Although the optimal pharmacotherapy regimen for hypertension is not yet determined, current guidelines recommend inclusion of a diuretic. The guidelines prefer to use diuretics as monotherapy or to use diuretics and an ACE inhibitor in combination therapy. However, recommendation of thiazide-type diuretics as initial therapy for most patients with hypertension needs to be reexamined. Combination therapy is probably a good initial strategy for high-risk patients, rather than starting with one drug and going slow.
Treatment with antihypertensive combination therapy (the angiotensin-converting enzyme (ACE) inhibitor benazepril plus the calcium-channel blocker amlodipine) is more effective than treatment with the ACE inhibitor and diuretic. Studies suggest that the calcium-channel blocker amlodipine effectively increases the availability of vascular endothelial nitric oxide and that the combined effects of amlodipine and an ACE inhibitor on nitric oxide are greater vs the effect with either drug alone.
In patients with hypertension who were at high risk for cardiovascular events, the benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing the primary composite outcome of cardiovascular events and death. The single-tablet benazepril-amlodipine combination reduced the risk of morbidity and mortality by 20% compared with conventional therapy. Putting patients on either combination doubled their control rate, so combination therapy is something clinicians need to think about, even if they want to keep the diuretic. But the drug that gives superior cardiovascular outcomes is the calcium-channel blocker and ACE inhibitor.
The cardiovascular benefits of specific classes of antihypertensive drugs may go beyond their effect on blood pressure. The combination of amlodipine and benazepril appears to synergistically reduce left ventricular hypertrophy and arterial stiffness, suggesting that they may protect target organs independently of the drugs' antihypertensive effects.
Jamerson K, Weber MA, Bakris GL, et al. 2008. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 359: 2417-2428.
Chobanian AV. 2008. Does it matter how hypertension is controlled? N Engl J Med. 359:2485-2488.