 |
|
Enhancing Drug Compliance in Lipid-Lowering Treatment
Judith H. LaRosa, PhD;
John C. LaRosa, MD
Arch Fam Med. 2000;9:1169-1175.
ABSTRACT
| |
Hyperlipidemia and the atherosclerotic conditions that result from it are well recognized as major contributors to coronary heart disease (CHD). Fortunately, several large-scale clinical trials have shown that there are effective treatments that can substantially lower atherogenic lipid levels and thereby reduce the risk of CHD mortality and morbidity. However, duplication of these dramatic trial results can be negatively affected in "real life" clinical practice by an important issue: compliance. No medications will work if patients do not take them. Unfortunately, patients who need lipid-lowering therapy are likely to need it long-term, perhaps for a lifetime. Yet, many do not adhere to the prescribed medication regimen. This article reviews some major studies of compliance for lipid-lowering drugs. The reasons why patients do not take them as prescribed vary: poor education, lack of understanding, cost, provider indifference, and others. Achieving compliance requires a multifaceted approach. It can be enhanced by encouraging patients to talk openly about their medication habits and by convincing them of the long-term benefits of reaching and maintaining target low-density lipoprotein cholesterol levels. Although more studies focusing on compliance specifically regarding CHD are needed, the current literature does provide some guidance.
INTRODUCTION
In 1999, the American Heart Association (AHA) estimated that 58.8 million Americans have some form of cardiovascular disease (CVD), with more than 12 million experiencing symptoms of coronary heart disease (CHD). The most recent figures suggest that 7 million of those 12 million patients with CHD experienced a myocardial infarction (MI), translating into approximately 1 coronary event every 29 seconds.1 Coronary heart disease accounts for 1 of almost every 5 deaths; 1 in every 2.4 deaths is attributable to CVD (including cerebral ischemia, aneurysms, and CHD), making CVD the leading killer, with a higher mortality rate than the next 7 leading causes of death combined.1
THE ROLE OF HYPERLIPIDEMIA
Hyperlipidemia is well recognized as a major contributor to acute MI, chronic CHD, and other cardiovascular events. Fortunately, there are a number of effective treatments, in addition to dietary intervention, that can substantially lower atherogenic cholesterol and triglyceride levels and thereby reduce the risk of CHD mortality and morbidity. These treatments include bile acid sequestrants (cholestyramine resin and colestipol hydrochloride), nicotinic acid (niacin), fibric acid derivatives (gemfibrozil and fenofibrates), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). Several large-scale clinical and angiographic trials2-7 have proven conclusively that lipid lowering prolongs life, reduces the frequency and numbers of cardiovascular events, and lessens the need for revascularization procedures. However, duplication of these dramatic trial results can be negatively affected in "real life" clinical practice by poor compliance. No medications, whatever their effectiveness, will work if patients do not take them.
PREVALENCE OF HYPERLIPIDEMIA
Hyperlipidemia in most westernized countries is widespread, largely because of diets that are high in fat content and lifestyles that do not incorporate enough physical activity.8 A recent estimate based on data from the Third National Health and Nutrition Examination Survey (NHANES III) suggests that approximately 28% (>50 million) of US adults older than 20 years have hyperlipidemia that warrants treatment.9 To ascertain what percentage of the overall population was eligible for treatment (according to risk criteria outlined by the National Cholesterol Education Program [NCEP] Adult Treatment Panel II [ATP II] guidelines; Table 1), researchers analyzed data from 7423 respondents to phase 2 of NHANES III.10 Their conclusion was that approximately 16.58% (29 million) of the more than 50 million who meet treatment criteria should receive dietary therapy and that 11.42% (21 million) are eligible for drug therapy. However, the majority of the eligible NHANES III patients (65%) indicated in the survey that they had received no intervention of any type. This analysis also determined that 82% of adults with established CHD, those at highest risk of fatal or nonfatal MI, are not achieving their NCEP low-density lipoprotein cholesterol (LDL-C) recommended target goal of 2.59 mmol/L (100 mg/dL) or less.
|
|
|
|
Table 1. Initial Low-Density Lipoprotein Cholesterol (LDL-C) Levels by Risk Group*
|
|
|
This study also included estimates of the prevalence of hyperlipidemia in specific subpopulations. Approximately 29% of whites, 24% of blacks, and 18% of Hispanics qualify for cholesterol-lowering treatment. The prevalence varies slightly between women and men; approximately 30% of men and 26% of women are in need of lipid-lowering treatment according to NCEP ATP II criteria.
