Aliskiren Monotherapy Does Not Cause Paradoxical Blood Pressure Rises

Stanton, Alice; Gradman, Alan H.; Schmieder, Roland E.; Nussberger, Juerg; Sarangapani, Ramesh; Prescott, Margaret F.

doi:10.1161/hypertensionaha.109.135772

Cited by 27 publications

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“…6) Aliskiren inhibits the renin-angiotensin (Ang) system at the rate-limiting step by reducing plasma renin activity and thereby prevents the formation of Ang I and II. The renin-angiotensin system (RAS) plays an integral part in the regulation of BP.…”

Section: )mentioning

confidence: 99%

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

Yoshitomi¹,

Kawanishi²,

Yamaguchi³

et al. 2013

Int. Heart J.

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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...

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Section: )mentioning

confidence: 99%

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

Yoshitomi¹,

Kawanishi²,

Yamaguchi³

et al. 2013

Int. Heart J.

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“…Notably, none of the 536 patients in whom PRA was measured and who received aliskiren (300 mg) exhibited an increase in systolic BP greater than 10 mm Hg or in diastolic BP greater than 5 mm Hg accompanied by an increase in PRA greater than 0.1 ng/mL per hour. The authors concluded that the incidence of "paradoxical" BP increases with aliskiren was similar to that seen during treatment with other drugs, and that BP elevation was not related to increased PRA [16].…”

Section: Implications Of the Reactive Rise In Plasma Renin Concentrationmentioning

confidence: 83%

“…Stanton et al [16] conducted a meta-analysis involving 4877 patients from eight aliskiren trials with placebo controls, active controls, or both. The incidence of paradoxical BP increases following at least 4 weeks of treatment with aliskiren (300 mg), high-dose ARBs (irbesartan, 300 mg; losartan, 100 mg; valsartan, 320 mg), ramipril (10 mg), HCTZ (25 mg), or placebo was determined.…”

Section: Implications Of the Reactive Rise In Plasma Renin Concentrationmentioning

confidence: 99%

Direct renin inhibition: An update

Pinto¹,

Gradman

2009

Current Science Inc

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Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action. When combined with agents that inhibit the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers, additional blood pressure reduction reflects more complete RAAS blockade. Concern that marked elevation in plasma renin concentration following aliskiren administration might lead to RAAS-induced paradoxical blood pressure increases appears unfounded, based upon analyses of patients participating in clinical trials. Studies in animals and humans indicate that aliskiren accumulates in renal tissue, blocks the intrarenal RAAS, and interferes with deleterious cellular effects of angiotensin II by mechanisms that may include enzymatic blockade of renin and prorenin at the site of the (pro)renin receptor. In patients with diabetic nephropathy, adding aliskiren to losartan resulted in an additional 20% reduction in urinary protein excretion. In patients with heart failure, aliskiren reduced brain natriuretic peptide levels when added to other RAAS inhibitors, suggesting an additional hemodynamic effect. The ASPIRE HIGHER clinical trials program is assessing whether the promising pharmacologic properties of aliskiren translate into long-term clinical benefits.

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“…The 'prohypertensive' hypothesis has not been shown in trials reporting on aliskiren efficacy in various populations [Menard and Azizi, 2007;Stanton et al 2010]. In contrast, aliskiren monotherapy has been shown to reduce blood pressure regardless of the PRA levels [Schmieder et al 2009;Stanton et al 2009].…”

Section: Paradoxical Effect Of Direct Renin Inhibitionmentioning

confidence: 99%

Direct renin inhibition: extricating facts from façades

Juncos¹

2013

Therapeutic Advances in Cardiovascular Disease

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Abstract:The renin-angiotensin system (RAS) affects vascular tone, cardiac output and kidney function. By these means the RAS plays a key role in the pathogenesis of arterial hypertension. As a result, RAS inhibition is highly effective not only in lowering blood pressure but also in reducing kidney disease progression (particularly when associated with proteinuria) and cardiovascular events.Among RAS blocking agents, direct renin inhibitors have shown not only excellent efficacy in hypertension control but also pharmacologic tolerance that is comparable with other reninangiotensin suppressors. Indeed, aliskiren, the only direct renin inhibitor available is effective in controlling blood pressure as monotherapy or in combination with other antihypertensive drugs, irrespective of patient's age, ethnicity or sex. It is also effective in patients with metabolic syndrome, obesity and diabetes. Long-term studies comparing 'hard endpoints' of aliskiren therapy versus treatment with other RAS inhibitors, including cardiac and kidney protection, are currently ongoing. Combined with other antihypertensive agents, aliskiren not only improves their hypotensive response but may also lessen the adverse effects of other drugs. In high-risk patients, however, precautions should be taken when combining two or more renin-angiotensin inhibiting agents, as tissue perfusion may be highly renin-dependent in these patients and serious adverse side effects could take place.

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Aliskiren Monotherapy Does Not Cause Paradoxical Blood Pressure Rises

Cited by 27 publications

References 20 publications

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

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

Direct renin inhibition: An update

Direct renin inhibition: extricating facts from façades

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