Amlodipine in hypertension: an overview of the clinical dossier.

The database on amlodipine, a calcium antagonist of the 1,4-dihydropyridine class, was obtained from clinical trials in the United States, Canada, and Europe. The clinical dossier describing the efficacy and safety of once-daily amlodipine in the treatment of hypertension is extensive, well organized, and logically designed. It shows that amlodipine is an effective antihypertensive drug, providing smooth 24-h blood pressure control without orthostatic hypotension, and that it is well tolerated as monotherapy and in combination with other antihypertensive drugs. A total of 18 clinical studies were reviewed; 1,091 patients received amlodipine whereas 805 received either placebo or another drug for comparison. The common entry criteria include a supine and standing diastolic blood pressure in the range 95-114 mg Hg. Blood pressure measurements were made 24 h after the last dose of amlodipine in all studies. Amlodipine is clearly superior to placebo and induces a clinically significant reduction in blood pressure (mean reductions 23/13 mm Hg supine, 24/12 upright in one representative study) with similar heart rates in the supine and standing positions. Blood pressure control shows a smooth profile over 24 h with once-daily dosing, and there is no tolerance with long-term administration of the drug. The useful clinical dose is in the range of 5-10 mg, which is well tolerated in comparison with clinical doses of atenolol, hydrochlorothiazide, or verapamil. Amlodipine can be used as monotherapy in a large proportion of patients but may also be combined with a beta-blocker, diuretic, or angiotensin converting enzyme inhibitor. Based on these observations, amlodipine may prove to be an attractive addition to our antihypertensive armamentarium.