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COMPARISON BETWEN LABETALOL AND METHYLDOPA IN THE TREATEMNT OF PRE-ECLAMPSIA.

Byline: Nosheen Akhtar, Zartaj Hayat and Fatima Nazim

Abstract

Objective: To compare the effects of labetalol and methyldopa on mean diastolic blood pressure in patients with pre-eclampsia.

Methodology: A randomized controlled trial was done in the Department of Gynecology and Obstetrics, Fauji Foundation Hospital, Rawalpindi, from 20th August 2013 to 31st march 2014. A total of 300 women with singleton pregnancy (20-37 weeks) diagnosed with pre-eclampsia were randomly assigned to labetalol (n=150) and methyldopa (n=150). The outcome was determined as reduction in mean diastolic blood pressure 48 hours after intervention with labetalol and methyldopa.

Results: In labetalol group, the mean age of patients was 32.57 +-4.3 years, while in methyldopa group it was 33.09 +-4.2 years (p value =0.290). In labetalol group, mean diastolic blood pressure was reduced from 100.9 +-6.8 mmHg to 93.5 +-7.2 mmHg (p value =0.000). In methyldopa group, it was reduced from 99.7 +-9.9 mmHg to 93.4 +-7.8 mmHg (p value =0.000). There was no statistical difference in the mean diastolic blood pressure between the two groups after intervention (p value = 0.909).

Conclusion: Both labetalol and methyldopa reduced diastolic blood pressure significantly after 48 hours of intervention. The efficacy of both drugs was equal in reducing diastolic blood pressure and the difference was statistically not significant.

Key Words: Pre-eclampsia, Diastolic blood pressure, Labetalol, Methyldopa

INTRODUCTION

Hypertension in pregnancy is a significant management problem. Approximately 12-22% of all pregnancies are complicated by hypertensive disorders, 70% of those are affected by gestational hypertension and 30% by essential hypertension. Prevalence of pre-eclampsia is 19% in Pakistan1. Pre-eclampsia is a multisystem disease, causing impaired intervillous blood flow leading to a state of oxidative stress that activates vascular endothelial cells, leading to wide spread effects of pre-eclampsia2. Pre-eclampsia can lead to maternal and fetal complications. Maternal complications include placental abruption, target organ damage (eclampsia, HELLP syndrome, renal failure and disseminated intravascular coagulation) and are associated with a very high maternal mortality (15%). Fetal complications include growth restriction and prematurity mainly related to worsening maternal condition3.

Management of pre-eclampsia is to control blood pressure as well as monitor fetal and maternal condition. Immediate delivery is done if patient develops signs and symptoms of fulminant pre-eclampsia such as headache, epigastric pain or platelet count 50 IU /liter4.

Commonly used anti-hypertensive drugs are methyldopa, labetalol, nifedipine and hydralazine5,6. In the absence of hypertensive crises methyldopa and oral labetalol are preferred drugs. Both these drugs are easily available in our country. Both drugs have been found effective in reducing blood pressure without any adverse effect on perinatal outcome7,8. Labetalol, is a combined alpha ([alpha]1) and beta ([beta]1/[beta]2) adrenergic receptor blocker with arteriolar vasodilator effect, thus reducing peripheral resistance and decreases blood pressure. Common side effects are dizziness, drowsiness and headache. Methyldopa is an agonist of pre-synaptic central nervous system [alpha]2 adrenergic receptors resulting in inhibition of sympathetic nervous system thus reducing blood pressure and it does not affect fetal hemodynamics7. Side effects of methyldopa are decreased mental alertness, fatigue or depression.

