 |
|
Long-term Persistence in Use of Statin Therapy in Elderly Patients
Joshua S. Benner, PharmD,ScD;
Robert J. Glynn, PhD,ScD;
Helen Mogun, MS;
Peter J. Neumann, ScD;
Milton C. Weinstein, PhD;
Jerry Avorn, MD
JAMA. 2002;288:455-461.
ABSTRACT
| |
Context Knowledge of long-term persistence with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy is limited because previous studies have observed patients for short periods of time, in closely monitored clinical trials, or in other unrepresentative settings.
Objective To describe the patterns and predictors of long-term persistence with statin therapy in an elderly US population.
Design, Setting, and Patients Retrospective cohort study including 34 501 enrollees in the New Jersey Medicaid and Pharmaceutical Assistance to the Aged and Disabled programs who were 65 years of age and older, initiated statin treatment between 1990 and 1998, and who were followed up until death, disenrollment, or December 31, 1999.
Main Outcome Measures Proportion of days covered (PDC) by a statin in each quarter during the first year of therapy and every 6 months thereafter; predictors of suboptimal persistence during each interval (PDC <80%) were identified using generalized linear models for repeated measures.
Results The mean PDC was 79% in the first 3 months of treatment, 56% in the second quarter, and 42% after 120 months. Only 1 patient in 4 maintained a PDC of at least 80% after 5 years. The proportion of patients with a PDC less than 80% increased in a log-linear manner, comprising 40%, 61%, and 68% of the cohort after 3, 12, and 120 months, respectively. Independent predictors of poor long-term persistence included nonwhite race, lower income, older age, less cardiovascular morbidity at initiation of therapy, depression, dementia, and occurrence of coronary heart disease events after starting treatment. Patients who initiated therapy between 1996-1998 were 21% to 25% more likely to have a PDC of at least 80% than those who started in 1990.
Conclusions Persistence with statin therapy in older patients declines substantially over time, with the greatest drop occurring in the first 6 months of treatment. Despite slightly better persistence among patients who began treatment in recent years, long-term use remains low. Interventions are needed early in treatment and among high-risk groups, including those who experience coronary heart disease events after initiating treatment.
INTRODUCTION
Cardiovascular disease accounts for 950 000 deaths annually in the United States, including 460 000 deaths from coronary heart disease (CHD).1 Eighty-five percent of those who die of CHD and 72% of those who experience a stroke each year are 65 years of age and older.1 Since 1994, 6 large clinical trials have shown that 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) significantly reduce the incidence of CHD-related morbidity and mortality and strokes in patients undergoing treatment for an average of 5 years.2-7 Analyses suggest that the benefits of statin treatment in patients 65 years of age and older are quite similar to those seen in younger patients.7-10 The recent National Cholesterol Education Program Adult Treatment Panel III recommendations expanded the treatment-eligible elderly population from 4.2 million to 9.7 million individuals11 and emphasized that adherence to lipid-lowering therapy is critical to achieving the full population effectiveness of primary and secondary prevention.12
Although the rate of statin use among the elderly has risen in recent years,13 a substantial treatment gap remains. Elderly patients fail to receive indicated lipid-lowering medications as often as 80% of the time,14-15 and even fewer achieve serum cholesterol goals.16 This may be because physicians fail to prescribe lipid-lowering medications, patients fail to obtain and consume them, or both. Little is known about long-term persistence with statin therapy among older patients in routine care settings because previous studies have preferentially enrolled younger patients,17-18 followed them for short periods of time,17, 19-21 or informed subjects that their medication use was being monitored,17-18,22 reducing the generalizability of the observed data. Previous studies are also of limited use to clinicians and policymakers because they fail to reveal changes in statin use over time. Targeting persistence-enhancing interventions so that they have the most leverage and potential benefit will require knowledge of the time during therapy when discontinuation is most likely, and which patient subgroups are at highest risk. In addition, long-term persistence rates are necessary to estimate the population-level costs and benefits of statins in actual practice.
To address these issues, we used a repeated measures approach to assess intensity and predictors of statin use among a large cohort of elderly patients for up to 10 years after treatment initiation. Our specific objectives were (1) to describe long-term trends in statin use, including changes over time; (2) to identify patient characteristics that predict poor long-term persistence; and (3) to determine whether the growing evidence in support of statin use has improved persistence over time.
METHODS
Patients
We conducted a retrospective cohort study covering the period 1990-1999 among enrollees of the New Jersey state Medicaid or Pharmaceutical Assistance to the Aged and Disabled (PAAD) programs who were 65 years of age and older and initiated therapy with a statin (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) between 1990 and 1998. To protect the confidentiality of program participants, all personal identifiers were removed prior to data analysis. Institutional review board approval was obtained for this research. To be eligible for Medicaid during this period required an annual income below the federal poverty level; PAAD provided pharmacy benefits to a less indigent population, with income ceilings over 200% of the federal poverty level. New Jersey Medicaid had no deductible, co-payment, or maximum benefit for drugs; the PAAD program had no deductible or maximum benefit, but required a $5 co-payment for each prescription filled. Neither program had any formulary restrictions.
