title: Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.
abstract: The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.
authors: Unit and Department of Clinical Medicine, University of Milano-Bicocca, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors: G
authors: G
authors: Mancia
authors: KRK Medical Research Institute, Dallas, TX, USA.
authors: G
authors: G
authors: Cha
authors: Hospital Universitario San Cecilio, Granada, Spain.
authors: B
authors: B
authors: Gil-Extremera
authors: Formerly in The Crouch Oak Family Practice, Addlestone, UK.
authors: P
authors: P
authors: Harvey
authors: National Research Institute, Los Angeles, CA, USA.
authors: A J
authors: AJ
authors: Lewin
authors: Fondazione Salvatore Maugeri-IRCCS, Pavia, Italy.
authors: G
authors: 0000-0002-6238-7277
authors: G
authors: Villa
authors: Oslo University Hospital Ullevaal, University of Oslo, Oslo, Norway.
authors: S E
authors: SE
authors: Kjeldsen
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; 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; C081643:candesartan