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Journal of Hypertension Nov 2017Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which... (Review)
Review
BACKGROUND
Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.
OBJECTIVE
The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.
METHODS
OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.
RESULTS
Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.
CONCLUSION
The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.
Topics: Antihypertensive Agents; Attention Deficit Disorder with Hyperactivity; Birth Weight; Child; Child Health; Female; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Infant, Low Birth Weight; Infant, Newborn; Labetalol; Maternal Exposure; Pregnancy; Premature Birth
PubMed: 28661961
DOI: 10.1097/HJH.0000000000001456 -
CNS Drugs Oct 2016
Review
Topics: Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Intestines; Levodopa; Parkinson Disease
PubMed: 27541607
DOI: 10.1007/s40263-016-0378-8 -
CNS Drugs May 2016Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor... (Review)
Review
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor fluctuations and dyskinesia when other treatments have not given satisfactory results.
OBJECTIVE
Our objective was to summarize the present evidence base for LCIG therapy through a systematic review of the literature.
METHODS
Studies were identified from the PubMed and EMBASE databases up to 12 March 2016 using the following search terms: Parkinson disease, duodopa, levodopa/carbidopa intestinal gel, levodopa-carbidopa intestinal gel, LCIG, l-dopa infusion, levodopa infusion, duodenal l-dopa infusion, and duodenal levodopa infusion. Data extraction focused on whether LCIG therapy improves motor and non-motor outcomes as well as quality of life in PD patients compared with conventional therapy, apomorphine infusion, or deep brain stimulation. Randomized controlled trials (RCTs) and observational studies, with or without a control group, that included more than ten patients were included. The search was limited to peer-reviewed articles published in full in the English language and involving humans.
RESULTS
Infusion of LCIG reduced "off" time, increased "on" time without increasing troublesome dyskinesias, and improved quality of life in three RCTs (one double-blind). Open-label follow-ups confirm these findings. The data evaluating long-term efficacy and safety are still limited.
CONCLUSIONS
The quality of evidence that LCIG is effective in reducing fluctuating motor symptoms and improving quality of life is moderate. Quality of evidence for reduction of non-motor symptoms is very low. Safety issues mainly relate to the intestinal infusion system. LCIG might be a useful treatment option in PD patients with severe motor fluctuations.
Topics: Antiparkinson Agents; Carbidopa; Drug Combinations; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 27138916
DOI: 10.1007/s40263-016-0336-5 -
BJOG : An International Journal of... Sep 2014Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been... (Review)
Review
BACKGROUND
Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings.
OBJECTIVES
To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension.
SEARCH STRATEGY
A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed.
SELECTION CRITERIA
Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg.
DATA COLLECTION AND ANALYSIS
Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects.
MAIN RESULTS
We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98-1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95-1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ~ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33).
CONCLUSIONS
Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum.
Topics: Administration, Oral; Antihypertensive Agents; Female; Humans; Hydralazine; Hypertension, Pregnancy-Induced; Labetalol; Methyldopa; Nifedipine; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic; Treatment Outcome; Vasodilator Agents
PubMed: 24832366
DOI: 10.1111/1471-0528.12737 -
The Cochrane Database of Systematic... Feb 2014Mild 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 the outcome.
OBJECTIVES
To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and reference lists of retrieved studies.
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-nine trials (4723 women) were included. Twenty-nine trials compared an antihypertensive drug with placebo/no antihypertensive drug (3350 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) (20 trials, 2558 women; risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; risk difference (RD) -0.10 (-0.13 to -0.07); number needed to treat to harm (NNTH) 10 (8 to 13)) but little evidence of a difference in the risk of pre-eclampsia (23 trials, 2851 women; RR 0.93; 95% CI 0.80 to 1.08). Similarly, there is no clear effect on the risk of the baby dying (27 trials, 3230 women; RR 0.71; 95% CI 0.49 to 1.02), preterm birth (15 trials, 2141 women; RR 0.96; 95% CI 0.85 to 1.10), or small-for-gestational-age babies (20 trials, 2586 women; RR 0.97; 95% CI 0.80 to 1.17). There were no clear differences in any other outcomes.Twenty-two trials (1723 women) compared one antihypertensive drug with another. Alternative drugs seem better than methyldopa for reducing the risk of severe hypertension (11 trials, 638 women; RR (random-effects) 0.54; 95% CI 0.30 to 0.95; RD -0.11 (-0.20 to -0.02); NNTH 7 (5 to 69)). There is also a reduction in the overall risk of developing proteinuria/pre-eclampsia when beta blockers and calcium channel blockers considered together are compared with methyldopa (11 trials, 997 women; RR 0.73; 95% CI 0.54 to 0.99). However, the effect on both severe hypertension and proteinuria is not seen in the individual drugs. 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: 24504933
DOI: 10.1002/14651858.CD002252.pub3 -
The Cochrane Database of Systematic... Apr 2013Postpartum 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., can... (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., can 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 medical therapy is better than placebo/no treatment; and (2) treat postpartum hypertension, by assessing whether (i) one 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 METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2013), 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
Nine trials are included.