Data came from a computerized database of linked pharmacy, physician, hospital, and nursing home claims. Medicaid and PAAD data were available for 1989 through 1999; Medicare data for the same population were available for 1989 through 1998. The date of a patient's first pharmacy claim for any statin between January 2, 1990, and December 31, 1998, was defined as that subject's index date. We restricted our analysis to new statin users by including only those enrollees who filled at least 1 prescription for any drug, but no statin prescriptions, during 3 consecutive 6-month intervals prior to the index date. To ensure complete ascertainment of medical and nursing home services, we also required at least 1 claim for any nondrug clinical service during each of these 3 preindex intervals.
Individuals were followed up from the index date until their death, program disenrollment, or December 31, 1999, whichever occurred first. Statin use was measured quarterly during the first year and at 6-month intervals thereafter. Since most elderly patients fill prescriptions for multiple medications,23 we assumed patients had disenrolled from their payer's program if they filled no prescriptions for any drug in 2 consecutive 6-month periods. If this occurred, statin use was not recorded for these or any subsequent intervals. We tested the sensitivity of results to this assumption by using thresholds of 6 months and 24 months without a prescription claim.
Outcome Measures
We use the term "adherence" to represent the degree of prescription-filling in a given interval, and "persistence" to represent the duration of time over which a patient continued to fill statin prescriptions. The quantity dispensed and number of days supplied from each filled prescription were used to calculate the proportion of days on which a patient had a statin available in each interval (proportion of days covered [PDC]). We then divided the cohort into 3 groups at each interval: adherent individuals were defined as those with a PDC of at least 80% in a given interval. Partially adherent individuals were those having a PDC of 20% to 79%; those with a PDC less than 20% were considered nonadherent. We considered partial adherence or nonadherence in a given interval to be signs of suboptimal persistence. Although the amount of clinical benefit achieved at each of these levels of statin use is unknown, we used them to make our results comparable with other studies of medication use.24-25 To determine whether patients who became nonadherent with statins switched to other types of lipid-lowering medications, we also calculated the proportion of these patients who filled at least 1 prescription for a nonstatin lipid-lowering prescription drug in the next interval.
Potential Predictors of Suboptimal Persistence
We studied several demographic and clinical characteristics available to a primary care physician when therapy is initiated to identify predictors of suboptimal persistence. Our selection of potential predictors was also informed by previous studies of chronic medication use in elderly patients.19-20,26-27 Demographic variables included age, sex, race, and prescription program (Medicaid or PAAD). Because individuals could not be dually eligible for Medicaid and PAAD prescription coverage, prescription program was a proxy for socioeconomic status. Clinical characteristics were identified based on hospital and outpatient diagnoses, medical procedures, and filled prescriptions during the 365 days prior to the index date. Of particular interest was the influence of pretreatment and posttreatment occurrences of CHD. We categorized patients with evidence of pretreatment CHD into 3 groups: evidence of angina or coronary angiography (CHD group 1); evidence of coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), or chronic CHD (CHD group 2); and evidence of acute MI (CHD group 3). Patients who met the criteria for more than 1 group were assigned to the most severe category. We assessed the influence on persistence of posttreatment CHD occurrences by creating time-varying covariates for events indicating group 2 and group 3 CHD, in the 12 months preceding a given 6-month interval. Other comorbid conditions assessed in the year prior to therapy included history of stroke, hypertension, congestive heart failure (CHF), diabetes, depression, and dementia.
Health services utilization variables were also based on the year prior to the start of statin therapy and included the frequency of hospitalizations and outpatient physician visits, number of different medications prescribed, Charlson comorbidity score,28-29 and residency in a long-term care facility on the index date. To test the hypothesis that persistence may have been better among patients who began therapy after publication of the major statin trials,2-6 we divided the cohort into groups based on their index year and then compared persistence during the follow-up period using 1990 as the referent year.
Statistical Methods
The mean and median PDC and the proportion of patients classified as adherent, partially adherent, and nonadherent were calculated for each interval. To identify significant predictors of suboptimal persistence over time, we used generalized linear models for repeated measures30 to estimate the probability that a subject had less than 80% PDC in each interval. The decline in persistence over time (in months) was assumed to be linear on the loge scale, based on comparisons of linear, quadratic, and log-linear univariate models.
Potential predictors of suboptimal persistence were considered statistically significant at the P<.05 level. The final multivariate model was adjusted for time since the index date and for all the characteristics listed above. All statistical procedures were performed using SAS version 8.2.31
RESULTS
Population Characteristics
A total of 34 501 new statin users met our inclusion criteria. Baseline characteristics of the study population are shown in Table 1. Most of the patients were white women, with an average age of 74 years when statin treatment was initiated. Two thirds of the population were enrollees in the PAAD program; the remainder received their drug benefits from Medicaid. Most patients began treatment with simvastatin or lovastatin.
|
|
|
|
Table 1. Characteristics of Study Population (N = 34 501)*
|
|
|
When classified according to the presence of CHD in the year prior to index, 22% of patients had evidence of angina or coronary angiography in the baseline year (group 1); another 15% had a PTCA, CABG, or treatment for chronic CHD (group 2); 7% experienced an acute myocardial infarction (MI) (group 3); and 55% had none of these markers of CHD. During the follow-up period, group 2 and group 3 CHD events occurred in 23% and 10% of patients, respectively. Hypertension was the most prevalent comorbid condition, followed by CHF, diabetes, depression, dementia, and stroke. Twenty-three percent of the cohort died during the follow-up period.
