Effects of telmisartan and amlodipine in combination on ambulatory blood pressure in stages 1-2 hypertension.

BACKGROUND: Evaluation of combination therapy with antihypertensive agents by clinic blood pressure (BP) measurements may yield results that differ from out-of-office BP readings. This is of clinical relevance because out-of-office BP values are of prognostic importance. We studied the effects of combining telmisartan and amlodipine on ambulatory BP in patients with stages 1-2 hypertension. METHODS: We conducted an 8-week, placebo-controlled, double-blind, 4x4 factorial design trial in which 562 patients with clinic diastolic BP at least 95 and 119 mmHg or less were randomized to receive telmisartan (0, 20, 40, or 80 mg) and/or amlodipine (0, 2.5, 5, or 10 mg). Ambulatory BP monitoring was performed at baseline and after 8 weeks of treatment; the end points of interest were the changes from baseline in 24-h systolic and diastolic BP. Secondary end points included the proportion of responders (> or =10 mmHg BP reduction from baseline and/or <130/80 mean 24-h BP) and controlled patients (<130/80 mmHg mean 24-h BP). RESULTS: Combination therapies of telmisartan and amlodipine lowered 24-h BP to a larger extent than the corresponding monotherapies at all doses. Mean reductions from baseline in 24-h BP for the combination of the highest doses of telmisartan (80 mg) and amlodipine (10 mg) were -22.4/-14.6 versus -11.9/-6.9 mmHg for amlodipine (10 mg) and -11.0/-6.9 mmHg for telmisartan (80 mg) (P<0.0001 for each comparison). In addition, BP response and control rates (24-h BP <130/80 mmHg) were significantly higher with the combination therapy versus the monotherapy groups. CONCLUSION: These findings show that telmisartan and amlodipine in combination provide substantial 24-h BP efficacy that is superior to either monotherapy in patients with stages 1 and 2 hypertension.

Evidence for the efficacy of ARBs across the cardiovascular continuum.

INTRODUCTION: Angiotensin II receptor blockers (ARBs) are antihypertensive agents with considerable evidence of efficacy and safety for the reduction of cardiovascular (CV) disease risk in numerous patient populations from one end of the CV continuum (i.e., primary prevention among patients with CV risk factors) to the other (i.e., secondary prevention in the post-MI setting). There are several agents within the ARB class, all of which have contributed to various degrees to this evidence base. SCOPE: This review presents the design and main results of large, well designed studies examining the CV risk-reducing properties of ARBs. The authors searched major literature databases (Embase, Medline, PubMed) for randomized, controlled studies published between January, 1995 and October, 2009 that compared ARBs with placebo or active controls and reported major CV outcomes (e.g., myocardial infarction, stroke) and/or mortality as the primary study endpoint(s). LIMITATIONS: Although many trials evaluating similar agents are presented, between-trial comparisons are inappropriate. The results of each study stand on their own merits and weaknesses, but do not provide any additional insight into the results of the other studies. RESULTS: Agents in the ARB class have demonstrated efficacy in reducing CV events and/or mortality in a number of different patient populations, from primary prevention studies in patients with pre-specified risk factors (e.g., hypertension and left-ventricular hypertrophy in the LIFE study) to secondary prevention (i.e., post-MI patients in the VALIANT study). Some studies have also demonstrated the statistical equivalence of ARBs to ACE inhibitors in certain populations (e.g., among post-MI patients in VALIANT and among a broad population of patients with vascular disease or diabetes in the ONTARGET). There are several major studies currently underway that will provide further information on the risk-reducing properties of ARBs in additional populations (e.g., patients with impaired glucose tolerance in the NAVIGATOR study). CONCLUSIONS: ARBs have demonstrated efficacy in reducing CV morbidity and mortality in a broad spectrum of CV disease states across the CV continuum. Ongoing research continues to provide additional evidence, with ongoing trials investigating their role in additional patient populations.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.

O papel do sistema renina-angiotensina-aldosterona no desenvolvimento da hipertensão arterial associada à obesidade / The role of the renin-angiotensin aldosterone system on obesity induced arterial hypertension

A presente revisão sobre a participação do sistema renina-angiotensina e obesidade aborda inicialmente os aspectos multifatoriais da fisiopatologia da hipertensão na obesidade. O papel da hemodinâmica, nessa síndrome, é caracterizado como um estado de aumento absoluto na volemia, aumento do débito cardíaco e resistência vascular periférica numericamente normal. Destaca o papel maior da insulina e do sistema nervoso simpático na vasoconstrição periférica e aumento na absorção de sódio pelos túbulos renais. Apresenta as evidências de que a obesidade experimental em animais leva a alterações na matrix da medula renal, promovendo alterações na dinâmica túbulo-glomerular e conseqüente aumento na secreção de renina. Focaliza a associação do sistema renina-angiotensina tecidual apontando para a importante expressão de genes de vários componentes do sistema no tecido adiposo. Enfatiza o papel da angiotensina II na transformação do preadipócito em adipócito via prostaciclinas. Por fim discute alguns aspectos do tratamento farmacológico anti-hipertensivo no paciente obeso, mostrando os benefícios do uso dos inibidores da enzima de conversão da angiotensina (ECA) como droga de primeira escolha nessa síndrome. Os inibidores da ECA apresentam eficácia superior aos diuréticos em monoterapia, menos efeitos colaterais eletrolíticos e metabólicos. Ao lado desses benefícios, há evidências mostrando aumento no número de receptores periféricos para insulina, sugerindo um favorável efeito no metabolismo da glicose.