PREVENTION
Four trials (358 women) compared furosemide, nifedipine capsules, or L-arginine with placebo/no therapy. For women with antenatal pre-eclampsia, postnatal furosemide is associated with a strong trend towards reduced use of antihypertensive therapy in hospital.
TREATMENT
For treatment of mild-moderate postpartum hypertension, three trials (189 women) compared timolol, oral hydralazine, or oral nifedipine with methyldopa. Use of additional antihypertensive therapy did not differ between groups (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.20 to 4.20; three trials), but the trials were not consistent in their effects. The drugs were well tolerated.For treatment of severe postpartum hypertension, two trials (120 women) compared intravenous hydralazine with either sublingual nifedipine or intravenous labetalol. There were no maternal deaths or hypotension. Use of additional antihypertensive therapy did not differ between groups (RR 0.58, 95% CI 0.04 to 9.07; two trials), but the trials were not consistent in their effects.
AUTHORS' CONCLUSIONS
For women with pre-eclampsia, postnatal furosemide may decrease the need for postnatal antihypertensive therapy in hospital, but more data are needed on substantive outcomes before this practice can be recommended. There are no reliable data to guide management of women who are hypertensive postpartum. Any antihypertensive agent used should be based on a clinician's familiarity with the drug. Future studies should include data on postpartum analgesics, severe maternal hypertension, breastfeeding, hospital length of stay, and maternal satisfaction with care.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Puerperal Disorders; Randomized Controlled Trials as Topic
PubMed: 23633317
DOI: 10.1002/14651858.CD004351.pub3 -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2013As many as 15% of women experience hypertension during pregnancy. Large proportions of them are receiving antihypertensive medications. This review investigated whether... (Review)
Review
As many as 15% of women experience hypertension during pregnancy. Large proportions of them are receiving antihypertensive medications. This review investigated whether hypertension itself, or the antihypertensive medications, adversely affect long term child neurocognitive development. The existing evidence suggests that methyldopa and labetalol probably do not adversely affect neurobehavioral development. Although an increasing body of evidence suggests adverse neurocognitive effects of the hypertension itself, none of the existing studies examined simultaneously the effects of both hypertension and the drugs used therapeutically. The confounding effects by indication must be addressed in future studies.
Topics: Animals; Antihypertensive Agents; Child; Child Development; Cognition; Female; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular
PubMed: 23542230
DOI: 10.1016/j.reprotox.2013.03.006 -
The Cochrane Database of Systematic... Feb 2012Diabetic kidney disease (DKD) is associated with increased morbidity and mortality, mostly relating to cardiovascular complications. The relevance of inflammation in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic kidney disease (DKD) is associated with increased morbidity and mortality, mostly relating to cardiovascular complications. The relevance of inflammation in the pathogenesis of DKD has been investigated in recent years, and it has been shown that inflammatory markers are higher in people with DKD compared with the wider population. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with favourable anti-inflammatory effects and immunoregulatory properties. The anti-inflammatory effects conferred by pentoxifylline may be beneficial in the management of DKD.
OBJECTIVES
To assess the benefits and harms of pentoxifylline for treating people with DKD.
SEARCH METHODS
We searched the Cochrane Renal Group's specialised register (January 2012), CENTRAL (Issue 12, 2011), MEDLINE, EMBASE and four Chinese biomedical literature databases (CBM-disc, 1979 to July 2009), Chinese Science and Technique Journals Database (VIP, until July 2009), China National Knowledge Infrastructure (CNKI, until July 2009) and WanFang database (until July 2009).
