Valsartan Anti-hypertensive Long-term Use Evaluation (VALUE)

• Valsartan Anti-hypertensive Long-term Use Evaluation (VALUE) outcome trial to compare a angiotensin II receptor blocker (ARB), valsartan, with a third-generation calcium channel blocker (CCB), amlodipine, in a general hypertensive population at high cardiovascular risk
  • participants were mainly previously treated (92%) patients with hypertension
    • randomisation to low-dose valsartan (80 mg) or amlodipine (5 mg)
      • this was followed titration of therapy at monthly inter-vals to achieve a target blood pressure < 140/90 mmHg i.e. to valsartan 160 mg or amlodipine 10 mg followed by introduction of diuretic (hydrochlorothiazide) and then free add-on therapy as necessary
      • 15,313 individuals were randomised at 942 sites in 31 countries, and average follow-up was 4.2 years
      • 90 patients were lost to follow-up
      • on entry to the study: average age of 67 years, BP 155/88 mmHg
        • nearly 50% had coronary heart disease
        • one third had diabetes
        • one third had hypercholesterolaemia
        • one quarter were smokers
        • about one in five had proteinuria
        • about one in five had left ventricular hypertrophy and/or cerebrovascular disease
        • one in eight had peripheral arterial disease
• Results
  • average blood pressure, 138/79 mmHg, at the end of the study
    • blood pressure was reduced by around 15/10mmHg during the course of the study
  • blood pressure levels were significantly lower in the amlodipine-treated patients
    • initially differences were more than 4/2 mmHg in favour of amlodipine
    • beyond six months the advantage in favour of amlodipine more than 2 mmHg for systolic blood pressure and 1–2 mmHg for diastolic blood pressure
  • the incidence of the composite cardiac outcome did not differ between the groups (hazard ratio 1.03, 95% confidence intervals 0.94–1.14; p=0.94) - this is despite the inferior blood pressure control of valsartan in comparison to amlodipine
  • no significant differences between the treatments for stroke or all-cause mortality
  • incidence of new-onset diabetes was significantly lower in valsartan-treated patients (23% reduction; p<0.0001)
  • both treatments were well tolerated - however significantly fewer discontinued therapy due to adverse events in the valsartan group (p=0.045) and peripheral oedema was much more common in the amlodipine group (33% vs. 15%, p<0.0001)
  • admission to hospital for heart failure was significantly lower with valsartan treated group
  • reaching blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits for subsequent major outcomes; the blood pressure response after just 1 month of treatment predicted events and survival

Reference:

1. Weber M et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004 Jun 19;363(9426):2049-51.
2. Julius S et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004 Jun 19;363(9426):2022-31