A prospective controlled trial of metoprolol-hydralazine treatment in hypertension during pregnancy. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. A randomized comparison of early with conservative use of antihypertensive drugs in the management of pregnancy-induced hypertension. Comparison of antihypertensive efficacy and perinatal safety of labetalol and methyldopa in the treatment of hypertension in pregnancy: a randomized controlled trial. Ephedrine and phenylephrine for avoiding maternal hypotension due to spinal anaesthesia for caesarean section. Effects on uteroplacental and fetal haemodynamics. Behavioral and physiological effects of a beta blocker and relaxation therapy on mild hypertensives. Beta-adrenergic blocking agents in the treatment of pregnancy-induced hypertension. [Management of severe pre-eclampsia/eclampsia. Comparison between nifedipine and hydralazine as antihypertensive agents]. Placebo-controlled trial of atenolol in treatment of pregnancy-associated hypertension.
In an open, controlled trial, treatment with a combination of metoprolol and hydralazine was compared with non-pharmacological management of mild and moderate hypertension in pregnancy. One hundred and sixty-one women participated in the study. The drug-treated group showed significantly better blood pressure control than the group not given antihypertensives. Induction of labor before term, because of maternal or fetal complications, was somewhat more frequent in the control group. Nine women in the treatment group and 5 in the control group developed albuminuria. Three infants in the drug-treated group died perinatally, and one in the control group. The outcome for the newborns was similar in both groups concerning birth weight, head circumference and Apgar score and in the frequencies of respiratory distress, bradycardia and hypoglycemia. The better blood pressure control achieved with these drugs makes it possible to treat the patient at home and reduce the risk of emergency delivery, but treatment does not seem to be mandatory for a good outcome of the pregnancy in cases of mild and moderate hypertension during pregnancy. Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent. Two treatment strategies were compared in 155 women with pregnancy-induced hypertension who were also given comprehensive non-pharmacological care. The mean gestation at entry was 28 weeks. As long as the diastolic blood pressure (DBP) remained below 106 mmHg, oxprenolol, or oxprenolol plus dihydralazine, were given to the early treatment group, and matching placebos to the control group. Open antihypertensive treatment was provided for patients whose DBP rose above 105 mmHg. Proteinuria occurred in seven women in each group. In the early treatment group, 13 of the 78 women were delivered by caesarean section; the corresponding numbers in the control group were 27 of 76 (17 vs 36%, 95% confidence interval (CI) of difference: 5-33%); the sections included seven and 16 in the early treatment and control groups, respectively, for severe hypertension and/or fetal distress. There were five perinatal deaths, two in the early treatment group and three in the control group. Early treatment did not influence gestational age at birth or birthweight. Respiratory distress syndrome occurred in four infants in the early treated group and in 10 in the control group; 14 infants in the former group and 26 in the latter were in hospital for more than 10 days (18 vs 35%; 95% CI of difference 4-32%). These results indicate that early antihypertensive treatment with oxprenolol is safe for the fetus and newborn in pregnancy-induced hypertension, but has no advantage over non-pharmacological care in terms of fetal growth. However, it may prevent acute hypertension in late pregnancy and associated fetal distress, and thus reduce the number of caesarean sections. Labetalol was compared with methyldopa in a randomized controlled trial involving 176 pregnant women with mild to moderate hypertension. Diastolic blood pressure below 86 mmHg was obtained in a similar proportion of women given labetalol or methyldopa. Intrauterine death occurred in four women treated with methyldopa, and the one neonatal death on day 1 occurred in the labetalol group. The average birthweight and the proportion of preterm or small-for-gestational-age babies were similar in both groups. Heart rate, blood pressure, blood glucose, respiratory rate, and Silverman score of the babies did not differ between the two treatment groups, whether the comparison was made for all the infants, or only for those that were preterm or small-for-gestational-age. These data indicate that maternal beta-blockade with labetalol is as safe as methyldopa for the fetus and the newborn. The effects of i.v. vasopressors on Doppler velocimetry of the maternal uterine and placental arcuate arteries and the fetal umbilical, renal and middle cerebral arteries were studied during spinal anaesthesia in 19 healthy parturients undergoing elective caesarean section. Fetal myocardial function was investigated at the same time by M-mode echocardiography. The patients were randomized into two groups, to be given either ephedrine or phenylephrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure decreased by more than 10 mmHg from the control value. Both the vasopressors restored maternal arterial pressure effectively. The ephedrine group showed no significant differences in any of the Doppler velocimetry recordings relative to the baseline values, but during the phenylephrine infusion the blood flow velocity waveform indices for the uterine and placental arcuate arteries increased significantly and vascular resistance decreased significantly in the fetal