1. Should developing countries continue to use older drugs for essential hypertension? A prescription survey in South Africa suggested that prescribers were generally non-compliant with the treatment guidelines for hypertension. At certain institutions methyldopa and hydrallazine are widely prescribed for essential uncomplicated hypertension. Neither of these drugs is recommended in the standard treatment guidelines for hypertension. However clinicians are able to prescribe these drugs since they are currently available on the essential drugs list for pregnancy induced hypertension. Methyldopa and reserpine continue to be recommended on treatment guidelines in developing countries. A search of the literature suggests that there are no reviews on the effectiveness of these drugs in essential hypertension. These drugs are more expensive than diuretics, beta blockers and ACEI. These drugs are associated with serious side effects. Results We were unable to locate any studies reporting on morbidity or mortality. Change in blood pressure was the only measure of efficacy reported. The methodological quality of studies was generally poor. Adverse events – the small sample size studies were not useful in identifying the adverse events associated with methyldopa, reserpine, hydrallazine. Studies that reported on withdrawals due to adverse events were summarised. Total number of studies included in the systematic review: Methyldopa – 85 studies Hydrallazine – 34 studies Reserpine – 19 studies Methods: Data Extraction and Analysis Data extraction Two independent reviewers used a data extraction form to record information about patient characteristics, BP change, morbidity or mortality, adverse effects, doses used, co-morbidity and length of study. Data analysis The studies were pooled to determine the: Relative risk of achieving blood pressure normalisation or response Mean change in systolic and diastolic blood pressure. Relative risk of experiencing an adverse event Relative risk for withdrawing due to an adverse event Pillay T, Hill SR. School of Medical Practice and Population Health,, Newcastle University, Australia. WHO Collaborating Centre for Training in Pharmacoeconomics and Rational Pharmacotherapy Conclusion There is no evidence about the effects of methyldopa, reserpine or hydrallazine on morbidity or mortality. The studies in this review report on blood pressure reduction as a measure of efficacy. The methodological quality of most studies of these reviews was poor. These drugs are associated with serious adverse events such as depression, haemolytic anaemia and lupus erythematosus. The overall risk-benefit profile of the older drugs is poor compared to diuretics, beta blockers and angiotensin converting enzyme inhibitors. Which are also cheaper. There is no justification for continuing the use of methyldopa, reserpine or hydrallazine in essential hypertension.. References Available on request Abstract Problem Statement: Older antihypertensives (methyldopa, reserpine and hydrallazine) are not favoured in international hypertension guidelines. However, developing countries continue to recommend older antihypertensive agents because they are considered to be less expensive. There are no systematic reviews on the efficacy of older antihypertensives. There can be significant differences in 30-day treatment costs. For example: Using Defined Daily Doses (DDD) and the Management Sciences for Health price guide, 1-day treatment costs are as follows: hydrochlorothiazide - US$ 0.10; atenolol - US$ 0.37; reserpine - US$ 1.10; captopril - US$1.58; hydrallazine - US$2.26; and methyldopa - US$3.91. Objectives: To comparative the efficacy and safety of older antihypertensives in essential hypertension. Design: Systematic reviews of randomised studies (RCTs) that included methyldopa, reserpine or hydrallazine Methods: A comprehensive literature search was conducted to identify RCTs of methyldopa, reserpine and hydrallazine. Studies that compared the older drugs to either diuretics, beta blockers and ACEI or placebo were eligible for inclusion. The outcomes were hypertension- related morbidity, mortality, reduction in blood pressure and incidence of adverse events. The quality of the selected studies was assessed by two reviewers using the Schultz criteria. Review manager software was used to meta-analyse the results. Results: There were 85 RCTs involving methyldopa, 34 involving hydralazine and 19 involving reserpine. Most of the studies were conducted in developed countries. The general quality of the RCTs for all 3 drugs was poor. None of studies reported on hypertension- related morbidity or mortality. Blood pressure response was reported as the only measure of efficacy. There were no statistically significant differences in blood pressure lowering with the older antihypertensives compared to any of the comparators. The adverse event reporting in studies was poor. Conclusions: There are no RCTs that report hypertension-related morbidity or mortality for any of the older antihypertensives. There is good evidence from systematic reviews to support the use of diuretics, beta blockers and ACEI in hypertension. There is no evidence from the literature to support the use of older antihypertensives in developing countries. Furthermore the prices of these older antihypertensives are significantly higher than diuretics, beta blockers and ACEI. Background and Setting Study Aims To assess the effect of older antihypertensives on Hypertension related morbidity and mortality Systolic and Diastolic blood pressure Adverse effects associated with these drugs Reserpine Hydrallazine combination therapy Methods: Literature search and quality of studies The following databases were searched using the Cochrane search strategy for RCT’s Medline (1966-2003) Embase (1980-2003) Cochrane African Trials Registry (MRC SA) The search included English and foreign languages studies. Quality of studies The quality of studies was assessed using the Schulz criteria for assessing methodological quality. Studies were assessed for allocation concealment, blinding, ITT analysis and allocation sequence. Cross over design studies were also assessed for whether the order of treatment was varied and the washout period was adequate. Two reviewers assessed the quality of studies independently and disagreement were resolved by consensus. Methyldopa Monotherapy Methyldopa Combination therapy Adverse effects The randomised controlled studies were not powered to detect adverse events for the 3 drugs. Case reports and the Uppsala database were used in addition to the RCTs. Methyldopa was less well tolerated than other antihypertensive drugs (especially beta blockers) and is associated with serious side effects e.g. haemolytic anaemia and hepatitis. Adverse events for hydrallazine were less serious than for methyldopa. The main serious adverse event was lupus erythematosis syndrome. The data confirmed the association between reserpine and depression. Withdrawals due to adverse events were higher with reserpine than other antihypertensives. Overall these drugs have a less favourable adverse event profile than new drugs fro hypertension.