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs studying the benefits and harms of pentoxifylline for DKD.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome in sufficiently similar patients. Results of dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Mean differences (MD) were calculated to assess the effects of treatment where outcomes were expressed on continuous scales, and standardised mean differences (SMD) calculated where different scales were used. Data was pooled using the random effects model. Adverse effects were assessed using descriptive techniques and where possible, risk differences (RD) with 95% CI.
MAIN RESULTS
We identified 17 studies that included a total of 991 participants with DKD which met our inclusion criteria. Overall, the methodological quality of included studies was low: 4/17 reported the method of randomisation, 13/17 did not; no study described the method of random allocation; 4/17 studies were considered to be at high risk of bias and 13/17 were considered to have unclear risk for incomplete outcome data reporting; 9/17 studies were at low risk bias and in 8/17 the risk of bias was unclear for selective outcome reporting.Compared with placebo, pentoxifylline significantly reduced serum creatinine (SCr) (MD -0.10 mg/dL, 95% CI -0.17 to -0.03), albuminuria (SMD -2.28, 95% CI -3.85 to -0.70) and overt proteinuria (MD -428.58 µg/min, 95% CI -661.65 to -195.50), but there was no difference in creatinine clearance (CrCl) (MD -5.18 mL/min, 95% CI -15.55 to 5.19). When compared with routine treatment alone, pentoxifylline did not significantly reduce SCr (MD 0.00 mg/dL, 95% CI -0.06 to 0.07) or blood pressure (systolic (SBP): MD -0.28 mm Hg, 95% CI -2.20 to 1.63; diastolic (DBP): MD -0.15 mm Hg, 95% CI -1.44 to 1.14), but did significantly reduce albuminuria (SMD 0.62, 95% CI 0.18 to 1.07) and proteinuria (MD 0.46 g/24 h, 95% CI 0.17 to 0.74). There was no significant difference in SCr (MD 0.00 mg/dL, 95% CI -0.08 to 0.07), albuminuria (MD -8.79 µg/min, 95% CI -27.18 to 9.59), proteinuria (MD -0.01 g/24 h, 95% CI -0.03 to 0.01) or blood pressure (SBP: MD 1.46 mm Hg, 95% CI -0.57 to 3.50; DBP: MD 1.37 mm Hg, 95% CI -0.23 to 2.98) between pentoxifylline and the active comparator (captopril or clonidine/methyldopa) for patients with type 1 and type 2 DKD. CrCl was significantly increased when pentoxifylline was compared to clonidine/methyldopa (MD 10.90 mL/min, 95% CI -1.40 to 20.40) but not with captopril (MD 3.26 mL/min, 95% CI -1.05 to 7.59). No data were available on the incidence of end-stage kidney disease (ESKD), time to ESKD, quality of life, or all-cause mortality. The adverse events of pentoxifylline were mild; no serious adverse events were reported in any of the included studies.
AUTHORS' CONCLUSIONS
From the available evidence, pentoxifylline seems to offer some beneficial effects in renal function improvement and reduction in albuminuria and proteinuria, with no obvious serious adverse effects for patients with DKD. However, most studies were poorly reported, small, and methodologically flawed. Evidence to support the use of pentoxifylline for DKD was insufficient to develop recommendations for its use in this patient population. Rigorously designed, randomised, multicentre, large scale studies of pentoxifylline for DKD are needed to further assess its therapeutic effects.
Topics: Albuminuria; Anti-Inflammatory Agents, Non-Steroidal; Diabetic Nephropathies; Humans; Pentoxifylline; Proteinuria; Randomized Controlled Trials as Topic
PubMed: 22336824
DOI: 10.1002/14651858.CD006800.pub2 -
The Cochrane Database of Systematic... Jul 2011The question of the target blood pressure in pregnant women with mild-moderate hypertension continues to be an area of debate. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The question of the target blood pressure in pregnant women with mild-moderate hypertension continues to be an area of debate.
OBJECTIVES
To compare tight versus very tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension for improving outcomes
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), CENTRAL (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to March 2011), and the metaRegister of Controlled Trials (31 March 2011). We handsearched citation lists of relevant publications, review articles, and included studies.
