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.

Impact of baseline blood pressure on the magnitude of blood pressure lowering by nifedipine gastrointestinal therapeutic system: refreshing the Wilder&rsquo;s principle

“… 15 The DISTINCT trial demonstrated that the maximal BP reduction amplitude was reached in the 4th week of treatment, either in NGTS or candesartan monotherapy, or in combination therapy groups. 20 Similar results were seen with NGTS monotherapy or combination of amlodipine/valsartan. 21 The TALENT trial even showed that the maximal BP reduction occurred 16 weeks after treatment in NGTS and telmisartan combination group.…”

“… 19 DISTINCT, an 8 week, double-blind, randomized study, showed that baseline BP significantly affected BP reduction amplitude for both mono-therapy (NGTS or candesartan) or combined therapy (NGTS/candesartan). 20 However, these studies used more than one drug and multiple doses, so clear impact of baseline BP on the magnitude of BP reduction might not be attributed by drugs used or doses taken. Therefore, the magnitude of BP reduction might not be accurately predicted.…”

Effectiveness and Tolerability of Nifedipine GITS in Patients with Chronic Kidney Disease and Uncontrolled Hypertension: A Prospective, Multicenter, Observational Study (ADRENAL)

“…In baseline SBP subgroups, we noted that mean change in SBP and DBP was related to the baseline SBP after 12 weeks nifedipine GITS 60 mg treatment; the higher the baseline SBP was, the greater the BP reduction. This finding is consistent with previous findings where patients with higher SBP at baseline and treated with nifedipine GITS reported greater reduction in BP than in patients with a lower baseline SBP [ 28 , 29 ]. In CKD stage subgroups, we observed a marked decrease in office SBP and DBP with conspicuous mean changes at week 12 irrespective of the CKD stage, and the mean change in SBP/DBP of each stage was basically consistent with the overall results.…”