HYVET (Hypertension in the Very Elderly Trial)
The HYVET trial was a landmark randomized, double-blind, placebo-controlled study that used indapamide sustained-release 1.5 mg (a thiazide-like diuretic) with optional addition of perindopril 2-4 mg (an ACE inhibitor) to treat hypertension in patients aged 80 years and older. 1, 2
Trial Design and Population
HYVET recruited 3,845 participants aged ≥80 years with sustained sitting systolic blood pressure of 160-199 mmHg and diastolic blood pressure of 90-109 mmHg after a 2-month single-blind placebo run-in period 1, 2
Participants were recruited from Eastern and Western Europe, China, Australasia, and Tunisia 1, 3
The trial compared active treatment (indapamide sustained-release 1.5 mg with optional perindopril 2-4 mg addition) versus matching placebo to reach a target blood pressure of less than 150/80 mmHg 2
The study was designed as a double-blind, placebo-controlled trial with an average follow-up of 5 years, though the actual median follow-up was approximately 2 years 1, 2
Primary and Secondary Outcomes
The primary endpoint was stroke events (fatal and non-fatal), with the trial designed to detect a 35% difference between placebo and active treatment with 90% power at the 1% level of significance 1
Secondary outcome measures included total mortality, cardiovascular mortality, cardiac mortality, stroke mortality, heart failure, cardiovascular events, and skeletal fractures 1, 3
Key Results
Active treatment reduced total mortality by 21% (hazard ratio 0.79, P=0.019), stroke by 30% (P=0.055), cardiovascular mortality by 23%, and heart failure by 64% 2
In the per-protocol analysis, strokes were reduced by 34% (P=0.026), total mortality by 28% (P=0.001), cardiovascular events by 37% (P<0.001), and heart failure by 72% (P<0.001) 2
Treatment benefits were consistent across pre-specified subgroups including age (80-84.9 vs ≥85 years), sex, history of cardiovascular disease, and baseline systolic blood pressure levels 2
Despite blood pressure lowering, treatment with the thiazide-like diuretic and ACE inhibitor did not increase and may have decreased fracture rate (hazard ratio 0.58,95% CI 0.33-1.00, P=0.0498) 3
Frailty Analysis
A post-hoc frailty analysis using a frailty index based on 60 potential deficits found no evidence that frailty modified the positive impact of antihypertensive treatment 4
Both frailer and fitter older adults with hypertension appeared to gain from treatment, with point estimates of hazard ratios for treatment effect decreasing as frailty index increased 4
Clinical Significance
HYVET provided definitive evidence that treating hypertension in patients aged 80 and older with indapamide-based therapy (with optional perindopril addition) reduces mortality and cardiovascular events, even in frail individuals 2, 4
This trial directly influenced current guidelines recommending blood pressure treatment in very elderly patients, with the 2020 International Society of Hypertension guidelines specifically citing HYVET as evidence for treating patients aged >80 years 5
The combination of a thiazide-like diuretic with an ACE inhibitor proved both effective and safe in this vulnerable population, establishing this regimen as a preferred approach for very elderly hypertensive patients 6, 2