Addition of chlorthalidone to slow-release nifedipine in the treatment of arterial hypertension: A controlled study versus placebo (original) (raw)
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The Netherlands Journal of Medicine, 1997
Objectiue: To compare the efficacy and tolerability of felodipine extended release (ER) 2.5 mg (F2.5) and 5 mg (F5) once daily with nifedipine Retard 10 mg (N20) and 20 mg (N40) twice daily as additional therapy in patients who remained hypertensive despite treatment with an ACE-inhibitor, P-blocker or diuretic. Design and methods: In a multicentre, double-blind parallel study, 61 men and 54 women, aged 35-75, with a supine diastolic blood pressure between 95 and 115 mmHg were randomised to treatment with F2.5, F5, N20 or N40 for 8 weeks, with optional doubling of the dose after 4 weeks. Blood pressure was measured at the office after 0, 4 and 8 weeks and by 24-h ambulatory monitoring (ABPM) after 0 and 4 weeks. Spontaneously reported adverse events and a subjective symptom assessment questionnaire were used for side-effect profiling. Results: Mean office systolic/diastolic blood pressure was clinically relevantly reduced in all treatment groups after 4 weeks by 8/7, 12/9, 1 l/9 and 18/l 1 mmHg for F2.5, F5, N20 and N40, respectively, and after 8 weeks (F2.5-5: 17/l 1 mmHg; F5-10: 18/14 mmHg; N20-40: 19/14 mmHg; N40-80: 25/14 mmHg) with no statistically significant differences between these groups. The lowest dose of felodipine (F2.5) was the least effective. After 4 weeks the ABPM showed consistent 24-h reductions in blood pressure (4/2; 8/5; 7/5; 10/6 mmHg, respectively) over 24 h for the felodipine ER 5 mg group only and for both nifedipine groups. No statistically significant difference between these groups was found. An office responder does not appear to be identical to an ambulatory one and vice versa. The adverse events, mostly oedema, flushing and headache, were dose-related.
Nifedipine in the treatment of hypertension: report of a double-blind controlled trial
British Journal of Clinical Pharmacology, 1982
The effect of oral nifedipine has been examined in patients with hypertension in whom arterial pressure was not adequately controlled by the combination of a ,3-adrenoceptot antagonist (or a-methyldopa) and a diuretic. 2 In 42 patients, nifedipine (10 mg capsules) was added to the existing therapy in a final dose of 20-60 mg daily. Six patients had to stop the drug on account of side-effects. In the 36 patients who continued treatment, arterial pressure fell by an average of 24/9 mmHg supine and 26/10 mmHg standing. 3 In 11 of these patients who subsequently completed a double-blind, cross-over, placebo controlled trial, nifedipine (30-60 mg daily) was found to reduce arterial pressure by an average of 19/11 mmHg supine and 21/12 mmHg standing. 4 In all 11 patients who were changed to a sustained release preparation of nifedipine, control of arterial pressure was at least as good as it had been when taking the capsules.
European Journal of Clinical Pharmacology, 1985
The pharmacodynamic and pharmacokinetic profiles of nifedipine and nisoldipine were compared in a double blind, placebo-controlled study. Nisoldipine, 10 mg significantly reduced systolic blood pressure but nifedipine 20 mg retard did not, although both drugs had significant pharmacodynamic effects as evidenced by increased heart rates. The terminal elimination half-life in plasma was similar for both drugs with a mean of 2 h. The pharmacodynamics of nisoldipine were studied in 8 hypertensives following both acute and chronic administration. Antihypertensive efficacy was demonstrated after acute dosing and was maintained over 4 weeks of twice daily treatment as monotherapy.
Cardiovascular Drugs and Therapy, 1990
To investigate the hypotensive and hemodynamic effects of plain and extended-release (ER) formulations of felodipine added to a diuretic in the treatment of moderate essential hypertension, we studied 18 patients in a randomized, double-blind, cross-over study. Blood pressure (BP), heart rate (HR), hemodynamics (bioimpedance), foot volume (Archimedes' principle), and symptoms were evaluated after a 1-month placebo washout, after 1-month's treatment with a fixed combination of hydrochlorothiazide 50 mg plus amiioride 5 mg (HA), and then after felodipine 5 mg twice daily (F) or felodipine ER 10 mg daily (FER) (doubleblind phase), each given for 2 weeks in a randomized sequence together with the diuretic. All measurements were performed at the end of the dosing interval. At baseline, supine SBP/DBP was 175.6 _+ 12.9/113.4 • 8.1 mmHg; HR was 77.3 +_ 7.0 beats/min; CO was 5.3 -+ 1.4 l/min; SVR was 2166 _~ 707 dynes sec. em ', and'foot volume was 433 ~ 195 ml (FV). HA induced a reduction (p < 0.05) in BP; one patient had a DBP = 90 mmHg and was excluded from the combination study; eight patients had a DBP reduction of >-10 mmHg (responders), and their blood pressure was mainly reduced by a fall in SVR. HR, CO, and FV were unchanged. The addition of felodipine to a diuretic induced a further significant (p < 0.001) reduction in BP with respect to HA alone, with no differences between F and FER. All patients had a DBP fall > 10 mmHg, which had no relationship to their response to the diuretic. The antihypertensive effect of felodipine was due to a reduction in SVR (p < 0.05). CO and HR were significantly (p > 0.05) increased by felodipine added to HA. FV was increased by felodipine. During felodipine treatment, side effects were significantly decreased in comparison with placebo. Thus, a once-daily administration of 10 mg extended-release felodipine was equieffective with felodipine 5 mg twice daily in hypertensives who were sufficiently controlled by diuretic alone. The antihypertensive effect of felodipine is due to a reduction in SVR and is not prevented hv diuretic treatment_
The American Journal of Cardiology, 1983
The immediate hemodynamic effects of a new calcium-channel blocking agent nitrendipine were studied in 12 patients with mild established essential hypertension. According to the response to mean arterial pressure, patients were classified into responders (decrease >10 mm Hg, 7 patients) and nonresponders (< 10 mm Hg, 5 patients). The decrease in arterial pressure in responders was associated with a significant (p <0.01) decrease in total peripheral resistance and a significant (p <0.05) increase in heart rate, cardiac index, and left ventricular ejection rate. The plasma norepinephrine level was significantly (p <0.05) increased in the responders. The response to upright tilt was qualitatively similar to pretreatment values. Thus, nitrendipine lowered arterial pressure as a result of arteriolar dilatation associated with a reflexive increase in heart rate and cardiac index. These hemodynamic properties make the drug particularly apt for use in combination with beta-adrenergic blockade for the treatment of arterial hypertension.
