Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Oral nifedipine is recommended along with labetalol and hydralazine for treatment of severe hypertension during pregnancy by most authorities. Although nifedipine is cheap and easily administered, the usage pattern among health care providers suggests a strong preference for labetalol despite lack of evidence for the same. OBJECTIVES: To determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. SEARCH STRATEGY: We systematically searched for articles comparing oral nifedipine with intravenous labetalol for the treatment of severe hypertension during pregnancy in any language, over Medline, Cochrane Central Register of Clinical Trials and Google Scholar from inception till February 2014. SELECTION CRITERIA: We included all RCTs that compared intravenous labetalol with oral nifedipine for treatment of severe hypertension during pregnancy, addressing relevant efficacy and safety outcomes. DATA COLLECTION AND ANALYSIS: Eligible studies were reviewed, and data were extracted onto a standard form. We used Cochrane review manager software for quantitative analysis. Data were analysed using a fixed effect model. MAIN RESULTS: The pooled analysis of seven trials (four from developing countries) consisting of 363 woman-infant pairs showed that oral nifedipine was associated with less risk of persistent hypertension (RR 0.42, 95% CI 0.18-0.96) and reported maternal side effects (RR 0.57, 95% CI 0.35-0.94). However, on sensitivity analysis the outcome 'persistent hypertension' was no longer significant. Other outcomes did not reach statistical significance. CONCLUSION: Oral nifedipine is as efficacious and safe as intravenous labetalol and may have an edge in low resource settings. TWEETABLE ABSTRACT: Although studies to date are few in number and small, nifedipine shows promise for severe hypertension in pregnancy.

Intravenous labetalol compared with intravenous nicardipine in the management of hypertension in critically ill patients.

BACKGROUND: Critically ill patients with acute hypertension often require titratable rapid blood pressure (BP) reductions using parenteral administration of drugs. There are few comparative studies available to make informed drug product selection decisions. The purpose of this study was to evaluate the short-term clinical outcomes and costs of intravenous labetalol or intravenous nicardipine in the management of hypertension in critically ill patients. METHODS: This study was a retrospective analysis of consecutive patients receiving intravenous labetalol or intravenous nicardipine in the intensive care unit with acute elevations in either systolic (>160 mm Hg) or diastolic (>90 mm Hg) BP. Patient demographics, clinical characteristics, and short-term clinical outcomes were abstracted from the medical record. Hospital costs were calculated from hospital billing forms. RESULTS: A total of 189 patients receiving labetalol and 193 patients receiving nicardipine were included in the analysis. The average hourly dose was 37.3 ± 9.4 mg/h for labetalol compared with 7.1 ± 5.6 mg/h for nicardipine (P < .001). The average total dose of labetalol was 170.9 ± 32.6 mg compared with 112.2 ± 29.1 mg for nicardipine (P = .02). The duration of therapy was significantly shorter for labetalol (8.2 ± 6.2 hours) compared with nicardipine (15.8 ± 4.4 hours) (P = .03). There were a greater number of dose titrations with labetalol (6.1 ± 6.2) than with nicardipine (4.7 ± 4.9), but this difference was not significantly different (P = .29). There were no significant differences in the magnitude of the average change in systolic (P = .79) or diastolic (P = .82) BP between labetalol and nicardipine. The proportion of patients achieving their BP targets was significantly greater with nicardipine (83%) than with labetalol (67%) (P = .04). The proportion of patients requiring an alternate antihypertensive agent was significantly greater with labetalol than with nicardipine (31% vs 17%; P = .02). The total number of all-cause adverse events was significantly greater with labetalol (61%) than with nicardipine (48%) (P = .04). Labetalol was associated with a significantly greater incidence of hypotension and bradycardia or atrioventricular block compared with nicardipine. There was no significant difference in the frequency of other adverse events between these 2 drugs. The median hospital costs were not significantly different between patients receiving labetalol and patients receiving nicardipine. CONCLUSION: Our study suggests that nicardipine is a more effective antihypertensive agent than labetalol in an unselected group of patients who develop hypertension in the intensive care unit setting. A major advantage of nicardipine compared with labetalol was fewer adverse effects. Nicardipine was associated with less hypotension and bradycardia or atrioventricular block, resulting in a lower rate of drug discontinuation compared with labetalol.

Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial.

OBJECTIVES: To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. DESIGN: A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. SETTING: Five hospitals in England. PARTICIPANTS: Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). INTERVENTIONS: Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. MAIN OUTCOME MEASURES: The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. RESULTS: 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. CONCLUSIONS: Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.