Patient Compliance with statins

Source: http://www.jr2.ox.ac.uk/bandolier/booth/cardiac/patcomp.html

Clinical bottom line

The majority of patients for whom statins are prescribed in clinical practice either stop taking the drug altogether or take less than the prescribed dose within a year. This is likely to reduce or remove any benefit, and may even cause harm.

Cohort studies of patients prescribed statins show variable but disappointingly high rates of discontinuation of therapy and poor adherence to drug regimens [1, 2, 3, 4, 5], and failure to reach targets for cholesterol reduction in those who continue with therapy [6].

Discontinuation of therapy

Discontinuation rates at five years in clinical trials range from 6-30%, but in clinical practice the rates are much higher. Studies show that the number of patients continuing therapy falls sharply in the first few months of treatment, followed by a more gradual decline. In the USA it is estimated that only about 50% of patients continue at six months, and 30-40% at one year [7]. Similar rates have been found in Australia [4], and the same problem exists in the UK [8].

Failure to reach cholesterol target levels

This may in part be due to prescribing of insufficient doses of the statin, and at an individual patient level, there may be some who are less responsive to statins than the average. However poor response to treatment seems primarily to be due to patients not taking the drug as prescribed (e.g. intermittent use, reduced dosage).

Benner et al [2] used prescription records to study patterns of use in a cohort of 34,501 elderly (65 years or more) patients using statins. They measured the proportion of days covered (PDC) by drug therapy, and the proportion of patients judged to be adherent (taking at least 80% of prescribed drug), partially adherent (20-79% of prescribed drug), or non-adherent (less than 20% of prescribed drug), in each six-month period for a total of 10 years after initiation of therapy.

Patients could move between adherence groups in different time periods. Most patients lost from the partially adherent group moved into the non-adherent group. Of those who became non-adherent, only 4% had a prescription for another lipid-lowering drug dispensed, and adherence to that drug was also poor. Adverse effects rates are low and could account for only a small amount of the non-adherence. Although this study involved elderly patients from one geographical area (New Jersey), it is in broad agreement with other studies [1, 3, 4].

We do not know how much adherence is required to achieve some, if not maximum, benefit from statin therapy, or the effects of intermittent adherence, or drug holidays. In WOSCOPS, however, patients who took at least 75%of their prescribed dose of pravastatin had significantly lower rates of non-fatal MI, revascularisation procedures, death from any cause, and cardiovascular death, compared to those who took less than 75% of their prescribed dose [9]. Patients taking statins for secondary prevention following MI had reduced risk of recurrent MI or death if they took 80% or more of their prescribed medication over the study period (maximum follow up 6 years) [10]. Other studies have shown that withdrawal of statins [11] or sudden reduction of dose [12] can increase the rate of thrombotic events.

There is no single cause of failure to comply with prescribed medication, and the problem is not restricted to statins. Some general predictors of compliance with medications for prevention of coronary heart disease have emerged and are summarised below.

Poor Compliance

Female
Age under 45 years
Age over 75 years
Low socio-economic status
Non-white
Multiple daily dosing
Multiple drug regimens
Primary prevention, asymptomatic, feeling in good health
Lack of knowledge about disease, need for treatment and side effects
Some comorbidity e.g. dementia, depression, MI after statin started

Good Compliance

Prior good compliance
Feeling in bad health
Good relationship with physician, understanding of need for treatment
Some comorbidity e.g. diabetes, hypertension, stroke, CHF

There have been a number of reviews of interventions to improve patient compliance [7, 8]. In brief, most interventions have a positive effect in the short term, but to be successful in the long-term a sustained multi-factorial approach is required. A combination of patient-focused, physician-focused, and system-focused interventions works best.

Comment

In order to achieve maximum benefit from statin therapy patients need to take the drug at an appropriate dose, probably for the rest of their lives. The majority of patients for whom statins are prescribed in clinical practice either stop taking the drug altogether or take less than the prescribed dose within a year. This is likely to reduce or remove any benefit, and may even cause harm.

Reference

1. J Avorn et al. Persistence of use of lipid-lowering medications. A cross-sectional study. JAMA 1998 279: 1458-1462.
2. JS Benner et al. Long-term persistence in use of statin therapy in elderly patients. JAMA 2002 288: 455-461.
3. CA Jackevicius et al. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002 288: 462-467.
4. LA Simons et al. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust 1996 164: 208-211.
5. J Larsen et al. High persistence of statin use in a Danish population: compliance study 1993-1998. Br J Clin Pharmacol 2002 53: 375-378.
6. JP Frolkis et al. Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practice. Am J Med 2002 113: 625-629.
7. Third report on National Cholesterol Education Program expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. IX Adherence. Circulation 2002 106: 3359-3366.
8. S Carter D Taylor. A Question of Choice: Compliance in Medicine Taking. Medicines Partnership 2003, www.medicines-partnership.org
9. J Shepherd et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. New Engl J Med. 1995 333: 1301-1307.
10. L Wei et al. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart 2002 88: 229-233.
11. C Heeschen et al. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002 105: 1446-1452.
12. M Thomas, J Mann. Increased thrombotic vascular events after change of statin. Lancet 1998 352: 1830-1831.

The economics of statin medications