Placebo‐Controlled Trial of Once‐A‐Day Isradipine Monotherapy in Mild to Moderately Severe Hypertension

The efficacy and safety of once‐daily dosing of isradipine, a new calcium antagonist vasodilator, was evaluated in a multicenter, placebo‐controlled trial in hypertensive patients who had supine diastolic blood pressure (SDBP) 100–119 mm Hg. After a 3‐week single‐blind placebo washout patients randomly received either isradipine, 5 mg once daily, or a matching placebo; if SDBP remained ≥95 mm Hg or ≤10 mm Hg below baseline at four weekly clinic visits, isradipine was increased at weekly intervals by 5 mg once daily up to 20 mg and maintained during weeks 5 and 6. At week 6 mean supine blood pressure 24 hours after dosing had declined from 163 ± 20/105 ± 5 (N = 78) to 146 ± 17/92 ± 7 mm Hg (N = 60) on isradipine, 14.5 mg once daily, and from 163 ± 20/105 ± 6 (N = 85) to 157 ± 18/99 ± 10 mm Hg (N = 64) on placebo ( P < .001 between groups). Standing blood pressure decreased from 159 ± 20/104 ± 8 to 144 ± 18/93 ± 11 mm Hg with isradipine and from 160 ± 22/105 ± 9 to 154 ± 19/101 ± 11 mm Hg with placebo ( P < .001 between groups) without signs or symptoms of postural hypotension. A SDBP ≤ 90 mm Hg or a ≥ 10 mm Hg fall below baseline was achieved in 41 of 78 isradipine‐treated (53%) and 18 of 85 placebo‐treated subjects (21%). Four isradipine‐treated and 11 placebo‐treated patients were discontinued because of inadequate blood pressure control. Adverse effects in patients receiving isradipine and placebo included headaches (34.5% vs. 17.4%), weakness (7.1% vs. 0%), and palpitations (8.3% vs. 1.2%). Thus, isradipine, 5–20 mg once daily is safe and effective in lowering blood pressure over 24 hours in about one‐half of patients with mild to moderately severe hypertension.