 |
|
Use of Simvastatin Treatment in Patients With Combined Hyperlipidemia in Clinical Practice
Ralph M. Vicari, MD;
George J. Wan, PhD, MPH;
A. Michael Aura, MD;
Charles M. Alexander, MD;
Leona E. Markson, ScD;
Steven M. Teutsch, MD, MPH;
for the Simvastatin Combined Hyperlipidemia Registry Group
Arch Fam Med. 2000;9:898-905.
ABSTRACT
| |
Objective To describe and understand current care of simvastatin-treated patients with combined hyperlipidemia in routine clinical practice.
Design A 6-month prospective observational study. Demographics, simvastatin dosage, cardiac risk factors, and lipid profile were collected from August 1997 to December 1998 at 20 sites (230 patients) across the United States.
Results Overall mean percentage of reduction in total cholesterol levels was 27% (P<.001), low-density lipoprotein cholesterol (LDL-C) was 35% (P<.001), and triglyceride values was 28% (P<.001). Among those patients with low baseline high-density lipoprotein cholesterol (HDL-C) values (<0.91 mmol/L [<35 mg/dL]) (N = 49), there was a 17% increase in HDL-C (P .001); 35% of these patients achieved National Cholesterol Education Program HDL-C goal (ie, 0.91 mmol/L [ 35 mg/dL]). Coronary heart disease (CHD) patients were given significantly higher initial doses (mean, 15.1 mg) compared with non-CHD patients (mean, 11.5 mg) (P.001). Overall, 74% of patients achieved LDL-C goal (52% on starting dose, 22% after 1 titration). Among those patients who were not at goal and had a follow-up lipid profile result available, only 1 patient (2%) was at the maximum dose (80 mg); 69% were receiving 20 mg or less. Approximately 63% of patients with CHD, 80% of patients with 2 or more risk factors, and 91% of patients with fewer than 2 risk factors achieved LDL-C goal.
Conclusions Multiple factors contribute to LDL-C goal achievement in a usual care setting. A significant opportunity exists to increase the number of patients who achieve LDL-C goal by appropriate dose titration and/or give patients a higher initial dose of simvastatin.
INTRODUCTION
THE BENEFIT of statin therapy in primary and secondary prevention of coronary heart disease (CHD) is well established1-7; yet, only a small number of eligible patients are currently being treated to the low-density lipoprotein cholesterol (LDL-C) goal recommended by the National Cholesterol Education Program Adult Treatment Panel II (NCEP).8-12
CURRENT CARE PRACTICES
The American Heart Association, the American College of Cardiology, and the NCEP have all developed guidelines for improving care of patients with dyslipidemia.11-14 However, physician adherence to these guidelines remains suboptimal. A large "treatment gap" continues to exist between therapies recommended by national guidelines for patients with CHD and the care that they actually receive. This treatment gap has been extensively documented in both Europe15 and the United States.8, 16-21 In addition, community-based retrospective studies of patients with CHD report that 43% to 67% have lipid tests, 27% to 39% of patients are given lipid therapy, and 9% to 11% of the total CHD population are treated to an LDL-C level of 2.59 mmol/L or lower (100 mg/dL) (23%-31% of the total population are treated to an LDL-C level of 3.36 mmol/L [130 mg/dL]).8-10
NEED FOR APPROPRIATE DOSE TITRATION AND HIGHER STARTING DOSAGES
Although patients are treated, they may not be treated to recommended goals. Failure to achieve treatment goal may be caused by inappropriate lipid medication use, low initial dosage, low-potency lipid medication use, patient noncompliance, or inadequate dose titration.22 The lower goal for patients with CHD or multiple CHD risk factors (RFs) also illustrate the difficulty of achieving LDL-C goal. Several clinical trials have documented the efficacy of simvastatin on improvement in the lipid profile using forced-dose titration (this occurs when a patient is started on an initial dose of medicine and subsequently receives increasing doses of the medication per study protocol),23-27 but studies of treatment with simvastatin in usual care settings are needed to guide selection of an appropriate starting dose and subsequent titration. A higher starting dose may be helpful for patients who require large LDL-C decreases to achieve the LDL-C goal.