Although both drugs are known to be effective in reducing blood pressure which drug is better than the other is yet not known. Moreover, the efficacy of both drugs is studied well in the west but the result of these studies are controversial. The reviews published in Cochrane libraries could not conclude their findings on one drug and suggested more studies on anti-hypertensive treatment of the pre-eclampsia. Moreover thorough literature search showed that no study regarding the efficacy of these drugs is conducted in Pakistan. We therefore conducted this study to compare the efficacy of two drugs because further research was needed due to variable results in blood pressure (BP) control by these drugs in different studies. We wanted to explore drug with better control of blood pressure so that it may constitute the basis of some novel recommendations in our setup.

METHODOLOGY

This was a single blind randomized control trial conducted in Fauji foundation Hospital, Rawalpindi from 20th August 2013 to 31st March 2014. Approval of study was taken from hospital ethical and research committee. All women at gestational age 20-37 weeks with singleton pregnancy diagnosed with pre-eclampsia were included in the study. Among those women presenting with pre-eclampsia who fulfill the inclusion criteria were offered to participate in the study. A written informed consent was also obtained from women after explaining in details the purpose and benefits of the study.

All the cases with essential hypertension, already taking anti-hypertensive medication, depression, congestive heart failure, heart block or bronchial asthma, multiple pregnancy, fulminant pre-eclampsia (platelet count 50 IU/liter, persistent symptoms like headache, epigastric pain, visual disturbance) and those with eclampsia (generalized tonic colonic convulsions usually in association with pre-eclampsia) were excluded from this study.

A total of 300 women (150 patients in each group) were included in the study. The sample was calculated by WHO sample size calculator with level of significance =5%, power of test =80%, pooled standard deviation =1.03, test value of the population mean =85.489 and anticipated population mean =89.699. After detailed history and examination all women who were included in the trial were randomly allocated into two groups by lottery method. Women in group A were subjected to labetalol while women in group B were subjected to methyldopa. The standard dose was started as described in Bristish National Formulary (BNF) after measuring baseline blood pressure using standard mercury sphygmomanometer (dose was decided according to diastolic blood pressure detailed below in Table 1).

All the women were kept under observation and blood pressure was recorded after every four hours as per NICE guidelines for the management of pre-eclampsia. Measurement of blood pressure 48 hours post-treatment was used to calculate the mean diastolic blood pressure and was recorded on proforma. Strict exclusion criteria were followed to control confounders and bias in the study results. All the observations and blood pressure recordings were done by the researcher. The statistical software used for data analysis was SPSS version 16.0. For numerical variables like age, gravidity, baseline diastolic BP, follow up diastolic BP, mean +- SD were calculated. Student-t test was used to compare the mean diastolic BP in two groups while keeping p value of <0.05 as significant. Mean diastolic BP in both groups was stratified among age and parity to see the effect modifications. All results were presented as tables.

RESULTS

The mean age of the patients of the whole study population (n=300), was 32.83 +-4.3 years. The mean age of patients in labetalol group was 32.57 +-4.3 years while in methyldopa group it was 33.09 +-4.2 years. We compared the demographic variables of the patients between group A and B including age and gravidity. No statistically significant difference was found between the two groups regarding these variables (Table 2).

The mean baseline diastolic blood pressure in labetalol group was 100.93 +-6.7 mmHg and it reduced to 93.47 +-7.23 48 hours post-treatment showing statistically significant difference, (p =0.000). In methyldopa group, mean baseline diastolic blood pressure was 99.77 +-9.97 mmHg and statistically significant reduction was seen 48 hours post-treatment with follow up mean diastolic BP of 93.37 +-7.89 (p value =0.000). We compared the mean baseline and follow up diastolic blood pressure between both treatment groups. The difference was statistically insignificant (Table 3).

We also stratified the follow up diastolic BP in both groups with regards to different age categories (Table 4) and gravidity categories (Table 5).

DISCUSSION

The mean age of patients was comparable in both groups A and B (32.6 and 33.1 years) respectively. Most of the patients (70%) were between 26 and 35 years in this study in both groups. A previous study by Guzick et al10 reported that age was linearly related with pregnancy induced hypertension. However, in contrast Venkateswaramurty and colleagues11 found out that younger age group (18-25 years) was involved in majority (59%). Similarly, Verma et al12 reported that majority of their cases were between 19 to 24 years in both labetalol group (51.1%) and methyldopa group (64.4%).

