Background and objective: Hypertension guidelines emphasise the need to treat high blood pressure (BP) early and aggressively, giving fixed-dose combinations special consideration. Hitherto, it has not been assessed in a sequential way whether hypertensive patients with inadequately controlled hypertension with an angiotensin II receptor antagonist/hydrochlorothiazide combination benefit from a dose increase of the diuretic. We investigated the efficacy and safety of valsartan 160mg/hydrochlorothiazide 25mg combination in patients with hypertension that was not adequately controlled by valsartan 160mg/hydrochlorothiazide 12.5mg.
Patients and methods: This was a multicentre, single-group, prospective study of 646 patients with moderate hypertension (diastolic BP [DBP] 100-109mm Hg). Patients were treated for 4 weeks with valsartan 160mg/hydrochlorothiazide 12.5mg (phase 1: weeks 1-4). In case of non-response (DBP >/=90mm Hg; n = 224) patients were treated for a further 4 weeks with valsartan 160mg/hydrochlorothiazide 25mg (phase 2: weeks 5-8). The primary efficacy measure was a change in mean sitting trough DBP at study end compared with the beginning of phase 2 in the intention-to-treat (ITT) population (n = 221).
Results: Mean age of patients at entry was 58.6 years; 53.7% of patients were female. In phase 1, systolic BP (SBP)/DBP decreased from a baseline value of 161.9/103.3mm Hg by -16.1/-12.4mm Hg (normalisation rate 38.3%, response rate 64.5%). In phase 2, in the ITT non-responder population the additional SBP/DBP decrease was -8.4/-8.3mm Hg. Overall, the normalisation rate in all patients was 55.4% and the responder rate was 76.3%.Tolerability of both the valsartan 160mg/hydrochlorothiazide 12.5mg and the valsartan 160mg/hydrochlorothiazide 25mg combinations was very good, and the switch to the higher dose did not result in an increase in adverse events (AEs) or laboratory abnormalities. Only 16.6% of patients in phase 1 and 10.3% of patients in phase 2 experienced one or more AEs.
Conclusion: In patients with moderate hypertension, first-line therapy with the fixed-dose valsartan/hydrochlorothiazide combination leads to high normalisation and response rates. Patients with hypertension not controlled by valsartan 160mg/ hydrochlorothiazide 12.5mg clearly benefit from dose titration to valsartan 160mg/hydrochlorothiazide 25mg with a clinically relevant additional BP response and have excellent tolerability.