COMPLIANCE IN CLINICAL TRIALS
The stark contrast in benefit experienced by those who are compliant with their therapy compared with those who are not was illustrated by the West of Scotland Coronary Prevention Study (WOSCOPS),4 a primary prevention study. Patients who took 75% or more of their lipid-lowering medication (the HMG-CoA reductase inhibitor pravastatin sodium) reduced their risk of death from any cause by one third more than those who took less than 75%.11 By the end of the study's 5-year follow-up, 1693 (26%) of the 6595 patients were noncompliant (according to the 75% criteria). The relative risk reduction for cardiovascular death among the compliant cohort was 37% compared with 32% for the noncompliers, and the risk reduction for coronary death or nonfatal MI was as high as 38% among the compliers compared with 31% among the noncompliers.11 Most dramatic was the reduced need for revascularization procedures, such as percutaneous transluminal angioplasty or coronary artery bypass graft; the more than 75% compliers evidenced a 46% reduction in the need for such procedures compared with a 37% reduction for the less compliant patients.12
The Scandinavian Simvastatin Survival Study (4S) group reviewed patient progress 1 year after the conclusion of this trial.13 A questionnaire to assess 1-year posttrial cholesterol levels and ongoing adherence to lipid-lowering treatment was sent to 785 study participants. The response rate was 94% (n = 741). Analysis revealed that 63% of the patients (n = 467) were still taking their lipid-lowering medications (mostly simvastatin); 36% (n = 270) were no longer taking any type of lipid-lowering medication; 26% indicated they stopped treatment at the study's conclusion; and 11% said they stopped treatment sometime during the first posttrial year. Of those who elected not to continue use of their drugs, 38% blamed acquisition cost and 30% said that they stopped because their cholesterol levels were now "normal."
Although most of the patients adhered to their prescribed regimen, the strong trend was to reduce the dose, which resulted in higher cholesterol levels than were observed during the trial. During the trial, the average dosage was 27 mg/d; in the 1-year posttrial survey, participants reported taking an average dosage of 14 mg/d. Researchers speculated that cost was an important factor in the choice to use lower doses; reimbursement for cholesterol-lowering drugs in Finland (the locus of 4S) is only 50%.
THE COMPLEXITIES OF COMPLIANCE
Patients who need lipid-lowering therapy are likely to need it for many years, if not for the rest of their lives.10 Such lengthy treatment schedules require a clear understanding by patient and physician as to the need for compliance to the regimen. Yet, many patients remain noncompliant, and this noncompliance can take many forms (Table 2): outright refusal, underdosing or overdosing, taking doses at the wrong time, taking drug "holidays" in which doses are forgotten or skipped for several days, and "whitecoat compliance" in which patients take the prescribed medication appropriately only before a physician visit. Treatment discontinuation rates have been predicted to be 50% after 1 year and 85% by the end of 2 years.14 This is especially true with medications prescribed for long periods.
|
|
|
|
Table 2. Various Types of Noncompliance and Reasons Offered
|
|
|
Finally, noncompliant patients must be distinguished from nonresponsive patients. Incorrectly identifying noncompliant patients as nonresponsive can result in inappropriate dosage modification and possibly more intensive and invasive levels of treatment.15 Even patients who do appear to be responsive can have poor levels of compliance. Achievement of normal lipid levels may simply reflect a variation in biological response, thereby giving a false picture of the drug's efficacy and tolerability.
