Blood pressure control by the nifedipine GITS–telmisartan combination in patients at high cardiovascular risk: the TALENT study

Abstract

on behalf of the TALENT investigatorsBackground Guidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an angiotensin receptor antagonist among the priorital ones to employ. AimsTo determine in hypertensive patients at high cardiovascular risk whether combining Nifedipine GITS at low dose and telmisartan reduced ambulatory and clinic blood pressure (BP) more than the combination components, controlled BP early after treatment initiation and allowed to also obtain a better long-term BP control compared to initiating treatment with the combination components and moving to the combination later.Methods Four hundred and five patients with a clinic SBP > -135 mmHg and with diabetes, a metabolic syndrome or organ damage were randomized to once-a-day telmisartan 80 mg, nifedipine GITS 20 mg or the combination of the two drugs in a 1 : 1 : 2 ratio for 8 weeks in the context of a multicenter double-blind study design. Patients on monotherapy were then moved to combination treatment and all three groups were followed for an additional 16-week period. Both 24-h and clinic BP were measured before treatment and at various times during treatment. ResultsIn the per-protocol patients (n U 327), baseline demographic and clinical characteristics were similar between the three groups. Baseline 24-h SBP values were 136.2 W 11.6 mmHg (mean W SD), 137.2 W 12.5 mmHg and 136.8 W 11.7 mmHg in the telmisartan monotherapy, nifedipine GITS monotherapy and combination therapy, respectively. The corresponding clinic values were 151.7 W 11.8, 151.3 W 11.9 and 151.1 W 11.8 mmHg, respectively. All treatments lowered 24-h SBP significantly (P < 0.0001) but combination treatment (8 weeks) reduced it significantly more than monotherapies (10.8 W 0.8 vs.6.6 W 1.1 mmHg and 8.0 W 1.2 mmHg; P U 0.001 and 0.037). Similar data were obtained for clinic SBP for which the combination showed a significantly greater BP reduction (12.6 W 0.6 vs. 8.6 W 0.7 mmHg and 9.3 W 0.8 mmHg; P U 0.003 and 0.024) also after 2 weeks of treatment. Moving from monotherapy to combination therapy increased the antihypertensive effect and made both ambulatory and clinic SBP superimposable in the three groups after 16 and 24 weeks of treatment. Similar findings were obtained for DBP.Conclusion Combination treatment with nifedipine GITS low dose and telmisartan provides a greater and earlier clinic and ambulatory BP reduction than the combination components in monotherapy. Initiating treatment with the combination did not result in any better longer term BP control compared to starting treatment with monotherapy and moving to the combination later.

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

“…The superior BP reductions of combination therapy were maintained throughout the 8‐week study. The results are also consistent with previous studies of combination therapy consisting of a CCB and an ARB 28, 29, 30, 31. Importantly, a greater and earlier effect on BP control via combination therapy has the potential to provide greater CV benefit, as suggested by meta‐analysis2 and by review of major clinical trials with CCB/RAS blocker therapies 32…”

Effect of Long-Term Antihypertensive Treatment on White-Coat Hypertension

“…The most obvious explanation is that, as also shown in our patients by the tertiles data, not only office but also ABP reductions are proportional to baseline BP values, which means that little BP lowering effect can be expected when, as in WCH, the initial ABP is normal or low. However, in other antihypertensive treatment studies, 36,37 ABP has been reduced below the baseline values exhibited by the WCH patients of the present study, and we have thus to consider the possibility that the easy response of office BP to treatment that characterized WCH prevented lower ABP values from being achieved. Furthermore, in our WCH patients, ABP often showed not just no change but an increase, which was consistent in patients with baseline ABP in the lowest tertile.…”

Ambulatory Blood Pressure in Untreated and Treated Hypertensive Patients at High Altitude

“…34 Another novel and clinically relevant contribution of our study is the information on the BP effects at high altitude of a commonly used and guideline-supported combination treatment between an ARB and a slow release calcium antagonist. 16,17 Two previous studies reported that β-blockers have a limited effect in preventing the 24-hour BP increase that occurs at high altitude, 8,28 and their use (particularly of carvedilol) is associated with lower SpO 2 , worse tolerability, and exercise capacity. 8,35 In the healthy participants of HIGHCARE-HIMALAYA, we observed that BP-lowering effect of telmisartan monotherapy was maintained ≤3400 m but not at higher altitudes (5400 m), with no tolerability issues.…”

“…17 In the hypertensive participants of the present study, the combined treatment with telmisartan and nifedipine was effective and safe at an altitude (3260 m) similar to the lower altitude reached in HIGHCARE-HIMALAYA, with BP values that remained lower than in placebo-treated subjects, as it occurred at sea level. Moreover, the active treatment group had higher SpO 2 at high altitude (possibly because of the dilatory effect of nifedipine on pulmonary vasculature leading to improved ventilation:perfusion ratio), even if no differences in acute mountain sickness were found between treatment groups.Our study has several elements of strengths including: (1) adequate sample size, (2) controlled double-blind design, and (3) assessment of the BP effect of high altitude and treatment by ambulatory BP monitoring, an approach that is prognostically superior to conventional BP measurements 16 and that better reflects the high altitude-related BP alterations. 17 The study also has some inevitable limitations.…”

“…15,16 Furthermore, the calcium antagonist nifedipine lowers pulmonary pressure typically elevated at high altitude and is used in prevention and treatment of high-altitude pulmonary edema. 4 Aims of the present study were to extend the information on the acute effects of high altitude on conventional and 24-hour BP obtained in previous studies in normotensive volunteers 8,17 to hypertensive subjects residing at sea level, and to determine whether the efficacy of antihypertensive treatment with the combination of an ARB (telmisartan) and a slow release calcium antagonist (nifedipine gastrointestinal therapeutic system [GITS]) is maintained at high altitude.…”