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Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials.

ABSTRACT: OBJECTIVE: To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination. DESIGN: Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose. SUBJECTS: 40,000 treated patients and 16,000 patients given placebo. MAIN OUTCOME MEASURES: Placebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs. RESULTS: All five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, beta blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose. CONCLUSIONS: Combination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.

SUBMITTER: Law MR

PROVIDER: S-EPMC162261 | biostudies-literature | 2003 Jun

REPOSITORIES: biostudies-literature

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Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials.

Law M R MR Wald N J NJ Morris J K JK Jordan R E RE

BMJ (Clinical research ed.) 20030601 7404

<h4>Objective</h4>To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.<h4>Design</h4>Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium cha ...[more]

PMID: 12829555

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Project description:OBJECTIVE:To define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease. DESIGN:Collaborative prospective meta-analysis of randomised trials. DATA SOURCES AND ELIGIBILITY:Participating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm. MAIN OUTCOME MEASURES:Major cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death. PARTICIPANTS:26 trials (152,290 participants), including 30,295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73 m(2). DATA EXTRACTION:Individual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model. RESULTS:Compared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/? blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity). CONCLUSIONS:Blood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

Project description:RATIONALE AND OBJECTIVE:Salt reduction remains a global challenge and different salt reduction strategies have been studied in China. This study is to systematically evaluate evidence from randomised controlled trials (RCT) in China and inform the effective salt reduction strategies. DESIGN:Systematic review and meta-analysis. DATA SOURCES:MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Wanfang Data and the China National Knowledge Infrastructure databases through October 2019. ELIGIBILITY CRITERIA:RCTs conducted in China with at least 4?weeks' duration of study and blood pressure (BP) reported. DATA EXTRACTION AND SYNTHESIS:Data were screened, extracted and appraised by two independent reviewers. The quality of study was assessed using a modified Cochrane Collaboration's risk of bias tool. The primary outcome was the difference in BP change from baseline to the end of study between interventions and control. The effects were pooled using a random effects model and associated factors were explored by a meta-regression. RESULTS:We identified 24 studies involving 10?448 participants, including 8 studies on health education (4583 participants), 2 studies on salt restriction diet (162 participants), 1 study on salt restriction spoon (50 participants) and 13 studies on salt substitute (5653 participants). Six studies on salt substitute and three studies on health education were identified with high quality. Pooled results from the six studies showed that salt substitutes significantly reduced systolic BP (-5.7?mm Hg; 95%?CI -8.5 to -2.8) and diastolic BP (-2.0?mm Hg; 95%?CI -3.5 to -0.4). The School-EduSalt study showed that the school-based health education significantly reduced systolic BP among parents (-2.3?mm Hg; 95%?CI -4.5 to -0.04). CONCLUSIONS:Among four salt reduction strategies studied in China with RCT design, only salt substitute was proved effective in lowering BP by the pooled effect from multiple studies with high quality. More well-designed studies are warranted for other strategies.

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Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials.

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Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials.

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