title: Effects on blood pressure and cardiovascular risk of variations in patients' adherence to prescribed antihypertensive drugs: role of duration of drug action.
abstract: OBJECTIVE
  To determine the effects of imperfect adherence (i.e. occasionally missing prescribed doses), and the influence of rate of loss of antihypertensive effect during treatment interruption, on the predicted clinical effectiveness of antihypertensive drugs in reducing mean systolic blood pressure (SBP) and cardiovascular disease (CVD) risk.
  
  
  METHODS
  The effects of imperfect adherence to antihypertensive treatment regimens were estimated using published patterns of missed doses, and taking into account the rate of loss of antihypertensive effect when doses are missed (loss of BP reduction in mmHg/day; the off-rate), which varies between drugs. Outcome measures were the predicted mean SBP reduction and CVD risk, determined from the Framingham Risk Equation for CVD.
  
  
  RESULTS
  In patients taking 75% of prescribed doses (typical of clinical practice), only long-acting drugs with an off-rate of ∼1 mmHg/day were predicted to maintain almost the full mean SBP-lowering effect throughout the modelled period. In such patients, using shorter-acting drugs (e.g. an off-rate of ∼5-6 mmHg/day) was predicted to lead to a clinically relevant loss of mean SBP reduction of > 2 mmHg. This change also influenced the predicted CVD risk reduction; in patients with a baseline 10-year CVD risk of 27.0% and who were taking 75% of prescribed doses, a difference in off-rate from 1 to 5 mmHg/day led to a predicted 0.5% absolute increase in 10-year CVD risk.
  
  
  CONCLUSIONS
  In patients who occasionally miss doses of antihypertensives, modest differences in the rate of loss of antihypertensive effect following treatment interruption may have a clinically relevant impact on SBP reduction and CVD risk. While clinicians must make every effort to counsel and encourage each of their patients to adhere to their prescribed medication, it may also be prudent to prescribe drugs with a low off-rate to mitigate the potential consequences of missing doses.
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. adam.lowy@novartis.com
authors.forename: A
authors.initials: A
authors.lastname: Lowy
authors.forename: V C
authors.initials: VC
authors.lastname: Munk
authors.forename: S H
authors.initials: SH
authors.lastname: Ong
authors.forename: M
authors.initials: M
authors.lastname: Burnier
authors.forename: B
authors.initials: B
authors.lastname: Vrijens
authors.forename: E P
authors.initials: EP
authors.lastname: Tousset
authors.forename: J
authors.initials: J
authors.lastname: Urquhart
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence; D055553:Prescription Drugs / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D055553:Prescription Drugs