Sandy D Shamon, Marco I Perez

Many antihypertensive agents exist today for the treatment of primary hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, or both). Randomised controlled trials (RCTs) have been carried out to investigate the evidence for these agents. There is, for example, strong RCT evidence that thiazides reduce mortality and morbidity. Some of those trials used reserpine as a second-line therapy. However, the dose-related blood pressure reduction with this agent is not known. The primary objective of this review was to quantify the dose-related efficacy of reserpine versus placebo or no treatment in reducing systolic blood pressure (SBP) or diastolic blood pressure (DBP), or both.We also aimed to evaluate the dose-related effects of reserpine on mean arterial blood pressure (MAP) and heart rate (HR), as well as the dose-related effects on withdrawals due to adverse events. We searched the Cochrane Hypertension Group Specialised Register (January 1946 to October 2016), CENTRAL (2016, Issue 10), MEDLINE (January 1946 to October 2016), Embase (January 1974 to October 2016), and ClinicalTrials.gov (all dates to October 2016). We also traced citations in the reference sections of the retrieved studies. Included studies were truly randomised controlled trials (RCTs) comparing reserpine monotherapy to placebo or no treatment in participants with primary hypertension. We assessed methods of randomisation and concealment. We extracted and analysed data on blood pressure reduction, heart rate, and withdrawal due to adverse effects. We found four RCTs (with a total of 237 participants) that met the inclusion criteria, none of which we found through the 2016 update search. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction in participants taking reserpine compared with placebo (weighted mean difference (WMD) -7.92, 95% confidence interval (CI) -14.05 to -1.78). Because of significant heterogeneity across the trials, a significant effect in diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) could not be found. A dose of reserpine 0.5 mg/day or greater achieved the SBP effects. However, we could not determine the dose-response pattern because of the small number of trials. We did not combine data from the trial that investigated Rauwiloid against placebo with reserpine data from the remaining three trials. This is because Rauwiloid is a different alkaloid extract of the plant Rauwolfia serpentina, and the dose used is not comparable to reserpine. None of the included trials reported withdrawals due to adverse effects. Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. However, we could not make definite conclusions regarding the dose-response pattern because of the small number of included trials. More RCTs are needed to assess the effects of reserpine on blood pressure and to determine the dose-related safety profile before the role of this drug in the treatment of primary hypertension can be established.