title: Impact of prolonged antihypertensive duration of action on predicted clinical outcomes in imperfectly adherent patients: comparison of aliskiren, irbesartan and ramipril.
abstract: 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.
  
  
  OBJECTIVE
  To quantify the effects of adherence level and duration of action on estimated mean systolic BP (SBP) reduction and cardiovascular disease (CVD) risk.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  To offset the effects of imperfect adherence, a common challenge with antihypertensives, for better BP management it may be prudent to prescribe 'forgiving' drugs.
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. michel.burnier@chuv.ch
authors.forename: M
authors.initials: M
authors.lastname: Burnier
authors.forename: Y
authors.initials: Y
authors.lastname: Brede
authors.forename: A
authors.initials: A
authors.lastname: Lowy
mesh_terms: D000368:Aged; D000577:Amides / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000077405:Irbesartan; D008297:Male; D055118:Medication Adherence; D017257:Ramipril / Q000627:therapeutic use; D012307:Risk Factors; D013777:Tetrazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D005650:Fumarates; D013777:Tetrazoles; C446481:aliskiren; D000077405:Irbesartan; D017257:Ramipril