title: Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results.
abstract: OBJECTIVE
  DISTINCT (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) aimed to determine the dose-response and tolerability of nifedipine GITS and/or candesartan cilexetil therapy in participants with hypertension.
  
  
  METHODS
  In this 8-week, multinational, multicentre, randomized, double-blind, placebo-controlled study, adults with mean seated DBP of at least 95 to less than 110 mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60 mg and candesartan cilexetil (C) 4, 8, 16 or 32 mg, or placebo. The primary endpoint, change in DBP from baseline to Week 8, was analysed using the response surface model (RSM); this analysis was repeated for mean seated SBP.
  
  
  RESULTS
  Overall, 1381 participants (mean baseline SBP/DBP: 156.5/99.6 mmHg) were randomized. Both N and C contributed independently to SBP/DBP reductions [P < 0.0001 (RSM)]. A positive dose-response was observed, with all combinations providing statistically better blood pressure (BP) reductions from baseline versus respective monotherapies (P < 0.05) and N60C32 achieving the greatest reduction [-23.8/-16.5 mmHg; P < 0.01 versus placebo (-5.3/-6.7 mmHg) and component monotherapies]. Even very low-dose (N20 and C4) therapy provided significant BP-lowering, and combination therapy was similarly effective in different racial groups. N/C combination demonstrated a lower incidence of vasodilatory adverse events than N monotherapy (18.3 versus 23.6%), including headache (5.5 versus 11.0%; P = 0.003, chi-square test) and peripheral oedema over time (3.6 versus 5.8%; n.s.).
  
  
  CONCLUSIONS
  N/C combination was effective in participants with hypertension and showed an improved side effect profile compared with N monotherapy.
authors.affiliation: aOslo University Hospital Ullevaal, University of Oslo, Oslo, Norway bVirginia Commonwealth University, Richmond, Virginia, USA cHannover Medical School, Hannover, Germany dKRK Medical Research Institute, Dallas, Texas, USA eHospital Universitario San Cecilio, Granada, Spain fThe Crouch Oak Family Practice, Surrey, UK gHuisartsenpraktijk De Regenboog, Antwerp, Belgium hNational Research Institute, Los Angeles, California, USA iFondazione S. Maugeri - IRCCS, Pavia jUniversity of Milano-Bicocca, Milan, Italy.
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Domenic
authors.initials: D
authors.lastname: Sica
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Gloria
authors.initials: G
authors.lastname: Cha
authors.forename: Blas
authors.initials: B
authors.lastname: Gil-Extremera
authors.forename: Peter
authors.initials: P
authors.lastname: Harvey
authors.forename: Frank
authors.initials: F
authors.lastname: Heyvaert
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lewin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005006:Ethnicity; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D009543:Nifedipine; C077793:candesartan cilexetil; C081643:candesartan