In the current study, majority of subjects were found to be multiparous in both groups i.e. 136 (95.5%) in group A and 143 (95.2%) in group B. Similarly, most of the cases were multigravida in both groups A and B (74.7% and 75.5%) respectively. In contrast Verma and colleagues12 found out that primigravida and nulliparous women were in majority (60%) with hypertension during pregnancy12. These findings were also quoted in other studies by Redman et al13 and Plouin et al14. There is a need to study in depth the difference regarding parity and age of presentation of pre-eclampsia as in our study the mean age of whole study group was slightly older age which was contrary to other studies where mean age of presentation was younger age group. Similarly, in our study, majority of women with pre-eclampsia were multigravidas which is in contrast to other studies where nulliparous ladies were having pre-eclampsia predominantly.

This difference may be attributed to the fact that this hospital provides services to families of retired army personnel so majority of women are of higher age group and multiparaous.

Regarding the efficacy of study interventions (labetalol and methyldopa) in controlling diastolic blood pressure it was proven that both labetalol and methyldopa significantly reduced diastolic BP. We found out that labetalol decreased diastolic to 93.5 +-7.2 mmHg and methyldopa succeeded in bringing down diastolic BP to 93.4 +-7.8 mmHg after 48 hours of intervention. There was no difference in the mean decrease in diastolic blood pressure between the two groups after intervention (p value =0.91). Similar findings were quoted by Verma et al12. In their study, mean diastolic BP after treatment with labetalol was 78.44 +-8.24 mmHg and with methyldopa it was 77.55 +-5.28 mmHg eight days after treatment and the difference was statistically not significant between the two treatment groups12. Similarly in another study mean diastolic blood pressure after treatment was 81 +-5 mmHg in both groups showing no difference in two drugs8.

Venkateswaramurty and colleagues11 reported that methyldopa decreased diastolic BP from 102.3 +-13.3 mmHg at baseline to 85.9 +-7.6 mmHg after treatment.

The Cochrane review of 35 randomized controlled trials including 3573 women found that anti-hypertensive drugs are effective in lowering blood pressure; however there is no evidence to show which drug is the most effective15. Patel et al16 reported that treatment with methyldopa was associated with reduction in diastolic blood pressure by 30 mmHg at 72 hours post-intervention and labetalol was associated with reduction of 36 mmHg in diastolic BP after similar time with statistically significant difference. In another study conducted by Barathi17, mean diastolic blood pressure after treatment with labetalol was 85.48 +-0.869 and after methyldopa it was 89.69 +-1.186 and the reduction in labetalol group was significant.

In a study by Subhedar et al18 the reduction in mean arterial pressure was compared between labetalol and methyldopa and it was found that both drugs significantly reduced diastolic blood pressure from the baseline value. The reduction after treatment with labetalol was more than with methyldopa (p =.0008) which is contrary to our study.

In the study conducted by El Qarmalawi et al19, significant fall in BP was seen in 81.4% in labetalol group as compared to 68.5% in the methyldopa group showing labetalol to be better than methyldopa. In another study, the diastolic BP in labetalol group was reduced to 123 +-9mmHg/79 +-7 mmHg from baseline BP of 150 +-9mmHg/100 +-8mmHg (p value <0.05) while in methyldopa group it was reduced from 148 +-8 mmHg/102 +-9mmHg to 125 +-10mmHg/82 +-6 mmHg on 7th day after treatment (p 110 mmHg###500mg stat and then eight hourly###200 mg stat and then BD

Table 2: Comparison of mean age and gravidity between both groups (n =150 each)

###Labetalol Group###Methyldopa Group

###Variables###P value

###(n=150)###(n=150)