Long-term therapy with slow-release nifedipine in essential hypertension
Cardiovascular Drugs and Therapy, 1990
The purpose of this study, designed as an open multicenter trial, was to test the antihypertensive efficacy, patient acceptability, and side effects of long-term treatment with slow-release nifedipine in a large population. The drug was studied in 330 outpatients with essential hypertension, WHO stage 1-2, recruited in 20 hospital centers. After washout period was completed, nifedipine (20 mg bid) was given for 1 month (phase 1). Then, the treatment was extended for 4 months (phase 2) with variable doses (range 20-80 mg daily). No other antihypertensive drugs were administered during phase 1. However diuretics, beta blockers, or captopril were added to nifedipine during phase 2 in 11 patients. Seventy patients did not meet criteria for inclusion at washout. During phase 1 and 2, 66 additional patients were excluded due to side effects, the need of other antihypertensive drugs, or noncompliance. Systolic blood pressure significantly lowered (10% or more) in 84% patients in phase 1 and in 76% in phase 2. No responders were 6.1% and 3.6~, respectively. Diastolic blood pressure was normalized in 60% of patients after 5 months of therapy. Effects on blood pressue were equal in young patients and in the .elderly, but a minimal rise in heart rate was recorded in younger patients. At least one side effect occurred in 46.6c~ patients, mainly headache (15.4%), hot flashes (13.3%), ankle edema (12.8G), or palpitation (6.6%). Sixteen patients (8.2~) were obliged to stop nifedipine treatment due to the severity of the side effects. This trial confirms the efficacy of nifedipine in hypertension, both in young and in aged patients. The adherence of patients to the twice-daily regimen was very good, without the development of tolerance in long-term treatment. The drug does not affect the physiologic cardiovascular response to standing, but induces several relatively common, very seldom severe, adverse reactions.
Cardiovascular Drugs and Therapy, 1988
The two dihydropyridine calcium antagonists, nicardipine and nifedipine, were compared in 12 patients with both stable angina pectoris and systemic hypertension using a double-blind, crossover protocol. After a 2-week placebo run-in period, each patient was randomized to either nicurdipine or nifedipine; each drug was titrated up to either blood pressure normalization, appearance of adverse effects, or maximal dosage (40 mg, three times a day with nicardipine and 30 rag, three times a day with nifedipine) and then administered for 4 weeks. Maximal symptom-limited exercise tests were performed at the end of the placebo run-in and each treatment period, 3 and 8 hours after drug administration. Nicardipine and nifedipine were used at the mean doses of 100 _+ 20 rag/day and 57 +_ 20 rag/day, respectively. Both drugs reduced, significantly and similarly, standing and supine blood pressure, frequency of anginal episodes, and nitreglycerin consumption. At 3 hours after drug administration, exercise duration and time to l-ram ST depression increased significantly from 402 _+ 84 and 306 _+ 108 seconds, respectively, with placebo; to 533 _+ 135 and 442 +_ 138 seconds during nicardipine; and to 518 +_ 118 and 437 + 133 seconds during nifedipine, with a concomitant reduction of peak ST depression. Both submaximal and maximal exercise diastolic blood pressure were significantly reduced by the two calcium antagonists whereas systolic blood pressure was decreased n~y at submaximal but not at maximal exercise; the heart rate was not significantly modified by the two drugs at any exercise stage. The rate-pressure product decreased from 169 _+ 17 to 151 _+ 25 with nieardipine and 152 +_ 24 with nifedipine at submaximal exercise, but was not signiftcantly modified at the onset of l-ram ST depression and maximal exercise. Thus, nicardipine and nifedipine showed a similar hypotensive and antianglnal activity; the only important difference between the two drugs emerged from the exercise tests performed 8 hours after drug administration; although nifedipine still maintained a slight antianginal activity, nicardipine showed a significantly greater anti-ischemic and hemodynamic activity at that time.