COMPLIANCE IN "REAL LIFE" SETTINGS
Many of the major lipid-lowering studies14 have documented significant noncompliance rates. This foreshadows a challenge to physicians working in the much more informal setting of a primary care or specialized practice. Few practices have the resources available for the consistent and proactive patient education and follow-up that are the hallmarks of clinical trials. These trials also have the luxury of being able to carefully select patient groups, which may yield subjects who are more motivated or involved than average.15 If compliance is difficult to effect in a clinical trial, how high might the discontinuation rates be in a family or cardiology practice?
In an effort to compare nonadherence in clinical trials with that experienced in primary care practice, Andrade et al15 studied discontinuation patterns of lipid-lowering therapies among 2369 patients in 2 health maintenance organizations (HMOs). New users of lipid-lowering drugs were followed up for 2 years, and rates of discontinuation were compared with results from 30 published clinical trials. Patients were prescribed bile acid sequestrants, niacin, gemfibrozil, and lovastatin. Use of all agents, except the statin, was discontinued among the HMO patients at higher rates, and more quickly, than was recorded by the clinical trials. On average, 32% of all the HMO patients discontinued their therapies within 190 days. Within the trial populations, similar rates were observed after a full year. In both groups, discontinuation rates were largely dependent on the type of drug class used. By the end of 1 year, patients in both cohorts found adherence to bile acid sequestrant regimens the most difficult (Table 3). Only lovastatin (the sole HMG-CoA reductase inhibitor used in this analysis) showed virtually the same rates of patient discontinuation after 1 year: 16% of patients in the clinical trials and 15% of the HMO patients.15
|
|
|
|
Table 3. Percentage of Discontinuations After 1 Year by Drug Class*
|
|
|
A more recent retrospective HMO study of compliance was completed by Sung et al.16 A total of 772 patients who had been prescribed various lipid-lowering medications (HMG-CoA reductase inhibitors, 55%; gemfibrozil, 22%; bile acid sequestrants, 16%; and niacin, 6.5%) were included.16 Patients were followed up for 2 years. Analysis of the study data showed that only 37% of participants had adhered to their lipid-lowering regimens throughout the study period (defined as taking at least 90% of all doses). An additional 38% discontinued therapy altogether by the end of the 2 years. Ages in this study population ranged from 34 to 82 years (mean, 60.8 years), and the population was evenly divided by sex (47.8% women).
The analysis revealed that variables such as female sex, experience in being compliant with other medication regimens, perceived quality of health, complexity of dosing regimen (ie, once or twice daily), and treatment for multiple comorbidities strongly influenced compliance rates (Table 4).16 In general, the researchers concluded that patients most likely to be compliant with lipid-lowering medications are those who have experience in being compliant with other medications and those who perceive their health as poor. Compliance in this study was not found to be related to age, ethnicity, education, employment, or marital status.
|
|
|
|
Table 4. Patient Variables and Their Effects on Rates of Adherence*
|
|
|
A study conducted by Avorn et al,17 which sought to detect how compliance patterns are affected by socioeconomic status and comorbidities in patients under very different types of health care systems (5611 patients in the United States and 1676 patients in Canada), found that continuation rates were significantly higher for statin users (64.3%; lovastatin, pravastatin, and simvastatin) than for patients taking other lipid-lowering agents (36.6%; clofibrate, cholestyramine, gemfibrozil, niacin, and probucol). In the United States, the study included older (all older than 65 years), mostly very-low-income patients enrolled from the New Jersey Medicaid and Assistance for the Aged and Disabled programs. Participants from Canada were randomly drawn from the universal health care system in Quebec, in which all citizens older than 65 years are automatically enrolled.