CHD AND TREATMENT FOR DYSLIPIDEMIA
The association between dyslipidemia and CHD is well documented.28-31 It has been suggested that statin therapy may have a wider application in the treatment of dyslipidemia in addition to reducing LDL-C levels.24, 32 For example, a recent study indicated that in patients with elevated triglyceride levels, the more effective the statin is in lowering LDL-C levels, the more effective it will also be in reducing triglycerides.24 Statin therapy may also provide benefits to patients with a low or below average high-density lipoprotein cholesterol (HDL-C) level.2, 23, 33-35 Epidemiological and interventional studies have shown that a low HDL-C level is associated with an increased risk of CHD.34-44 For each 0.03-mmol/L (1-mg/dL) increase in the level of HDL-C, there is a 2% decrease in CHD risk in men and a 3% decrease in women.45 A recent clinical trial among male CHD patients with low levels of HDL-C (1.03 mmol/L [40 mg/dL]) reported that a 6% increase (ie, 0.05-mmol/L [2-mg/dL] increase from baseline) in HDL-C level was associated with a 22% risk reduction in major coronary events.46
COMBINED HYPERLIPIDEMIA
Combined hyperlipidemia is defined as elevations in both total cholesterol or LDL-C levels and triglyceride levels.27 It accounts for 10% to 20% of those with elevated cholesterol levels.47-48 Combined hyperlipidemia occurs in up to 7% of the entire US population and up to 16% of diabetic patients.49 Patients with combined hyperlipidemia are at greater risk of coronary heart disease compared with patients with elevated LDL-C levels alone50-53 and may especially benefit from statin therapy.
RESEARCH AIMS
This study described the treatment of patients with combined hyperlipidemia treated with simvastatin in a usual care setting. The long-term safety and efficacy of simvastatin has been well documented,24, 26, 54-67 including reductions in cardiovascular deaths and economic benefits associated with simvastatin treatment.7, 68-69 Despite information obtained in clinical trials,27, 70 relatively little is known regarding changes in the lipid profile and LDL-C goal attainment in combined hyperlipidemia patients treated with simvastatin in usual care practice. This study described the process of care, improvement in the lipid profile, and LDL-C goal achievement in patients with combined hyperlipidemia treated with simvastatin in everyday clinical practice. Specific objectives were to describe the use of simvastatin therapy to improve the lipid profile as measured by (1) percentage of reduction of triglycerides, (2) percentage of reduction of total cholesterol, (3) percentage of reduction of LDL-C, and (4) percentage of increase in HDL-C; and to determine the percentage of patients reaching NCEP LDL-C goal based on cardiac RF status across the range of simvastatin dosages.
PATIENTS AND METHODS
STUDY DESIGN
In a 6-month prospective observational study of patients newly treated with simvastatin, data (N = 230) were collected from August 1997 to December 1998 at 20 sites across the United States. Patients continued to participate in the study until LDL-C goal was achieved, up to a maximum of 24 weeks ("completers"). One hundred sixty-nine (73%) of 230 patients "completed" the study, while 3 patients with a missing starting dose were excluded from the analyses. Twenty-one patients did not reach goal on starting dose and continued to receive the starting dose over the 24 weeks. Thirty-seven patients did not reach goal on the starting dose and after the initial upward dose titration. Among these, 26 patients were titrated upward a second time and 11 patients did not have another dose increase. Follow-up data were insufficient to determine the percentage of patients achieving LDL-C goal in this group of 37 patients at the end of 24 weeks. There were 20 sites (227 patients) from a variety of health care delivery environments (3 multispecialty group, 10 cardiology, 5 internal medicine group, 1 research foundation, and 1 staff model health maintenance organization) across the United States. Patients in this study were being treated with simvastatin in a usual care environment; there were no study-specific guidelines, formal interventions, or protocol requirements. However, general treatment suggestions to treat eligible patients as recommended by NCEP guidelines12 and to follow the prescribing information for simvastatin were provided to sites. Sites were also asked to counsel patients in the appropriate low-fat, low-cholesterol diet. At the time the study was initiated, the recommended starting dose for simvastatin was 10 mg daily. Doubling of the dose every 4 to 6 weeks as necessary to achieve NCEP goals based on cardiovascular RF status was also recommended. Note that there was a change in the recommended starting dose for simvastatin after the last patient was enrolled with the dose raised from 10 to 20 mg. The maximum dose was raised to 80 mg at the same time. Baseline patient demographics and laboratory values were collected with follow-up laboratory value at 6 ± 2, 12 ± 2, 18 ± 2, and 24 ± 2 weeks if ordered by the physician to achieve NCEP goals. When the patient achieved LDL-C goal, there was no further study follow-up.
