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Cardiovascular disease remains the leading cause of death in North America . It has been shown that the treatment of dyslipidaemia with statins significantly reduces morbidity and/or mortality among patients with coronary artery disease, and also in patients with dyslipidaemia [2–6]. According to clinical trials, statins start to demonstrate benefits on cardiovascular morbidity and mortality only after 1–2 years of use [2–6]. Findings from new trials showed that atorvastatin  reduced the rate of cardiovascular disease among patients with acute coronary syndrome. Heart Protection Study, a landmark study involving 20 556 patients at high risk of coronary artery disease showed that simvastatin decreased the total death rate and reduced the rate of all cardiovascular events . With adjustment for lack of compliance, the actual effect may be increased by 1.5-fold . Additionally, the Anglo-Scandinavian Cardiac Outcomes Trial investigators  compared the benefits of atorvastatin vs. placebo on the combined outcome of nonfatal myocardial infarction and fatal coronary artery disease among hypertensive patients with a total cholesterol level lower than 6.5 mmol l−1, and provides other evidence for primary prevention with statin therapy among patients at high risk of coronary artery disease .
For both primary and secondary prevention, statins have to be used on a long-term basis to achieve the potential benefit. Clinical guidelines consequently highlight the need to assess and promote compliance with prescribed treatment for dyslipidaemia . On the other hand, observational studies assessing persistence with statins, mainly conducted in elderly subjects, found 1-year persistence rates of 25–85%[11–14]. A recent Canadian study among elderly subjects with or without recent acute coronary syndrome has shown a persistence rate of only 40% at 2 years among patients with acute coronary syndrome, 36% for those with chronic coronary artery disease, and 26% among patients in primary prevention . The long-term persistence in use of statin therapy among elderly US patients remains also low .
Based on a Cardiovascular Life Expectancy Model to estimate the benefits of risk factor modification in the primary and secondary prevention of cardiovascular disease, forecasting benefits of treating hyperlipidaemia have shown that high-risk individuals had more benefits than lower-risk individuals, younger individuals more than elderly, and men more than women [17, 18]. Middle-aged patients have the highest level of forecasting benefit, and little is known about long-term persistence rate of these therapies in a real-life setting, as well as its determinants. In order to target persistence enhancing interventions, we require the knowledge of the time during therapy when discontinuation is most likely, and which patient subgroups are at highest risk. The aim of our study was to evaluate the persistence rate of middle-aged patients newly treated with statin, and to study its relation with age, gender, cardiovascular risk factors and use of health care services for primary and secondary prevention.
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Considering that at least 1–2 years of treatment are necessary to reduce cardiovascular morbidity and/or mortality, the observed low persistence with treatment is likely to attenuate treatment effectiveness. An understanding of predictors of long-term persistence with statins has implications for the approach to the management of individual patient.
We found that persistence with statin therapy in the secondary prevention cohort had fallen to 71 and 45% at 6 months and 3 years, respectively. In the primary prevention cohort, persistence with statin therapy had fallen to 65% after the first 6 months of treatment, and after 3 years, had declined to 35%. The rates of persistence are low over time. Our study identifies patient characteristics that can be used to predict poor persistence. Our results suggest that newly treated middle-aged patients with dyslipidaemia concurrent with coronary artery disease, and those with other cardiovascular risk factors such as age, male, diabetes, hypertension were the most likely to persist with statin therapy. The predictors of suboptimal persistence identified here add information to previous work in which we observed lower persistence in patients who had the greatest number of pharmacies and prescribing physicians, and greater use of health care services.
Clinical trials evaluating the efficacy of statins in secondary prevention trials had 5-year persistence rates at 81 and 94%[2–4]; and among primary prevention trials, a 5-year persistence rates was at 70%[5, 6]. Observational studies assessing persistence with statins have been mainly done in periods which excluded the new products, and were evaluated among elderly subjects and mainly with lovastatin therapy [11–14]. They did not separate into primary and secondary prevention, except for one study which was conducted in elderly subjects. The results of these studies found 1-year persistence rates of only 25–85% for patients who started a therapy with lipid-lowering drugs [11–14]. Recent studies among elderly subjects with or without acute coronary syndrome show a low rate of compliance , and the persistence declines substantially over time . The rates of persistence at 2 years were only 40% for patients with acute coronary syndrome, 36% for patients with chronic coronary artery disease, and at 26% for primary prevention .
