Efficacy of ramipril versus enalapril in patients with mild to moderate essential hypertension.

This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a further four weeks. After a placebo washout phase of four weeks, the patients were crossed over to the alternative treatment. The decrease in average 24-hour ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The corresponding reduction in for systolic blood pressure was also greater with ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For the difference in the drop of 24-hour ambulatory diastolic blood pressure between ramipril and enalapril the lower level of the 90% confidence interval (CI) is above the clinically relevant difference of -3mmHg. This is an indication that ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg dose) in decreasing blood pressure in patients with mild-to-moderate essential hypertension. The duration of adequate antihypertensive effect was relatively long for both ramipril and enalapril; however, ramipril tended to have a more prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic trough/peak ratio than enalapril, resulting in a more uniform antihypertensive effect over the 24-hour treatment period. Both ramipril and enalapril were well tolerated and the two treatment groups had similar safety profiles.

Nocturnal hypotension and ACE inhibitors.

Thirty essential hypertensive subjects had their BP measured by 24h ambulatory monitoring before (first placebo period) and after exposure to antihypertensive therapy with either enalapril (four weeks) or nitrendipine (six weeks). Similar measures of BP were obtained during a second placebo period intercalated between the two active drugs. The 24h averages of systolic and diastolic pressures were higher during placebo (148 +/- 3/91 +/- 1 mmHg, respectively) than during treatment periods. Four weeks of treatment with enalapril reduced arterial pressure to a 24h average of 137 +/- 1/86 +/- 1 mmHg while nitrendipine given for six weeks lowered BP to an average of 135 +/- 1/84 +/- 1 mmHg. The antihypertensive effect of the drugs was of a comparable magnitude (P > 0.05). In addition both drugs produced analogous reductions in BP during the day (07.00 to 23.00 h). In contrast, the nocturnal fall in BP was significantly greater during treatment with nitrendipine. Average systolic and diastolic pressures between 23.00 h and 07.00 h were 133 +/- 1 mmHg and 82 +/- 2 mmHg with enalapril compared with 129 +/- 3 mmHg (P < 0.01) and 77 +/- 3 mmHg (P < 0.01) with nitrendipine, respectively. These data suggest that antihypertensive agents show important differences in terms of their action on the mechanisms that regulate BP during sleep. Medications that amplify the otherwise physiological fall in BP during sleep may add risk to patients with impaired coronary vasodilator reserve owing to ventricular hypertrophy, coronary atherosclerosis, or both.

[Ambulatory ergometric and pressurometric results with a daily dose of 240 mg of diltiazem in labile hypertensive patients with threshold ergometry]. / Resultados ergométricos y presurométricos ambulatorios con 1 dosis diaria de 240 mg de diltiazem en hipertensos labiles con ergometría limítrofe.

The pharmacological treatment of hypertension raises not only the dilemma of the election of the most suitable drugs given to each patient, but also that of an effective control of the antihypertensive effect as well as undesirable reactions, including an accentuated hypotension. Continuous ambulatory monitoring (CAM) is an effective form of diagnosis and therapeutic control of hypertension. In order to evaluate the efficacy and tolerance of a new concentration of diltiazem (240 mg) in tablets of sustained release, for a single daily intake, a double blind, randomized, crossed study with placebo, was performed in 20 patients with mild to moderate hypertension and a positive ergometric test. Clinical, electrocardiographic, ergometric and CAM controls were carried out. A significant difference was observed for diltiazem monodosis 240 mg in relation to placebo with respect to the reduction of systolic and diastolic pressures, not only in clinical controls but also during the CAM, in both diurnal and nocturnal periods during 24 hours. In ergometric studies, a significant difference was also noted in the following parameters: total time of exercise, burden in kilos, systolic and diastolic blood pressure and the underlevel of ST. It is concluded that diltiazem monodosis, 240 mg, led to a sustained antihypertensive action throughout the 24 hours, with good clinical tolerance, improving ergometry and CAM. We suggest that diltiazem is a first choice drug for there patients in whom the exclusive treatment of hypertension has not prevented, up to now, the occurrence of ischemic cardiopathy.

Evaluation of the antianginal effect of isosorbide-5-mononitrate in patients with chronic stable angina pectoris.

The antianginal and anti-ischemic properties of isosorbide-5-mononitrate (ISMN) were evaluated in 40 patients with chronic stable angina pectoris in a randomized double-blind parallel-group placebo-controlled study. After 2 weeks' placebo run-in period the patients were randomized to either ISMN, orally 20 mg 2-3 times daily (titrated) or placebo. They underwent bicycle exercise stress test at the end of the placebo period and after 4 weeks of treatment. Compared with placebo ISMN increased the exercise performance, reduced ST-segment depression, anginal frequency and sublingual nitroglycerin consumption. All these changes were statistically significant. It may be concluded that ISMN is an effective antianginal and anti-ischemic agent in patients with chronic stable angina pectoris.