Findings paralleled those from the study by Sung et al,16 in that patients perceiving their health to be poor (those with several CHD risk factors) had higher rates of compliance and those who used multiple drugs for several conditions found it more difficult to adhere to lipid-lowering therapy. By the end of the 1-year study period, the Quebec cohort had slightly better rates of compliance (62.2%) than did the US cohort (59%). Despite close to 100% coverage of drug acquisition cost (patients in the Canadian system paid nothing for their drugs and the US participants paid no more than $2 for each prescription filled), the poorest patients (those receiving Medicaid in New Jersey) were 58% more likely to discontinue their therapy than were those with higher incomes.17
REASONS FOR NONCOMPLIANCE
The reasons why patients discontinue their therapies vary. Therefore, it is important to ascertain the factors that promote noncompliance and the interventions that reduce it.18 Commonly cited reasons for noncompliance include not being convinced of the need for treatment, fear of adverse effects, difficulty in managing more than 1 dose a day, or multiple drug regimens.19 Compliance is predictably poor for interventions designed to reduce undesirable daily behavior (eg, eating the wrong things, smoking). Rates of compliance are even worse if there appears to be a long lag time between the unhealthy behaviors and/or nonadherence to treatment and the ultimate health consequences. Like hypertension and smoking, hypercholesteremia is a chronic, painless condition that is usually perceived by the patient as having deleterious health consequences that are far in the future. Other factors that may be associated with noncompliance include socioeconomic barriers (such as an unsupportive spouse or an inability to pay drug acquisition costs), lack of knowledge about the disease, attitude toward taking medication, psychological state, and the relationship with the physician.14
In a review that focused on the importance of compliance for patients with familial hypercholesterolemia, Rand18 observed that poor adherence is most frequent when the treatment is preventive rather than curative, especially if the treated condition is largely asymptomatic, as hyperlipidemia is. Rand's article indicates that to ensure good compliance, patients need to be convinced that their lipid-lowering treatment is necessary. This may be especially true for primary prevention patients (those who have elevated cholesterol levels and perhaps other risk factors for CHD but have not yet evidenced an MI or other coronary event).12 Candidates for primary prevention are usually asymptomatic and by all appearances healthy. Still, there is solid clinical evidence to show that encouraging compliance in these patients is worthwhile: both the Framingham Study20 and the Cholesterol and Recurrent Events Trial (CARE)3 showed that most cardiovascular events occur in people with "average" but not normal cholesterol levels. In the Framingham Study, most MIs occurred in men who had a total cholesterol level of 5.83 mmol/L (225 mg/dL) and an LDL-C level of 3.88 mmol/L (150 mg/dL).20
Secondary prevention patients may be easier to persuade and motivate, since they have experienced an MI or other manifestation of overt heart disease.14 In addition, this patient group experiences approximately 50% of all MIs and 70% of all deaths due to CHD.21
THE PHYSICIAN'S RESPONSIBILITY
The role of the physician is important in fostering compliance and detecting when patients depart from the prescribed regimen. In a recent study22 that compared prescription frequency of various regimens after a revascularization procedure, it was found that lipid-lowering drugs were prescribed much less frequently than were antiplatelet or anticoagulant drugs.
A new, as yet unpublished survey confirms that despite the wide publicity of the findings of cholesterol-lowering studies, such as 4S, WOSCOPS, and CARE, physicians are still giving more emphasis to conditions such as hypertension. The Reassessing European Attitudes About Cardiovascular Treatment survey polled more than 5000 citizens and 750 clinicians throughout the United Kingdom, Germany, France, Italy, and Sweden. Results were presented in October 1999 in Venice, Italy, at the Fifth International Symposium on Multiple Risk Factors in Cardiovascular Disease. The survey showed that most members of the public knew that smoking (70%) and hypertension (65%) posed a risk factor for heart disease and cardiovascular events. In comparison, only half of the citizens knew that cholesterol is associated with cardiovascular events, less than a third knew their own cholesterol levels, and less than a quarter understood the difference between LDL-C and high-density lipoprotein cholesterol. Only 29% reported that their physician ever tests for or talks about cholesterol levels, in contrast to 68% who indicated that their physician regularly checks blood pressure and talks about it. Interestingly, the survey did find that 31% of the general public said they would be willing to take lifelong cholesterol-lowering therapy if their physicians indicated it was needed.