Patterns of Use Over Time
The mean, median, and interquartile range for the PDC observed at each interval over the 10-year period are shown in Figure 1. Statin use declined sharply and early after initiation of therapy, from a mean PDC of 79% in the first 3 months, to 56% after 6 months, and 50% after 12 months. In subsequent years, the mean PDC continued to decline gradually, to a low of 35% after 60 months, but then increased slightly to 42% after 120 months. The median PDC declined much more rapidly than the mean, from 91% after 3 months to 0 at 54 months. Median persistence remained 0 until 102 months, when it began to increase slightly among the relatively small number of remaining patients. These results were robust to changes in the number of inactive months required for a subject to be considered disenrolled from the payer program.
|
|
|
|
Figure 1. Mean, Median, and Interquartile Range of the Proportion of Days Covered (PDC) by Statin for Each Interval
Boxes represent the interquartile range; vertical whiskers extend to the maximum and minimum observation for each interval. No. is the number of subjects evaluated at each interval. Median PDC was 0 from months 54 through 96.
|
|
|
The proportion of patients who were adherent with statin therapy was 60%, 43%, 26%, and 32% after 3, 6, 60, and 120 months, respectively (Figure 2). Virtually none of the cohort were defined as nonadherent during the first 3 months of therapy (because initial supplies were typically 30-90 days). However, nonadherent patients comprised 29% of the population at 6 months and 56% at 60 months, after which the proportion remained approximately constant until the final 2 years of follow-up when persistence improved slightly. A large proportion of patients were partially adherent early on, but this group narrowed over time, comprising 40%, 29%, and 18% of the cohort after 3, 6, and 60 months, respectively, with most of these patients transitioning into the nonadherent group. Of those who became nonadherent with statin therapy, only 4% filled a prescription for a nonstatin lipid-lowering medication in the next interval, and fewer than 1% had a PDC of at least 80% with that medication. Thus, very few patients could have been misclassified as nonadherent due to switching from statins to other lipid-lowering drugs.
|
|
|
|
Figure 2. Proportion of Patients Classified as Adherent, Partially Adherent, and Nonadherent at Each Interval
See Figure 1 for number of patients evaluated at each interval.
|
|
|
Predictors of Suboptimal Persistence
Results of the multivariate model are shown in Table 2. Long-term use was especially low for patients of black and other nonwhite races, regardless of socioeconomic status, as well as for recipients of Medicaid, regardless of race. After adjusting for all other characteristics studied, black Medicaid recipients had 2.7 times the odds of suboptimal persistence compared with white PAAD recipients. In addition, patients 75 years of age and older had 19% greater odds of poor long-term persistence. Patients treated for depression or dementia were more likely to have suboptimal persistence, while the opposite was true for those with hypertension, stroke, CHF, or diabetes. The odds of suboptimal persistence were slightly higher among patients who were hospitalized in the year prior to initiating therapy and among those with the greatest number of other prescribed medications. Patients who resided in a nursing home were significantly more likely to remain on their prescribed regimen.
|
|
|
|
Table 2. Association Between Potential Predictors and Suboptimal Persistence*
|
|
|
Overall, more severe CHD was associated with greater use of statins. Patients with group 1, group 2, and group 3 evidence of CHD were 14%, 27%, and 41% less likely, respectively, to have suboptimal persistence, compared with patients without CHD. However, those who experienced an acute MI had 20% greater odds of suboptimal persistence in the year after the event, compared with those who did not have any CHD event. A similar but smaller effect was observed among patients who experienced a group 2 CHD event during follow-up.
Compared with those who began statin therapy in 1990, patients who started between 1992 and 1993 were about 15% more likely to reduce or omit therapy during the follow-up period. However, patients who initiated therapy more recently (1996-1998) were 21% to 25% less likely to stop or reduce their statin use.
COMMENT
Despite burgeoning evidence of the capacity of lipid-lowering therapy to reduce cardiovascular morbidity and mortality, these findings indicate that their actual use in typical populations of older patients is likely to substantially undercut this potential. A better understanding of the magnitude and predictors of long-term persistence with statins has implications for the approach to managing individual patients, as well as the design and evaluation of population-level cardiovascular risk reduction programs. To our knowledge, this is the first study to observe statin use in routine care settings for a follow-up period comparable to that of the pivotal statin trials.2-6 Because our cohort was large and typical of many older populations in the United States, it can suggest the proportion of patients expected to have suboptimal persistence with statin therapy at a given point in time under routine conditions. The findings also identify several previously unstudied patient characteristics that can be used to predict poor persistence.