DESCRIPTION OF PATIENTS
Patients with an elevated LDL-C (ie, greater than NCEP goal based on cardiovascular RF status) and triglycerides (>5.17 mmol/L [>200 mg/dL]) were eligible for participation in this study. If LDL-C was not available because of elevated triglyceride levels, a total cholesterol value of greater than 6.21 mmol/L (>240 mg/dL) was needed. A patient's cardiac RF status as defined by NCEP was classified as follows: (1) low risk if no CHD and fewer than 2 RFs (LDL-C goal, <4.13 mmol/L [<160 mg/dL]); (2) multiple risk if no CHD and 2 or more RFs (LDL-C goal, <3.36 mmol/L [<130 mg/dL]); or (3) CHD if definite CHD or other atherosclerotic disease (LDL-C goal, 2.59 mmol/L [100 mg/dL]).12 Patients were either newly diagnosed hypercholesterolemic patients with no previous exposure to statins or previously diagnosed patients who had not been receiving statins or other lipid medications for at least 3 months. Patients with diabetes mellitus were not excluded. Patients with hypersensitivity or with known contraindications to simvastatin or other statins were not eligible for participation in this study.
STATISTICAL PROCEDURES
Descriptive statistics were performed for patient demographics, simvastatin dosage, titration, cardiac RF status, and baseline lipid profiles. The main outcome measures were the percentage of reduction of LDL-C levels from baseline, percentage of reduction of total cholesterol levels from baseline, percentage of reduction of triglyceride levels from baseline, percentage of increase of HDL-C levels from baseline, and percentage of patients achieving NCEP goal for LDL-C levels. Final simvastatin dosage was defined as the dose recorded before the last available follow-up lipid profile, titration as any increase from starting dose, and titration steps as the number of times dose was increased. For analyses by site, the mean percentage of patients at LDL-C goal based on cardiac RF status was computed. Risk factor status, starting dose, and titration steps were described by sites above and below the mean percentage at NCEP LDL-C goal. For the analysis between LDL-C change and dosage, the median percentage of change in LDL-C values by dose was reported because of outliers in the frequency distribution. The mean percentage of change from baseline level in the lipid profile of patients who had either reached NCEP goal or completed 24 weeks was compared using 2-tailed t tests. The baseline and follow-up lipid profile stratified by HDL-C levels (<0.91 mmol/L [<35 mg/dL], 0.91 mmol/L [35 mg/dL]) were also compared using 2-tailed t tests. Percentages were compared using  2 test. A 2-tailed value of P<.05 was considered significant. Statistical procedures were performed using SPSS 9.0 for Windows71 and SAS System for Windows Version 6.12.72
RESULTS
PATIENT DEMOGRAPHICS
The cohort was 48% female and 87% white. The mean age was 63 years (range, 26-95 years). Diabetes mellitus was reported in 29% of the patients. Regarding cardiac RF status, 24% were low-risk (<2 RFs), 29% had 2 or more RFs, and 47% had CHD. This analysis included patients given an initial dose of simvastatin at 5 mg (n = 19), 10 mg (n = 137), 20 mg (n = 65), and 40 mg (n = 6) per day. The mean baseline total cholesterol level was 6.9 mmol/L (267 mg/dL); LDL-C level, 4.29 mmol/L (166 mg/dL) (median, 4.19 mmol/L [162 mg/dL]); HDL-C level, 1.08 mmol/L (42 mg/dL); and median baseline triglyceride level, 3.04 mmol/L (269 mg/dL).
INITIAL STARTING DOSE
Regardless of baseline LDL-C level, patients were initially given similar doses of simvastatin (P = .95) (Table 1). In addition, CHD patients were given significantly higher initial doses (mean, 15.1 mg) compared with non-CHD patients (mean, 11.5 mg) (P.001). Patients given a lower initial dose were not titrated more frequently compared with patients given higher initial doses (Table 2).
|
|
|
|
Table 1. Baseline Low-Density Lipoprotein Cholesterol (LDL-C) and Risk Factors by Starting Dose*
|
|
|
|
|
|
|
Table 2. Starting Dose by Number of Titration Steps Over 24 Weeks
|
|
|
TREATMENT TO LDL-C GOAL AND TITRATION
As shown in Figure 1, 74% of patients achieved NCEP LDL-C goal (52% on starting dose, 22% after 1 titration) with a mean simvastatin dose of 20.3 mg/d. Among those patients who were not at goal and had follow-up lipid results available, only 1 patient (2%) was at the maximum dose (80 mg); 69% were given 20 mg or less. Fewer than 40% of patients with CHD achieved goal on a starting dose compared with 64% of other patients (P.001). Sites were classified into 2 distinct categories: above or below the mean percentage at LDL-C goal (12 and 8 sites, respectively). Those sites that had fewer patients reaching NCEP LDL-C goal were more likely to treat a higher percentage of CHD patients. Sites with more patients achieving goal were not any more likely to start patients on a higher dose of simvastatin than sites with less goal achievement. Approximately 63% of patients with CHD, 80% of patients with 2 or more RFs, and 91% of patients with fewer than 2 RFs achieved LDL-C goal (Table 3).
