Antihypertensive drug therapy for mild-to-moderate hypertension during pregnancy

The risk of developing severe hypertension was halved with the use of antihypertensive drugs. However, antihypertensive drugs were not associated with any change in the risk of pre-eclampsia, fetal-neonatal death, preterm birth, or having a small-for-gestational-age baby.

RHL Commentary by Lubano K, Qureshi Z

1. EVIDENCE SUMMARY

This review (1) evaluates the effects of using antihypertensive drug therapy for mild-to-moderate hypertension in pregnancy, which is a common condition. Antihypertensive drugs are often used in the belief that lowering mild-to-moderate blood pressure will prevent progression to more severe disease, and thereby improve substantive outcomes.

The review included 46 trials involving 4282 women. Overall, twenty-eight trials (involving 3200 women) compared an antihypertensive drug with a placebo or no antihypertensive drug. Mild-to-moderate hypertension was defined only in some trials. As noted by the review authors, in the included trials there was a lack of standardization for severity and type of hypertension (with variation in diastolic blood pressure, use of fifth Korotkoff sound), gestational age at entry into the trial, and definition of 'small for gestational age'.

Outcomes

Severe hypertension: There was a halving in the risk of developing severe hypertension associated with the use of antihypertensive drugs [19 trials, 2409 women; relative risk (RR) 0.50; 95% confidence interval (CI) 0.41 to 0.61]. As per these findings, 8 –13 women would need to be treated (NNT) to prevent one episode of severe hypertension.

Pre-eclampsia: There was no difference in the risk of pre-eclampsia associated with the use of antihypertensive drugs in the 22 trials (2702 women) reporting this outcome (RR 0.97; 95% CI 0.83 to 1.13)

Other outcomes: There was no difference associated with the use of antihypertensive drugs in the risk of fetal-neonatal death (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), small-for-gestational-age babies (19 trials, 2437 women; RR 1.04; 95 % CI 0.84 to 1.27) or in any other outcome.

Nineteen trials (1282 women) compared one antihypertensive drug with another. Beta blockers were more effective than methyldopa for reducing the risk of severe hypertension (10 trials, 539 women, RR 0.75 (95 % CI 0.59 to 0.94); NNT was 12 (95 % CI 6 to 275). There was no clear difference between any of the alternative drugs for the risk of developing proteinuria/pre-eclampsia. Other outcomes were only reported by a small proportion of studies, and there were no clear differences.

The review authors used appropriate methods for: search and retrieval of trials; extraction, analysis and presentation of data. However, it is worth noting that individual studies included in the review had few women, which may make it impossible to reach meaningful conclusions about the effectiveness of antihypertensive drugs in preventing outcomes such as pre-eclampsia. This aspect has been clearly noted by the reviewers. (1)

2. RELEVANCE TO UNDER-RESOURCED SETTINGS

2.1. Magnitude of the problem

The classification of hypertensive disorders of pregnancy has been characterized as "nonuniform, confusing, and steeped in tradition" (2). The lack of consensus with regard to diagnostic protocols, such as correct patient positioning and the particular Korotkoff phase used to document the blood pressure reading, is reflected in the studies as noted by the reviewers (1).This therefore presents a problem in estimation of the magnitude of the condition.

Studies conducted in Kenya on hypertensive disorders of pregnancy report prevalence rates HDP ranging from 1.5% to 9% (3,4). There is, however, a paucity of data regarding the extent of maternal/perinatal morbidity and mortality resulting from hypertensive disorders of pregnancy.

2.2. Applicability of the results

The results of this review are applicable to under-resourced settings in general. We believe that regardless of the setting, trials are likely to give similar results. There are no pathophysiological differences in the illness in different populations that may lead to a different response in different settings. Since most antihypertensive drugs are available in different settings and can be taken orally at home, implementation of this intervention is likely to be easy in clinical practice. However, concerns about treatment compliance, continuous availability of drugs and regular follow-up of individual women need to be addressed based on specific contexts. Because of the multi-etiological basis and the unknown cause of hypertension in each individual, the treatment response may vary form woman to woman, necessitating close individualized care plan.

In some resource-constrained settings, dietary deficiencies, such as those of calcium, magnesium, iron and other micronutrients, may alter potential benefits of the treatment. There may be differences in baseline risk that may affect the number needed to treat to achieve a positive outcome. However, there is lack of evidence to support or refute this assumption.

2.3. Implementation of the intervention

It is not clear whether antihypertensive drug therapy for mild-to-moderate hypertension is indeed worthwhile. The only benefit noted in the review was progression to severe hypertension. If this warrants treatment, then the treatment options should be discussed between the woman and her physician. Implementation of the intervention itself involves easily available tools (for measurement of blood pressure) and orally administered drugs (antihypertensives), which should be feasible in most resource- constrained settings.

For this intervention to be implemented it will be necessary to assess current practices regarding the treatment of women with mild-to-moderate hypertension. There will also be a need to develop standardized clinical guidelines and job aids to update staff knowledge and skills. A clear statement of service delivery objectives for pregnant women should be made. Service restructuring, where necessary to reflect evidence-based approaches and referral networks for client care, should be considered. Address the logistics of supplies, equipment and drugs within facilities as it is appropriate. An effective monitoring and evaluation with objective indicators of effectiveness should be put in place as well. Specific clearly defined messages to raise awareness and importance of compliance with treatment for the individual women is necessary on a structured continuous basis.

In most settings treatment of mild-to-moderate hypertension is a common practice. The explanation of the expected benefit of reduction in risk of severe hypertension and lack of evidence for other benefits is the critical new aspect. The financial and educational challenges are minimal; however these aspects need to be considered within the local context.

3. RESEARCH

Given that this review did not have sufficient data for the majority of outcomes (reduction in fetal-neonatal death, preterm births, and small-for-gestational-age babies) related to treatment of mild-to-moderate hypertension large multi-centre randomized controlled trials on the impact of blood pressure treatment on substantive health outcomes are needed.

The short- and long-term implications of halving of the risk of progression to severe hypertension in individual women needs to the assessed independently of the obstetric outcomes in the index pregnancy in the context of hypertensive progressive organ damage e.g. damage to the kidneys, central nervous system, cardiovascular system, and retinal-ocular changes.

There is also a need for research in all settings to understand the effects of antihypertensive drugs on different outcomes that may be subject to geographical, socioeconomic, demographic, and genetic variations. Subgroup analyses will definitely be necessary to assess specific outcomes for both the mother and fetus/neonate.

References

  • Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002252. DOI: 10.1002/14651858.CD002252.pub2.
  • American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Technical Bulletin No. 219, January 1996.
  • Mati JKG. Studies of pregnancy hypertension. MD Thesis. Nairobi, Kenya: University of Nairobi; 1975.
  • Kibaru J.G. Outcome of pregnancy in patients with hypertensive disease. M. Med thesis. Nairobi, Kenya: University of Nairobi; 1992.

This document should be cited as: Lubano K, Qureshi Z. Antihypertensive drug therapy for mild-to-moderate hypertension during pregnancy: RHL commentary (last revised: 8 October 2007). The WHO Reproductive Health Library; Geneva: World Health Organization.

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