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The Cochrane Database of Systematic... Jan 2007Mild to moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mild to moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve outcome.
OBJECTIVES
To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to November 2005), LILACS (1984 to November 2005) and EMBASE (1974 to November 2005).
SELECTION CRITERIA
All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy defined, whenever possible, as systolic blood pressure 140 to 169 mmHg and diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data.
MAIN RESULTS
Forty-six trials (4282 women) were included. Twenty-eight trials compared an antihypertensive drug with placebo/no antihypertensive drug (3200 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) (19 trials, 2409 women; relative risk (RR) 0.50; 95% confidence interval (CI) 0.41 to 0.61; risk difference (RD) -0.10 (-0.12 to -0.07); number needed to treat (NNT) 10 (8 to 13)) but little evidence of a difference in the risk of pre-eclampsia (22 trials, 2702 women; RR 0.97; 95% CI 0.83 to 1.13). Similarly, there is no clear effect on the risk of the baby dying (26 trials, 3081 women; RR 0.73; 95% CI 0.50 to 1.08), preterm birth (14 trials, 1992 women; RR 1.02; 95 % CI 0.89 to 1.16), or small-for-gestational-age babies (19 trials, 2437 women; RR 1.04; 95 % CI 0.84 to 1.27). There were no clear differences in any other outcomes. Nineteen trials (1282 women) compared one antihypertensive drug with another. Beta blockers seem better than methyldopa for reducing the risk of severe hypertension (10 trials, 539 women, RR 0.75 (95 % CI 0.59 to 0.94); RD -0.08 (-0.14 to 0.02); NNT 12 (6 to 275)). There is no clear difference between any of the alternative drugs in the risk of developing proteinuria/pre-eclampsia. Other outcomes were only reported by a small proportion of studies, and there were no clear differences.
AUTHORS' CONCLUSIONS
It remains unclear whether antihypertensive drug therapy for mild to moderate hypertension during pregnancy is worthwhile.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Placebo Effect; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic
PubMed: 17253478
DOI: 10.1002/14651858.CD002252.pub2 -
The Cochrane Database of Systematic... Jan 2005Postpartum blood pressure (BP) is highest three to six days after birth when most women have been discharged home. A significant rise in BP may be dangerous (e.g., lead... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum blood pressure (BP) is highest three to six days after birth when most women have been discharged home. A significant rise in BP may be dangerous (e.g., lead to stroke), but there is little information about how to prevent or treat postpartum hypertension.
OBJECTIVES
To assess the relative benefits and risks of interventions to: (1) prevent postpartum hypertension, by assessing whether 'routine' postpartum administration of oral antihypertensive therapy is better than placebo/no treatment; and(2) treat postpartum hypertension, by assessing whether (i) oral antihypertensive therapy is better than placebo/no therapy for mild-moderate postpartum hypertension; and (ii) one antihypertensive agent offers advantages over another for mild-moderate or severe postpartum hypertension.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register (March 2004), MEDLINE (1966 to May 2003), EMBASE (1980 to January 2003), bibliographies of retrieved papers and personal files.
SELECTION CRITERIA
For women with antenatal hypertension, trials comparing a medical intervention with placebo/no therapy. For women with postpartum hypertension, trials comparing one antihypertensive with either another or placebo/no therapy.
DATA COLLECTION AND ANALYSIS
We extracted the data independently and were not blinded to trial characteristics or outcomes. We contacted authors for missing data when possible.
MAIN RESULTS
Six trials are included.
PREVENTION
Three trials (315 women; six comparisons) compared furosemide or nifedipine capsules with placebo/no therapy. There are insufficient data for conclusions about possible benefits and risks of these management strategies. Most outcomes included data from only one trial. No trial reported severe maternal hypertension or breastfeeding.
TREATMENT
In two trials (106 women; three comparisons), oral timolol or hydralazine were compared with oral methyldopa for treatment of mild to moderate postpartum hypertension. In one trial (38 women; one comparison), oral hydralazine plus sublingual nifedipine were compared with sublingual nifedipine for treatment of severe postpartum hypertension. The need for additional antihypertensive therapy did not differ between groups (relative risk 4.24, 95% confidence interval 0.96 to 18.84; three trials, N = 144 women), but three antihypertensive drugs were studied. All were well tolerated.
