Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Oct 3:347:f5680.
doi: 10.1136/bmj.f5680.

Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials

Blood Pressure Lowering Treatment Trialists' Collaboration; T Ninomiya, V Perkovic, F Turnbull, B Neal, F Barzi, A Cass, C Baigent, J Chalmers, N Li, M Woodward, S MacMahon
Collaborators
Review

Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials

Blood Pressure Lowering Treatment Trialists' Collaboration et al. BMJ. .

Abstract

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/β 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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: VP has received honoraria from Astra Zeneca, Merck, and Servier for scientific presentations and is a trial steering committee and/or advisory board member for Abbvie, Astellas, Baxter, Boehringer Ingelheim, Janssen, and Vitae: JC, MW, and SM have received honoraria from Servier for scientific presentations relating to blood pressure; SM and JC were principal investigators on ADVANCE, a blood pressure lowering trial funded by Servier and the Australian National Health and Medical Research Council; BN has received blood pressure related research support from Servier and honoraria for scientific presentations related to blood pressure from Novartis, Tanabe, and Servier.

Figures

None
Fig 1 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo for risk of major cardiovascular events according to kidney function status. P value for homogeneity indicates consistency of effect of treatment regimen among subgroup. Overall mean difference in systolic and diastolic blood pressure during follow-up in actively treated/first listed regimens v control/second listed regimens, calculated by weighting difference observed in each contributing trial by number of patients in trial. Negative values indicate lower mean systolic and diastolic blood pressure during follow-up in actively treated/first listed groups than in control/second listed groups
None
Fig 2 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo per 5 mm Hg reduction in systolic blood pressure over time on risk of major cardiovascular events according to kidney function status. Pooled estimates estimated with relative risk model weighted for blood pressure reduction. Values show relative risk per 5 mm Hg reduction in systolic blood pressure over time. *Data from HOPE trial not available for analysis of three GFR categories
None
Fig 3 Effects of more intensive v less intensive blood pressure lowering regimens for risk of major cardiovascular events according to kidney function status
None
Fig 4 Effects of blood pressure lowering regimens based on different drug classes for risk of major cardiovascular events according to kidney function status
None
Fig 5 Proportional increase in risk ratio of treatment effect on major cardiovascular events for every 10 mL/min/1.73 m2 decrement in eGFR
None
Fig 6 Associations between systolic blood pressure reduction and risk reduction for major vascular events according to kidney function status. Centre of each circle is placed at estimates of risk ratio for each trial. Area of each circle is proportional to variance of log odds ratio. Fitted lines represent summary meta-regressions for total major cardiovascular events. Intercepts were 0.96 (0.93 to 1.01) for eGFR ≥60 mL/min/1.73 m2 and 0.97 (0.89 to 1.04) for eGFR <60 mL/min/1.73 m2
None
Fig 7 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo per 5 mm Hg reduction in systolic blood pressure over time on risk of major cardiovascular events according to proteinuria status
See this image and copyright information in PMC

Comment in

References

    1. Perkovic V, Cass A, Patel A, Suriyawongpaisal P, Barzi F, Chadban S, et al; InterASIA Collaborative Group. High prevalence of chronic kidney disease in Thailand. Kidney Int 2008;73:473-9. - PubMed
    1. Chadban SJ, Briganti EM, Kerr PG, Dunstan DW, Welborn TA, Zimmet PZ, et al. Prevalence of kidney damage in Australian adults: the AusDiab kidney study. J Am Soc Nephrol 2003;14(7 suppl 2):S131-8. - PubMed
    1. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003;41:1-12. - PubMed
    1. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108:2154-69. - PubMed
    1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296-305. - PubMed

MeSH terms

Substances