Renin-angiotensin-aldosterone system in the elderly: rational use of aliskiren in managing hypertension

Figures & data

Figure 1 The renin-angiotensin-aldosterone system and points of pharmacological intervention.

Abbreviations: ACE, angiotensin converting enzyme; Ang I, angiotensin I; Ang II, angiotensin II; ARB, angiotensin receptor blocker; AT1, angiotensin type 1 receptor.

Table 1 Major clinical trials of aliskiren

Reference	Publication year	Number of patients	Treatment	Main results
Gradman et al^Citation64	2005	652	Aliskiren 150–600 Irbesartan 150 Placebo	Dose ranging study, all aliskiren doses showing significant effect on SBP and DBP compared to placebo. Plateau at 300 mg aliskiren with similar effect of aliskiren 150 mg and irbesartan 150 mg
Villamil et al^Citation65	2007	2776	Aliskiren 75–300 HCTZ 6.25–25 Aliskiren/HCTZ 75–300/6.25–25	Dose ranging study, all aliskiren doses showing significant dose-dependent effect on DBP compared to placebo. Aliskiren 150–300 mg, all HCTZ doses and all combinations superior to placebo in SBP effect. Aliskiren lowered PRA
Oh et al^Citation66	2007	672	Aliskiren 150–600 Placebo	Dose ranging study, all aliskiren doses showing significant dose-dependent effect on SBP and DBP compared to placebo. Aliskiren resulted in PRA reductions and increased PRC
Kushiro et al^Citation67	2006	455	Aliskiren 75–300 Placebo	Aliskiren produced a significant and dose-dependent reduction in SBP and DBP compared to placebo. Placebo-like tolerability of aliskiren
Pool et al^Citation68	2007	1123	Aliskiren 75–300 Valsartan 80–320 Aliskiren/valsartan 75–300/80–320 Valsartan/HCTZ 160/12.5 Placebo	Aliskiren and valsartan both produced dose-related reductions in SBP and DBP. Co-administration more effective than either monotherapy and comparative to valsartan/HCTZ. Well tolerated
Dietz^Citation69	2008	694	Aliskiren 150 Atenolol 50	Similar blood pressure reduction with aliskiren and atenolol. Combination was more effective than either monotherapy
Jordan et al^Citation70	2007	490	Aliskiren 150-aliskiren/HCTZ 300/25 Irbesartan 150-irbesartan/HCTZ 300/25 Amlodipine 5-amlodipine/HCTZ 10/25 Placebo/HCTZ 25	BP lowering similar for aliskiren/HCTZ as for irbesartan/HCTZ and amlodipine/ HCTZ. Aliskiren/HCTZ tolerated similar to placebo/HCTZ
Oparil S et al^Citation71	2007	1797	Aliskiren 150–300 Valsartan 160–320 Aliskiren/valsartan 150/160–300/320 Placebo	Combination of aliskiren and valsartan more effective in reducing both SBP and DBP than either monotherapy alone
Stanton et al^Citation72	2003	226	Aliskiren 37.5–300 Losartan 100	Similar dose-dependent reduction in ABPM for aliskiren and losartan
Uresin et al^Citation73	2007	837	Aliskiren 150–300 Ramipril 5–10 Aliskiren/ramipril 5/150–10/300	Patients with diabetes. Aliskiren well tolerated either alone or in combination with ramipril. Combination treatment reduced BP 4.6/2.1 over monotherapy
Andersen et al^Citation74	2008	842	Aliskiren 150–300 (HCTZ 12.5–25) Ramipril 5–10 (HCTZ 12.5–25)	Aliskiren provided significantly better SBP and DBP reduction and higher rates of BP control than ramipril-based therapy
Dahlöf^Citation75	2007	8481	Aliskiren 150–300 Placebo (meta-analysis)	Aliskiren 150 and 300 mg treatment resulted in a significant 12.5/10.1 and 15.2/11.8 mmHg lowering in BP compared to 6.2/5.9 mmHg for placebo
Parving H-H et al^Citation76 AVOID trial	2008	599	Aliskiren 150–300 Placebo	Pts with diabetes and nephropathy optimally treated with losartan at baseline. UACR reduced 20% by aliskiren treatment compared to placebo without significant reductions in BP. UACR reduction of 50% or more was seen twice as often in aliskiren group
McMurray et al^Citation77 ALOFT	2008	302	Aliskiren 150 Placebo	Pts with CHF and HT on baseline treatment with ACE-I (or ARB) and beta-blocker. Aliskiren was well tolerated and showed favorable neurohormonal effects (pro-BNP lowering)
Solomon et al^Citation78 ALLAY	2008	460	Aliskiren Losartan Aliskiren/losartan	Aliskiren and losartan equally effective in reducing left ventricular hypertrophy, with no additional effect from combination therapy
Verdecchia et al^Citation79	2007	355	Aliskiren 75–300 Lisinopril 10	Elderly population (65 years and older) with HT. Aliskiren was well tolerated. All treatment groups lowered mean seated SBP and DBP compared to baseline
Schmieder et al^Citation80	2008	1124	Aliskiren 300 (amlodipine 5–10) HCTZ 25 (amlodipine 5–10)	Post-hoc analysis comparing elderly and very elderly to younger pts with HT. After 52 weeks aliskiren provided significantly greater reductions in SBP and PP among elderly and very elderly as compared to younger pts. Aliskiren was well tolerated and more effective than HCTZ
Yarows et al^81–82	2008	1797	Aliskiren Valsartan Aliskiren/valsartan	Subgroup analysis comparing elderly with younger patients. Aliskiren monotherapy and aliskiren/valsartan combinations were equally well tolerated in elderly as in younger pts. Combination treatment more effective than monotherapy in SBP lowering and control rates among elderly pts
Gradman et al^Citation83	2008	776	Aliskiren 150 Aliskiren 300 Placebo	Pooled analysis of 8 RCTs comparing efficacy of aliskiren among elderly vs younger pts with HT. Aliskiren 150 and 300 mg lowered BP significantly compared with placebo independent of age in pts with hypertension
Duprez et al^Citation84 AGELESS	2008	900	Aliskiren 150–300 (HCTZ 12.5–25) (amlodipine 5–10) Ramipril 5–10 (HCTZ 12.5–25) (amlodipine 5–10)	Dose escalating study of aliskiren-HCTZ-amlodipine vs ramipril-HCTZ-amlodipine among elderly pts with HT. Aliskiren-based therapy was superior to ramipril-based therapy at 12 weeks and non-inferior at 36 weeks in msSBP lowering. A higher control rate and less need for add-on therapy was seen for aliskiren compared with ramipril therapy

Abbreviations: ABPM, ambulatory blood pressure monitoring; ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; BNP, brain natriuretic peptide; BP, blood pressure; CHF, congestive heart failure; HCTZ, hydrochlorothiazide; HT, hypertension; DBP, diastolic blood pressure; SBP, systolic blood pressure; msSBP, mean seated systolic blood pressure; PRA, plasma renin activity; PRC, plasma renin concentration; PP, pulse pressure; RCTs, randomized clinical trials; UACR, urinary albumin to creatinine ratio.

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