We found actual persistence to be far less than that reported in trials, where 5-year cumulative discontinuation rates ranged from just 6% to 30%.2-6 By contrast, we found that only 26% of patients were still taking their regimens at a high level after 5 years. This finding extends previous works by our group and by investigators in Australia, who found a 1-year mean of 64% of days with statin available19 and a 1-year discontinuation rate of 60%,20 respectively. Our results differ from those of Andrade et al,21 who found a 1-year discontinuation rate of 15% among patients taking lovastatin in 2 health maintenance organizations. We also found lower utilization than other practice-based studies that monitored persistence over extended periods.18, 22 Patients in these studies may have remained on their regimens longer because they were relatively younger, healthier, and of higher socioeconomic status, or received dietary counseling and lipid clinic-based disease management. Patients in the latter 2 studies were also informed that their medication use was being monitored, and one study18 relied on patient-reported medication use, which overstates actual use.32
Comparing our findings with studies of other chronic medications in this population, the mean persistence 12 months after an initial statin prescription (50%) was about the same as the rate we found for antihypertensives (43%),27 but lower than for medication for glaucoma (69%)33 or CHF (70%).34 Rudd24 has pooled data from short-term electronic monitoring of therapy for several chronic diseases to estimate the frequency distribution of adherent, partially adherent, and nonadherent patients to be 50% to 60%, 30% to 40%, and 5% to 10%, respectively. Although we observed a similar distribution in the first 3 months of therapy, long-term persistence was substantially worse in our cohort. This may have been because electronic pill containers can serve to increase adherence by raising patients' awareness of their medication-taking habits.17 In any case, our findings make it clear that for statins, persistence must be assessed over years rather than months to realize its true clinical and public health impact.
The predictors of suboptimal persistence identified here add new information to previous work19 in which we observed lower persistence among the poorest and oldest patients, as well as those who used the greatest number of prescription drugs. Our analysis confirms that these socioeconomic disparities exist in a much larger cohort of statin users and continue for several years after initiation of therapy. We also found significant disparities in persistence among black and other nonwhite races, which is of particular concern because blacks and Mexican-Americans have a higher prevalence of CHD than whites.1 Patients treated for depression were also less likely to persist in statin use, consistent with our recent observation that depressive symptoms correlate with poor persistence with antihypertensive medications.35
Patients with higher levels of baseline CHD persisted better than their healthier counterparts, suggesting that these patients' perceived cardiovascular risk influenced their medication-taking behavior. A history of stroke, CHF, diabetes, or hypertension also predicted better persistence. By contrast, those who had an MI after starting statin therapy were significantly less likely to continue their statin use following the event, perhaps because they perceived the drug to be ineffective. This finding is alarming given that clinical trials have shown statins to be most effective when used for secondary prevention.36
We observed moderately higher persistence among patients who initiated statin therapy after the publication of pivotal trials in the mid-1990s. This finding is consistent with those of Jackevicius et al,37 who reported an increase in prescribing of statins among elderly patients after the publication of the 4S trial.2 This suggests that the results of major clinical trials may affect patients' decisions to continue therapy, physicians' persistence in prescribing therapy, or both.
These results should be interpreted in light of some limitations. First, the study cohort consisted of patients 65 years of age and older, most of whom were women with moderate to low incomes. Although this population is representative of many elderly people in the United States, especially those who receive lipid-lowering medications,14 different results may have been observed in a more affluent cohort or one that included more men. Statin therapy may have been discontinued by the prescriber for clinically appropriate reasons such as adverse drug events, lack of efficacy, or conversion to nonstatin lipid-lowering therapy. However, lipid-lowering therapy is most often lifelong, adverse drug events are rare with the statins, and we found switching from statins to other lipid-lowering medications to be extremely rare in this population. While we could not measure use of statins obtained from physician samples or out-of-state pharmacies, these scenarios are unlikely since this population's prescriptions were provided free of charge or for a nominal co-payment. In settings where patients must pay for much or all of their statin therapy out-of-pocket, it is likely that persistence could be even worse. The poor persistence we observed also cannot be attributed to death or disenrollment from the payer system because we did not calculate adherence for the interval in which death occurred, and we required ongoing use of any medication as evidence of continuous enrollment. The latter requirement may have misclassified a few nonadherent subjects as disenrolled from their program; but to the extent that this occurred, the results presented herein actually underestimate the true statin discontinuation rate.
These data seem to indicate a slight improvement in persistence 9 to 10 years after the earliest members of the cohort began their statin therapy. However, these findings occurred among surviving, continuously enrolled elderly patients, or about one third of patients who initiated therapy in 1990-1991. This may therefore reflect a "survivor effect" among these patients as well as a secular trend toward improved persistence among all patients at the end of the decade after the publication of pivotal statin trials.
Our findings have important implications for clinicians and other decision makers responsible for the appropriate use of lipid-lowering medications. They make it clear that one cannot assume that long-term persistence in typical settings will approach the levels observed in prospective trials. Accordingly, predictions of population-wide health benefits of statin therapy38 based on these trials may be overly optimistic given the poor persistence we observed. Recent meta-analyses suggest that the most effective persistence-enhancing interventions for long-term treatments consist of combinations of more convenient care, information, counseling, reminders, reinforcement, and other forms of supervision or attention.39-41 Our findings suggest that such interventions should be initiated early in therapy and targeted to patients most likely to become nonadherent. Given that our cohort faced little or no out-of-pocket cost for medications, such interventions should focus on other barriers to persistence. These data contribute to the evidence that studies demonstrating clinical benefit also improve persistence of use. Therefore, improving patients' understanding of their cardiovascular risk, their medication regimen, and the potential benefits of persistence with statin therapy may further enhance persistence. These and other interventions to improve persistence deserve further study.
