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Should very old frail people still get blood-pressure pills?

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In 2,656 HYVET participants aged 80+, frailty did not cancel the benefit of indapamide±perindopril: stroke HR 0.64 and CV-event HR 0.59, with no significant FI×treatment interaction.

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No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over

Warwick J, Falaschetti E, Rockwood K, et al. · BMC medicine · 2015

doi.org/10.1186/s12916-015-0328-1Read the full paper ↗233 citationscc by

Study at a glance

Design
RCT — Secondary frailty-index analysis of HYVET, a double-blind placebo-controlled antihypertensive RCT in people aged ≥80.
N
N=2656 · HYVET randomized 3,845; FI calculable in 2,656 with extra QoL data (1,324 placebo; 1,332 active).
Population
Hypertensive adults aged 80+ in HYVET (mean age ~83.5; ~61% women).
Outcome
Stroke, cardiovascular events, and total mortality; interaction of treatment with baseline 60-item frailty index.

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

What they did

Built a 60-deficit frailty index at entry for HYVET participants who completed a quality-of-life questionnaire, then fit Cox models for stroke, CV events, and death with a treatment×FI interaction, stratified by region and adjusted for age and sex.

What they found

Median FI was 0.17 (IQR 0.11–0.24). Active treatment still cut fatal/non-fatal stroke (HR 0.64) and CV events (HR 0.59); total mortality HR 0.83 was not significant. Interaction p-values were 0.52, 0.73, and 0.61. Point estimates even suggested larger relative benefit at higher FI, with wide CIs.

The limits

What it doesn't show

FI was missing in 1,189 randomized patients (slightly higher MMSE in those without FI), so the frailest of the frail may be under-represented; HYVET already excluded many very sick elders.

Key terms

HYVET
Hypertension in the Very Elderly Trial: double-blind RCT of indapamide SR 1.5 mg ± perindopril vs placebo in people ≥80 (NCT00122811).
Frailty index (FI)
Proportion of 60 potential deficits present at entry (median 0.17).
Treatment×frailty interaction
Test of whether antihypertensive benefit shrinks as FI rises; none was significant.
Indapamide SR
Active-arm thiazide-like diuretic 1.5 mg, with optional perindopril 2–4 mg.
Very elderly hypertension
HYVET population: mean age ~83.5 years with sitting SBP ~173 mmHg.

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FI was available for about:

Common questions

How many people had an FI?

2,656 of 3,845 randomized HYVET participants.

Did frailty wipe out treatment benefit?

No—no significant interaction for stroke, CV events, or death.

Stroke HR on active treatment?

0.64 (95% CI 0.42–0.96) after FI, age, and sex adjustment.

What drug was studied?

Indapamide sustained-release 1.5 mg ± perindopril 2–4 mg vs placebo.

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