The Atherosclerosis Risk in Communities Study23 showed that hypertension is adequately treated and controlled to almost twice the extent of hypercholesterolemia, indicating that physician education about the importance of controlling hypertension has been more effective than education regarding controlling elevated cholesterol levels. This may be due, in part, to the longer time that the benefits of antihypertensive therapy have been appreciated. Nevertheless, inattention to lipid lowering is unjustified. This is especially underscored when it is understood that the scientific evidence showing that lipid-lowering therapy reduces fatal and nonfatal end points is at least as solid as that demonstrating the benefits of blood pressure control. Not only that, but the side effect profiles of the most commonly prescribed lipid-lowering drugs, the statins, are generally less bothersome than that of most agents used to treat hypertension.
To achieve the substantial benefits of lipid-lowering therapy that have been demonstrated by the major clinical and angiographic trials (eg, 4S, CARE, WOSCOPS, Long-term Intervention With Pravastatin in Ischaemic Disease Study, Post Coronary Artery Bypass Graft Trial, Lipoprotein and Coronary Atherosclerosis Study),2-7 lipid-lowering regimens must be more frequently prescribed and adhered to. Failure to do so will put the patient at continued high risk for MI or other coronary events.21
RECOMMENDATIONS TO IMPROVE ADHERENCE
To counteract poor compliance, clinicians should take the following steps:
- Make it clear to patients that they themselves perceive the medication as being important and beneficial. This may be especially true in the first few weeks of treatment, when patients are likely to be most interested in being educated about their condition and most receptive to instruction on regimen adherence.14
- Provide clear instructions—both verbal and written—regarding the details about when the drug(s) is to be taken and how often and what the patient should do if he or she forgets a dose. The Canadian Coalition on High Blood Pressure Control provided support for this approach when it issued recommendations for increasing patient compliance.24
- Tailor the drug regimen to the patient's individual schedule or lifestyle and for other medications. If, for example, a patient indicates it may be inconvenient to take a medication at a certain time each day, it may be best to prescribe one that can be taken at any time throughout the day rather than those that should only be taken in the evening.14
- Review the importance of compliance and ask patients about it at each office visit. The literature is replete with studies to show that physicians consistently overestimate compliance rates and that they typically ask questions about compliance that can be answered by the patient with a simple yes or no.18 Asking specific, open-ended questions is more effective in communicating to the patient the importance of the therapeutic regimen.14
- Prescribe once-a-day regimens whenever possible. Medications that must be taken more than once a day are likely to be poorly adhered to.24
- Maintain continuing discussions among patient and physician and other members of the health care team. Allowing patients to feel they can ask questions and pose objections without being rushed or judged will help them to acknowledge their hesitations in taking or sticking with certain medications.18 This may help both the patient and the physician to identify barriers to medication taking that can perhaps be overcome by problem-solving suggestions, by additional education, or by asking the patient's family to get involved.
- Be cognizant of other factors that may preclude compliance. Ascertaining those barriers, although time-consuming, can be ultimately beneficial.
- If cost is an issue, be aware that many states and some pharmaceutical companies provide cost reductions or samples.
- Pay special attention to incorporating lipid-lowering medications with other medications already being used by the patient, thereby reducing confusion and enhancing compliance.
- If a partner does not support the medication regimen, consider partner counseling.
Other compliance-enhancement strategies can include the following14-25:
- Teach patients to self-monitor accurately so they can gain firsthand appreciation for the importance of health care behaviors; this can incorporate a personal medication diary to note when a drug was taken or missed and if anything unusual occurred after consumption (eg, adverse events).
- Establish regular contact with the patient over the telephone or via mail to reinforce the continued interest of the clinician and health care team members in the patient's success.
- Provide cognitive aids for the patient and health care staff. These can include visual reminders such as chart notations, self-stick notes, calendar notations, and refrigerator notes.
