Division of Clinical Research and Training

Apollo – A randomized controlled trial of aliskiren in the prevention of Major Cardiovascular events in elderly people

Details

a) Background:

1. CVD increases substantially with aging, but it is not an inevitable consequence of age. Risk can be reduced with aggressive management of CV risk factors.
2. CVD and risk factors (hypertension) are major determinants of physical and cognitive disability and dependence in the elderly, with resultant increased disease burden
3. Elderly subjects, with and without CVD, would benefit from BP lowering.
4. Activated RAAS plays major role in pathogenesis of CVD. Blockade of RAAS by Aliskiren, by lowering BP and having other BP-independent vascular protective effects, will very likely reduce CVD risk and enhance successful aging.
5. Current recommendations to treat SBP to >140 mm Hg, in elderly people are based on consensus and extrapolation from epidemiologic data.
6. Considerable uncertainty (clinical equipoise) remains regarding definition and treatment of elevated BP in vast majority of elderly.

b) Aim/objective:

We studied the unclear question whether blood pressure (BP) lowering  reduces cardiovascular disease (CVD) in elderly individuals with systolic BP <160 mm Hg.

c) Methods & Results:

We initiated a randomized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure (SBP) between 130 and 159 mm Hg, for 5 years. Following 5-week active run-in, participants were randomized to aliskiren (300 mg) or placebo, and to an additional antihypertensive [hydrochlorothiazide (25 mg) or amlodipine (5 mg)], or their respective placeboes. Study was terminated by sponsor after 1759 subjects (age 72.1 ± 5.2 years, 88% receiving at least one antihypertensive) were randomized and followed for 0.6 year. Study drugs were well tolerated with few serious adverse events during run-in and after randomization, with no significant differences between treatment groups. By design, three levels of BP reductions were achieved, adjusted mean BP reductions of 3.5/1.7 mm Hg (P < 0.001) by aliskiren, 6.8/3.3 mm Hg (P < 0.001) by hydrochlorothiazide or amlodipine, and 10.3/5.0 mm Hg (P < 0.001) by double therapy compared with placebo. Twenty-five major CVD events occurred. Non-significant trends towards fewer CVD events with greater BP reductions are evident: hazard ratios (HR) 0.82 [95% confidence interval (CI): 0.37-1.81] for 3.5 mm Hg SBP reduction; HR 0.45 (95% CI: 0.19-1.04) for 6.8 mm Hg; and HR 0.25 (0.05-1.18) for 10.3 mm Hg reduction for primary composite of CV death, MI, stroke, or significant heart failure.

e) Total recruitment & no. of sites:

Global 1759 from 145 sites in 17 countries; India  124 from 20 sites.

f) Conclusion:

Sizeable reductions in BP, with potential for substantial CVD reduction, can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension.

g) Publication status (Name & year): Eur Heart J. 2014

h) Publication link:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994823/

i) Updated as on: 30^th June 2023