AUTHOR INFORMATION
Author Contributions: Study concept and design: Benner, Glynn, Avorn.
Acquisition of data: Mogun, Avorn.
Analysis and interpretation of data: Benner, Glynn, Mogun, Neumann, Weinstein, Avorn.
Drafting of the manuscript: Benner.
Critical revision of the manuscript for important intellectual content: Benner, Glynn, Mogun, Neumann, Weinstein, Avorn.
Statistical expertise: Benner, Glynn, Weinstein.
Obtained funding: Benner, Glynn, Avorn.
Administrative, technical, or material support: Mogun, Weinstein, Avorn.
Study supervision: Neumann, Weinstein, Avorn.
Funding/Support: Dr Benner was supported during this project by a National Research Service Award from the US Agency for Healthcare Research and Quality and Harvard School of Public Health. This work was also funded in part by research grants AG-18395 and AG-18833 from the National Institute on Aging. No support was received from any pharmaceutical company for this research. Sponsors had no role in the design or conduct of the study, or in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.
Acknowledgment: We thank Garrett Fitzmaurice, PhD, Alex Federman, MD, MPH, Allison Smitten, and Susan Duty for their analytic assistance.
Financial Disclosures: Drs Avorn, Glynn, and Benner and Ms Mogun have received research grant support from Bristol-Myers Squibb, Inc. Dr Benner has received speaker's honoraria from Pfizer, Inc.
Corresponding Author and Reprints: Joshua S. Benner, PharmD, ScD, Division of Pharmacoepidemiology & Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Suite 341, Boston, MA 02115 (e-mail: jbenner{at}post.harvard.edu).
Author Affiliations: Division of Pharmacoepidemiology & Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (Drs Benner, Glynn, and Avorn, and Ms Mogun), and Center for Risk Analysis, Harvard School of Public Health, (Drs Benner, Neumann, and Weinstein), Boston, Mass. Dr Benner is currently Director of Health Economics with Epinomics Research, Inc, Alexandria, Va.
REFERENCES
| |
1. 2001 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association; 2000.
2. The Scandinavian Simvastatin Survival Study Group. 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. Shepherd J, Cobbe SM, Ford I, et al for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307.
FREE FULL TEXT
4. Sacks FM, Pfeffer MA, Moye LA, et al for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001-1009.
FREE FULL TEXT
5. The Long-term Intervention with Pravastatin in Ischaemic Disease (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. N Engl J Med. 1998;339:1349-1357.
FREE FULL TEXT
6. Downs JR, Clearfield M, Weis S, et al for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998;279:1615-1622.
FREE FULL TEXT
7. MRC/BHF Heart Protection Study. Preliminary results. Available at: http://www.hpsinfo.org/. Accessed November 14, 2001.
8. Miettinen TA, Pyorala K, Olsson AG, et al. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation. 1997;96:4211-4218.
FREE FULL TEXT
9. Hunt D, Young P, Simes J, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID trial. Ann Intern Med. 2001;134:931-940.
FREE FULL TEXT
10. Lewis SJ, Moye LA, Sacks FM, et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range: results of the Cholesterol and Recurrent Events (CARE) Trial. Ann Intern Med. 1998;129:681-689.
FREE FULL TEXT
11. Fedder DO, Koro CE, L'Italien GJ. New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy. Circulation. 2002;105:152.
FREE FULL TEXT
12. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
FREE FULL TEXT
13. Jackevicius CA, Anderson GM, Leiter L, Tu JV. Use of the statins in patients after acute myocardial infarction. Arch Intern Med. 2001;161:183-188.
FREE FULL TEXT
14. McCormick D, Gurwitz JH, Lessard D, et al. Use of aspirin,  -blockers, and lipid-lowering medications before recurrent acute myocardial infarction. Arch Intern Med. 1999;159:561-567.
FREE FULL TEXT
15. Lemaitre RN, Furberg CD, Newman AB, et al. Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study. Arch Intern Med. 1998;158:1761-1768.
FREE FULL TEXT
16. Majumdar SR, Gurwitz JH, Soumerai SB. Undertreatment of hyperlipidemia in the secondary prevention of coronary artery disease. J Gen Intern Med. 1999;14:711-717.
FULL TEXT
|
ISI
| PUBMED
17. Schwed A, Fallab CL, Burnier M, et al. Electronic monitoring of compliance to lipid-lowering therapy in clinical practice. J Clin Pharmacol. 1999;39:402-409.
ABSTRACT
18. Eriksson M, Hadell K, Holme I, et al. Compliance with and efficacy of treatment with pravastatin and cholestyramine. J Intern Med. 1998;243:373-380.
FULL TEXT
|
ISI
| PUBMED
19. 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
20. Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust. 1996;164:208-211.