- Ask the patient to buy and use a medication container to organize each day's allotment of pills by week or month or a medication reminder system that comes equipped with clocking devices and/or alarm.
CONCLUSIONS
Strict adherence to lipid-lowering medications, along with dietary therapy, is crucial if the significant health benefits of cholesterol lowering are to be realized. However, many studies show that compliance with such long-term therapy is low and erodes further as time goes on. Clinicians need to recognize the widespread prevalence of noncompliance and realize that many, if not most, of their patients will not take their prescribed medications as directed. In the final analysis, attention to compliance is as vital as selecting the proper regimen in the first place. Without it, treatment will lose much of its effectiveness.
AUTHOR INFORMATION
Accepted for publication September 11, 2000.
We thank Michelle Rizzo for her excellent editorial assistance.
Reprints: Judith H. LaRosa, PhD, Department of Preventive Medicine and Community Health, State University of New York Health Science Center at Brooklyn, 450 Clarkson Ave, Box 43, Brooklyn, NY 11203.
From the Departments of Preventive Medicine and Community Health (Dr J. H. LaRosa) and Medicine (Dr J. C. LaRosa), State University of New York Health Science Center at Brooklyn.
REFERENCES
| |
1. American Heart Association. 1999 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association; 1998.
2. Pedersen TR. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389.
FULL TEXT
|
ISI
| PUBMED
3. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: the Cholesterol and Recurrent Events Trial (CARE) investigators. N Engl J Med. 1996;335:1001-1009.
FREE FULL TEXT
4. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia: West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301-1307.
FREE FULL TEXT
5. LIPID Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels: the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349-1357.
FREE FULL TEXT
6. Post Coronary Artery Bypass Graft (Post-CABG) Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med. 1997;336:153-162.
FREE FULL TEXT
7. Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol. 1997;80:278-286.
FULL TEXT
|
ISI
| PUBMED
8. Kannel WB. Contribution of the Framingham Study to preventive cardiology. J Am Coll Cardiol. 1990;15:206-211.
ISI
| PUBMED
9. Hoerger TJ, Bala MV, Bray JW, Wilcosky TC, LaRosa J. Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatment-eligible United States adults. Am J Cardiol. 1998;82:61-65.
FULL TEXT
|
ISI
| PUBMED
10. National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation. 1994;89:1333-1445.
PUBMED
11. Shepherd J. Tomorrow's world: atherosclerosis in the year 2000. Neth J Med. 1997;50:221-227.
FULL TEXT
|
ISI
| PUBMED
12. West of Scotland Coronary Prevention Study Group. Compliance and adverse event withdrawal: their impact on the West of Scotland Coronary Prevention Study (WOSCOPS). Eur Heart J. 1997;18:1718-1724.
FREE FULL TEXT
13. Strandberg TE, Lehto S, Pyorala K, Kesaniemi A, Oksa H. Cholesterol lowering after participation in the Scandinavian Simvastatin Survival Study (4S) in Finland. Eur Heart J. 1997;18:1725-1727.
FREE FULL TEXT
14. Insull W. The problem of compliance to cholesterol altering therapy. J Intern Med. 1997;241:317-325.
FULL TEXT
|
ISI
| PUBMED
15. Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs: do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med. 1995;332:1125-1131.
FREE FULL TEXT
16. Sung JCY, Nichol MB, Venturini F, Bailey KL, McCombs JS, Cody M. Factors affecting patient compliance with antihyperlipidemic medications in an HMO population. Am J Manag Care. 1998;4:1421-1430.
ISI
| PUBMED
17. Avorn J, Monette J, Lacour A, et al. Persistence of use of lipid-lowering medications: a cross-national study. JAMA. 1998;279:1458-1462.
FREE FULL TEXT
18. Rand CS. Measuring adherence with therapy for chronic diseases: implications for the treatment of heterozygous familial hypercholesterolemia. Am J Cardiol. 1993;72:68D-72D.
