Antihypertensive activity of verapamil: impact of dietary sodium. The VERSAL Study Group.

OBJECTIVE: To define the influence of dietary salt intake on the antihypertensive effect of slow-release verapamil 240 mg once a day in a population with mild-to-moderate essential hypertension. DESIGN: Parallel, randomized, multicentre study. METHODS: Patients were advised to follow a moderately low salt diet (Low-salt group). After a 2-week run-in period, those patients with 24-h urinary sodium excretion (UNa) < or = 120 mmol/day and a diastolic blood pressure (DBP) between 90 and 114 mmHg were randomly assigned to verapamil + Low-salt or verapamil + unrestricted-salt diet (High-salt group) for 28 days. Compliance with diets was defined as Low-salt UNa < or = 120 mmol/day and High-salt UNa > 120 mmol/day with UNa increased by > or = 60 mmol/day over the level attained at the end of the run-in period. RESULTS: Significant reductions in mean systolic blood pressure (SBP) and DBP were found in both the Low-salt (n = 235) and High-salt (n = 183) groups. The therapeutic goal (DBP < 90 mmHg) was achieved in 38.3% of patients in the Low-salt and 44.8% of patients in the High-salt group. Office blood pressure results were confirmed by ambulatory 24-h blood pressure monitoring in a subsample of patients. Verapamil reduced mean blood pressure throughout the nycthemeral cycle without any significant difference between the two groups. CONCLUSION: The restriction in sodium intake does not have an additive effect on the antihypertensive effect of the slow-channel calcium antagonist verapamil.

Do changes in dietary salt influence blood pressure of hypertensive patients pharmacologically controlled with verapamil? The Salt-Switching-Study (SSS).

To study how changes in dietary salt influence the blood pressure (BP) of pharmacologically controlled hypertensive patients, we have selected from a large multicenter trial two subgroups of 14 and 16 patients who attained BP control (office DBP < 90 mm Hg) after a 4-week treatment with verapamil SR 240 mg once daily, either under an unrestricted salt diet (high-salt; 14 patients) or under a moderately restricted salt diet (low-salt; 16 patients). All of them were switched to the opposite dietary salt regimen and continued on verapamil for 4 more weeks (Salt-Switching-Period). Office BP and ambulatory blood pressure monitoring (ABPM) were registered before and after the Salt-Switching-Period. Salt intake was checked by urinary sodium excretion (UNa). Patients switching from high- to low-salt reduced UNa from 180.9 +/- 22.9 to 89 +/- 28 mM Na/24h (P < 0.001) and patients switching from low- to high-salt increased UNa from 85 +/- 38.4 to 175.8 +/- 57.5 mM Na/24h (P < 0.001). No significant changes in BP were found by ABPM either in the group switching from high- to low-salt or in the group switching from low- to high-salt. In the latter group, a significant increase was observed in office DPB but not in SBP. Short-term changes in salt intake seem to have little influence on the BP of patients pharmacologically controlled with verapamil.

Comparative study of gallopamil versus nifedipine in patients with ischemic heart disease.

In order to compare the anti-ischemic activity of gallopamil and nifedipine, a cross-over, double-blind, randomised trial was carried out in 30 male out-patients with a history of stable exertional angina, proven coronary disease and a positive stress test (ST-segment depression > or = 1 mm). After a first 1-week wash-out period on placebo, the patients were randomised to gallopamil, 150 mg/day (50, 50 and 50) or nifedipine, 30 mg/day (10, 10 and 10) for 28 days. After a second 1-week wash-out period active treatments were crossed for another 28 days. At the end of each drug or placebo period, a physical examination, laboratory tests and a stress test were performed. Oral short-acting nitrates were permitted throughout the trial periods. Twenty-one patients finished all periods of the study. Both drugs reduced the maximum ST-segment depression during the exercise test: from 2.45 +/- 0.97 mm (placebo) to 1.95 +/- 0.82 mm (gallopamil, P < 0.05) and from 2.50 +/- 0.93 mm (placebo) to 1.75 +/- 0.84 mm (nifedipine, P < 0.05). Gallopamil but not nifedipine increased stress tolerance significantly: from 486 +/- 156 s (placebo) to 598 +/- 138 s (gallopamil, P < 0.05) and from 509 +/- 113 s (placebo) to 567 +/- 191 s (nifedipine, NS). No significant differences were found between drugs. Both calcium antagonists, gallopamil and nifedipine, showed similar efficacy in treating myocardial ischemia.

[A clinical study of the verapamil and captopril combination in hypertensive patients uncontrolled by monotherapy. An evaluation by recording the 24-hour ambulatory blood pressure]. / Estudio clínico de la asociación verapamilo y captopril en pacientes hipertensos no controlados con monoterapia. Valoración mediante el registro de presión arterial ambulatoria durante 24 horas.

BACKGROUND: By measuring ambulatory blood pressure monitoring (ABPM), the pharmacologic association of verapamil plus captopril in essential hypertensive patients not responding to isolated monotherapy of these drugs was studied since a synergism has been described between these two drugs. METHODS: A lineal clinical trial with a previous period of selection (PeSe) in which verapamil and captopril were administered in two consecutive phases was carried out in 57 essential hypertensive patients of 52 +/- 19 years of age with those controlling their blood pressure (BP) being excluded. Following a lavage phase the remaining subjects were included in the experimental period (ExPe) in wash out the association of verapamil 120 mg+captopril 25 mg was administered and if the BP was not controlled this was increased to 240 mg + 50 mg, respectively. ABPM was performed prior to and at the end of the ExPe. RESULTS: Of the 57 patients 21 were excluded in the SePe due to control or adverse effects. Of the 26 individuals who passed into the ExPe 20 presented mild-moderate HTA (M-HTA) and 6 severe HTA (S-HTA). In the M-HTA group, the reduction of BP (in mmHg) was 157 +/- 15/106 +/- 5 to 147 +/- 12/97 +/- 7 (p < 0.05/p < 0.001), five controlled BP, in the remaining subjects the reduction in the following phase was 150 +/- 11/100 +/- 6 at 136 +/- 11/93 +/- 6 (p < 0.01/p < 0.01). In the S-HTA group the BP descended in the ExPe from 184 +/- 15/121 +/- 6 to 167 +/- 24/107 +/- 10 (p < 0.05/p < 0.05). The 24 hour measurement of BP in the ExPe decreased from 140 +/- 13/96 +/- 8 to 124 +/- 10/86 +/- 7 (p < 0.001/p < 0.001). BP descended significantly in all the hours with the exception of the hours 24, 1, 6, 7, and 5. CONCLUSIONS: The association of verapamil-captopril demonstrates efficacy and synergism in hypertensive patients previously uncontrolled by monotherapy of these drugs.