ISI
| PUBMED
21. 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
22. Hiatt JG, Shamsie SG, Schectman G. Discontinuation rates of cholesterol-lowering medications. Am J Manag Care. 1999;5:437-444.
ISI
| PUBMED
23. Redelmeier DA, Tan SH, Booth GL. The treatment of unrelated disorders in patients with chronic medical diseases. N Engl J Med. 1998;338:1516-1520.
FREE FULL TEXT
24. Rudd P. Compliance with antihypertensive therapy: a shifting paradigm. Cardiol Rev. 1994;2:230-240.
25. Insull W. The problem of compliance to cholesterol altering therapy. J Intern Med. 1997;241:317-325.
FULL TEXT
|
ISI
| PUBMED
26. Monane M, Bohn RL, Gurwitz JH, et al. Compliance with antihypertensive therapy among elderly Medicaid enrollees. Am J Public Health. 1996;86:1805-1808.
FREE FULL TEXT
27. Monane M, Bohn RL, Gurwitz JH, Glynn RJ, Levin R, Avorn J. The effects of initial drug choice and comorbidity on antihypertensive therapy compliance. Am J Hypertens. 1997;10:697-704.
FULL TEXT
|
ISI
| PUBMED
28. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373-383.
FULL TEXT
|
ISI
| PUBMED
29. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45:613-619.
FULL TEXT
|
ISI
| PUBMED
30. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika. 1986;73:13-22.
FREE FULL TEXT
31. SAS version 8.2. Cary, NC: SAS Institute Inc; 2000.
32. Choo PW, Rand CS, Inui TS, et al. Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy. Med Care. 1999;37:846-857.
FULL TEXT
|
ISI
| PUBMED
33. Gurwitz JH, Glynn RJ, Monane M, et al. Treatment for glaucoma: adherence by the elderly. Am J Public Health. 1993;83:711-716.
FREE FULL TEXT
34. Monane M, Bohn RL, Gurwitz JH, Glynn RJ, Avorn J. Noncompliance with congestive heart failure therapy in the elderly. Arch Intern Med. 1994;154:2109-2110.
FREE FULL TEXT
35. Wang PJ, Bohn RL, Knight E, Glynn RJ, Mogun H, Avorn J. Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors. J Gen Intern Med. In press.
36. La Rosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999;282:2340-2346.
FREE FULL TEXT
37. Jackevicius CA, Anderson GM, Leiter L, Vu JV. Use of the statins in patients after acute myocardial infarction: does evidence change practice? Arch Intern Med. 2001;161:183-188.
FREE FULL TEXT
38. Brier KL, Tornow JJ, Ries AJ, Weber MP, Downs JR. Forecasting patient outcomes in the management of hyperlipidemia. Arch Intern Med. 1999;159:569-575.
FREE FULL TEXT
39. Haynes RB, McKibbon KA, Kanani R. Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications. Lancet. 1996;348:383-386.
FULL TEXT
|
ISI
| PUBMED
40. 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
41. Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care. 1998;36:1138-1161.
FULL TEXT
|
ISI
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLES
Adherence With Statin Therapy in Elderly Patients With and Without Acute Coronary Syndromes
Cynthia A. Jackevicius, Muhammad Mamdani, and Jack V. Tu
JAMA. 2002;288(4):462-467.
ABSTRACT
| FULL TEXT
Elderly Patients' Adherence to Statin Therapy
William B. Applegate
JAMA. 2002;288(4):495-497.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Lipid Profile Components and Risk of Ischemic Stroke: The Northern Manhattan Study (NOMAS)
Willey et al.
Arch Neurol 2009;66:1400-1406.
ABSTRACT
| FULL TEXT
Derivation and Validation of the ASK-12 Adherence Barrier Survey
Matza et al.
The Annals of Pharmacotherapy 2009;43:1621-1630.
ABSTRACT
| FULL TEXT
Association between prescription burden and medication adherence in patients initiating antihypertensive and lipid-lowering therapy
Benner et al.
Am J Health Syst Pharm 2009;66:1471-1477.
ABSTRACT
| FULL TEXT
Optimizing the Start Time of Statin Therapy for Patients with Diabetes
Denton et al.
Med Decis Making 2009;29:351-367.
ABSTRACT
Management of Hyperlipidemia in Older Adults
Alexander et al.
J CARDIOVASC PHARMACOL THER 2009;14:49-58.
ABSTRACT
Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack
Chaturvedi et al.
Neurology 2009;72:688-694.
ABSTRACT
| FULL TEXT
Copayment Levels and Medication Adherence: Less Is More
Choudhry
Circulation 2009;119:365-367.
FULL TEXT
Impact of a Prescription Copayment Increase on Lipid-Lowering Medication Adherence in Veterans
Doshi et al.
Circulation 2009;119:390-397.
ABSTRACT
| FULL TEXT
Contrasting Measures of Adherence with Simple Drug Use, Medication Switching, and Therapeutic Duplication
Martin et al.
The Annals of Pharmacotherapy 2009;43:36-44.
ABSTRACT
| FULL TEXT
Associations of Kidney Function with Cardiovascular Medication Use after Myocardial Infarction
Winkelmayer et al.
CJASN 2008;3:1415-1422.