Resultados ergometricos y presurometricos ambulatorios con 1 dosis diaria de 240 mg de diltiazem en hipertensos labiles con ergometria limitrofe / Ambulatory ergometric and pressurometric results with a daily dose of 240 mg of diltiazem in labile hypertensive patients with threshold ergometry

El monitoreo ambulatorio contínuo (MAC) constituye un eficiente elemento de diagnóstico y control terapéutico de la hipertensión arterial (HA). Con la finalidad de evaluar la eficacia y tolerancia de una nueva concentración de diltiazem (240 mg), en comprimidos de liberación programada para una toma diaria, se realizó un estudio doble ciego en 20 pacientes clínicos, electrocardiográficos, ergométricos y de MAC en los períodos basales, placebo y con droga activa. Se observó una diferencia significativa para diltiazem monodosis 240 mg en relación al placebo, en lo que se refiere al descenso de la presión arterial (PA) sistólica y diastólica, no sólo en los controles clínicos sino también durante el MAC tanto en el período diurno como en el nocturno. Esto ocurrió con el promedio de 24 horas y con el porcentaje de registros anormales. En los estudios ergométricos también se observó una diferencia estadísticamente significativa para diltiazem en los siguientes parámetros: tiempo total de la prueba, carga en Kilos, PA sistólica, y desnivel del ST. Se concluye que el diltiazem monodosis 240 mg fue capaz de mantener una eficaz acción antihipertensiva sostenida a lo largo de las 24 horas, con muy buena tolerancia clínica, induciendo una mejoría evidente en la ergtométría y en el MAC, lo que la hace una droga de primera elección en pacientes en los cuales el tratamiento exclusivo de la hipertensión arterial, hasta, ahora, no ha mejorado el pronóstico de la cardiopatia isquémica

Resultados ergométricos y presurométricos ambulatorios con 1 dosis diaria de 240 mg de diltiazem en hipertensos labiles con ergometría limítrofe. / [Ambulatory ergometric and pressurometric results with a daily dose of 240 mg of diltiazem in labile hypertensive patients with threshold ergometry]

The pharmacological treatment of hypertension raises not only the dilemma of the election of the most suitable drugs given to each patient, but also that of an effective control of the antihypertensive effect as well as undesirable reactions, including an accentuated hypotension. Continuous ambulatory monitoring (CAM) is an effective form of diagnosis and therapeutic control of hypertension. In order to evaluate the efficacy and tolerance of a new concentration of diltiazem (240 mg) in tablets of sustained release, for a single daily intake, a double blind, randomized, crossed study with placebo, was performed in 20 patients with mild to moderate hypertension and a positive ergometric test. Clinical, electrocardiographic, ergometric and CAM controls were carried out. A significant difference was observed for diltiazem monodosis 240 mg in relation to placebo with respect to the reduction of systolic and diastolic pressures, not only in clinical controls but also during the CAM, in both diurnal and nocturnal periods during 24 hours. In ergometric studies, a significant difference was also noted in the following parameters: total time of exercise, burden in kilos, systolic and diastolic blood pressure and the underlevel of ST. It is concluded that diltiazem monodosis, 240 mg, led to a sustained antihypertensive action throughout the 24 hours, with good clinical tolerance, improving ergometry and CAM. We suggest that diltiazem is a first choice drug for there patients in whom the exclusive treatment of hypertension has not prevented, up to now, the occurrence of ischemic cardiopathy.

Resultados ergometricos y presurometricos ambulatorios con 1 dosis diaria de 240 mg de diltiazem en hipertensos labiles con ergometria limitrofe / Ambulatory ergometric and pressurometric results with a daily dose of 240 mg of diltiazem in labile hypertensive patients with threshold ergometry

