RESUMEN
BACKGROUND: Low systolic blood pressure (SBP) is a risk factor for adverse outcomes in patients with heart failure (HF). Valsartan improved morbidity rates in the Valsartan Heart Failure Trial (Val-HeFT) despite a reduction in SBP. The aim of the present study was to investigate the relationship between the SBP-lowering effects of valsartan and its cardiovascular protective effects in this population. METHODS AND RESULTS: Baseline measurements and changes in SBP at 4 months were related to mortality and morbidity rates. The effects of valsartan on these end points were compared in quartiles of baseline SBP with multivariable Cox proportional hazards regression models that included a test for interaction between the effects of valsartan treatment and baseline SBP and examined the effects of changes in SBP on the valsartan effect. The mean+/-SD baseline SBP in all patients (n=5010) was 124+/-18 mm Hg. Patients in the lowest quartile of SBP (SBP Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico
, Presión Sanguínea/efectos de los fármacos
, Insuficiencia Cardíaca/tratamiento farmacológico
, Tetrazoles/uso terapéutico
, Valina/análogos & derivados
, Anciano
, Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología
, Método Doble Ciego
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Factores de Riesgo
, Tetrazoles/farmacología
, Resultado del Tratamiento
, Valina/farmacología
, Valina/uso terapéutico
, Valsartán
RESUMEN
A 68-year-old man was hospitalised with a vascular occlusion in the left leg. After treatment with urokinase he developed multiple intracerebral haemorrhages. The occlusion and the intracerebral haemorrhages evoked by urokinase were caused by embolisation originating from a cardiac metastasis of a renal-cell carcinoma. Cardiac surgery was performed, but complete removal of the tumour was not possible. The process of embolisation continued and the patient died a few weeks after diagnosis. Cardiac metastasis is seen in 10% of all cancer patients. Most of these metastases remain without symptoms. Left ventricular metastasis of renal-cell carcinoma without involvement of the inferior V. cava is very rare. If embolic occlusion of one or more vascular areas is present, transthoracic echography of the heart should be performed. Early detection and surgical treatment prevent further embolisation which may result in a better prognosis.
Asunto(s)
Carcinoma de Células Renales/secundario , Hemorragia Cerebral/etiología , Neoplasias Cardíacas/secundario , Embolia Intracraneal/etiología , Neoplasias Renales/patología , Anciano , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/cirugía , Resultado Fatal , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/cirugía , Humanos , Masculino , Pronóstico , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversos , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoAsunto(s)
Fluoxetina/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Torsades de Pointes/inducido químicamente , Anciano de 80 o más Años , Femenino , Fluoxetina/uso terapéutico , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Angina de Pecho/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Esfuerzo Físico/fisiología , Adolescente , Antagonistas Adrenérgicos beta/administración & dosificación , Adulto , Anciano , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Amlodipino/uso terapéutico , Angina de Pecho/etiología , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/clasificación , Diltiazem/administración & dosificación , Diltiazem/efectos adversos , Diltiazem/uso terapéutico , Mareo/inducido químicamente , Método Doble Ciego , Combinación de Medicamentos , Electrocardiografía/efectos de los fármacos , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Mibefradil , Persona de Mediana Edad , Isquemia Miocárdica/prevención & control , Tetrahidronaftalenos/administración & dosificación , Tetrahidronaftalenos/efectos adversos , Tetrahidronaftalenos/uso terapéutico , Factores de TiempoRESUMEN
AIMS: The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. METHODS: A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. RESULTS: Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. CONCLUSIONS: Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Angina de Pecho/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Ejercicio Físico/fisiología , Adolescente , Adulto , Anciano , Amlodipino/efectos adversos , Amlodipino/uso terapéutico , Angina de Pecho/fisiopatología , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Diltiazem/efectos adversos , Diltiazem/uso terapéutico , Mareo/inducido químicamente , Método Doble Ciego , Quimioterapia Combinada , Prueba de Esfuerzo/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Mibefradil , Persona de Mediana Edad , Medición de Riesgo , Tetrahidronaftalenos/efectos adversos , Tetrahidronaftalenos/uso terapéuticoRESUMEN
The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95-114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placebo run-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP > or =90 mmHg and a decrease of < 10 mmHg) were treated for an additional 6 weeks with a dose increase of 10 mg. At each clinic visit, sitting and standing blood pressure and heart rate were measured approximately 24 hours after the last dose of study drug was taken. Compared with placebo, barnidipine lowered blood pressure, with a trend toward a dose-response relationship over the dose range 10-30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10-30 mg) administered once daily is well tolerated and reduces blood pressure in patients with mild to moderate hypertension.
Asunto(s)
Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Nifedipino/análogos & derivados , Anciano , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Edema/inducido químicamente , Femenino , Rubor/inducido químicamente , Cefalea/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/efectos adversos , Nifedipino/uso terapéuticoRESUMEN
OBJECTIVE: To compare the antihypertensive efficacy and systemic tolerability of valsartan, a new angiotensin II receptor antagonist, with placebo and with an angiotensin converting enzyme (ACE) inhibitor, enalapril. DESIGN: A total of 348 adult outpatients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind, parallel, study. Patients were allocated randomly in a ratio of 2:2:1 to receive 80 mg valsartan once a day, 20 mg enalapril once a day, or placebo for 8 weeks in general practice. Patients were assessed at 4 and 8 weeks of therapy. MAIN OUTCOME MEASURES: The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Secondary variables included the change in sitting systolic blood pressure (SSBP) and response rates at 8 weeks. RESULTS: Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo. Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of -9.5 mmHg for valsartan and -9.4 mmHg for enalapril (-4.5 mmHg for placebo). No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP. Response rates at 8 weeks were significantly greater for valsartan (54%) and enalapril (58%) than for placebo (20%), with no significant difference between the two active treatments. Both valsartan and enalapril demonstrated a consistent antihypertensive effect over time, with 90% of patients with a response at 4 weeks responding at 8 weeks. Both of the treatments were tolerated well. Although the incidence of coughing was generally low in the study, more cases were reported with enalapril (three) than with valsartan (one) or placebo (none). CONCLUSIONS: The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension. Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing.
