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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 -
Advances in Therapy Jun 2021Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in... (Review)
Review
INTRODUCTION
Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson's disease (PD) when other treatments have not given satisfactory results. Reduction in 'off'-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on 'off'-time.
METHODS
Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and 'off'-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: 'off'-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes.
RESULTS
Twenty-seven studies were included in this review. The improvement in 'off'-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. 'Off'-time was reduced from baseline to end of follow-up by 38-84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of 'off'-time demonstrated mean relative reductions of 47-82% at 3-6 months and up to 83% reduction at 3-5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device.
CONCLUSION
In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing 'off'-time.
INFOGRAPHIC
Video Abstract.
Topics: Activities of Daily Living; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Observational Studies as Topic; Parkinson Disease; Quality of Life; Retrospective Studies
PubMed: 34018146
DOI: 10.1007/s12325-021-01747-1 -
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 -
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 -
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 -
Minerva Medica Dec 2019We have performed a systematic literature review to evaluate the current evidence of the pharmacokinetic (PK), efficacy and safety profile of oral melevodopa/carbidopa...
INTRODUCTION
We have performed a systematic literature review to evaluate the current evidence of the pharmacokinetic (PK), efficacy and safety profile of oral melevodopa/carbidopa fixed combination in the management of motor fluctuations in patients with Parkinson disease (PD).
EVIDENCE ACQUISITION
Search has been started from common libraries and was then restricted to articles of studies in humans with melevodopa/carbidopa as fixed combination. Abstracts of international congresses have been also explored. The search has led to the identification of one PK study and five efficacy/safety studies that included more 743 PD patients overall, 488 of which treated with melevodopa/carbidopa effervescent tablets (Sirio®, Chiesi Farmaceutici S.p.A., Parma, Italy).
EVIDENCE SYNTHESIS
Melevodopa/carbidopa has a more rapid absorption, less apparent drug accumulation, less inter-patient variability and more effective LD delivery after the early morning and early afternoon dose compared to standard LD. Although they differed in used dose regimens, duration of treatment and endpoints, the results of the efficacy/safety studies suggest that treatment with melevodopa/carbidopa may determine improvements in motor fluctuations compared to treatment with standard LD/CD formulations, with no increased risk of adverse effects or LD-induced dyskinesias.
CONCLUSIONS
Data from literature have shown that melevodopa/carbidopa in a highly soluble formulation as effervescent oral tablets is effective in improving control of motor complications in PD patients compared to conventional levodopa. Further research is needed to confirm this evidence in large controlled trials and to explore if melevodopa/carbidopa may have a potential role in the earlier phases of the disease or in special PD populations.
Topics: Antiparkinson Agents; Carbidopa; Drug Combinations; Humans; Levodopa; Parkinson Disease
PubMed: 31965781
DOI: 10.23736/S0026-4806.19.06330-4 -
Drug Design, Development and Therapy 2020Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD)...
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD) patients and effectively reduces poor mobility and dyskinesia.
METHODS
Electronic databases were searched up to January 1, 2018. The inclusion criteria for this review were as follows: LCIG vs oral medication in advanced PD patients.
RESULTS
Five trials, with a total of 198 patients, met all the inclusion criteria. The quality score of these studies ranged from 3 to 5. Two clinical trials showed that compared with oral medication, LCIG had a better treatment effect on on-time with troublesome dyskinesia (TSD) ( = 0.02) and on-time without TSD ( < 0.00001) in advanced PD patients. In addition, four of the 5 studies showed that the LCIG may have better efficacy than oral medication for improving the scores of the UPDRS, and two studies found that LCIG demonstrated better efficacy for improving the PDQ-39 scores. The video recording results indicated a potential decline in both dyskinesia and the "off" state in LCIG-treated patients. The incidence of adverse events was not significantly different between the LCIG and oral medication groups.
CONCLUSION
Compared with oral treatment, LCIG exerts its effectiveness, mostly by reducing the time of on-time with TSD, increasing the time of on-time without TSD and scores of UPDRS and PDQ-39. It is suggesting that LCIG was likely to be a new type of administration used in clinical applications. However, due to methodological flaws, these findings should be viewed with caution, and more RCTs are needed in the field to complement our findings.
Topics: Administration, Oral; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease
PubMed: 32161444
DOI: 10.2147/DDDT.S229621 -
Neurologia I Neurochirurgia Polska 2023Polyneuropathy (PNP) is a known complication of levodopa-carbidopa intestinal gel (LCIG) therapy of advanced Parkinson's Disease (PD). The overall prevalence of PNP in...
Polyneuropathy (PNP) is a known complication of levodopa-carbidopa intestinal gel (LCIG) therapy of advanced Parkinson's Disease (PD). The overall prevalence of PNP in PD is estimated to be 42.1% (as shown in a review by Romagnolo et al. 2018), and the most common type is chronic axonal polyneuropathy. There is a group of acute/subacute onset demyelinating polyneuropathies, which is far less common, although it seems to be an important factor leading to the rapid discontinuation of LCIG treatment. In this systematic review, we present data on demyelinating polyneuropathy with acute/subacute onset; we identified nine papers including prospective assessments and case reports, with detailed information on 15 patients. In all patients, despite treatment with corticosteroids, intravenous immunoglobulins (IVIG) or plasma exchange (PE), the LCIG therapy was terminated. We also present a case of subacute demyelinating polyneuropathy with effective treatment and continuation of LCIG therapy.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Antiparkinson Agents; Prospective Studies; Polyneuropathies; Drug Combinations; Gels
PubMed: 36628506
DOI: 10.5603/PJNNS.a2023.0001