Blood pressure-lowering efficacy of reserpine for primary hypertension.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: Included studies were truly randomised controlled trials (RCTs) comparing reserpine monotherapy to placebo or no treatment in participants with primary hypertension. DATA COLLECTION AND ANALYSIS: We assessed methods of randomisation and concealment. We extracted and analysed data on blood pressure reduction, heart rate, and withdrawal due to adverse effects. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Blood pressure lowering efficacy of beta-blockers as second-line therapy for primary hypertension.

BACKGROUND: Beta-blockers are one of the more commonly prescribed classes of anti-hypertensive drugs, both as first-line and second-line. OBJECTIVES: To quantify the effect on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and withdrawals due to adverse effects of beta-blocker therapy when given as a second-line drug in adult patients with primary hypertension. SEARCH STRATEGY: CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (1966-Aug 2009), EMBASE (1988-Aug 2009) and bibliographic citations of articles and reviews were searched. SELECTION CRITERIA: Double-blind, randomized controlled trials comparing a beta-blocker in combination with a drug from another class of anti-hypertensive drugs compared with that drug alone for a duration of 3 to 12 weeks in patients with primary hypertension were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality of each included study. MAIN RESULTS: 20 double-blind RCTs evaluated the BP lowering efficacy of beta-blockers as second-line drug in 3744 hypertensive patients (baseline BP of 158/102 mmHg; mean duration of 7 weeks). The BP reduction from adding a beta-blocker as the second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. A reduction in BP was seen with adding a beta-blocker to thiazide diuretics or calcium channel blockers at doses as low as 0.25 times the manufacturer's recommended starting dose. The BP lowering efficacy of beta-blockers as a second drug was 6/4 mmHg at 1 times the starting dose and 8/6 mmHg at 2 times the starting dose. Beta-blockers reduced heart rate by 10 beats/min at 1 to 2 times the starting dose. Beta-blockers did not statistically significantly increase withdrawals due to adverse effects but this was likely due to the lack of reporting of this outcome in 35% of the included RCTs. AUTHORS' CONCLUSIONS: Addition of a beta-blocker to diuretics or calcium-channel blockers reduces BP by 6/4mmHg at 1 times the starting dose and by 8/6 mmHg at 2 times the starting dose. When the blood pressure lowering effect of beta-blockers from this review was compared to that of thiazide diuretics from our previous review (Chen 2009), second-line beta-blockers reduce systolic BP to the same extent as second-line thiazide diuretics, but reduce diastolic BP to a greater degree. The different effect on diastolic BP means that beta-blockers have little or no effect on pulse pressure whereas thiazides cause a significant dose-related decrease in pulse pressure. This difference in the pattern of BP lowering with beta-blockers as compared to thiazides might be the explanation for the fact that beta-blockers appear to be less effective at reducing adverse cardiovascular outcomes than thiazide diuretics, particularly in older individuals.

Failure of psychological interventions to lower blood pressure: a randomized controlled trial.

BACKGROUND: Previous studies have suggested that psychological interventions may be effective in reducing blood pressure. Using rigorous methodology and 24-hour monitoring of ambulatory blood pressure, we compared 2 psychological interventions with treatment using a first-line antihypertensive drug in terms of their efficacy in lowering blood pressure in patients with mild primary hypertension. METHODS: In this prospective, open-label randomized controlled trial (RCT), 65 adult patients with mild, uncomplicated hypertension were randomly assigned to receive one of the following interventions for 12 weeks: (1) pharmacotherapy with hydrochlorothiazide 12.5 titrated to 25 mg/d ; (2) individualized behavioural psychotherapy, consisting of ten 1-hour sessions of stress reduction training with a psychologist; or (3) self-help psychotherapy, consisting of a 1.5-hour session with a psychologist and then daily sessions that involved reading a self-help manual and listening to an audiotape. The primary outcome measure was mean change in ambulatory blood pressure from baseline to week 12. Resting blood pressure readings were taken in the clinic, and adverse events were recorded. RESULTS: Monitoring of ambulatory blood pressure over 24 hours showed that hydrochlorothiazide therapy significantly reduced both systolic and diastolic blood pressure relative to baseline, and that this reduction was significantly greater than that achieved with either individualized behavioural psychotherapy or self-help psychotherapy (mean reduction [standard error; SE] -11.03 [2.53] / -6.06 [1.56] mm Hg v. -0.08 [2.38] / 0.29 [1.47] mm Hg v. -1.23 [2.83] / -0.71 [1.75] mm Hg, respectively; p = 0.01). Neither form of psychological therapy significantly lowered 24-hour ambulatory blood pressure relative to baseline. CONCLUSION: For patients with primary elevated blood pressure, 2 psychological interventions did not lower 24-hour ambulatory blood pressure, whereas hydrochlorothiazide reduced blood pressure, as expected. The findings of this RCT represent an important addition to the evidence for health care practitioners and for patients seeking psychological interventions to reduce blood pressure.

Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event.

BACKGROUND: Acute cardiovascular events represent a therapeutic challenge. Blood pressure lowering drugs are commonly used and recommended in the early phase of these settings. This review analyses randomized controlled trial (RCT) evidence for this approach. OBJECTIVES: To determine the effect of immediate and short-term administration of anti-hypertensive drugs on all-cause mortality, total non-fatal serious adverse events (SAE) and blood pressure, in patients with an acute cardiovascular event, regardless of blood pressure at the time of enrollment. SEARCH STRATEGY: MEDLINE, EMBASE, and Cochrane clinical trial register from Jan 1966 to February 2009 were searched. Reference lists of articles were also browsed. In case of missing information from retrieved articles, authors were contacted. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing anti-hypertensive drug with placebo or no treatment administered to patients within 24 hours of the onset of an acute cardiovascular event. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed risk of bias. Fixed effects model with 95% confidence intervals (CI) were used. Sensitivity analyses were also conducted. MAIN RESULTS: Sixty-five RCTs (N=166,206) were included, evaluating four classes of anti-hypertensive drugs: ACE inhibitors (12 trials), beta-blockers (20), calcium channel blockers (18) and nitrates (18). Acute stroke was studied in 6 trials (all involving CCBs). Acute myocardial infarction was studied in 59 trials. In the latter setting immediate nitrate treatment (within 24 hours) reduced all-cause mortality during the first 2 days (RR 0.81, 95%CI [0.74,0.89], p<0.0001). No further benefit was observed with nitrate therapy beyond this point. ACE inhibitors did not reduce mortality at 2 days (RR 0.91,95%CI [0.82, 1.00]), but did after 10 days (RR 0.93, 95%CI [0.87,0.98] p=0.01). No other blood pressure lowering drug administered as an immediate treatment or short-term treatment produced a statistical significant mortality reduction at 2, 10 or >/=30 days. There was not enough data studying acute stroke, and there were no RCTs evaluating other acute cardiovascular events. AUTHORS' CONCLUSIONS: Nitrates reduce mortality (4-8 deaths prevented per 1000) at 2 days when administered within 24 hours of symptom onset of an acute myocardial infarction. No mortality benefit was seen when treatment continued beyond 48 hours. Mortality benefit of immediate treatment with ACE inhibitors post MI at 2 days did not reach statistical significance but the effect was significant at 10 days (2-4 deaths prevented per 1000). There is good evidence for lack of a mortality benefit with immediate or short-term treatment with beta-blockers and calcium channel blockers for acute myocardial infarction.

Blood pressure lowering efficacy of reserpine for primary hypertension.

BACKGROUND: Many antihypertensive agents exist today for the treatment of primary hypertension (systolic blood pressure >/=140 mmHg and/or diastolic blood pressure >/=90 mmHg). Randomised controlled trials have been carried out to investigate the evidence for these agents.There is, for example, strong RCT evidence that thiazides reduce mortality and morbidity. Reserpine has been used as a second-line therapy in some of those trials. However, the dose-related blood pressure reduction with this agent is not known. OBJECTIVES: To investigate the dose-related effect of reserpine on blood pressure, heart rate and withdrawals due to adverse events. SEARCH STRATEGY: The databases CENTRAL, EMBASE, and MEDLINE were searched. We also traced citations in the reference sections of the retrieved studies. SELECTION CRITERIA: Included studies were truly randomised controlled trials comparing reserpine monotherapy to placebo or no treatment in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: Methods of randomization and concealment were assessed. Data on blood pressure reduction, heart rate,and withdrawal due to adverse effects were extracted and analysed. MAIN RESULTS: Four RCTs (N =237) were found that met the inclusion criteria. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction in patients taking reserpine compared to placebo (WMD -7.92, 95% CI -14.05, -1.78). Due to significant heterogeneity across trials, a significant effect in diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) could not be found. The SBP effects were achieved with 0.5 mg/day or greater. However, the dose-response pattern could not be determined because of the small number of trials. Data from the trial that investigated Rauwiloid against placebo was not combined 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. AUTHORS' CONCLUSIONS: 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.

Treatment blood pressure targets for hypertension.

BACKGROUND: When treating elevated blood pressure, doctors need to know what blood pressure (BP) target they should try to achieve. The standard of clinical practice for some time has been