title: Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis.
abstract: OBJECTIVE
  To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes.
  
  
  METHODS
  Systematic review and bayesian network meta-analysis of randomised clinical trials.
  
  
  METHODS
  Electronic literature search of PubMed, Medline, Scopus, and the Cochrane Library for studies published up to December 2011.
  
  
  METHODS
  Randomised clinical trials of antihypertensive therapy (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their combinations) in patients with diabetes with a follow-up of at least 12 months, reporting all cause mortality, requirement for dialysis, or doubling of serum creatinine levels.
  
  
  METHODS
  Bayesian network meta-analysis combined direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects.
  
  
  RESULTS
  63 trials with 36,917 participants were identified, including 2400 deaths, 766 patients who required dialysis, and 1099 patients whose serum creatinine level had doubled. Compared with placebo, only ACE inhibitors significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90), and only β blockers showed a significant difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39). Comparisons among all treatments showed no statistical significance in the outcome of dialysis. Although the beneficial effects of ACE inhibitors compared with ARBs did not reach statistical significance, ACE inhibitors consistently showed higher probabilities of being in the superior ranking positions among all three outcomes. Although the protective effect of an ACE inhibitor plus calcium channel blocker compared with placebo was not statistically significant, the treatment ranking identified this combination therapy to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel blockers (1.2%), and ARBs (0.4%).
  
  
  CONCLUSIONS
  Our analyses show the renoprotective effects and superiority of using ACE inhibitors in patients with diabetes, and available evidence is not able to show a better effect for ARBs compared with ACE inhibitors. Considering the cost of drugs, our findings support the use of ACE inhibitors as the first line antihypertensive agent in patients with diabetes. Calcium channel blockers might be the preferred treatment in combination with ACE inhibitors if adequate blood pressure control cannot be achieved by ACE inhibitors alone.
authors.affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Hon-Yen
authors.initials: HY
authors.lastname: Wu
authors.forename: Jenq-Wen
authors.initials: JW
authors.lastname: Huang
authors.forename: Hung-Ju
authors.initials: HJ
authors.lastname: Lin
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liao
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Peng
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Hung
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
authors.forename: Yu-Kang
authors.initials: YK
authors.lastname: Tu
authors.forename: Kuo-Liong
authors.initials: KL
authors.lastname: Chien
mesh_terms: D018674:Adrenergic Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D015220:Calcium Channels / Q000627:therapeutic use; D003404:Creatinine / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000150:complications / Q000401:mortality; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018674:Adrenergic Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015220:Calcium Channels; D004232:Diuretics; D003404:Creatinine