|
|
|
|
Outcome of therapy for patients evaluated over 24 weeks. Information regarding starting dose was missing for 3 patients, and there was insufficient follow-up data for the dose increase and no dose change (noted now with asterisk) to determine the percentage of patients achieving National Cholesterol Education Program Adult Treatment Panel II (NCEP) low-density lipoprotein cholesterol (LDL-C) goal in this group of 37 patients at the end of 24 weeks.
|
|
|
|
|
|
|
Table 3. Low-Density Lipoprotein Cholesterol (LDL-C) Achievement by Risk Factor Status*
|
|
|
MEAN PERCENTAGE OF CHANGE IN THE LIPID PROFILE
Overall, mean percentage of reduction in total cholesterol levels was 27% (P<.001), in LDL-C levels was 35% (P<.001), and in triglyceride levels was 28% (P<.001). Among those patients with low baseline HDL-C values (<0.91 mmol/L [<35 mg/dL] (n = 49), there was a 17% increase in HDL-C levels (P.001) (Table 4); 35% of these patients achieved NCEP HDL goal (HDL-C, 0.91 mmol/L [35 mg/dL]).
|
|
|
|
Table 4. Mean Percentage Change in Lipid Parameters*
|
|
|
DOSE-RESPONSE RELATIONSHIP
The relationship between final simvastatin dose and median percentage of change in LDL-C was also examined. The median (SD) percentage of change in LDL-C was -29.9 (17.4) for 5 mg (n = 13), -34.1 (13.4) for 10 mg (n = 83), -41.6 (19.6) for 20 mg (n = 65), -43.5 (21.7) for 40 mg (n = 28), and -49.1 (31.4) for 80 mg (n = 7) (P.001 compared with baseline for all dosages).
COMMENT
Most patients in this study reached LDL-C goal; however, the findings from this study raise a number of clinical treatment considerations. First, there seems to be an underuse of titration in clinical practice. For example, this study found that most patients (61%) received starting doses of simvastatin and the dosage of simvastatin was not titrated. Second, CHD patients seemed to be given higher doses compared with non-CHD patients. Third, the percentage of patients achieving guideline-defined LDL-C goals vary for individuals with fewer than 2 RFs, multiple RFs, or CHD. For example, 74% of patients achieved LDL-C goal with simvastatin monotherapy. Close to 63% of patients with CHD, 80% of patients with 2 or more RFs, and 91% of patients with fewer than 2 RFs achieved LDL-C goal. Similar levels of LDL-C were achieved with initial dose and titration among the groups. The lower rates of goal achievement in patients with CHD and multiple RFs were caused by the more stringent LDL-C goals specified by NCEP. One possible explanation why more patients who receive lipid-altering therapy do not reach their LDL-C goal is because they may require a greater reduction in LDL-C than many medications can provide at usual starting doses.57 It is important to note that goal attainment is dependent on the patient's CHD risk.11, 73 Lastly, a higher initial dose (eg, 40 mg of simvastatin) may be beneficial for patients who need large LDL-C reductions to achieve goal. The Food and Drug Administration recently approved a 40-mg starting dose of simvastatin for patients who require a large reduction in LDL-C levels (>45%).74 Whether approval of this starting dose will increase the number of patients who attain LDL-C goal in clinical practice is unknown. Possible strategies for improving the treatment of patients with combined hyperlipidemia treated with simvastatin include titrating patients more systematically, giving patients a higher initial dose, and improving patient adherence to treatment. Numerous clinical trials have described the impact of forced-dose titration of simvastatin therapy on improvement in the lipid profile23-27; however, few studies have observed dose titration of simvastatin in everyday clinical practice. The observed positive dose response is consistent with the prescribing information for simvastatin.74 In addition, our results suggest that giving patients higher initial doses of simvastatin (ie, 40 mg/d) may improve LDL-C goal attainment.61-63 By giving patients a higher initial dosage, LDL-C goal attainment may be facilitated, the number of visits required may be decreased, and patient satisfaction may improve. The need for appropriate dose titration and/or higher starting dosages of statins should be carefully examined in the routine treatment of patients in clinical practice.
