronary artery disease risk factors, with the additional option of ARBs in patients with type 2 diabetes. According to JNC 7, the BP goal should be < 130/80 mm Hg in such highrisk patients, who may require combination drug therapy when their BP is > 20/10 mm Hg higher than goal.

"With their lower goals," said Dr. Bakris, "these higher-risk patients may not only require 3 drugs, but possibly are going to need 4 drugs to get BP where it needs to be."

That was one take-home message from the Study of Hypertension and the Efficacy of Lotrel in Diabetes (SHIELD), in which 214 patients with type 2 diabetes were randomized to initial antihypertensive therapy with either enalapril or a combination of amlodipine and benazepril (Bakris G, et al. J Clin Hypertens. 2003;5:202-209). After 4 weeks, dosages were titrated upward to achieve the treatment goal of < 130/85 mm Hg.Time from randomization to the first treatment success (defined as the first achievement of the target BP),was significantly shorter in the combination therapy group than in the monotherapy group (5.3 weeks and 6.4 weeks, respectively; P < .0001) (Figure 3). If patients failed to reach target BP by week 8, hydrochlorothiazide 12.5 mg/day was added to their treatment regimen. By intention-to-treat analysis, nearly twice as many combination therapy patients as monotherapy patients were at goal (63% vs 37%; P < .0002) at week 12 (Figure 4).

The evidence base also supports initial combination therapy in another well-recognized high-risk group?African Americans.Treatment guidelines recently established by the International Society on Hypertension in Blacks identified a BP of < 140/90 mm Hg as an appropriate target in patients with uncomplicated hypertension, whereas < 130/80 mm Hg was the recommended goal for those with diabetes or nondiabetic renal disease (Douglas JG, et al. Arch Intern Med. 2003;163:525-541). In both groups, initial combination therapy was recommended for patients who were

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15/10 mm Hg higher than goal.

"Many physicians will not necessarily think of starting with 2 drugs in their diabetic patients with a BP of 145/90 mm Hg," Dr. Bakris said."The message of this report is that you probably do need to start with 2 drugs or you are not going to get to recommended goal BP."