Underestimation of 24-hour hypotensive efficacy of nifedipine GITS versus enalapril: ambulatory recording as an adjunct to clinical blood pressure measurement.

AIMS: Short-acting calcium entry blockers should be used primarily in slow-release form. Furthermore, studies of the antihypertensive efficacy of drugs can be negatively influenced by between 15% and 30% of the enrolled patients not being hypertensive according to ambulatory blood pressure (BP) measurement. Thus, a randomized double-blind multicenter parallel-group study was conducted to compare the effect of nifedipine GITS (gastrointestinal therapeutic system) with enalapril. METHODS AND RESULTS: After a 2-week placebo run-in period, 186 patients with a sitting diastolic BP > or = 95 mmHg were enrolled for an 8-week treatment period. They received 30-60 mg nifedipine GITS or 5-10 mg enalapril. Diastolic BP fell comparably from 99 to 87 mmHg (p < 0.01) in the nifedipine GITS group, and from 100 to 88 mmHg (p < 0.01) in the enalapril group. The increase in BP 2 h before waking, however, was suppressed significantly more by nifedipine. Furthermore, this study highlighted the existence of "whitecoat" hypertension in a number of patients, especially when clinical BP was used to identify hypertension. Of the patients who had been identified as hypertensive before randomization by standardized BP measurement, 53 (28.5%) were identified as non-hypertensives by 24-h BP monitoring. This led to an underestimation of the efficacy of the antihypertensive therapy. CONCLUSION: Nifedipine GITS as well as enalapril are comparably effective antihypertensive drugs.

24 h anti-anginal and anti-ischaemic effects with once daily felodipine. A double-blind comparison with nifedipine, twice daily, and placebo in patients with stable exercise induced angina pectoris.

The effects, as monotherapy, of felodipine ER 10 mg o.m. and nifedipine SR 20 mg b.d. were compared in a double-blind, randomized, placebo-controlled, three-way cross-over trial in 43 patients with stable exercise-induced angina pectoris. The exercise tests were performed at the end of dosage interval (i.e. 24 h after felodipine ER, 12 h after nifedipine SR) and at the expected peak time of 3 h post dose. Felodipine and nifedipine improved exercise duration by 66 and 50 s, respectively, (P < 0.001) compared with placebo at the end of the dosing interval. Time to the end of exercise showed no statistically significant difference between the two calcium antagonists. The onset of anginal pain and time to 1 mm ST depression were significantly more delayed by felodipine ER than nifedipine SR (22 s and 19 s, respectively, P < 0.05). Both felodipine and nifedipine decreased the pain score and rate pressure product at the highest comparable work load. Overall tolerability was good for both drugs.

Relation of regression of left ventricular hypertrophy to changes in ambulatory blood pressure after long-term therapy with perindopril versus nifedipine.

Casual as well as ambulatory 24-hour blood pressure (BP) and echocardiographic parameters were studied in 40 patients with untreated or insufficiently treated mild to moderate essential hypertension. Left ventricular (LV) hypertrophy was assessed before and after 24 weeks of therapy with either the converting enzyme inhibitor perindopril or the calcium antagonist nifedipine. The design was a double-blind parallel study with a placebo run-in period. Patients received a daily oral dosage of either 4 to 8 mg of perindopril or 40 to 80 mg of nifedipine in slow-release form. A diuretic (25 mg/day of hydrochlorothiazide) was added in nonresponders (greater than 90 mm Hg casual diastolic BP). Once-daily perindopril and twice-daily nifedipine comparably reduced both casual and ambulatory BP throughout 24 hours (p less than 0.01) without affecting 24-hour heart rate. Six subjects withdrew from the nifedipine group and 4 from the perindopril group. After 12 and 24 weeks of therapy, LV hypertrophy was significantly reduced by both agents. Before active treatment was begun, LV mass index was more closely correlated to 24-hour (p less than 0.001) than to casual BP. This correlation disappeared after treatment with both agents. The correlation between ambulatory systolic day-time BP and LV mass was only still present (r = 0.54; p less than 0.05) after 24 weeks of treatment with nifedipine. It is concluded that regression of LV hypertrophy during converting enzyme inhibition or calcium antagonism may be partly independent of dosage and magnitude of 24-hour BP decrease.