renal arteries. Healthy fetuses seem to tolerate these changes in uteroplacental circulation well, however, since the Apgar scores for the newborns and the acid-base values in the umbilical cord were within the normal range in both groups. The results suggest that some caution is required when selecting the specific vasopressor agent, the dosage and the mode of administration for the treatment of maternal hypotension secondary to spinal anaesthesia for caesarean section. In this industrial-based study we compared the blood pressure (BP)-lowering effectiveness of relaxation, a beta blocker, and the combined use of these two treatments in 47 untreated, mildly hypertensive blue collar steel workers. Using a randomized two by two factorial design, patients received either nadolol or placebo drug daily, and either a relaxation training or an education program, each lasting 8 weeks. A pre-intervention and post-intervention stress test measured response of heart rate and BP to mental and physical tasks. BP assessments were done at baseline, post-intervention, 1 month, and 3 month follow-up. Change in several self-report measures was determined. Results showed that beta blocker was more effective in lowering BP than placebo, but relaxation was not more effective in lowering BP than health education. The combined effect of beta blocker and relaxation was not superior to beta blocker alone. Compliance with relaxation practice was not superior to compliance with medication. We conclude that pharmacologic treatment is superior to the relaxation therapy tested. Fifty-one women with pregnancy-induced hypertension (PIH) were randomly allocated to one of three treatment groups: A: hydralazine (13); B: hydralazine and propranolol (17); and C: hydralazine and pindolol (19). All women fulfilled the pretreatment criteria and were of similar age, numbers of previous pregnancies and had systolic blood pressure (SBP) of between 140 and 160 mmHg and diastolic blood pressure (DBP) of between 95 and 110 mmHg. Hypertension was treated equally well by all three regimens (mean SBP was 133.6, 130 and 134 mmHg, respectively). Heart rate was significantly higher than baseline in group A and lower in groups B and C, as is to be expected with beta-blocker treatment. Side-effects were more frequent in group A than in groups B and C, 62% of the patients on hydralazine monotherapy complained of palpitations compared to 35% on combination treatment. Fetal outcome differed in the various groups. Birth weight was significantly lower in group B, where regimen included propranolol, compared to that of group C, for whom the regimen included pindolol (3,044.7 +/- 443.8 and 2,709.6 +/- 485.5 gm, p < 0.05). Mean blood glucose of the newborns were similar in groups A and C (76.5 +/- 16.5 and 78.6 +/- 15 gm%) and significantly lower in group B (62.6 +/- 14 gm%, p < 0.02). In conclusion, blood pressure was equally well treated in all three treatment groups. However, more maternal side-effects occurred in group A, the group treated with hydralazine monotherapy, while propranolol in combination with hydrazaline (group B) had some negative effects on fetal development which did not occur in pindolol/hydrazaline combination. The objective was to compare the fetal and maternal effects between parenteral hydralazine and sublingual nifedipine used like antihypertensive drugs in the management of severe preeclampsia. Study design was prospective, comparative, longitudinal, randomized clinical trial. It was carried out at Centro Medico Nacional IMSS Torreon, Coah. Gynecology and Obstetrics Department. The patients were women in the last trimester of pregnancy with severe preeclampsia were randomized to receive parenteral hydralazine or sublingual nifedipine as antihypertensive drugs. The only difference observed in this study was the Apgar of neonates whose mothers received hydralazine, that was significatively lesser than the Apgar of neonates whose mothers received nifedipine. Both medicaments are a good alternative as antihypertensive drugs in severe preeclampsia. Neonates whose mothers received Nifedipine had a higher Apgar. Atenolol was compared with placebo in a randomised and double-blind prospective study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest. Atenolol given once daily significantly reduced blood-pressure, prevented proteinuria, and reduced the number of hospital admissions. Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group, whose babies had a high morbidity. Respiratory distress syndrome occurred only in the placebo group. Intrauterine growth retardation, neonatal hypoglycaemia, and hyperbilirubinaemia occurred with the same frequency in the two groups. Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups. There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy. Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby.
Improvement in control of maternal blood pressure with use of beta-blockers would be worthwhile only if it were reflected in substantive benefits for mother and/or baby, and none have been clearly demonstrated. The effect of beta-blockers on perinatal outcome is uncertain; the worrying trend to an increase in SGA infants is partly dependent on one small outlying trial. Large randomised trials are needed to determine whether antihypertensive therapy in general (rather than beta-blocker therapy specifically) results in greater benefit than risk, for treatment of mild-moderate pregnancy hypertension. If so, then it would be appropriate to consider which antihypertensive is best, and beta-blockers should be evaluated.
[Note: the seventeen reports in the awaiting classification section of the review may alter the conclusions of the review once assessed.]