Impact of prolonged antihypertensive duration of action on predicted clinical
outcomes in imperfectly adherent patients: comparison of aliskiren, irbesartan
and ramipril.
Author(s): Burnier M, Brede Y, Lowy A.
Affiliation(s): Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
michel.burnier@chuv.ch
Publication date & source: 2011, Int J Clin Pract. , 65(2):127-33
BACKGROUND: Most patients miss occasional doses of antihypertensives. The use of
'forgiving' drugs (i.e. drugs with duration of action longer than the 24-h dosing
interval) may allow an adequate blood pressure (BP) reduction to be maintained
despite missed doses.
AIM: To quantify the effects of adherence level and duration of action on
estimated mean systolic BP (SBP) reduction and cardiovascular disease (CVD) risk.
METHOD: For 1250 patients, we simulated 256-day dosing histories with
realistically distributed drug holidays based on a study of electronically
monitored dosing records. Adherence was set to the desired level by altering the
proportion of doses missed. Mean office SBP-lowering effect (aliskiren 300 mg,
-14.1 mmHg; irbesartan 300 mg, -13.3; ramipril 10 mg, -10.1 mmHg) and the rate of
SBP increase after stopping treatment (off-rate; aliskiren, 1.0 mmHg/day;
irbesartan, 3.6 mmHg/day; ramipril, 4.0 mmHg/day) were taken from the results of
a randomised, double-blind trial. SBP was averaged over time and patient to
estimate mean reductions in SBP and 10-year CVD risk (Framingham risk equation,
baseline absolute 10-year CVD risk: 27%).
RESULTS: Predicted reductions in SBP and CVD risk with aliskiren were larger and
less affected by imperfect adherence than the reductions with irbesartan or
ramipril. For aliskiren, reducing adherence from 90% to 60% led to a predicted
rise in SBP of 1.0 mmHg and three additional CVD events per 1000 treated
patients; larger predicted differences were observed for irbesartan (2.5 mmHg;
7.5 events/1000 treated patients) and ramipril (2.2 mmHg; 6.7 events/1000 treated
patients).
CONCLUSION: To offset the effects of imperfect adherence, a common challenge with
antihypertensives, for better BP management it may be prudent to prescribe
'forgiving' drugs.
Erratum in
Int J Clin Pract. 2011 Jul;65(7):820.
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