Long-Term Antihypertensive Efficacy and Safety of the Oral Direct Renin Inhibitor Aliskiren
Why the study?
Does aliskiren improve blood pressure reduction compared to hydrochlorothiazide in patients with essential hypertension?
Population
1,124 patients with essential hypertension (mean sitting diastolic blood pressure 95 to 109 mm Hg)
Comparison
Aliskiren 150 mg once daily, forced titration to… vs Hydrochlorothiazide 12.5 mg once daily, forced…
Design
RCT, randomized, double-blind
Follow-up
52 weeks
Authors
Discussion
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Implication
Aliskiren may be preferred over hydrochlorothiazide for sustained BP control; extends RCT evidence for direct renin inhibition to 1 year.
Key Points
- To evaluate the long-term antihypertensive efficacy and safety of the direct renin inhibitor aliskiren compared with the standard diuretic hydrochlorothiazide in essential hypertension.
- A randomized, double-blind, multicenter trial randomized 1124 patients with essential hypertension (mean sitting diastolic blood pressure 95 to 109 mm Hg) after a 2- to 4-week placebo run-in.
- Patients received once-daily aliskiren 150 mg (n=459), hydrochlorothiazide 12.5 mg (n=444), or placebo (n=221), with forced titration at week 3, placebo reassignment at week 6, and optional add-on amlodipine (5 to 10 mg) from week 12 for uncontrolled blood pressure.
- Efficacy outcomes were evaluated up to 52 weeks in the intention-to-treat population using the last observation carried forward method.
- At week 12 monotherapy, aliskiren 300 mg produced superior blood pressure reductions compared to hydrochlorothiazide 25 mg (-17.4/-12.2 versus -14.7/-10.3 mm Hg; P<0.001).
- Blood pressure reductions were significantly greater with aliskiren-based therapy versus hydrochlorothiazide-based therapy at week 26 (-20.3/-14.2 versus -18.6/-13.0 mm Hg; P<0.05) and week 52 (-22.1/-16.0 versus -21.2/-15.0 mm Hg; P<0.05 for diastolic blood pressure).
- Overall adverse event rates were 65.2% with aliskiren and 61.5% with hydrochlorothiazide, while hypokalemia was significantly less frequent with aliskiren (0.9% versus 17.9%; P<0.0001).
Structured PICO
Does aliskiren improve blood pressure reduction compared to hydrochlorothiazide in patients with essential hypertension?
P
Population
1,124 patients with essential hypertension (mean sitting diastolic blood pressure 95 to 109 mm Hg)
I
Intervention
Aliskiren 150 mg once daily, forced titration to 300 mg at week 3, with optional addition of amlodipine 5-10 mg from week 12 for uncontrolled BP, over 52 weeks
C
Comparator
Hydrochlorothiazide 12.5 mg once daily, forced titration to 25 mg at week 3, with optional addition of amlodipine 5-10 mg from week 12 for uncontrolled BP, over 52 weeks
O
Outcome
Blood pressure reductions (mean sitting systolic BP/mean sitting diastolic BP) at week 26 and week 52surrogate
Aliskiren provides significantly greater long-term blood pressure reduction compared to hydrochlorothiazide in patients with essential hypertension, with a lower risk of hypokalemia.
Cite This Study
Schmieder et al. (2009) studied this question.