These data also suggest that simvastatin increases HDL-C values and improves the lipid profile in patients with combined hyperlipidemia. The increase in HDL-C also seems to be greater among patients with low baseline HDL-C levels. Moreover, these results are consistent with recent clinical trials using simvastatin in patients with combined hyperlipidemia, suggesting that the magnitude of HDL-C increase is inversely correlated with baseline HDL-C values.25, 27, 70, 75
While this study did not have a comparison group of patients who were not treated with simvastatin, the results reported here are, however, consistent with published clinical trials.27, 70 The changes in the lipid profile and percentage of patients reaching the LDL-C goal could have been associated with changes in physician practice behavior related to the widespread dissemination of national treatment guidelines for dyslipidemia. The use of automated reminders to physicians, disease management tools, and physician and patient education activities may further enhance LDL-C goal attainment.76-78 Additional research is needed to measure the impact of these interventions in clinical practice.
Simvastatin therapy is an efficacious and safe treatment for patients with combined hyperlipidemia and may also benefit high-risk patients with low HDL-C levels and elevated triglyceride levels. Multiple factors contribute to LDL-C goal achievement in a usual care setting. A significant opportunity exists to increase the number of patients who achieve goal by appropriate dose titration and/or giving patients requiring large percentage reductions in LDL-C level a higher initial dosage.
AUTHOR INFORMATION
| |
Accepted for publication January 31, 2000.
This study was supported by a grant from Merck and Co Inc, West Point, Pa (Drs Vicari and Aura).
| Simvastatin Combined Hyperlipidemia Registry Group
H. Morgan Ashurst, MD, Internal Medicine Center, Mobile, Ala; A. Michael Aura, MD, Tri-State Internal Medicine, Shreveport, La; Robert Berkowitz, MD, Cardiology Associates of Bergen/Pasaic, Fairlawn, NJ; Selvyn Bleifer, MD, Cardiovascular Medical Group of Southern California, Beverly Hills; Bruce Bower, MD, Connecticut Multi-Specialty Group, Hartford; William Ervin, MD, InterMed Group, Portland, Me; Louis Essandoh, MD, Patuxent Medical Group Inc, Annapolis, Md; J. Gary Evans, MD, Northeast Florida Endocrinology, Diabetes, and Osteoporosis Center, Jacksonville; Robert Filuk, MD, San Jose Medical Research Foundation, San Jose, Calif; John Golden, MD, Kaiser Permanente Medical Center, Fairfax, Va; Frank Green, MD, Nassar, Smith and Pinkerton Cardiology Inc, Indianapolis, Ind; Mitchell Greenspan, MD, Buxmont Cardiology Associates, Hershey, Pa; Tedd Goldfinger, DO, Desert Cardiology, Tucson, Ariz; Richard Guthrie, MD, St Paul Heart Clinic, St Paul, Minn; Terry Henkel, MD, Cardiovascular Associates, Springs Medical Center, Louisville, Ky; David Kandath, MD, Saratoga Cardiology Associates, Saratoga Springs, NY; Irving Loh, MD, Ventura Heart Institute, Thousand Oaks, Calif; Hari Malik, MD, Cedarwood Medical Center, St Joseph, Mich; Donald McElroy, MD, HeartCare Midwest, Peoria, Ill; Brian McNamara, MD, Cardiology Associates of Fort Worth, Fort Worth, Tex; James O'Keefe, Jr, MD, Cardiovascular Consultants, Kansas City, Mo; Rajul Patel, MD, Maricopa Medical Center, Phoenix, Ariz; Barry Ramo, MD, New Mexico Heart Institute, Albuquerque; George Rodgers, MD, Austin Heart, Austin, Tex; Daniel Streja, MD, Affiliates in Medical Specialties, Medical Group Inc, West Hills, Calif; Ralph M. Vicari, MD, Melbourne Internal Medicine Associates, Melbourne, Fla; Daniel Wise, MD, Mid Carolina Cardiology, Charlotte, NC.
|
|
Corresponding author: Ralph M. Vicari, MD, Melbourne Internal Medicine Associates, 200 E Sheridan Rd, Melbourne, FL 32901.
From the Melbourne Internal Medicine Associates, Melbourne, Fla (Dr Vacari); US Medical and Scientific Affairs, Merck and Co Inc, West Point, Pa (Drs Wan, Alexander, Markson, and Teutsch); and Tri-State Internal Medicine, Shreveport, La (Dr Aura).
REFERENCES
1. Ross SD, Allen IE, Connelly JE, et al. Clinical outcomes in statin treatment trials: a meta-analysis. Arch Intern Med. 1999;159:1793-1802.
FREE FULL TEXT
2. Downs JR, Clearfield M, Weis S, et al, for the Air Force/Texas Coronary Atherosclerosis Prevention Study. 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
3. Eisenberg DA. Cholesterol lowering in the management of coronary artery disease: the clinical implications of recent trials. Am J Med. 1998;104(2A):2S-5S.
4. 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
5. West of Scotland Coronary Prevention Study Group. Baseline risk factors and their association with outcome in the West of Scotland Coronary Prevention Study. Am J Cardiol. 1997;79:756-762.
FULL TEXT
|
ISI
| PUBMED
6. 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
7. The Scandinavian Simvastatin Study Group. Randomized 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
8. Sueta CA, Chowdhury M, Boccuzzi SJ, et al. Analysis of the degree of undertreatment of hyperlipidemia and congestive heart failure secondary to coronary heart disease. Am J Cardiol. 1999;83:1303-1307.
FULL TEXT
|
ISI
| PUBMED
9. Harnick DJ, Cohen JL, Schechter CB, Fuster V, Smith DA. Effects of practice setting on quality of lipid-lowering management in patients with coronary artery disease. Am J Cardiol. 1998;81:1416-1420.
FULL TEXT
|
ISI
| PUBMED
10. McBride P, Schrott HG, Plane MB, Underbakke G, Brown RL. Primary care practice adherence to National Cholesterol Education Program guidelines for patients with coronary heart disease. Arch Intern Med. 1998;158:1238-1244.
FREE FULL TEXT
11. The Expert Panel. 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
12. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-3023.
FREE FULL TEXT
13. Ryan TJ, Anderson EM, Braniff BA, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1996;28:1328-1428.
FULL TEXT
|
ISI
| PUBMED
14. Smith SC Jr, Blair SN, Criqui MH. Preventing heart attack and death in patient with coronary heart disease. Circulation. 1995;92:2-4.
15. A British Cardiac Society survey of the potential for the secondary prevention of coronary heart disease: ASPIRE (Action in Secondary Prevention through Intervention to Reduce Events). Heart. 1996;75:334-342.
FREE FULL TEXT
16. Danias PG, O'Mahony S, Radford MJ, Korman L, Silverman DI. Serum cholesterol levels are underevaluated and undertreated. Am J Cardiol. 1998;81:1353-1356.
FULL TEXT
|
ISI
| PUBMED
17. Benson VM. Dyslipidemia treatment guidelines and management systems in Kaiser Permanente. Am J Cardiol. 1997;80:85H-88H.
FULL TEXT
|
ISI
| PUBMED
18. Bramlet DA, King H, Young L, Witt JR, Stoukides CA, Kaul AF. Management of hypercholesterolemia: practice patterns for primary care providers and cardiologists. Am J Cardiol. 1997;80:39H-44H.
FULL TEXT
|
ISI
| PUBMED
19. Gerber J. Implementing quality assurance programs in multigroup practices for treating hypercholesterolemia in patients with coronary artery disease. Am J Cardiol. 1997;80:57H-61H.
20. Simpson RJ, Sueta CA, Boccuzzi SJ, et al. Performance assessment model for guideline-recommended pharmacotherapy in the secondary prevention of coronary artery disease and treatment of left ventricular dysfunction. Am J Cardiol. 1997;80:53H-56H.
21. Pearson TA, McBride PE, Houston-Miller N, Smith SC Jr. Organization of preventive cardiology service. J Am Coll Cardiol. 1996;27:1039-1047.
FULL TEXT
|
ISI
| PUBMED
22. Pearson TA, Peters TD. The treatment gap in coronary artery disease and heart failure: community standards and the post-discharge patient. Am J Cardiol. 1997;80:45H-52H.
FULL TEXT
|
ISI
| PUBMED
23. Crouse JR, Frohlich J, Leiv O, Mercuri M, Tobert JA. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol. 1999;83:1476-1477.
FULL TEXT
|
ISI
| PUBMED
24. Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertriglyceridemia. Am J Cardiol. 1998;81:66B-69B.
25. Tikkanen MJ, Laakso M, Ilmonen M, et al. Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM: a multicenter comparison study. Diabetes Care. 1998;21:477-481.
ABSTRACT
26. Raal FJ, Pilcher GJ, Illingworth DR, et al. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis. 1997;135:249-256.
FULL TEXT
|
ISI
| PUBMED
27. Bruckert E, De Gennes JL, Malbecq W, Baigts F. Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia. Clin Cardiol. 1995;18:621-629.
ISI
| PUBMED
28. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847.
FREE FULL TEXT
29. Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham Study. JAMA. 1987;257:2176-2180.
FREE FULL TEXT
30. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986;256:2823-2828.
