Monitoring adherence to drug treatment by using change in cholesterol concentration: secondary analysis of trial data

BMJ. 2011 Jan 21:342:d12. doi: 10.1136/bmj.d12.

Abstract

Objective: To estimate the accuracy of monitoring cholesterol concentration for detecting non-adherence to lipid lowering treatment.

Design: Secondary analysis of data on cholesterol concentration in the LIPID (long term intervention with pravastatin in ischaemic disease) study by using three measures of non-adherence: discontinuation of treatment, allocation to placebo arm, less than 80% of pills taken.

Setting: Randomised placebo controlled trial in Australia and New Zealand.

Participants: 9014 patients with previous coronary heart disease.

Interventions: Pravastatin 40 mg or placebo daily.

Main outcome measures: Sensitivity, specificity, area under the receiver operating characteristics (ROC) curve, post-test probability.

Results: Monitoring of cholesterol concentration had modest ability for detecting complete non-adherence. One year after the start of treatment, half (1957/3937) of the non-adherent patients and 6% (253/3944) of adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was reasonable (area under the curve 0.89). Cholesterol monitoring, however, had weak ability for detecting partial non-adherence. One year after the start of treatment, 16% (34/213) of partially adherent and 4% (155/3585) of fully adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was poor (area under the curve 0.65). For typical pre-test probabilities of non-adherence ranging from low (25%) to high (75%), the post-test probabilities indicate continuing uncertainty after lipid testing. A patient with no change in low density lipoprotein cholesterol concentration has a post-test probability of being completely non-adherent of between 67% and 95% and a post-test probability of being partially non-adherent of between 48% and 89%. A patient with a decrease in concentration of 1.0 mmol/L has a post-test probability of being completely non-adherent of between 7% and 40% and a post-test probability of being partially non-adherent of between 21% and 71%.

Conclusions: Monitoring concentration of low density lipoprotein (or total) cholesterol has modest ability to detect complete non-adherence or non-persistence with pravastatin treatment and weak ability to detect partial non-adherence. Results of monitoring should be considered as no more than an adjunct to careful discussion with patients about adherence.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Biomarkers / metabolism
  • Cholesterol, LDL / metabolism*
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Medication Adherence*
  • Pravastatin / therapeutic use*
  • ROC Curve

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pravastatin