AUTHORS' CONCLUSIONS
There are no reliable data to guide management of women who are hypertensive postpartum or at increased risk of becoming so. If a clinician feels that hypertension is severe enough to treat, the agent used should be based on his/her familiarity with the drug. Future studies of prevention or treatment of postpartum hypertension should include information about use of postpartum analgesics and outcomes of severe maternal hypertension, breastfeeding, hospital length of stay, and maternal satisfaction with care.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Puerperal Disorders; Randomized Controlled Trials as Topic
PubMed: 15674943
DOI: 10.1002/14651858.CD004351.pub2 -
Hypertension in Pregnancy 2004To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. (Comparative Study)
Comparative Study Review
OBJECTIVE
To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy.
METHODS
A systematic review of randomized controlled trials (RCTs), observational studies (N >/= 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% CI.
RESULTS
Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); 1 study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (- 0.06, 0.11); chi2 = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% CI (0.49, 1.07); chi2 = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% CI (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26).
CONCLUSIONS
Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease.
Topics: Administration, Oral; Animals; Antihypertensive Agents; Bradycardia; Dose-Response Relationship, Drug; Female; Fetus; Heart Rate; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third; Randomized Controlled Trials as Topic
PubMed: 15369649
DOI: 10.1081/PRG-120028291 -
The Annals of Pharmacotherapy Sep 2004To systematically review the literature regarding the efficacy and safety of nonestrogen treatments for menopause-associated vasomotor symptoms not due to cancer or... (Review)
Review
OBJECTIVE
To systematically review the literature regarding the efficacy and safety of nonestrogen treatments for menopause-associated vasomotor symptoms not due to cancer or chemotherapy.
DATA SOURCES
Pertinent literature and clinical studies were identified by searching MEDLINE (1966-February 2004) and EMBASE (1959-February 2004) using the key search terms vasomotor symptoms, hot flashes, and menopause. Bibliographies of relevant articles were reviewed for additional references.
STUDY SELECTION AND DATA EXTRACTION
English-language articles reporting efficacy and safety of nonestrogen treatment modalities for perimenopausal and postmenopausal vasomotor symptoms were evaluated. All articles identified from the data sources were evaluated, and all information deemed relevant was included. Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data. Studies evaluating treatment of vasomotor symptoms from other causes, such as cancer or chemotherapy, were excluded.
DATA SYNTHESIS
Prescription medications reviewed for efficacy and safety in postmenopausal vasomotor symptoms include clonidine hydrochloride, danazol, gabapentin, methyldopa, mirtazapine, progestins, propranolol hydrochloride, selective serotonin-reuptake inhibitors (SSRIs), and venlafaxine. Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover.
CONCLUSIONS
According to this systematic literature review, postmenopausal vasomotor treatments that have been shown to be safe and effective in short-term use include black cohosh, exercise, gabapentin, medroxyprogesterone acetate, SSRIs (ie, paroxetine hydrochloride), and soy protein. Initial, small reports are suggestive for efficacy in menopausal vasomotor symptoms with megestrol acetate and venlafaxine.
Topics: Exercise Therapy; Female; Hot Flashes; Humans; Menopause; Nonprescription Drugs; Postmenopause; Randomized Controlled Trials as Topic; Vasomotor System
PubMed: 15292498
DOI: 10.1345/aph.1D610 -
The Cochrane Database of Systematic... 2003Antihypertensives, such as beta-blockers, are used for pregnancy hypertension in the belief these will improve outcome for mother and baby. (Review)
Review
BACKGROUND
Antihypertensives, such as beta-blockers, are used for pregnancy hypertension in the belief these will improve outcome for mother and baby.
OBJECTIVES
To assess whether oral beta-blockers are better than placebo, or no beta-blocker, and have advantages over other antihypertensives, for women with mild to moderate pregnancy hypertension.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2002), MEDLINE (1966 to May 2002), bibliographies of retrieved papers and personal files.
SELECTION CRITERIA
Trials comparing beta-blockers with placebo or no therapy, or other antihypertensives, for women with mild to moderate pregnancy hypertension.
DATA COLLECTION AND ANALYSIS
We extracted the data independently and were not blinded to trial characteristics or outcomes. Whenever possible, we contacted authors for missing data.
