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In 511 people with mild-to-moderate Alzheimer disease, 8 mg nilvadipine daily for 78 weeks was safe but no better than placebo on ADAS-Cog 12 (p=0.465).

Source

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial

Lawlor B, Segurado R, Kennelly S, et al. · PLoS medicine · 2018

doi.org/10.1371/journal.pmed.1002660Read the full paper ↗133 citationscc by

Study at a glance

Design
RCT — Phase III investigator-led double-blind RCT of 8 mg sustained-release nilvadipine vs placebo for 78 weeks across 23 European centres (NILVAD)
N
N=511 · 577 screened; 511 randomised (258 placebo, 253 nilvadipine); mITT n=498
Population
Adults >50 years with mild-to-moderate probable Alzheimer disease (NINCDS-ADRDA; SMMSE 12–26) at 23 academic centres in nine European countries
Outcome
ADAS-Cog 12 progression (primary); gated CDR-sb; function, safety

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Randomised 511 eligible participants (258 placebo, 253 nilvadipine) at 23 centres in nine countries to once-daily 8 mg sustained-release nilvadipine or matched placebo for 78 weeks, with ADAS-Cog 12 as the primary outcome in a 498-person mITT set.

What they found

No treatment benefit on the co-primary (p=0.465). 78-week ADAS-Cog 12 decline was 9.63 on placebo vs 9.41 on nilvadipine. Secondary CDR-sb and Disability Assessment for Dementia were also null. Deaths were similar (3 vs 4); AEs (1,129 vs 1,030) and SAEs (146 vs 101) were higher on nilvadipine.

The limits

What it doesn't show

The trial cannot rule out benefit at a pre-dementia stage; diagnosis lacked amyloid biomarkers, so some non-Alzheimer dementia was likely included.

Key terms

Nilvadipine
Dihydropyridine calcium-channel blocker licensed for hypertension; tested here as a possible Alzheimer disease disease-modifier.
ADAS-Cog 12
Alzheimer's Disease Assessment Scale cognitive subscale; the a priori primary outcome.
CDR-sb
Clinical Dementia Rating sum of boxes; gated co-primary, only promoted if ADAS-Cog succeeded.
mITT
Modified intention-to-treat analysis set (n=498).
SMMSE
Standardised Mini-Mental State Examination; entry required score ≥12 and <27 (mean 20.4).
NILVAD
EU-funded Phase III investigator-driven trial (NCT02017340).

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Randomised N was:

Common questions

How many were randomised?

511 (258 placebo, 253 nilvadipine) of 577 screened.

What dose and duration?

8 mg sustained-release nilvadipine once daily for 78 weeks (~18 months).

Did cognition slow?

No; primary p=0.465, similar ADAS-Cog 12 decline at 78 weeks.

Was it safe?

Generally yes, but AEs and SAEs were more frequent on nilvadipine.

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