FREE FULL TEXT
31. NIH Consensus conference: lowering blood cholesterol to prevent heart disease. JAMA. 1985;253:2080-2086.
FREE FULL TEXT
32. Kesäniemi YA. Serum triglycerides and clinical benefit in lipid-lowering trials. Am J Cardiol. 1998;81:70B-73B.
33. Ballantyne CM, Herd JA, Ferlic LL, et al. Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation. 1999;99:736-743.
FREE FULL TEXT
34. Gotto AM Jr. Prognostic and therapeutic significance of low levels of high-density lipoprotein cholesterol: current perspectives. Arch Intern Med. 1999;159:1038-1040.
FREE FULL TEXT
35. Harper CR, Jacobson TA. New perspectives on the management of low levels of high-density lipoprotein cholesterol. Arch Intern Med. 1999;159:1049-1057.
FREE FULL TEXT
36. Barter PJ, Rye KA. High density lipoproteins and coronary heart disease. Atherosclerosis. 1996;121:1-12.
FULL TEXT
|
ISI
| PUBMED
37. NIH Consensus Development Panel on Triglyceride, High-Density Lipoprotein, and Coronary Heart Disease. NIH Consensus conference: triglyceride, high-density lipoprotein, and coronary heart disease. JAMA. 1993;269:505-510.
FREE FULL TEXT
38. Assmann G, Schulte H, for the Prospective Cardiovascular Munster Study. Relation of high-density lipoprotein cholesterol and triglyceride to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Am J Cardiol. 1992;70:733-737.
FULL TEXT
|
ISI
| PUBMED
39. Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease: the Framingham Study. Ann Epidemiol. 1992;2:23-28.
PUBMED
40. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations in coronary heart disease risk in the Helsinki Heart Study: implications for treatment. Circulation. 1992;85:37-45.
FREE FULL TEXT
41. Jacobs DR, Mebane IL, Bangdiwala SI, et al. High density lipoprotein cholesterol as a predictor of cardiovascular disease mortality in men and women: the follow-up study of the Lipid Research Clinics Prevalence Study. Am J Epidemiol. 1990;131:32-47.
FREE FULL TEXT
42. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA. 1986;256:2835-2838.
FREE FULL TEXT
43. Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic diseases: new perspectives on the Framingham Study. Ann Intern Med. 1979;90:85-91.
44. Castelli WP, Doyle JT, Gordon T, et al. HDL cholesterol and other lipids in coronary heart disease: the Cooperative Lipoprotein Phenotyping Study. Circulation. 1977;55:767-772.
FREE FULL TEXT
45. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation. 1989;79:8-15.
FREE FULL TEXT
46. Rubins HB, Robins SJ, Collins D, et al, for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341:410-418.
FREE FULL TEXT
47. Heiss G, Tamir I, Davis CE, et al. Lipoprotein-cholesterol distributions in selected North American populations: the Lipid Research Clinics Program Prevalence Study. Circulation. 1980;61:302-315.
FREE FULL TEXT
48. Lipid Research Clinics Program Epidemiological Committee. Plasma lipid distributions in selected North American populations: the Lipid Research Clinics Program Prevalence Study. Circulation. 1979;60:427-439.
FREE FULL TEXT
49. National Center for Health Statistics. Plan and Operation of the Third National Health and Nutrition Examination Survey, 1988-1994. Hyattsville, Md: National Center for Health Statistics; 1994. Vital and Health Statistics, Series 1, No. 32.
50. Dart A, Jerums G, Nicholson G, et al. A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin and simvastatin in patients with hypercholesterolemia. Am J Cardiol. 1997;80:39-44.
51. Schaefer EJ, Genest JJ Jr, Ordovas JM, Salem DN, Wilson PW. Familial lipoprotein disorders and premature coronary artery disease. Atherosclerosis. 1994;108(suppl):S41-S54.
52. Austin MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb. 1991;11:2-14.
FREE FULL TEXT
53. Hokanson JE, Austin MA, Zambon A, Brunzell JD. Plasma triglyceride and LDL heterogeneity in familial combined hyperlipidemia. Arterioscler Thromb. 1993;13:427-434.
FREE FULL TEXT
54. Plosker GL, McTavish D. Simvastatin: a reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolemia. Drugs. 1995;50:334-363.