ABSTRACT
| FULL TEXT
Trends in Statin Use and Low-Density Lipoprotein Cholesterol Levels Among US Adults: Impact of the 2001 National Cholesterol Education Program Guidelines
Mann et al.
The Annals of Pharmacotherapy 2008;42:1208-1215.
ABSTRACT
| FULL TEXT
Effects of Cerivastatin Withdrawal on Statin Persistence
Reaume et al.
The Annals of Pharmacotherapy 2008;42:956-961.
ABSTRACT
| 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
Effect of Pretreatment With Statins on Ischemic Stroke Outcomes
Reeves et al.
Stroke 2008;39:1779-1785.
ABSTRACT
| FULL TEXT
Uric acid lowering therapy: prescribing patterns in a large cohort of older adults
Solomon et al.
Ann Rheum Dis 2008;67:609-613.
ABSTRACT
| FULL TEXT
A substantial cause of preventable illness
Avorn and Shrank
BMJ 2008;336:956-957.
FULL TEXT
A Randomized Trial of Direct-to-Patient Communication to Enhance Adherence to {beta}-Blocker Therapy Following Myocardial Infarction
Smith et al.
Arch Intern Med 2008;168:477-483.
ABSTRACT
| FULL TEXT
Menopausal symptoms and adjuvant therapy-associated adverse events
Hadji
Endocr Relat Cancer 2008;15:73-90.
ABSTRACT
| FULL TEXT
Do patients' expectations influence their use of medications?: Qualitative study
Dolovich et al.
cfp 2008;54:384-393.
ABSTRACT
| FULL TEXT
Achieving Vascular Risk Factor Targets: A Survey of a London General Practice
Levine et al.
ANGIOLOGY 2008;59:36-46.
ABSTRACT
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
Using Computer-Based Decision Support to Close the "Know Do" Gap in Lipid-Lowering Therapy
Avorn and Choudhry
Circulation 2008;117:336-337.
FULL TEXT
Family practice patients' adherence to statin medications
Natarajan et al.
cfp 2007;53:2144-2145.
ABSTRACT
| FULL TEXT
Use of statins and beta-blockers after acute myocardial infarction according to income and education
Rasmussen et al.
J. Epidemiol. Community Health 2007;61:1091-1097.
ABSTRACT
| FULL TEXT
Patient Knowledge of Coronary Risk Profile Improves the Effectiveness of Dyslipidemia Therapy: The CHECK-UP Study: A Randomized Controlled Trial
Grover et al.
Arch Intern Med 2007;167:2296-2303.
ABSTRACT
| FULL TEXT
Statin Protection Against Influenza and COPD Mortality
Fedson and Frost
Chest 2007;132:1406-1407.
FULL TEXT
Statins Blunt HAART-Induced CD4 T-Cell Gains but Have No Long-Term Effect on Virologic Response to HAART
Rodriguez et al.
J Int Assoc Physicians AIDS Care (Chic Ill) 2007;6:198-202.
ABSTRACT
Predicting adherence to immunosuppressant therapy: a prospective analysis of the theory of planned behaviour
Chisholm et al.
Nephrol Dial Transplant 2007;22:2339-2348.
ABSTRACT
| FULL TEXT
Adherence to Lipid-lowering Therapy and the Use of Preventive Health Services: An Investigation of the Healthy User Effect
Brookhart et al.
Am J Epidemiol 2007;166:348-354.
ABSTRACT
| FULL TEXT
How can adherence to lipid-lowering medication be improved? A systematic review of randomized controlled trials
Schedlbauer et al.
Fam Pract 2007;24:380-387.
ABSTRACT
| FULL TEXT
Adherence to Statin Therapy Under Drug Cost Sharing in Patients With and Without Acute Myocardial Infarction: A Population-Based Natural Experiment
Schneeweiss et al.
Circulation 2007;115:2128-2135.
ABSTRACT
| FULL TEXT
Physician Follow-up and Provider Continuity Are Associated With Long-term Medication Adherence: A Study of the Dynamics of Statin Use
Brookhart et al.
Arch Intern Med 2007;167:847-852.
ABSTRACT
| FULL TEXT
Effect of Monitoring Bone Turnover Markers on Persistence with Risedronate Treatment of Postmenopausal Osteoporosis
Delmas et al.
J. Clin. Endocrinol. Metab. 2007;92:1296-1304.
ABSTRACT
| FULL TEXT
Relationship Between Adherence to Evidence-Based Pharmacotherapy and Long-term Mortality After Acute Myocardial Infarction
Rasmussen et al.
JAMA 2007;297:177-186.
ABSTRACT
| FULL TEXT
Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study
Penning-van Beest et al.
Eur Heart J 2007;28:154-159.
ABSTRACT
| FULL TEXT
Statins and the Risk of Lung, Breast, and Colorectal Cancer in the Elderly
Setoguchi et al.
Circulation 2007;115:27-33.
ABSTRACT
| FULL TEXT
Relationship Between Medicare's Hospital Compare Performance Measures and Mortality Rates
Werner and Bradlow
JAMA 2006;296:2694-2702.
ABSTRACT
| FULL TEXT
Potentially Unintended Discontinuation of Long-term Medication Use After Elective Surgical Procedures
Bell et al.