El monitoreo ambulatorio contínuo (MAC) constituye un eficiente elemento de diagnóstico y control terapéutico de la hipertensión arterial (HA). Con la finalidad de evaluar la eficacia y tolerancia de una nueva concentración de diltiazem (240 mg), en comprimidos de liberación programada para una toma diaria, se realizó un estudio doble ciego en 20 pacientes clínicos, electrocardiográficos, ergométricos y de MAC en los períodos basales, placebo y con droga activa. Se observó una diferencia significativa para diltiazem monodosis 240 mg en relación al placebo, en lo que se refiere al descenso de la presión arterial (PA) sistólica y diastólica, no sólo en los controles clínicos sino también durante el MAC tanto en el período diurno como en el nocturno. Esto ocurrió con el promedio de 24 horas y con el porcentaje de registros anormales. En los estudios ergométricos también se observó una diferencia estadísticamente significativa para diltiazem en los siguientes parámetros: tiempo total de la prueba, carga en Kilos, PA sistólica, y desnivel del ST. Se concluye que el diltiazem monodosis 240 mg fue capaz de mantener una eficaz acción antihipertensiva sostenida a lo largo de las 24 horas, con muy buena tolerancia clínica, induciendo una mejoría evidente en la ergtométría y en el MAC, lo que la hace una droga de primera elección en pacientes en los cuales el tratamiento exclusivo de la hipertensión arterial, hasta, ahora, no ha mejorado el pronóstico de la cardiopatia isquémica (AU)

Efficacy of a fixed-dose combination of 40 mg penbutolol with 6 mg piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo.

The antihypertensive efficacy and tolerability of a fixed-dose combination containing 40 mg penbutolol (a beta-blocking agent) and 6 mg piretanide (a diuretic) in comparison to placebo was investigated in a double-blind, crossover study in 20 patients with mild to moderate essential hypertension. After a 1-week period on placebo, patients were allocated at random to receive 1 tablet daily for 4 weeks of either the combination preparation or placebo and were then crossed over to the alternative medication for a further 4 weeks. The reduction in systolic and diastolic blood pressure both at rest, during maximal ergometric exercise and isometric word load, and also in the diurnal blood pressure profile over 24 hours was significantly greater in the group treated with the fixed-dose combination than in the placebo group. Pulse rate was also decreased to a greater extent. Mean diastolic blood pressure before exercise was reduced to normal (85.5 mmHg) after 4-weeks' treatment with the fixed-dose combination. Biochemical, haematological and urinary parameters showed no clinically relevant changes after either treatment. One patient complained of transient dizziness during treatment with the fixed-dose combination. No patient withdrew prematurely from the study because of side-effects.

A fixed-dose combination of furosemide and spironolactone in digitalized congestive heart failure patients.

Twenty-three optimally digitalized patients with congestive heart failure completed a 4-week treatment period with a fixed-drug association of 20 mg furosemide plus 50 mg spironolactone. Eleven patients responded with a 75% decrease in cardiac failure score on a daily dose of 1 capsule of the combination. The remaining 12 patients were initiated on the same dose, but needed, at the end of the first 14 days, an additional capsule (making a daily total of 40 mg furosemide and 100 mg spironolactone) over the next 2 weeks. On this dose, the patients achieved an average reduction of 52% in their cardiac failure score. There were no treatment failures. Electrolyte abnormalities and side-effects were not observed. The combination product, in a daily dose of 1 or 2 capsules, was found useful and well tolerated in the management of congestive heart failure.

The treatment of non-digitalized congestive heart failure patients with a fixed-dose combination of furosemide and spironolactone.

Seventeen non-digitalized congestive heart failure patients were treated with only the fixed-dose combinations of 20 mg furosemide and 50 mg spironolactone or 20 mg furosemide and 100 mg spironolactone, in a daily dose of 1 or 2 capsules, over a 4-week period. The selected patients had a severity rating ranging between Grades III and IV. Ten of these patients had a severe grade of dyspnoea. Assessments were made on the basis of the reduction in cardiac failure score, extent of reduction in oedema, and relief of dyspnoea. Safety variables measured included laboratory, echocardiographic and side-effect monitoring. By the end of the 4-week study period, significant reduction (46% to 51%) in cardiac score and complete relief of dyspnoea with no adverse effects on safety variables were recorded. These results indicate that it is possible to treat patients with congestive heart failure safely with the fixed-dose combination product without the concurrent use of digitalis.

Efficacy of a low fixed-dose combination of penbutolol with piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo.

A double-blind crossover study was carried out in 20 patients with mild to moderate essential hypertension to assess the efficacy and tolerability of a low fixed-dose combination containing 20 mg penbutolol (a beta-blocking agent) and 3 mg piretanide (a diuretic) in comparison to placebo over a period of 4 weeks. Active drug treatment in the 20 patients studied was preceded by a 1-week period of placebo. The results showed that there was an effective significant reduction in systolic and diastolic blood pressure compared with initial levels in the fixed-dose combination group, when compared to the placebo group, both at rest, during maximal ergometric and isometric work load, and also in the diurnal blood pressure profile over 24 hours. Pulse rate also decreased in the combination group. The biochemical, haematological and urinary parameters showed no clinically relevant changes in either group during the entire study period. Minor side-effects definitely or probably associated with the treatment were observed in both groups but were generally mild and did not interfere with treatment. No patient withdrew prematurely from the trial.