Skip to main content

Advertisement

Log in

Impact of better adherence to statin agents in the primary prevention of coronary artery disease

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Statins reduce cardiovascular morbidity and mortality after continuous treatment. Studies have shown that less than 50% of patients take 80% or more of prescribed doses 1 year after starting therapy.

Objective

To evaluate the impact of statin adherence on the incidence of coronary artery disease (CAD).

Methods

A cohort of 115,290 patients was reconstructed using the Régie de l’assurance maladie du Québec databases. Patients aged 45 to 85 years, without indication of cardiovascular disease (CVD), and newly treated with statins between 1999 and 2004 were eligible. A nested case-control design was used to study CAD. Every case was matched for age and duration of follow-up with randomly selected controls. The adherence level was measured by calculating the medication possession ratio. Rate ratios (RR) of CAD were determined through conditional logistic regression adjusted for several covariates.

Results

The mean patient age was 63 years, 54% had hypertension, 26% had diabetes, and 41% were males. The proportion of patients with high adherence level to statins (≥ 80%) was 74% during the first year and 53% after 1 year of follow-up. High adherence was associated with a risk reduction of 18% [RR: 0.82 (95% CI: 0.77-0.87)] compared to an adherence level of <20%. Developing a CVD during follow-up, being male, having been diagnosed with hypertension or diabetes, or having a high chronic disease score increased the risk of CAD.

Conclusion

Our study suggests that better adherence to statin agents is associated with a significant risk reduction of CAD. Adherence to statin agents needs to be improved so that patients can benefit from the full protective effects of statin therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fondation des maladies du coeur du Canada (2003) Le fardeau croissant des maladies cardiovasculaires et des accidents vasculaires cérébraux au Canada. Report no. 1-89624-32-4. Health Canada, Ottawa

  2. Writing Group Members: Thom T, Haase N, Rosamond W, Howard V, Rumsfeld J, Manolio T, Zheng Z-J, Flegal K, O’Donnell C, Kittner S, Lloyd-Jones D, Goff DC Jr, Hong Y; Members of the Statistics Committee and Stroke Statistics Subcommittee: Adams R, Friday G, Furie K, Gorelick P, Kissela B, Marler J, Meigs J, Roger V, Sidney S, Sorlie P, Steinberger J, Wasserthiel-Smoller S, Wilson M, Wolf P (2006) Heart disease and stroke statistics—2006 update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113:e85–e151

  3. Mark DB, Van de Werf FJ, Simes RJ, White HD, Wallentin LC, Califf RM, Armstrong PW, for the VIGOUR Group (2007) Cardiovascular disease on a global scale: defining the path forward for research and practice. Eur Heart J 28:2678–2684

    Article  PubMed  Google Scholar 

  4. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847

    PubMed  CAS  Google Scholar 

  5. Schnohr P, Jensen JS, Scharling H, Nordestgaard BG (2002) Coronary heart disease risk factors ranked by importance for the individual and community. A 21 year follow-up of 12 000 men and women from The Copenhagen City Heart Study. Eur Heart J 23:620–626

    Article  PubMed  CAS  Google Scholar 

  6. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lana F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937–952

    Article  PubMed  Google Scholar 

  7. Lloyd-Jones DM, Wilson PW, Larson MG, Leip R, Beiser A, D’Agostino RB, Cleeman JI, Levy D (2003) Lifetime risk of coronary heart disease by cholesterol levels at selected ages. Arch Intern Med 163:1966–1972

    Article  PubMed  Google Scholar 

  8. Cholesterol Treatment Trialists’ (CTT) Collaborators (2005) Efficacy and safety of cholesterol lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomized trials of statins. Lancet 366:1267–1278

    Article  Google Scholar 

  9. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr (1998) Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279:1615–1622

    Article  PubMed  CAS  Google Scholar 

  10. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Östergren J, for the ASCOT Investigators (2003) Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial- Lipid Lowering Arm (ASCOT-LLA): a multicentre randomized controlled trial. Lancet 361:1149–1158

    Article  PubMed  CAS  Google Scholar 

  11. Heart Protection Study Collaborative Group (2003) MRC/BHF heart protection study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomized placebo-controlled trial. Lancet 361:2005–2016

    Article  Google Scholar 

  12. Sever PS, Poulter NR, Dahlöf B, Wedel H (2005) Different time course for prevention of coronary and stroke events by atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOTT-LLA). Am J Cardiol 96:39F–44F

    Article  PubMed  CAS  Google Scholar 

  13. Colhoum HM, Betteridge DJ, Durrington PN, Hitman GA, Neil AW, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH (2004) Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet 364:685–696