Asunto(s)
Angiotensina II/antagonistas & inhibidores , Antihipertensivos/uso terapéutico , Enalapril/uso terapéutico , Hipertensión/tratamiento farmacológico , Tetrazoles/uso terapéutico , Valina/análogos & derivados , Adulto , Factores de Edad , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tetrazoles/efectos adversos , Valina/efectos adversos , Valina/uso terapéutico , ValsartánRESUMEN
In a randomized, double-blind, cross-over, multicenter study with a placebo run-in phase, the efficacy and safety of two oral formulations of diltiazem, standard three or four times daily (t.i.d. or q.i.d.) and controlled release twice daily (b.i.d.), were compared in 49 patients with stable angina pectoris. ST-segment depression at maximum exercise 12 h after tablet intake was less frequently observed with diltiazem controlled release than with standard diltiazem (34 of 49, 69% vs. 43 of 49, 88%, p = 0.007). In patients with ST-segment depression after both treatments (n = 33), the average time to 1-mm ST-segment depression was 55.4 +/- 19.9 s longer with diltiazem controlled release than with standard diltiazem [476 +/- 195 vs. 422 +/- 163 s, p = 0.009; 95% confidence interval (CI) 14.8-96 s]. Reduction in mean number of anginal attacks and nitroglycerin (NTG) intake was not significantly different between treatment with standard diltiazem and diltiazem controlled release. The incidence of side effects was low and not different between the two treatments. Both formulations are equally effective in reducing the number of anginal attacks and are well tolerated. Diltiazem controlled release is more effective than standard diltiazem in preventing myocardial ischemia 12 h after tablet intake. Thus, diltiazem controlled release allows twice-daily intake frequency and may therefore be preferable to standard diltiazem in treatment of stable angina pectoris.
Asunto(s)
Angina de Pecho/tratamiento farmacológico , Diltiazem/uso terapéutico , Adulto , Anciano , Preparaciones de Acción Retardada , Diltiazem/administración & dosificación , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Prueba de Esfuerzo , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In a randomized, double-blind, multicenter study, the efficacy of diltiazem controlled-release (CR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 56 patients with stable exertional angina pectoris. Fifty-one patients (28 receiving diltiazem CR, 23 receiving metoprolol), completed a follow-up period of 8 weeks. Thirty-nine patients (20 receiving diltiazem CR, 19 receiving metoprolol), completed a follow-up period of 32 weeks. Maximal exercise testing was performed at baseline and after 8, 20, and 32 weeks of treatment. Most exercise parameters were not significantly different between the patients on diltiazem CR and those on metoprolol. However, exercise duration was longer and maximal work load was higher in patients on diltiazem CR than in patients on metoprolol, and significant differences were observed at 20 weeks of treatment (p = 0.006 and p = 0.008, respectively). At all times during treatment, heart rate at maximal exercise and rate-pressure product at maximal exercise were significantly lower in the patients treated with metoprolol. In conclusion, monotherapy with diltiazem CR is at least as effective as monotherapy with metoprolol in patients with stable angina pectoris. As compared to metoprolol, diltiazem CR has a minor depressing effect on rate-pressure product, resulting in a favorable effect on exercise duration.
Asunto(s)
Angina de Pecho/tratamiento farmacológico , Diltiazem/administración & dosificación , Metoprolol/uso terapéutico , Adulto , Anciano , Angina de Pecho/fisiopatología , Presión Sanguínea/efectos de los fármacos , Preparaciones de Acción Retardada , Diltiazem/efectos adversos , Diltiazem/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Metoprolol/efectos adversos , Persona de Mediana Edad , Descanso/fisiología , Factores de TiempoRESUMEN
A multicenter, double-blind study was performed to compare the antianginal efficacy and safety of the new dihydropyridine calcium antagonist amlodipine with the benzothiazepine calcium antagonist diltiazem in patients with stable exertional angina pectoris. Following a 2-week placebo run-in period, 39 patients were randomized to receive amlodipine (2.5-10 mg once daily) and 41 patients to receive diltiazem (60-120 mg three times daily) in an 8-week double-blind treatment phase. The study used standardized bicycle exercise testing as a primary efficacy assessment. Patients also recorded angina frequency and nitroglycerin (NTG) tablet consumption/ week. Treatment with amlodipine and diltiazem resulted in an improvement in total exercise time, time to angina and total work, mean ST-segment deviation at maximum common load, median number of angina attacks/week, and NTG tablet consumption/week. The incidence and severity of possibly treatment-related side effects and laboratory test abnormalities were comparable for both drugs. The most frequently reported side effects were dizziness, headache, peripheral edema, and nausea. Two patients withdrew from diltiazem treatment due to pruritus in one case and severe headache and moderate dyspnea in the other. No amlodipine-treated patients withdrew due to side effects. In conclusion, this study demonstrated that the antianginal efficacy and tolerability of amlodipine is equivalent to diltiazem, but amlodipine has the advantage of once-daily dosing.