24-hour noninvasive oscillometric blood pressure monitoring: evaluation of the antihypertensive circadian profile of nitrendipine.

The understanding of blood pressure (BP) and heart rate (HR) variation, circadian changes, and the responses to nonclinical situations has been improved by automated ambulatory recordings. The antihypertensive efficacy of a once-daily regimen (10/20 mg) of nitrendipine was evaluated in detail using the lightest available portable device equipped with an oscillometric blood pressure (BP) recorder (SpaceLabs 90202, weight 480 g) devoid of any electrode. A good antihypertensive effect throughout the day in 20 outpatients could be demonstrated. No significant change of BP could be found in early morning and wake-up period; HR was not significantly affected after 6 weeks of oral therapy.

Effects of diltiazem alone and combined with mefruside on cardiovascular response at rest and during exercise, carbohydrate metabolism and serum lipoproteins in patients with systemic hypertension.

The antihypertensive effects of the calcium antagonist diltiazem, both alone and combined with the diuretic mefruside, were assessed over 14 months in 36 patients with essential hypertension. Patients received 180 or 270 mg/day; those with inadequate response were given 270 mg/day plus mefruside, 20 mg/day. Both monotherapy and combination therapy significantly reduced blood pressure (BP) at rest and during exercise. However, adding mefruside did not significantly decrease BP below that achieved with diltiazem alone. After 14 months of therapy, the percentage of responders (patients with at least 10% reduction in diastolic BP at rest) was 64% for all patients, 100% (by definition) for those receiving diltiazem alone and 47% for those receiving the combination. Diltiazem decreased heart rate by 6% (4 beats/min at rest) (p less than 0.05). Combined therapy with mefruside did not further reduce heart rate. There were few adverse effects and no undesirable metabolic effects with either monotherapy or combined therapy. Plasma renin activity, aldosterone levels, carbohydrate metabolism, serum lipoprotein levels and routine laboratory test results were unchanged in both groups at the end of the study. Thus, diltiazem is an effective antihypertensive agent and apparently the combination of diltiazem and mefruside does not potentiate the antihypertensive effect of diltiazem alone during long-term therapy.

Antihypertensive and metabolic effects of diltiazem and nifedipine.

The antihypertensive effect of diltiazem (180-270 mg/day) and nifedipine (40-60 mg/day) in slow-release forms was assessed over 8 weeks in a double-blind parallel study in 40 subjects with essential hypertension at rest and during exercise. Blood pressure was comparably reduced in both groups at rest as well as during exercise. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) after 8 weeks of therapy were 53% at rest and 75% during exercise in the diltiazem group and 78% and 50%, respectively, in the nifedipine group. Diltiazem decreased heart rate by 8% (p less than 0.01), while nifedipine did not affect it. As a consequence, myocardial oxygen consumption, as judged by the pressure-rate product, was reduced by diltiazem. Resting plasma norepinephrine levels were increased significantly after 8 weeks of diltiazem therapy. Plasma epinephrine, renin, aldosterone, glucose, insulin, and lactate and routine laboratory parameters were unchanged at the end of the study. No significant changes in total cholesterol and triglyceride levels were observed after 8 weeks. Whereas therapy with diltiazem resulted in an 8% fall in low density lipoprotein cholesterol after 8 weeks (p less than 0.05), nifedipine induced a drop in very low density lipoprotein cholesterol (p less than 0.05) after 8 weeks of therapy. We conclude that both diltiazem and nifedipine are effective antihypertensive agents lacking undesirable metabolic side effect. Diltiazem, however, had the advantage of lowering heart rate and myocardial oxygen consumption.