    Article  Google Scholar 

  14. Mizuno K, Nakaya N, Ohashi Y et al (2008) Usefulness of pravastatin in primary prevention of cardiovascular events in women: analysis of the management of elevated cholesterol in the primary prevention group of adult Japanese (MEGA study). Circulation 4:494–502

    Article  Google Scholar 

  15. Law MR, Wald NJ, Rudnicka AR (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 326:1423

    Article  PubMed  CAS  Google Scholar 

  16. Jackevicius CA, Mamdani M, Tu JV (2002) Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 288:462–467

    Article  PubMed  Google Scholar 

  17. Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J (2002) Long-term persistence in use of statin therapy in elderly patients. JAMA 288:455–461

    Article  PubMed  Google Scholar 

  18. Perreault S, Blais L, Lamarre D, Dragomir A, Berbiche D, Lalonde L, Laurier C, St Maurice F, Collin J (2005) Persistence and determinants of statin therapy among middle-aged patients for primary and secondary prevention. Br J Clin Pharmacol 59:564–573

    Article  PubMed  CAS  Google Scholar 

  19. Bouchard MH, Dragomir A, Blais L, Bérard A, Pilon D, Perreault S (2007) Impact of adherence to statins on coronary artery disease in primary prevention. Br J Clin Pharmacol 63(6):698–708

    Article  PubMed  CAS  Google Scholar 

  20. Nelson MR, Reid CM, Ryan P, Willson K, Yelland L (2006) Self-reported adherence with medication and cardiovascular disease outcomes in the Second Australian National Blood Pressure Study (ANBP2). MJA 185(9):487–489

    PubMed  Google Scholar 

  21. International Classification of Diseases (1977) Manual of the international statistical classification of diseases, injuries, and causes of death, 9th edn. World Health Organization, Geneva

    Google Scholar 

  22. Minister of Supply and Services (1986) Canadian classification of diagnostic, therapeutic, and surgical procedures, 2nd edn. Statistics Canada Health Division, Ottawa

    Google Scholar 

  23. Régie de l’assurance maladie du Québec (2003) Liste des médicaments Québec Canada. Régie de l’assurance maladie, Québec

  24. Ministère de la Justice du Québec (2004) Rapport annuel de gestion 2003–2004. Government of Québec, Québec

  25. Tamblyn R, Lavoie G, Petrella L, Monette J (1995) The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Quebec. J Clin Epidemiol 48:999–1009

    Article  PubMed  CAS  Google Scholar 

  26. Wilchesky M, Tamblyn RM, Huang A (2004) Validation of diagnostic codes within medical services claims. J Clin Epidemiol 57:131–141

    Article  PubMed  Google Scholar 

  27. Tamblyn R, Reid T, Mayo N, McLeod P, Churchill-Smith M (2000) Using medical services claims to assess injuries in the elderly: sensitivity of diagnostic and procedure codes for injury ascertainment. J Clin Epidemiol 53:183–194

    Article  PubMed  CAS  Google Scholar 

  28. Monfared A, Rahme E, LeLorier J (2004) Accuracy of ICD-9 diagnosis code ‘410’ to identify episodes of hospitalizations for acute myocardial infarction in RAMQ. First Canadian Therapeutics Congress, 21–22 August 2004, Halifax, Canada

  29. Lubin J, Gail M (1984) Biased selection of controls for case control analyses of cohort studies. Biometrics 40:63–75

    Article  PubMed  CAS  Google Scholar 

  30. Peterson AM, Nau DP, Cramer JA, Peterson AM, Nau DP, Cramer JA, Benner J, Gwadry-Sridhar F, Nichol M (2007) A checklist for medication compliance and persistence studies using retrospective databases. Value Health 10:3–12

    Article  PubMed  Google Scholar 

  31. Osterberg L, Blaschke T (2005) Adherence to medication. N Engl J Med 353:487–497

    Article  PubMed  CAS  Google Scholar 

  32. LaRosa JC, He J, Vupputuri S (1999) Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 282:2340–2346

    Article  PubMed  CAS  Google Scholar 

  33. Kendrach M, Kelly-Freeman M (2004) Approximate equivalent rosuvastatin doses for temporary statin interchange programs. Ann Pharmacother 38:1286–1292

    Article  PubMed  CAS  Google Scholar 

  34. Jones P, Kafonet S, Laurora I, Hunninghake D (1998) Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia. Am J Cardiol 81:582–587

    Article  PubMed  CAS  Google Scholar 

  35. Von Korff M, Wagner EH, Saunders K (1992) A chronic disease score from automated pharmacy data. J Clin Epidemiol 45:197–203

    Article  Google Scholar 

  36. Essebag V, Platt R, Abrahamowicz M, Pilote L (2005) Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Method 5:5–11

    Article  Google Scholar 

  37. Greenland S (2001) Sensitivity analysis, Monte Carlo risk analysis and Bayesian uncertainty assessment. Risk Anal 21:579–583