Our results differ from those of Andrade et al. who found a 1-year persistence rate of 85% among patients taking lovastatin, but are in agreement with those found among patients older than 65 years with and without cardiovascular disease . Gaps exist between recommendations and actual practice, for prevention as well as treatment.
Considering only an exclusive use, we observed higher rate of persistence for treatment with pravastatin and simvastatin for the primary and secondary prevention. Simvastatin and pravastatin are the statin agents with the strongest clinical evidence supporting their use at the time of study period [2–4,6]. However, we could not exclude, particularly among patients for secondary prevention cohort, that the statin prescription may be from hospital department, and this fact may be a contributing factor to higher persistence. We could also argue that the perception of the doctor influences the rate of persistence but we could not exclude the possibility of a lack of efficacy or adverse drug effect. For instance, as shown in Table 2, the mean dose used of fluvastatin or lovastatin (expected LDL cholesterol reduction ≥25%) may have conducive to a lack of efficacy compared with those used for pravastatin and simvastatin (expected LDL cholesterol reduction ≥30%) . Moreover, since the incidence of myopathy associated with statin therapy is dose-related  the mean dose used of atorvastatin may have induced an higher incidence rate of adverse effects compared with those used for pravastatin and simvastatin.
The efficacy of statin therapy in reducing the risk of coronary artery disease, particularly among middle-aged patients, has been well established among patients whether in primary or secondary prevention [2–9], showing a decrease of cardiovascular morbidity and/or mortality, particularly with high-risk and/or coronary artery disease patients if taken on regular basis [2–9]. Recent evidence demonstrated the early benefits of statin therapy and the potential harm of sudden cessation of statin agents after an acute myocardial infarction [31–34]. This fact emphasizes the importance of compliance with statin therapy.
Nonpersistence with dyslipidaemic agents is not an isolated problem because we observed this phenomenon for the treatment of many other chronic diseases. For instance, the persistence at 12 months after an initial statin prescription for the primary and secondary cohorts (53% and 62%) was about the same as the rate we found for antihypertensive agents (65%)  but lower than medication for cardiac heart failure (70%) .
We have identified several limitations of this study. First, the lack of information on clinical data on each patient, such as lipid values. Second, the lack of information on the discontinuation by the prescriber for clinical reasons such as adverse drug reaction or lack of efficacy. Third, we used several markers in an attempt to exclude patients with some other medical conditions, but the conditions may have been miscoded. Fourth, we were not able to control for the potential misclassification of drug use without a prescription (physician samples) or any change in lifestyle. Fifth, the evaluation of drug use is based on dispensation instead of drug administration and may lead to a nondifferential information bias.
Using administrative databases to measure drug exposure presents many advantages over other means of data collection, such as interview or self-administered questionnaires. First, using administrative databases we avoid recall bias which is known as a major source of bias in research. Second, it is usually difficult for patients to report the medications they are taking when details, such as the exact name, dose and quantity, are required [37–41]. Third, the use of computerized databases allows us to capture drug history over a long period of time.
This finding reflects the need for patients, physicians and pharmacists to identify those dyslipidaemic individuals who may benefit from targeted patient counselling and drug monitoring. More studies of innovative approaches to follow prescriptions of chronic diseases are needed . A realistic new chronic disease model of disease management involving implementation of programme including patient-professional partnership, multidisciplinary team, self-management education, clinical information systems, decision support and clinical indicators needs to be developed. A new chronic disease model needs also to promote studies of indicator performance and cost-effectiveness analyses [43–48].
We conclude that in current practice, barriers to persistence occur early in the course of statin therapy, and the rate of persistence is low among patients in both primary and secondary prevention. Because long-term persistence with statin therapy is essential for clinical benefits, we suggest that educational strategies must be developed if policy makers are to succeed at promoting optimal drug utilization based on evidence-based statin treatments. The critical issue is the education of physicians and patients concerning persistence with treatment. This issue has enormous clinical, public health, and economic implications.