title: A Systematic Review of Add-on Pharmacologic Therapy in the Treatment of Resistant Hypertension.
abstract: BACKGROUND
  The objective of this systematic review was to evaluate the efficacy and safety of add-on pharmacologic therapies in the treatment of resistant hypertension (RH), defined as blood pressure (BP) above target despite three antihypertensive agents.
  
  
  METHODS
  A systematic search was performed in MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and Google Scholar (inception to June 2016) to identify randomized controlled trials (RCTs) that compared any antihypertensive agent with control in patients with RH. Outcomes of interest included differences in BP, cardiovascular events, and serious adverse events. The Cochrane Collaboration's tool for assessing risk of bias in RCTs was used to evaluate the quality of the included trials.
  
  
  RESULTS
  Six RCTs were identified, including 749 participants. Four RCTs compared spironolactone with placebo and two used an active comparator. Four of the six studies did not report sufficient information regarding methods. A quantitative meta-analysis was not performed because of clinical heterogeneity among the RCTs. Compared with placebo, spironolactone reduced mean office BP by ~10 to 20 mmHg/~3 to 9 mmHg and home BP by ~10/4 mmHg. Compared with doxazosin or bisoprolol, spironolactone reduced clinic and home systolic BP, but not diastolic BP. Hyperkalemia occurred in ~3% of patients receiving spironolactone. Cardiovascular events were not consistently reported. All trials were limited by low enrollment, short follow-up, and inconsistent reporting of clinically meaningful outcomes and/or serious adverse events.
  
  
  CONCLUSIONS
  Spironolactone has the best evidence as add-on pharmacologic therapy in patients with RH, but data are limited.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Anita P
authors.initials: AP
authors.lastname: Tataru
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. arden.barry@ubc.ca.|Primary Care Clinic, Chilliwack General Hospital, Lower Mainland Pharmacy Services, Chilliwack, BC, Canada. arden.barry@ubc.ca.
authors.forename: Arden R
authors.initials: AR
authors.lastname: Barry
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013148:Spironolactone / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D013148:Spironolactone