TY - JOUR
T1 - Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile
T2 - DISTINCTrandomized trial results
AU - Kjeldsen, Sverre E.
AU - Sica, Domenic
AU - Haller, Hermann
AU - Cha, Gloria
AU - Gil-Extremera, Blas
AU - Harvey, Peter
AU - Heyvaert, Frank
AU - Lewin, Andrew J.
AU - Villa, Giuseppe
AU - Mancia, Giuseppe
PY - 2014
Y1 - 2014
N2 - Objectives: 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 110mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60mg 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: 156.5/99.6mmHg) 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/-16.5mmHg; 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.). Conclusion: N/C combination was effective in participants with hypertension and showed an improved side effect profile compared with N monotherapy.
AB - Objectives: 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 110mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60mg 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: 156.5/99.6mmHg) 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/-16.5mmHg; 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.). Conclusion: N/C combination was effective in participants with hypertension and showed an improved side effect profile compared with N monotherapy.
KW - Candesartan cilexetil
KW - Combination therapy
KW - DISTINCT study
KW - Essential hypertension
KW - Nifedipine GITS
KW - Vasodilatory side effects
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UR - http://www.scopus.com/inward/citedby.url?scp=84927743127&partnerID=8YFLogxK
U2 - 10.1097/HJH.0000000000000331
DO - 10.1097/HJH.0000000000000331
M3 - Article
C2 - 25144296
AN - SCOPUS:84927743127
VL - 32
SP - 2488
EP - 2498
JO - Journal of Hypertension
JF - Journal of Hypertension
SN - 0263-6352
IS - 12
ER -