MAIN RESULTS
Twenty-nine trials (approximately 2500 women) are included. Thirteen trials (1480 women) compared beta-blockers with placebo/no beta blocker. Oral beta-blockers decrease the risk of severe hypertension (relative risk (RR) 0.37, 95% confidence interval (CI) 0.26 to 0.53; 11 trials, N = 1128 women) and the need for additional antihypertensives (RR 0.44, 95% CI 0.31 to 0.62; 7 trials, N = 856 women). There are insufficient data for conclusions about the effect on perinatal mortality or preterm birth. Beta-blockers seem to be associated with an increase in small-for-gestational-age (SGA) infants (RR 1.36, 95% CI 1.02 to 1.82; 12 trials; N = 1346 women). Maternal hospital admission may be decreased, neonatal bradycardia increased and respiratory distress syndrome decreased, but these outcomes are reported in only a small proportion of trials. In 13 trials (854 women), beta-blockers were compared with methyldopa. Beta-blockers appear to be no more effective and probably equally as safe. Single small trials have compared beta-blockers with hydralazine, nicardipine or isradipine. It is unusual for women to change drugs due to side effects.
REVIEWER'S CONCLUSIONS
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.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Antihypertensive Agents; Female; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic
PubMed: 12917933
DOI: 10.1002/14651858.CD002863 -
Hypertension in Pregnancy 2002To establish which antihypertensive medications are safe for use while breastfeeding, by reviewing the available evidence. (Review)
Review
OBJECTIVE
To establish which antihypertensive medications are safe for use while breastfeeding, by reviewing the available evidence.
METHODS
Reports of studies examining the transfer of antihypertensive medications to breastmilk were identified from multiple MEDLINE and EMBASE searches, manual review of bibliographies of articles and textbooks on drug use during lactation. The reports were reviewed and the results were compiled.
RESULTS
Prospective cohort studies and case reports constituted the only available evidence. Compilation of these results found that the milk to plasma (M/P) ratios varied widely across the beta-blocker family, the beta-blockers with low protein binding having the highest M/P ratios. The angiotensin-converting enzyme (ACE) inhibitors, methyldopa, and some calcium channel blockers had low M/P ratios.
CONCLUSION
The available data to date indicate that ACE inhibitors, methyldopa, beta-blockers with high protein binding, and some calcium channel blockers all appear to be safe treatments of hypertension in a nursing mother. The data suggest that drugs to be avoided are beta-blockers with low protein binding. However, the available evidence is limited and further studies are needed to confirm these findings.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Breast Feeding; Calcium Channel Blockers; Female; Humans; Hypertension; Lactation; Methyldopa; Milk, Human
PubMed: 12044345
DOI: 10.1081/PRG-120002912 -
The Cochrane Database of Systematic... 2001Mild-moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more... (Review)
Review
BACKGROUND
Mild-moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve outcome.
OBJECTIVES
To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.
SEARCH STRATEGY
Relevant trials were identified in the register of trials maintained by the Cochrane Pregnancy and Childbirth Group. In addition, the Cochrane Controlled Trial Register, MEDLINE, and EMBASE were searched. Date of last search: October 2000.
SELECTION CRITERIA
All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy, defined whenever possible as systolic blood pressure 140-169 mmHg and diastolic blood pressure 90-109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two reviewers.
MAIN RESULTS
Overall, this review includes 40 studies (3797 women), 24 of which compared an antihypertensive drug with placebo/no antihypertensive drug (2815 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) [17 trials, 2155 women; relative risk (RR) 0.52 (95% confidence interval (CI) 0.41 to 0.64); risk difference (RD) -0.09 (-0.12 to -0.06); number needed to treat (NNT) 12 (9 to 17)] but little evidence of a difference in the risk of pre-eclampsia [19 trials, 2402 women; RR 0.99 (0.84 to 1.18)]. Similarly, there is no clear effect on the risk of the baby dying [23 trials, 2727 women; RR 0.71(0.46 to 1.09)], preterm birth [12 trials, 1738 women; RR 0.98 (0.85 to 1.13)], or small for gestational age babies [17 trials, 2159 women; RR 1.13 (0.91 to 1.42)]. There were no clear differences in any other outcomes. Seventeen trials (1182 women) compared one antihypertensive drug with another. There is no clear difference between any of these drugs in the risk of developing severe hypertension, and proteinuria/pre-eclampsia. Other antihypertensive agents seem better than methyldopa for reducing the risk of the baby dying [14 trials, 1010 subjects, RR 0.49 (0.24 to 0.99); RD -0.02 (-0.04 to 0.00); NNT 45 (22 to 1341)]. Other outcomes were only reported by a small proportion of studies, and there were no clear differences.
