Impact of supportive measures on drug adherence in patients with essential hypertension treated with valsartan: the randomized, open-label, parallel group study VALIDATE.
OBJECTIVE
The majority of treated hypertensive patients do not achieve target blood pressure (BP) levels of less than 140/90 mmHg. One key reason is inadequate adherence with the prescribed drug regimen. Dosing regimens are either not executed as prescribed (noncompliance) or patients stop taking the medication (nonpersistence). It has been demonstrated that adherence with angiotensin receptor antagonists such as valsartan is high due to the tolerability profile of this drug class. The present study was designed to evaluate whether drug adherence could further be improved by the use of supportive measures.


METHODS
Twenty-eight centers were randomized to provide pharmacological treatment with or without a set of supportive measures (e.g. structured physician-patient interaction, printed information about hypertension, reminder stickers, 24 h timer, and home BP measurement device). Two hundred and two patients with grade 1 hypertension (BP at baseline 149.8 +/- 6.2/93.9 +/- 4.4 mmHg) who were either newly diagnosed or who had not been treated for at least 1 year were included in this trial. All patients entered the 34-week treatment phase with valsartan 160 mg daily. Titration to valsartan 160 mg/hydrochlorothiazide 12.5 mg was allowed if necessary. Drug adherence was assessed by electronic monitors (Medication Event Monitoring System).


RESULTS
Patients treated with a valsartan-based therapy receiving supportive measures as compared with the standard care group demonstrated an initially higher level of adherence with a maximum absolute difference of 7.8% (P = 0.041). This difference did not persist over the observation period but faded with time. In parallel, execution of the dosing regimen (compliance) was also improved in the intervention group during the early months of treatment but this effect also disappeared by the end of the observation period. In contrast, persistence in the two groups slowly but continuously separated over time. Estimated absolute difference in persistence at the end of the 34-weeks study between the two groups was 7.6% (95.9 vs. 88.3%) reflecting a 66% lower hazard of discontinuation in the intervention group (P = 0.073). BP control improved more in patients with the supportive measures.


CONCLUSIONS
Drug adherence improved initially with the use of supportive measures. However, this effect faded with time mainly because of the short-lived improvement in the quality of execution (compliance) achieved. In contrast, a longer lasting effect of the chosen supportive measures on persistence could be demonstrated, which, however, at least under the conditions of the present study, did not translate into a persistent improvement of medication adherence.
Düsing
Rainer
R
Medizinische Klinik und Poliklinik 1, Universitätsklinikum Bonn, Bonn, Germany.
Handrock
Renate
R
Klebs
Sven
S
Tousset
Eric
E
Vrijens
Bernard
B
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068756:Valsartan; D014633:Valine