    Article  PubMed  CAS  Google Scholar 

  38. Steenland K, Greenland S (2004) Monte Carlo sensitivity analysis and Bayesian analysis of smoking as an unmeasured confounder in a study of silica and lung cancer. Am J Epidemiol 160:384–392

    Article  PubMed  Google Scholar 

  39. Kiortsis DN, Bruckert GE, Turpin G (2000) Factors associated with low compliance with lipid-lowering drugs in hyperlipidemic patients. J Clin Pharm Ther 25:445–451

    Article  PubMed  CAS  Google Scholar 

  40. Kirkland SA, Maclean DR, Langille DB, Joffres Mr, McPherson KM, Andreou P (1999) Knowledge and awareness of risk factors for cardiovascular disease among Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992. CMAJ 161:S10–S16

    PubMed  CAS  Google Scholar 

  41. Rasmussen JN, Chong A, Alter DA (2007) Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 297:177–186

    Article  PubMed  CAS  Google Scholar 

  42. Thavendiranathan P, Bagai A, Brookhart A, Choudhry NK (2006) Primary prevention of cardiovascular diseases with statin therapy. A meta-analysis of randomized controlled trials. Arch Intern Med 166:2307–1313

    Article  PubMed  CAS  Google Scholar 

  43. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J et al (2005) Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. NEJM 352:29–38

    Article  PubMed  CAS  Google Scholar 

  44. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH et al (2005) C-reactive protein levels and outcomes after statin therapy. NEJM 352:20–28

    Article  PubMed  CAS  Google Scholar 

  45. Stamler J, Vaccaro O, Neaton JD, Wentworth D (1993) Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 16:434–444

    Article  PubMed  CAS  Google Scholar 

  46. Smith SC (2006) Current and future directions of cardiovascular risk prediction. Am J Cardiol 97:28A–32A

    Article  PubMed  Google Scholar 

  47. O’Leary DH, Polak JF, Kronmal RA, Manolia TA, Burke GL, Wolfson SK, for The Cardiovascular Health Study Collaborative Research Group (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older patients. Cardiovascular Health Study Collaborative Research Group. NEJM 340:14–22

    Article  PubMed  Google Scholar 

  48. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, Browner D (1992) Mortality over a period of 10 years in patients with peripheral arterial disease. NEJM 326:381–386

    PubMed  CAS  Google Scholar 

  49. Wilhelmsen L, Rosengren A, Eriksson H, Lappas G (2001) Heart failure in the general population of men–morbidity, risk factors and prognosis. J Intern Med 249:252–261

    Article  Google Scholar 

  50. McMurray JJ, Steward S (2000) Epidemiology, aetiology, and prognosis of heart failure. Heart 83:596–602

    Article  PubMed  CAS  Google Scholar 

  51. Kannel WB (2000) Incidence and epidemiology of heart failure. Heart Fail Rev 5:167–173

    Article  PubMed  CAS  Google Scholar 

  52. Salas M, Hofman A, Stricker BH (1999) Confounding by indication: an example of variation in the use of epidemiology terminology. Am J Epidemiol 149:981–983

    PubMed  CAS  Google Scholar 

  53. Simpson SH, Eurich DT, Majumdar SR, Padwall RS, Tsuyuki RT, Varney J, Johnson JA (2006) A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 333(7557):15–21

    Article  PubMed  Google Scholar 

  54. Rasmussen JN, Chong A, Alter DA (2007) Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 297(2):177–186

    Article  PubMed  CAS  Google Scholar 

  55. Daskalopoulo SS, Delaney JAC, Filion KB, Brophy JM, Mayo NE, Suissa S (2008) Discontinuation of statin therapy following an acute myocardial infarction: a population-based study. Eur Heart J 29(17):2083–2091

    Article  Google Scholar 

  56. Choo PW, Rand CS, Inui TS, Lee ML, Cain E, Cordeiro-Breault M, Platt R (1999) Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy. Med Care 37(9):846–857

    Article  PubMed  CAS  Google Scholar 

  57. Andrade SE, Kahler KH, Frech F, Chan KA (2006) Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf 15(8):565–574

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The Canadian Institutes of Health Research (CIHR) supported this work. Sylvie Perreault, Lyne Lalonde, Lucie Blais, and Anick Bérard are research scholars who receive financial support from the Fonds de recherche en santé du Québec.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sylvie Perreault.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perreault, S., Dragomir, A., Blais, L. et al. Impact of better adherence to statin agents in the primary prevention of coronary artery disease. Eur J Clin Pharmacol 65, 1013–1024 (2009). https://doi.org/10.1007/s00228-009-0673-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-009-0673-0

Keywords

Navigation