REVIEWER'S CONCLUSIONS
It remains unclear whether antihypertensive drug therapy for mild-moderate hypertension during pregnancy is worthwhile.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Placebo Effect; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic
PubMed: 11406040
DOI: 10.1002/14651858.CD002252 -
The Cochrane Database of Systematic... 2000Hypertension is a common complication of pregnancy. Antihypertensive drugs are widely used in the belief these will improve outcome for both the woman (such as... (Review)
Review
BACKGROUND
Hypertension is a common complication of pregnancy. Antihypertensive drugs are widely used in the belief these will improve outcome for both the woman (such as decreasing the risk of stroke or eclampsia) and her baby (such as decreasing the risk of preterm birth and its complications). Beta-blockers are a popular choice of antihypertensive agent during pregnancy; other choices include methyldopa and calcium channel blockers.
OBJECTIVES
The aim of this review is to assess whether oral beta-blockers are overall better than placebo, or no beta-blocker, for women with mild-moderate hypertension during pregnancy, and to assess whether oral beta-blockers have any advantages over other antihypertensive agents for women with mild-moderate hypertension during pregnancy. Both maternal outcomes (e.g., the incidence of severe hypertension) and perinatal outcomes (e.g., mortality) were of interest.
SEARCH STRATEGY
Register of trials maintained by the Cochrane Pregnancy and Childbirth Group, MEDLINE 1966-97, bibliographies of retrieved papers, personal files. Date of last search: June 2000.
SELECTION CRITERIA
Trials comparing beta-blockers with (i) placebo or no therapy, or (ii) other antihypertensive agents, for women with mild-moderate pregnancy hypertension (i.e., blood pressure under 170 mm Hg systolic, or 110 mm Hg diastolic).
DATA COLLECTION AND ANALYSIS
All data were extracted independently by two investigators, who were not blinded to outcome or other trial characteristics. Whenever possible, missing data were obtained by personal communication with authors. Discrepancies were resolved by discussion. The overview was divided into two comparisons: (i) beta-blockers versus placebo or no therapy, and (ii) beta-blockers versus other antihypertensives.
MAIN RESULTS
Twenty-seven trials, involving just under 2400 women, are included in this review. Fourteen trials (1516 women) compared beta-blockers with placebo/no beta blocker. Oral beta-blockers decrease the risk of severe hypertension (relative risk (RR) 0.37, 95% confidence interval (CI) 0.26-0.53) and the need for additional antihypertensive drugs (RR 0.44, 95% CI 0.31-0.62). There are insufficient data for any conclusions about the effect on perinatal mortality or preterm delivery. Beta-blockers seem to be associated with an increase in small for gestational age infants (RR 1.34, 95% CI 1.01-1.79). Maternal hospital admission may be decreased, neonatal bradycardia increased and respiratory distress syndrome decreased, but these outcomes are only reported in a very small proportion of trials. Eleven trials (787 women) compared beta-blockers with methyldopa. Beta-blockers appear to be no more effective and probably equally as safe (from maternal and perinatal perspectives) as methyldopa. Single small trials have compared beta-blockers with hydralazine and with nicardipine. It is unusual for women to change drugs due to side effects.
REVIEWER'S CONCLUSIONS
The improvement in control of maternal blood pressure with use of beta-blockers would be worthwhile only if it were reflected in other more substantive benefits for the mother and/or baby, and none have yet been clearly demonstrated. The effect of beta-blockers on perinatal outcome is uncertain, given that the worrying trend to an increase in small for gestational age infants is partly dependent on one small outlying trial. Large, randomised controlled trials are needed to determine whether antihypertensive therapy in general (rather than beta-blocker therapy specifically) results in benefits that outweigh the risks for treatment of mild-moderate pregnancy hypertension. If so, then it would be appropriate to look at which antihypertensive is best. Beta-blockers would remain a candidate class of agents.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Antihypertensive Agents; Female; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic
PubMed: 11034777
DOI: 10.1002/14651858.CD002863