HYVET

Treatment of Hypertension in Patients 80 years of Age or Older (2008)

Design: Double-blinded, placebo-controlled RCT

  • Intention-to-Treat Analysis
P N = 3845
SBP > 160mmHg
I Indapamide 1.5mg SR daily
* If needed to target BP of 150/80mmHg, perindopril 2 or 4mg daily was added
C Placebo
* If needed to target BP of 150/80mmHg, placebo daily was added
O Primary endpoint: fatal or non-fatal stroke

Secondary endpoints: death from any cause, death from cardiovascular causes, death from cardiac causes, death from stroke

Patients:

  • Active treatment: 83.6 + 3.2 yo vs. Placebo: 83.5 + 3.1 yo
  • BP:
    While sitting: 173/90.8
    While standing: 168/88.6
  • Orthostatic hypotension: ~32%
  • HR: 74.5 + 9
  • Cardiac history:
    • CVD ~11.5-12%
    • HTN: 90%
    • Antihypertensive treatment: 64-65%
    • Stroke 6.8%
    • MI: 3.1%
    • HF: 2.9%

Outcomes:

  • Median duration of f/u: 1.8 years
    • Active-treatment:
      25.8% indapamide alone, 23.9% + perindopril 2mg, 49.5% + perindopril 4mg
  • Surrogate markers:
    • Drop in sitting BP:
      Placebo: 14.5+18.5mmHg/6.8+10.5mmHg
      Active treatment: 29.5+15.4mmHg/12.9+9.5mmHg
    • Drop in standing BP:
      Placebo: 13.6+18.9mmHg/7.0+10.9mmHg
      Active treatment: 28.3+16.5mmHg/12.4+10.3mmH
  • Primary endpoint: 30% reduction in the rate (-1 to 51%, P = 0.06)
    • NNT = 11 strokes per 1000 patients treated for 2 years (0-21)
  • Death: 21% reduction in the rate (4-35, P = 0.02)
    • Cardiac-caused death NSS
  • Fatal stroke: 39% reduction in the rate (1-62, P = 0.05)
  • Fatal or non-fatal heart failure: 64% reduction (42-78, P<0.001)
  • Cardiovascular event (death from CV causes or stroke, MI or HF):
    34% reduction (18-47%, P < 0.001)

    • NSS for MI
    • SS for death from stroke (P = 0.06, crosses 1), death from CV causes (P = 0.06, crosses 1) and HF

Safety:

  • NSS in potassium levels, uric acid, glucose, or creatinine
  • Serious ADRs: Placebo (448/1912) vs. Active Tx (358/1933), P = 0.001

CHEP Guidelines:

  • In the very elderly (> 80 yo), SBP < 150mmHg (Grade C)
  • HYVET: BP reduced to 144/77mmHg (15/6.1mmHg lower than placebo group)
    • data safety and monitoring board stopped trial early due to SS efficacy outcomes

Take-away points:

  • ?Restriction to background therapy (more serious ADRs in placebo)
  • HYVET did not study other BP targets – ?benefit vs risk ratio of lower BP targets in this patient population
  • Targeting BP of 150/80 (50% reached target in HYVET after 2 years) with diuretic + ACEI in > 80 yo: SS for reduction in stroke (P=0.06, crosses 1), death from stroke, CV death (P = 0.06, crosses 1), heart failure
    (NSS for MI)

    • Patient population: majority did not have CVD, MI, HF, stroke or orthostatic hypotension – patient population studied was relatively healthy; therefore, results may not be applicable to the general elderly population
  • Safety: tolerability of SBP lowering in higher risk + frailer patients?
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