title: Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses.
abstract: DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.
authors.affiliation: Oslo University Hospital Ullevaal, University of Oslo, Oslo, Norway.
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.affiliation: KRK Medical Research Institute, Dallas, Texas, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Cha
authors.affiliation: Fondazione S. Maugeri-IRCCS, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villa
authors.affiliation: University of Milano-Bicocca, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D009543:Nifedipine; C077793:candesartan cilexetil
keywords: DISTINCT study; candesartan cilexetil; combination therapy; essential hypertension; nifedipine GITS; vasodilatory side effects
references.citation: Lancet. 1997 Sep 13;350(9080):757-64
references.pmid: 9297994
references.citation: J Hypertens. 2015 Jul;33(7):1321-41
references.pmid: 26039526
references.citation: Eur Heart J. 2013 Jul;34(28):2159-219
references.pmid: 23771844
references.citation: Health Technol Assess. 2003;7(31):1-94
references.pmid: 14604498
references.citation: Integr Blood Press Control. 2013 Jun 25;6:79-87
references.pmid: 23901292
references.citation: J Hum Hypertens. 2009 Aug;23(8):503-11
references.pmid: 19148104
references.citation: Clin Ther. 2008 Apr;30(4):587-604
references.pmid: 18498909
references.citation: J Hum Hypertens. 2010 Apr;24(4):263-73
references.pmid: 19890371
references.citation: J Cardiovasc Pharmacol. 2004 Feb;43(2):300-5
references.pmid: 14716221
references.citation: Blood Press. 1995 May;4(3):148-56
references.pmid: 7670648
references.citation: J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404
references.pmid: 12461301
references.citation: J Am Soc Hypertens. 2008 Jul-Aug;2(4):294-302
references.pmid: 20409909
references.citation: Curr Med Res Opin. 2012 Oct;28(10):1685-97
references.pmid: 22978777
references.citation: Ther Adv Drug Saf. 2015 Aug;6(4):166-76
references.pmid: 26301070
references.citation: J Clin Hypertens (Greenwich). 2007 May;9(5):355-64
references.pmid: 17485971
references.citation: J Cardiovasc Pharmacol. 1990;15 Suppl 4:S76-84
references.pmid: 1693735
references.citation: Am J Cardiol. 1998 Oct 15;82(8):961-5
references.pmid: 9794352
references.citation: Am J Med. 2011 Feb;124(2):128-35
references.pmid: 21295192
references.citation: Am J Med. 2009 Mar;122(3):290-300
references.pmid: 19272490
references.citation: Lancet. 2002 Dec 14;360(9349):1903-13
references.pmid: 12493255
references.citation: BMJ. 2003 Jun 28;326(7404):1427
references.pmid: 12829555
references.citation: J Hypertens. 2002 Aug;20(8):1461-4
references.pmid: 12172300
references.citation: J Hypertens. 2015 Feb;33(2):195-211
references.pmid: 25485720
references.citation: Clin Ther. 2007 Apr;29(4):563-80
references.pmid: 17617280
references.citation: J Hypertens. 2014 Jan;32(1):3-15
references.pmid: 24270181
references.citation: J Clin Hypertens (Greenwich). 2006 Jun;8(6):444-9
references.pmid: 16760685
references.citation: Hypertension. 2002 Nov;40(5):640-6
references.pmid: 12411456
references.citation: JAMA. 2014 Feb 5;311(5):507-20
references.pmid: 24352797
references.citation: Vasc Health Risk Manag. 2010 Sep 07;6:803-11
references.pmid: 20859549
references.citation: J Hypertens. 2014 Dec;32(12):2488-98; discussion 2498
references.pmid: 25144296
references.citation: J Hypertens. 2011 Mar;29(3):600-9
references.pmid: 21252701
references.citation: Lancet. 2005 Sep 10-16;366(9489):895-906
references.pmid: 16154016
references.citation: Am J Cardiol. 2001 Mar 15;87(6):727-31
references.pmid: 11249891
references.citation: J Cardiovasc Pharmacol. 2009 Nov;54(5):427-36
references.pmid: 19730391
references.citation: N Engl J Med. 2008 Dec 4;359(23):2417-28
references.pmid: 19052124