Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

Mancia, G; Cha, G.; Gil Extremera, B.; Harvey, P.; Lewin, A. J.; Villa, G.; Kjeldsen, S. E.; Agaiby, J.; Aggarwal, N.; Ainsworth, P.; Akhras, R.; Amaluan, V.; Ballarin, A.; Bardauskiene, L.; Berra, F. C.; Blagden, M.; Bodalia, B.; Borghi, C.; Bundy, C.; Burgess, L.; Buynak, R.; Cafferata, A.; Cahill, T.; Capiau, L.; Capuano, V.; Casanova, R.; Cecil, J.; Cha, G.; Chapman, J.; Chilvers, M.; Christensen, S.; Cho, Y. H.; Chung, W. B.; Cipollone, F.; Coca, A.; Colombo, H.; Contreras, E. M.; Crowley, D.; Cusco Prieto, B.; Decarlini, F.; Doh, J. H.; Dzongowski, P.; Dzyak, G.; Ellery, A.; Extremera, B. G.; Farias, E.; Farrington, C.; Fidelholtz, J.; Fouche, L.; Gabito, A.; Gainza, M.; Gani, M.; Gaunt, R.; Gelersztein, E.; Giuliano, M.; Glazunov, A.; Glorioso, N.; Goloschekin, B.; Gumbley, M.; Gupta, A.; Guzman, L.; J. W., Ha; Hart, R.; Harvey, P.; Haworth, D.; Henein, S.; Henry, D.; Her, S. H.; Heyvaert, F.; Hollanders, G.; Hominal, M.; Hong, B. K.; Hong, T. J.; Hwang, K. K.; Jacovides, A.; Jacqmein, J.; Jeon, H. K.; Jones, N.; Kanani, S.; Kang, H.; Karpenko, O.; Kenton, D.; Kimzey, N.; Kjeldsen, S. E.; Kovalenko, V.; Kushnir, M.; Lasko, B.; Lee, K. J.; Lee, N.; Lewin, A.; Litvak, M.; Luksiene, D.; Majul, C.; Mannarino, E.; Manuale, O.; Marcadis, A.; Miller, D.; Mills, R.; Misik, K.; Mortelmans, J.; O'Mahony, M.; O'Mahony, W.; Park, C.; Pedrinelli, Roberto; Petrulioniene, Z.; Pettyjohn, F.; Piskorz, D.; Poss, G.; Pudi, K.; Pyun, W. B.; Raad, G.; Raila, G.; Ramirez Espinosa, M. F.; Ramlachan, P.; Rhee, M.; Rudenko, L.; Ruiz, T. S.; Ryan, J.; Schacter, G.; Shin, J. H.; Short, D.; Sica, D.; Sirenko, Y.; Slapikas, R.; Somani, R.; Stanislavchuk, M.; Stewart, R.; Svishchenko, Y.; Sychov, O.; Teitelbaum, I.; Tseluyko, V.; Van Rensburg, D. J.; Vaquer Perez, J. V.; Via, L. M.; Vico, M.; Villa, G.; Vizir, V.; Vogel, D.; Wellmann, H.; Yoo, B. S.

doi:10.1038/jhh.2016.54

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.