Persistence and determinants of statin therapy among middle-aged patients free of cardiovascular disease

Aim. Statins have been shown to significantly reduce morbidity and mortality both in patients with coronary artery disease and in those with dyslipidemia when they are taken regularly. Middle-aged patients have the highest level of forecasting benefit, and little is known about the persistence rate of these therapies in a real-life setting.Objective. To evaluate the persistence rate of middle-aged patients initiating statin therapy as well as its relation to patients’ demographic and clinical characteristics.Methods. A cohort of 25,733 patients was reconstructed from prescription data recorded in the Régie de l’assurance maladie du Québec administrative database. All patients aged 50–64 years old who received at least one statin prescription between January 1, 1998 and December 31, 2000 for a new intention of treatment for dyslipidemia were included in the cohort and followed up until June 30, 2001. The date of the first prescription of statin was defined as the index date. The cumulative persistence rate was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of ceasing statins after adjustment. Results. Mean age of patients initiating statin agents was 58 years; 39%were male, 24% received social assistance, 19% had diabetes, 30% had hypertension and 11% had a respiratory disease at cohort entry. Persistence with statin therapy fell to 67% in the first 6 months after treatment and continued to decline over the next 3 years to 39%. At 3 years, persistence varied significantly with statin agents. After controlling for individual patients’ demographic and clinical characteristics, we found that patients who were prescribed fluvastatin, lovastatin and atorvastatin had a higher rate of cessation than those on simvastatin and pravastatin. The adjusted rate ratio of ceasing statin agents in patients with other risk factors of cardiovascular disease, such as diabetes (HR: 0.78; 0.75–0.82) or hypertension (HR: 0.72; 0.69–0.74), demonstrated a lower cessation rate. We observed lower persistence in patients who used the greatest number of pharmacies and prescribing physicians.Conclusion. This analysis indicates that barriers to persistence occur early in the therapeutic course. Overall persistence with statins is low, particularly among patients with few other cardiovascular risk factors.

[1]  Peter J. Neumann,et al.  Long-term persistence in use of statin therapy in elderly patients. , 2002, JAMA.

[2]  R. McPherson,et al.  Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update. , 2003, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[3]  S. Perreault,et al.  Treating hyperlipidemia for the primary prevention of coronary disease. Are higher dosages of lovastatin cost-effective? , 1998, Archives of internal medicine.

[4]  R. Collins,et al.  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 randomised controlled trial , 2003, The Lancet.

[5]  R. Platt,et al.  Discontinuation of antihyperlipidemic drugs--do rates reported in clinical trials reflect rates in primary care settings? , 1995, The New England journal of medicine.

[6]  D A Savitz,et al.  Recall accuracy for prescription medications: self-report compared with database information. , 1995, American journal of epidemiology.

[7]  L. Coupal,et al.  Impact of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease. , 1999, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[8]  P. Macfarlane,et al.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. , 1995, The New England journal of medicine.

[9]  N J Wald,et al.  Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis , 2003, BMJ : British Medical Journal.

[10]  Y. Moride,et al.  Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. , 1994, Journal of clinical epidemiology.

[11]  A. Paganini-Hill,et al.  Reliability of recall of drug usage and other health-related information. , 1982, American journal of epidemiology.

[12]  M. Dimatteo,et al.  Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. , 2000, Archives of internal medicine.

[13]  J. Avorn,et al.  Persistence of use of lipid-lowering medications: a cross-national study. , 1998, JAMA.

[14]  J. Avorn,et al.  Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors. , 2002, Journal of general internal medicine.

[15]  Moride Yola,et al.  Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. , 1994 .

[16]  W. März,et al.  Risk for myopathy with statin therapy in high-risk patients. , 2003, Archives of internal medicine.

[17]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[18]  David A. Belsley,et al.  Regression Analysis and its Application: A Data-Oriented Approach.@@@Applied Linear Regression.@@@Regression Diagnostics: Identifying Influential Data and Sources of Collinearity , 1981 .

[19]  P. Macfarlane,et al.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia , 1995 .

[20]  R. Goldbohm,et al.  Comparison of questionnaire information and pharmacy data on drug use , 1991, Pharmaceutisch Weekblad.

[21]  B. Davis,et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. , 1996, The New England journal of medicine.

[22]  A. B. Barnes,et al.  A comparison of pregnancy history recall and medical records. Implications for retrospective studies. , 1985, American journal of epidemiology.

[23]  A. Gotto,et al.  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. , 1998, JAMA.

[24]  J. Tu,et al.  Adherence With Statin Therapy in Elderly Patients With and Without Acute Coronary Syndromes , 2002 .

[25]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[26]  R. Tamblyn,et al.  The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Québec. , 1995, Journal of clinical epidemiology.

[27]  J. Simons,et al.  Apparent discontinuation rates in patients prescribed lipid‐lowering drugs , 1996, The Medical journal of Australia.

[28]  F. Jones,et al.  International Classification of Diseases , 1978 .

[29]  Muhammad Mamdani,et al.  Adherence with statin therapy in elderly patients with and without acute coronary syndromes. , 2002, JAMA.

[30]  J. Kragstrup,et al.  High persistence of statin use in a Danish population: compliance study 1993-1998. , 2002, British journal of clinical pharmacology.

[31]  S. Yusuf MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Commentary , 2002 .

[32]  AndrewJ. S. Coats MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[33]  H. Mcdonald,et al.  Interventions to enhance patient adherence to medication prescriptions: scientific review. , 2002, JAMA.

[34]  J. Slattery,et al.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. , 1994, Atherosclerosis. Supplements.

[35]  R. Collins,et al.  Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. , 1998, The New England journal of medicine.

[36]  M. Eriksson,et al.  Compliance with and efficacy of treatment with pravastatin and cholestyramine: a randomized study on lipid-lowering in primary care. , 1997, Journal of internal medicine.