Age (Mean +-SD)###32.6 +- 4.3###33.1 +- 4.1###0.31

###Primi-gravida###14 (9.5%)###07 (4.8%)###0.82

Gravidity

###Multi-gravida###136 (95.5%)###143 (95.2%)###0.90

Table 3: Comparison of baseline diastolic BP and follow up diastolic BP between both groups (n =150 each)

###Treatment###Std.###Std. Error

Diastolic BP###n###Mean###P value

###Group###Deviation###Mean

###Labetalol

###150###100.93###6.790###.554

Baseline###Group

###0.237

Diastolic BP###Methyldopa

###150###99.77###9.972###.814

###Group

###Labetalol

###150###93.47###7.234###.591

Follow up###Group

###0.909

Diastolic BP###Methyldopa

###150###93.37###7.890###.644

###Group

Table 4: Age groups stratification of mean follow up diastolic blood pressure between both treatment groups

###Treatment###Std.###Std. Error

Age stratification###n###Mean###P value

###Group###Deviation###Mean

###Labetalol

Follow up Diastolic BP###6###90.00###5.477###2.236

###Group

Age Groups= Up to 25###0.203

years###Methyldopa

###4###95.00###5.774###2.887

###Group

###Labetalol

Follow up Diastolic BP###41###90.37###7.105###1.110

###Group

Age Groups= 25.01 to###0.650

30 years###Methyldopa

###45###91.11###7.969###1.188

###Group

###Labetalol

Follow up Diastolic BP###63###93.81###6.822###.860

###Group

Age Groups= 30.01 to###0.393

35 years###Methyldopa

###58###95.00###8.429###1.107

###Group

###Labetalol

Follow up Diastolic BP###40###96.63###6.923###1.095

###Group

Age Groups= 35.01 and###0.034

above###Methyldopa

###43###93.37###6.789###1.035

###Group

Table 5: Gravidity wise stratification of mean follow up diastolic blood pressure between both treatment groups

###Treatment###Std. Devia-###Std. Error

###Gravidity###n###Mean###P value

###Group###tion###Mean

###Labetalol

###14###91.43###9.693###2.591

Follow up Diastolic BP###Group

###0.398

Primigravida###Methyldopa

###7###87.86###6.986###2.641

###Group

###Labetalol

###136###93.68###6.945###.596

Follow up Diastolic BP###Group

###0.964

Multigravida###Methyldopa

###143###93.64###7.854###.657

###Group

LIMITATIONS

Though sample size was appropriate but data regarding side effects of labetalol or methyldopa was not collected, so tolerability of treatment was not studied.

Similarly, we could not collect data regarding short term or long term effects of interventions on maternal and perinatal outcome. Many queries regarding hypertension in pregnancy and pre-eclampsia e.g. effect on protienuria and subsequent progression to severe pre-eclampsia remained unanswered. For better understanding of these queries we need large collaborative multi-centered studies.

CONCLUSION

Both labetalol and methyldopa reduced diastolic blood pressure significantly after 48 hours of intervention. The efficacy of both drugs was equal in reducing diastolic blood pressure and the difference was statistically not significant.

REFERENCES

1. Rathore R, Butt NF, Iqbal A, Khan MZU. Complications and outcome of patients of pre-eclampsia and eclampsia presenting to medical wards of Mayo hospital Lahore. Annals 2010; 16:17-9.

2. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33:130-7.

3. Begum F, Parveen T. Antihypertensives in hypertensive disorders of pregnancy. Bangladesh J Obstet Gynaecol 2008; 23:65-72.

4. Dekker G. Hypertension. In: James D, Steer PJ, Weiner CP, Gonik B, editors. High Risk pregnancy management options. London: Saunders; 2010:599-626.

5. Bharathi KN, Prasad KVSRG. A comparison of nifedipine with Methyldopa for control of blood pressure in mild to moderate pregnancy induced hypertension. J Clin Diagn Res 2010; 4:2406-9.