ISI
| PUBMED
55. Mauro VF, MacDonald JL. Simvastatin: a review of its pharmacology and clinical use. DICP. 1991;25:257-264.
ABSTRACT
56. Bilheimer DW. Long-term clinical tolerance of lovastatin and simvastatin. Cardiology. 1990;77(suppl 4):58-65.
57. Simvastatin to lower cholesterol. Drug Ther Bull. 1990;17:29-31.
58. Todd PA, Goa KL. Simvastatin: a review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs. 1990;40:583-607.
ISI
| PUBMED
59. Kastelein JP, Ose L, Stein EA, et al. Simvastatin 80 mg/day is effective and well tolerated: results from long-term studies in more than 1000 patients. Presented as a poster at: XIII International Drugs Affecting Lipid Metabolism; May 30-June 3, 1998; Florence, Italy.
60. Davidson MH, Plotkin D, Hunninghake D, et al. Efficacy and safety of simvastatin 40 and 80 mg/day in combined hyperlipidemia. Presented as a poster at: XIII International Drugs Affecting Lipid Metabolism; May 30-June 3, 1998; Florence, Italy.
61. Stein EA, Davidson MH, Dobs AS, et al, for the Expanded Dose Simvastatin US Study Group. The efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients. Am J Cardiol. 1998;82:311-316.
FULL TEXT
|
ISI
| PUBMED
62. Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol. 1997;79:38-42.
ISI
| PUBMED
63. Hunninghake DB, Melino MR, Stepanavage ME, et al. Targeting high-risk patients with hypercholesterolemia: the efficacy and safety of simvastatin 80 mg/day. Atherosclerosis. 1997;134:125-126.
64. Walker JF, Tolbert JA. The clinical efficacy and safety of lovastatin and MK-733: an overview. Eur Heart J. 1987;8:93-96.
65. Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during the 5 years of the Scandinavian Simvastatin Survival Study. Arch Intern Med. 1996;156:2085-2092.
FREE FULL TEXT
66. Boccuzzi SJ, Bocanegra TS, Walker JF, Shapiro DR, Keegan ME. Long-term safety and efficacy profile of simvastatin. Am J Cardiol. 1991;68:1127-1131.
FULL TEXT
|
ISI
| PUBMED
67. Walker JF. Simvastatin: the clinical profile. Am J Med. 1989;87(suppl 4A):44S-46S.
68. Johannesson M, Jonsson B, Kjekshus J, Olsson AG, Pedersen TR, Wedel H, for the Scandinavian Simvastatin Survival Study Group. Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary heart disease. N Engl J Med. 1997;336:332-336.
FREE FULL TEXT
69. Pedersen TR. Cholesterol lowering and the use of healthcare resources: results of the Scandinavian Simvastatin Survival Study. Circulation. 1996;93:1796-1802.
FREE FULL TEXT
70. Stein EA, Davidson MH, Dujovne CA, et al. Efficacy and tolerability of low-dose simvastatin and niacin, alone and in combination, in patients with combined hyperlipidemia: a prospective trial. J Cardiovasc Pharmacol Ther. 1996;1:107-116.
71. SPSS Base 9.0 User's Guide. Chicago, Ill: SPSS Inc; 1999.
72. SAS Institute Inc.. SAS Language and Procedures: Usage Version 6.12. Cary, NC: SAS Institute Inc; 1998.
73. Davidson MH, Nawrocki JW, Weiss SR, et al. Effectiveness of atorvastatin for reducing low-density lipoprotein cholesterol to National Cholesterol Education Program treatment goals. Am J Cardiol. 1997;80:347-348.
FULL TEXT
|
ISI
| PUBMED
74. Prescribing information for Zocor (simvastatin) [package insert]. Whitehouse Station, NJ: Merck & Co Inc; April 2000.
75. Ellen R, McPherson R. Long-term efficacy and safety of fenofibrate and a statin in treatment of combined hyperlipidemia. Am J Cardiol. 1998;81(suppl 4A):60B-65B.
76. Khoury AT, Wan GJ, Niedermaier ON, et al. Improved cholesterol management in coronary heart disease patients enrolled in a health maintenance organization. J Healthcare Quality. In press.
77. Khoury AT, Wan GJ, Niedermaier ON, et al. Use of computer-generated reminders in the management of coronary heart disease patients enrolled in a managed care organization [abstract]. J Managed Care Pharmacol. 2000;6:168.
78. Walsh MN, Wan GJ, Kuo LC, et al. Application of disease management principles to achieve national guideline-defined goals for patients with coronary heart disease [abstract]. J Gen Intern Med. 2000;15(suppl 1):153.
RELATED ARTICLE
The Archives of Family Medicine Continuing Medical Education Program
Arch Fam Med. 2000;9(9):887-891.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Compliance with Recommendations for Lipid Management among Patients with Type 2 Diabetes in an Academic Family Practice
Putzer et al.
J Am Board Fam Med 2004;17:101-107.
ABSTRACT
| FULL TEXT
|