19. Leupker RV. Patient adherence: a "risk factor" for cardiovascular disease. Heart Dis Stroke. 1993;2:418-421.
PUBMED
20. Gordon T, Kannel WB. Premature mortality from coronary heart disease: the Framingham Study. JAMA. 1971;215:1617-1625.
FREE FULL TEXT
21. Eisenberg D. The importance of lowering cholesterol in patients with coronary heart disease. Clin Cardiol. 1998;21:81-84.
ISI
| PUBMED
22. Delacretaz E, Michalopoulos PG, Ruiz J, Saner H, Meier B. Management of hyperlipidaemia after coronary revascularisation: follow-up study. BMJ. 1998;316:1499.
FREE FULL TEXT
23. Nieto FJ, Alonso J, Chambless LE, et al. Population awareness and control of hypertension and hypercholesterolemia: the Atherosclerosis Risk in Communities Study. Arch Intern Med. 1995;155:677-684.
FREE FULL TEXT
24. Chockalingam A, Bacher M, Campbell N, et al. Adherence to management of high blood pressure: recommendations of the Canadian Coalition for High Blood Pressure Prevention and Control. Can J Public Health. 1998;89:I5-I7.
25. Burke LE, Dunbar-Jacob JM, Hill MN. Compliance with cardiovascular disease prevention strategies: a review of the research. Ann Behav Med. 1997;19:239-263.
ISI
| PUBMED
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS)
Newman et al.
Diabetes and Vascular Disease Research 2008;5:177-183.
ABSTRACT
Beyond Established and Novel Risk Factors: Lifestyle Risk Factors for Cardiovascular Disease
Mozaffarian et al.
Circulation 2008;117:3031-3038.
FULL TEXT
Toward 'Pain-Free' Statin Prescribing: Clinical Algorithm for Diagnosis and Management of Myalgia
Jacobson
Mayo Clin Proc. 2008;83:687-700.
ABSTRACT
| FULL TEXT
Medication Adherence Following Coronary Artery Bypass Graft Surgery: Assessment of Beliefs and Attitudes
Khanderia et al.
The Annals of Pharmacotherapy 2008;42:192-199.
ABSTRACT
| FULL TEXT
Use of pictorial aids in medication instructions: A review of the literature
Katz et al.
Am J Health Syst Pharm 2006;63:2391-2397.
ABSTRACT
| FULL TEXT
AUDIT study. Evidence of global undertreatment of dyslipidaemia in patients with type 2 diabetes mellitus
Leiter et al.
British Journal of Diabetes & Vascular Disease 2006;6:31-40.
ABSTRACT
Population impact of stricter adherence to recommendations for pharmacological and lifestyle interventions over one year in patients with coronary heart disease
Gemmell et al.
J. Epidemiol. Community Health 2005;59:1041-1046.
ABSTRACT
| FULL TEXT
Association between short-term effectiveness of statins and long-term adherence to lipid-lowering therapy
Benner et al.
Am J Health Syst Pharm 2005;62:1468-1475.
ABSTRACT
| FULL TEXT
Adherence to Statin Therapy and LDL Cholesterol Goal Attainment by Patients With Diabetes and Dyslipidemia
Parris et al.
Diabetes Care 2005;28:595-599.
ABSTRACT
| FULL TEXT
Assessing adherence to statin therapy using patient report, pill count, and an electronic monitoring device
Cheng et al.
Am J Health Syst Pharm 2005;62:411-415.
FULL TEXT
Reducing the Risk of Coronary Heart Disease via Lipid Reduction
Spratt
JAOA: Journal of the American Osteopathic Association 2004;104:9S-13S.
ABSTRACT
| FULL TEXT
Benefits of Individualized Counseling by the Pharmacist on the Treatment Outcomes of Hyperlipidemia in Hong Kong
Lee et al.
J Clin Pharmacol 2004;44:632-639.
ABSTRACT
| FULL TEXT
Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study
Wei et al.
Heart 2002;88:229-233.
ABSTRACT
| FULL TEXT
|
