title: Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis.
abstract: BACKGROUND
  The comparative efficacy and safety of pharmacological agents to lower blood pressure in adults with diabetes and kidney disease remains controversial. We aimed to investigate the benefits and harms of blood pressure-lowering drugs in this population of patients.
  
  
  METHODS
  We did a network meta-analysis of randomised trials from around the world comparing blood pressure-lowering agents in adults with diabetic kidney disease. Electronic databases (the Cochrane Collaboration, Medline, and Embase) were searched systematically up to January, 2014, for trials in adults with diabetes and kidney disease comparing orally administered blood pressure-lowering drugs. Primary outcomes were all-cause mortality and end-stage kidney disease. We also assessed secondary safety and cardiovascular outcomes. We did random-effects network meta-analysis to obtain estimates for primary and secondary outcomes and we presented these estimates as odds ratios or standardised mean differences with 95% CIs. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities.
  
  
  RESULTS
  157 studies comprising 43,256 participants, mostly with type 2 diabetes and chronic kidney disease, were included in the network meta-analysis. No drug regimen was more effective than placebo for reducing all-cause mortality. However, compared with placebo, end-stage renal disease was significantly less likely after dual treatment with an angiotensin-receptor blocker (ARB) and an angiotensin-converting-enzyme (ACE) inhibitor (odds ratio 0·62, 95% CI 0·43-0·90) and after ARB monotherapy (0·77, 0·65-0·92). No regimen significantly increased hyperkalaemia or acute kidney injury, although combined ACE inhibitor and ARB treatment had the lowest rank among all interventions because of borderline increases in estimated risks of these harms (odds ratio 2·69, 95% CI 0·97-7·47 for hyperkalaemia; 2·69, 0·98-7·38 for acute kidney injury).
  
  
  CONCLUSIONS
  No blood pressure-lowering strategy prolonged survival in adults with diabetes and kidney disease. ACE inhibitors and ARBs, alone or in combination, were the most effective strategies against end-stage kidney disease. Any benefits of combined ACE inhibitor and ARB treatment need to be balanced against potential harms of hyperkalaemia and acute kidney injury.
  
  
  BACKGROUND
  Canterbury Medical Research Foundation, Italian Medicines Agency.
authors.affiliation: Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Primary Education, University of Ioannina, Ioannina, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavridis
authors.affiliation: Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland.
authors.forename: Eliano
authors.initials: E
authors.lastname: Navarese
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Salanti
authors.affiliation: Department of Medicine, Division of Nephrology and Immunology, University of Alberta, AB, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Wiebe
authors.affiliation: Department of Translational Medicine, Division of Nephrology and Transplantation, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; Diaverum Medical Scientific Office, Diaverum Sweden AB, Lund, Sweden.
authors.forename: Marinella
authors.initials: M
authors.lastname: Ruospo
authors.affiliation: Royal Free and University College Medical School, London, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, Australia; Diaverum Medical Scientific Office, Diaverum Sweden AB, Lund, Sweden; Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. Electronic address: gfmstrippoli@gmail.com.
authors.forename: Giovanni F M
authors.initials: GF
authors.lastname: Strippoli
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000401:mortality / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000401:mortality / Q000517:prevention & control; D003925:Diabetic Angiopathies / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000401:mortality / Q000517:prevention & control; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents