Effectiveness of the Direct Renin Inhibitor, Aliskiren, in Patients With Resistant Hypertension

Abstract

SummaryCurrently there is no consensus regarding which add-on therapy to use in resistant hypertension. We have conducted an open observational study of the use of aliskiren in resistant hypertensive patients. Forty-three patients with resistant hypertension were included in the study. The inclusion criteria were as follows: 1) office blood pressure (BP) > 140/90 mmHg despite treatment with at least three or more antihypertensive drugs; 2) no prior therapy with aliskiren; and 3) no renal insufficiency. Follow-up BP was determined at 1 and 3 months. Baseline BP was 153 ± 12/79 ± 12 mmHg. After 3 months, systolic BP (SBP) and diastolic BP (DBP) dropped significantly: 140 ± 19/73 ± 13 mmHg (P < 0.0001). Twenty-one patients (49%) had an office BP < 140/90 mmHg, and these patients were assigned to the good BP control group. Another 22 were placed into the poor BP control group. BP reductions from baseline in the good BP control group (SBP/ DBP: 19 ± 11/8 ± 7 mmHg) were larger than those in the poor BP control group (5 ± 15/3 ± 9 mmHg, P < 0.05). Mean BP (MBP) values at baseline, 1, and 3 months were higher in the poor BP control group. There was no significant difference in pulse pressure at baseline between the 2 groups. In multivariate analysis, only MBP at baseline correlated with lack of BP control. Aliskiren administration to resistant hypertensive patients was effective in reducing BP. The present findings suggest aliskiren may be useful as a fourth-line or fifth-line treatment added to other drugs in the treatment of resistant hypertension. (Int Heart J 2013; 54: 88-92) Key words: Uncontrolled hypertension, Pulse pressure, Mean blood pressure A lthough various authors use different definitions, resistant hypertension is defined as blood pressure (BP) that requires the use of four or more antihypertensive agents, whether controlled or uncontrolled. 1) Approximately 30% of adults who have hypertension are unaware of their condition, and about half of patients receiving treatment in Japan do not achieve the modest goal of < 140 / 90 mmHg. 2) In the absence of a definitive study, clinical trials have been largely relied upon as surrogate opportunities to estimate the prevalence of resistant hypertension. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is likely the most relevant, in that it included a large and diverse cohort, and, per protocol, subjects were to have continued escalation of their treatment regimen as long as the BP remained elevated. At the end of the 5-year treatment period, uncontrolled hypertension was common in ALLHAT, with 34% of subjects never having achieved BP control and with 27% of subjects receiving ≥ 3 antihypertensive medications. 3) Data from a large, community-based study indicated that 12.7% of hypertensive patients were uncontrolled on three or more medications. 4) Recently, de la Sierra, et al presented analysis of data from their large registry of Spanish patients who had 24-hour ambulatory BP monitoring performed. 5) They gathered dat...

Combined Aliskiren and L-arginine treatment reverses renovascular hypertension in an animal model

“…The hypotensive effect of ALSK is potentiated when used in combination with diuretics or blockers of the RAAS. 22 Moreover, monotherapy with L-ARG was able to reduce but not normalize SBP, as observed in this study and in previous studies from our laboratory. 16 However, our most important finding is that the combination of these therapies significantly reduced the blood pressure of the hypertensive rats.…”

Biomarkers Investigation for In-Hospital Death in Patients With Stanford Type A Acute Aortic Dissection

“…7) A previous study has identified some predictors of inhospital mortality in acute type B aortic dissection including age, abrupt onset of chest pain, hypertension, kidney failure, pulse deficit, abnormal electrocardiography (ECG) findings, and absence of a nocturnal blood pressure fall. [8][9][10] Since patients with AAD usually receive medical treatment during the acute phase, Kudo, et al 11) suggest that maximum aortic diameter of ≥ 40 mm or ulcer-like projections at onset are predictors of aortic events. Actually, there is growing evidence that multiple assessments of several biomarkers may provide complementary information about the risk of death in aortic dissection patients.…”

Antihypertensive Efficacy of the Direct Renin Inhibitor Aliskiren as Add-on Therapy in Patients with Poorly Controlled Hypertension

“…If the increases in aliskiren concentrations in the blood and antihypertensive effects are proportional, then that may explain the higher target BP achievement rate observed in the elderly patients. Trials of the antihypertensive effect and safety of aliskiren have been conducted in succession (19)(20)(21)(22)(23) following the ALTITUDE trial (13). The organ-protective effects of antihypertensive drugs are largely attributed to the decrease in BP, and aliskiren, which has a stable, 24-hour-long antihypertensive effect, appears to be useful for good BP management.…”