SELECTION CRITERIA
Randomized controlled trials of tight versus very tight control in pregnant women with mild or moderate pre-existing or non-proteinuric gestational hypertension.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We expressed results as risk ratio (RR) or mean differences, together with their 95% confidence intervals (CI).
MAIN RESULTS
We included two studies (256 participants) with mild-moderate pre-existing or non-proteinuric gestational hypertension. There was no evidence of a difference between tight and very tight control groups regarding severe pre-eclampsia (risk ratio (RR) 1.28, 95% CI 0.97 to 1.70; two trials, 256 participants). More women in the tight group were hospitalized during their pregnancy (RR 2.53, 95% CI 1.14 to 5.63; one trial, 125 participants). There was no evidence of a difference in other outcome measures including fetal distress, IUGR, neonatal admission to a NICU, perinatal deaths, induction of labor and cesarean delivery between the tight and the very tight control groups. Gestational age at delivery had a non-significant mean difference (MD) of -0.15 weeks between the tight and very tight control groups (MD -0.15, 95% CI -1.52 to 1.21, random-effects, T² = 0.75, I² = 77%; two trials, 256 participants). The MD in birthweight between the tight and the very tight control group was not significant (MD -100.00 grams, 95% CI -363.69 to 163.69; one trial, 125 participants).
AUTHORS' CONCLUSIONS
For pregnant women with non-severe pre-existing or non-proteinuric gestational hypertension, there is insufficient evidence to determine how tight control of hypertension should be achieved to improve maternal and fetal-neonatal outcomes.
Topics: Antihypertensive Agents; Female; Hospitalization; Humans; Hypertension, Pregnancy-Induced; Methyldopa; Outcome Assessment, Health Care; Perinatal Mortality; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic
PubMed: 21735406
DOI: 10.1002/14651858.CD006907.pub2 -
The Cochrane Database of Systematic... Oct 2009Hypertension is associated with an increased risk of stroke, myocardial infarction and congestive heart failure. Methyldopa is a centrally acting antihypertensive agent,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is associated with an increased risk of stroke, myocardial infarction and congestive heart failure. Methyldopa is a centrally acting antihypertensive agent, which was commonly used in the 1970's and 80's for blood pressure control. Its use at present has largely been replaced by antihypertensive drug classes with less side effects, but it is still used in developing countries due to its low cost. A review of its relative effectiveness compared to placebo on surrogate and clinical outcomes is justified.
OBJECTIVES
To quantify the effect of methyldopa compared to placebo in randomized controlled trials (RCTs) on all cause mortality, cardiovascular mortality, serious adverse events, myocardial infarctions, strokes, withdrawals due to adverse effects and blood pressure in patients with primary hypertension.
SEARCH STRATEGY
We searched the following databases: Cochrane Central Register of Controlled Trials (1960-June 2009), MEDLINE (2005-June 2009), and EMBASE (2007-June 2009). Bibliographic citations from retrieved studies were also reviewed. No language restrictions were applied.
SELECTION CRITERIA
We selected RCTs studying patients with primary hypertension. We excluded studies of patients with secondary hypertension or gestational hypertension.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5. Data for blood pressure were combined using the generic inverse variance method.
MAIN RESULTS
Twelve trials (N=595) met the inclusion criteria for this review. None of these studies evaluated the effects of methyldopa compared to placebo on mortality and morbidity outcomes. Data for withdrawals due to adverse effects were not reported in a way that permitted meaningful meta-analysis. Data from six of the twelve trials (N=231) were combined to evaluate the blood pressure lowering effects of methyldopa compared to placebo. This meta-analysis shows that methyldopa at doses ranging from 500-2250 mg daily lowers systolic and diastolic blood pressure by a mean of 13 (95%CI 6-20) / 8 (95% CI 4-13) mmHg. Overall, the risk of bias was considered moderate.
AUTHORS' CONCLUSIONS
Methyldopa lowers blood pressure to varying degrees compared to placebo for patients with primary hypertension. Its effect on clinical outcomes, however, remains uncertain.
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Methyldopa; Randomized Controlled Trials as Topic
PubMed: 19821316
DOI: 10.1002/14651858.CD003893.pub3