HYVET Study: Landmark Trial for Hypertension in Patients ≥80 Years
The Hypertension in the Very Elderly Trial (HYVET) is the definitive study that evaluated antihypertensive treatment in patients older than 80 years, demonstrating significant mortality and morbidity benefits. 1
Study Design and Population
HYVET was a randomized, double-blind, placebo-controlled trial that enrolled 3,845 patients aged ≥80 years from Europe, China, Australasia, and Tunisia. 1 The trial specifically targeted patients with sustained systolic blood pressure of 160-199 mmHg and diastolic pressure below 110 mmHg. 2, 1
Key enrollment criteria included:
- Mean age of participants: 83.6 years 1
- Mean baseline blood pressure: 173.0/90.8 mmHg while sitting 1
- Only 11.8% had a history of cardiovascular disease, meaning the majority were primary prevention patients 1
- Standing systolic blood pressure had to be >140 mmHg to exclude those with significant orthostatic hypotension 3
Treatment Protocol
The active treatment arm received indapamide sustained-release 1.5 mg daily, with perindopril 2-4 mg added as needed to achieve a target blood pressure of <150/80 mmHg. 1 This represents a thiazide-like diuretic plus ACE inhibitor combination strategy. 1
Primary Outcomes and Benefits
The trial demonstrated remarkable benefits across multiple endpoints:
- 30% reduction in fatal or nonfatal stroke (95% CI, -1 to 51; P=0.06) 1
- 39% reduction in death from stroke (95% CI, 1 to 62; P=0.05) 1
- 21% reduction in all-cause mortality (95% CI, 4 to 35; P=0.02) - this is particularly significant as it definitively answered concerns that treatment might increase mortality 1
- 23% reduction in cardiovascular death (95% CI, -1 to 40; P=0.06) 1
- 64% reduction in heart failure (95% CI, 42 to 78; P<0.001) 1
The median follow-up was 1.8 years, with a mean blood pressure reduction of 15.0/6.1 mmHg in the active treatment group compared to placebo at 2 years. 1
Subgroup Analysis Consistency
Importantly, benefits were consistent across all pre-specified subgroups, including men (HR 0.82), women (HR 0.77), those aged 80-84.9 years (HR 0.76), those aged ≥85 years (HR 0.87), patients with prior cardiovascular disease (HR 0.76), and those without (HR 0.81). 2 This consistency strengthens the generalizability of the findings.
The per-protocol analysis showed even more impressive results: 34% stroke reduction (P=0.026), 28% total mortality reduction (P=0.001), 37% cardiovascular event reduction (P<0.001), and 72% heart failure reduction (P<0.001). 2
Safety Profile
Active treatment was associated with fewer serious adverse events (358 in treatment group vs. 448 in placebo group; P=0.001), contradicting concerns about harm from treatment in this age group. 1
Impact on Guidelines
HYVET fundamentally changed hypertension management recommendations for the very elderly. Multiple international guidelines now cite HYVET as the primary evidence supporting treatment in patients ≥80 years, with most recommending a blood pressure target of <150/90 mmHg for this population. 4 The European Society of Cardiology specifically notes that treatment should be continued or initiated when patients turn 80, starting with monotherapy and adding a second drug if needed. 4
Important Caveats
HYVET patients were generally in good condition, raising questions about extrapolation to more fragile octogenarians. 4 There were too few patients aged ≥90 years to determine benefit at extreme age. 2 Real-world implementation may be challenging, as one retrospective study found that 40% of very elderly hypertensive patients had documented adverse drug reactions limiting further intervention. 5