6. Magee LA, Abalos E, von Dadelszen P, Sibai B, Easterling T, Walkinshaw S. How to manage hypertension in pregnancy effectively. Br J Clin Pharm 2011; 72:394-401.

7. Podymow T, August P. Update on the use of antihypertensive drugs in pregnancy. Hypertension 2008; 51:960-9.

8. Molvi SN, Mir S, Rana VS, Jabeen F, Malik AR. Role of antihypertensive therapy in mild to moderate pregnancy-induced hypertension: a prospective randomized study comparing labetalol with alpha methyldopa. Arch Gynecol Obstet 2012; 285:1553-62.

9. Bharathi KN, Prasad KVSRG, Jagannath P, Naik BC. Comparison of antihypertensive efficacy of labetolol, nifedipine and methyl dopa in Pregnancy induced hypertension. Pharmacologyonline 2009; 3:670-8.

10. Patel NK, Gadhavi M, Gorasia D, Pandya MR. Comparative evaluation of antihypertensive drugs in the management of pregnancy-induced hypertension. Int J Basic Clin Pharmacol 2012; 1:174-7.

11. Verma R, Lahon K, Tonpay SD, Kale VJ, Jain DK. A comparative randomised controlled parallel group study of efficacy and tolerability of labetalol versus methyldopa in the treatment of new onset hypertension during pregnancy. Int J Life Sci Pharma Res 2012; 2:23-31.

12. Ekele BA. Use of magnesium sulfate to manage pre-eclampsia and eclampsia in Nigeria: overcoming the odds. Ann Afr Med 2009; 8:73-5.

13. Guzek DS, Klein VR, Tyson JE, Lasky RE, Gant NF, rosenfeld CR. Risk factors for the occurrence of pregnancy induced hypertension. J Clin Exper Hyperten Preg 2009; 6:281-97.

14. Venkateswaramurthy N, John C, Perumal P. Study on anti-hypertensive in pre-eclampsia. Asian J Pharm Clin Res 2012; 5:126-8.

15. Redman CWG, Gallery ED, Mitchell MD. Fall in BP in response to volume expansion in pregnancy associated hypertension: why does it occur? Br Med J 1984; 2:177-82.

16. Plouin PF, Breart G, Maillard F, Papiernik E, Relier JP. Comparison of antihypertensive efficacy and perinatal safety of labetalol and methyldopy in the treatment of hypertension in pregnancy: A randomized controlled trial. Br J Obstet Gynecol 1988; 95:868-76.

17. Duley L, Henderson-Smart DJ, Meher S. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Sys Rev 2013; 7:CD001449.

18. Subhedar V, Inamdar S, Hariharan C, Subhedar S. Comparison of efficacy of labetalol and methyldopa in patients with pregnancy induced hypertension. Int J Reprod Contracept Obstet Gynecol 2013; 2:27-34.

19. El-Qarmalawi AM, Morsy AH, Al-Fadly A, Obeid A, Hashem M. Labetalol vs. methyldopa in the treatment of pregnancy-induced hypertension. Int J Gynaecol Obstet 1995; 49:125-30.

20. Qasim A, Siddiqui MH, Salam JU, Nusrat U. Labetalol versus methyldopa: efficacy in pregnancy induced hypertension. Gomal J Med Sci 2014; 12:233-6.

21. Sushrut D, Girija. Labetalol-An emerging first line drug for pregnancy induced hypertension. Indian J Clin Prac 2013; 23:640-1.

22. Pickles CJ, Symonds EM, Pipken BF. The fetal outcome in a randomized double-blind controlled trial of labetalol versus placebo in pregnancy induced hypertension. Br J Obstet Gynecol 1989; 96:38-43.
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Publication:Journal of Postgraduate Medical Institute
Article Type:Report
Geographic Code:9PAKI
Date:Mar 31, 2018
Words:3371
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