Arch Intern Med 2006;166:2525-2531.
ABSTRACT
| FULL TEXT
Did you take your medications?: The dentist's role in helping patients adhere to their drug regimen
Glick
Journal of the American Dental Association 2006;137:1636-1637.
FULL TEXT
Concordance with heart failure medications: what do patients think?
Hobbs
Fam Pract 2006;23:607-608.
FULL TEXT
Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus.
Ho et al.
Arch Intern Med 2006;166:1836-1841.
ABSTRACT
| FULL TEXT
Adherence and Persistence with Single-Dosage Form Extended-Release Niacin/Lovastatin Compared with Statins Alone or in Combination with Extended-Release Niacin
LaFleur et al.
The Annals of Pharmacotherapy 2006;40:1274-1279.
ABSTRACT
| FULL TEXT
Measurement of Adherence in Pharmacy Administrative Databases: A Proposal for Standard Definitions and Preferred Measures
Hess et al.
The Annals of Pharmacotherapy 2006;40:1280-1288.
ABSTRACT
| FULL TEXT
Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction
Gislason et al.
Eur Heart J 2006;27:1153-1158.
ABSTRACT
| FULL TEXT
The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions.
Shrank et al.
Arch Intern Med 2006;166:332-337.
ABSTRACT
| FULL TEXT
Medication-Attributed Adverse Effects in Placebo Groups: Implications for Assessment of Adverse Effects
Rief et al.
Arch Intern Med 2006;166:155-160.
ABSTRACT
| FULL TEXT
Depression and Medication Adherence in Outpatients With Coronary Heart Disease: Findings From the Heart and Soul Study
Gehi et al.
Arch Intern Med 2005;165:2508-2513.
ABSTRACT
| FULL TEXT
Statins and the Risk of Colorectal Cancer
Setoguchi et al.
NEJM 2005;353:952-954.
FULL TEXT
E-Prescribing And The Medicare Modernization Act Of 2003
Bell and Friedman
Health Aff (Millwood) 2005;24:1159-1169.
ABSTRACT
| FULL TEXT
Adherence to Medication
Osterberg and Blaschke
NEJM 2005;353:487-497.
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
Over-the-Counter Statins
Choudhry and Avorn
ANN INTERN MED 2005;142:910-913.
ABSTRACT
| FULL TEXT
Predictors of Adherence With Antihypertensive and Lipid-Lowering Therapy
Chapman et al.
Arch Intern Med 2005;165:1147-1152.
ABSTRACT
| FULL TEXT
Hyperlipidemia in Seniors: Too Much, Too Little, Too Late?
Hirth
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2005;60:595-597.
FULL TEXT
The 2003 Canadian recommendations for dyslipidemia management: Revisions are needed
Manuel et al.
CMAJ 2005;172:1027-1031.
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
Lipid Management in Patients With Coronary Artery Disease by a Clinical Pharmacy Service in a Group Model Health Maintenance Organization
Olson et al.
Arch Intern Med 2005;165:49-54.
ABSTRACT
| FULL TEXT
Impact of Concurrent Medication Use on Statin Adherence and Refill Persistence
Grant et al.
Arch Intern Med 2004;164:2343-2348.
ABSTRACT
| FULL TEXT
Long term persistence with statin treatment in daily medical practice
Mantel-Teeuwisse et al.
Heart 2004;90:1065-1066.
FULL TEXT
Self-Reported Morisky Score for Identifying Nonadherence with Cardiovascular Medications
Shalansky et al.
The Annals of Pharmacotherapy 2004;38:1363-1368.
ABSTRACT
| FULL TEXT
Ethnic and Sex Differences in the Prevalence, Treatment, and Control of Dyslipidemia Among Hypertensive Adults in the GENOA Study
O'Meara et al.
Arch Intern Med 2004;164:1313-1318.
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
Measurement, Correlates, and Health Outcomes of Medication Adherence Among Seniors
Vik et al.
The Annals of Pharmacotherapy 2004;38:303-312.
ABSTRACT
| FULL TEXT
Giving aspirin and ibuprofen after myocardial infarction
Kimmel and Strom
BMJ 2003;327:1298-1299.
FULL TEXT
Secondary Prevention of Coronary Heart Disease in the Elderly
Dornbrook-Lavender et al.
The Annals of Pharmacotherapy 2003;37:1867-1876.
ABSTRACT
| FULL TEXT
The use of cholesterol-lowering medications after coronary revascularization
Brophy et al.
CMAJ 2003;169:1153-1157.
ABSTRACT
| FULL TEXT
Polypharmacy and Medication Adherence in Patients With Type 2 Diabetes
Grant et al.
Diabetes Care 2003;26:1408-1412.
ABSTRACT
| FULL TEXT
Editorial: Hot Topics in Geriatrics
Morley
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2003;58:M30-36.
FULL TEXT
The ALLHAT Lipid Lowering Trial--Less Is Less
Pasternak
JAMA 2002;288:3042-3044.
FULL TEXT
Elderly Patients' Adherence to Statin Therapy
Applegate
JAMA 2002;288:495-497.
FULL TEXT
|
