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(Circulation. 2001;103:38.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Use of Lipid-Lowering Medications at Discharge in Patients With Acute Myocardial Infarction

Data From the National Registry of Myocardial Infarction 3

Gregg C. Fonarow, MD; William J. French, MD; Lori S. Parsons; Haili Sun, PhD; Judith A. Malmgren, PhD; for the National Registry of Myocardial Infarction 3 Participants

From the Ahmanson-UCLA Cardiomyopathy Center (G.C.F.), UCLA Division of Cardiology, and the Harbor-UCLA Medical Center (W.J.F.), Los Angeles, Calif, and the Cardiovascular Outcomes Research Center (L.S.P., H.S., J.A.M.), University of Washington.

Correspondence to Gregg C. Fonarow, MD, Ahmanson-UCLA Cardiomyopathy Center, UCLA Division of Cardiology, 47-123 CHS, 10833 Le Conte Ave, Los Angeles, CA 90095-1679. E-mail gfonarow{at}mednet.ucla.edu

	Abstract

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Background—The present study aimed to assess use of lipid-lowering medication at discharge in a current national sample of patients hospitalized with acute myocardial infarction and to evaluate factors associated with prescribing patterns.

Methods and Results—Demographic, procedural, and discharge medication data were collected from 138 001 patients with acute myocardial infarction discharged from 1470 US hospitals participating in the National Registry of Myocardial Infarction 3 from July 1998 to June 1999. Lipid-lowering medications were part of the discharge regimen in 31.7%. Among patients with prior history of CAD, revascularization, or diabetes, less than one half of the patients were discharged on treatment. In multivariate analysis, factors independently related to lipid-lowering use included history of hypercholesterolemia (odds ratio [OR] 4.93; 95% CI 4.79 to 5.07), cardiac catheterization during hospitalization (OR 1.29; 95% CI 1.24 to 1.34), care provided at a teaching hospital, (OR 1.26; 95% CI 1.22 to 1.32), use of ß-blocker (OR 1.43; 95% CI 1.39 to 1.48), and smoking cessation counseling (OR 1.51; 95% CI 1.44 to 1.59). Lipid-lowering medications were given less often to patients who were older (65 to 74 versus <55 years of age; OR 0.82; 95% CI 0.78 to 0.86), those with a history of hypertension (OR 0.92; 95% CI 0.89 to 0.95), and those undergoing coronary artery bypass graft surgery (OR 0.58; 95% CI 0.55 to 0.60).

Conclusions—Analysis of current practice patterns for the use of lipid-lowering medications in patients hospitalized with acute myocardial infarction reveals that a significant proportion of high-risk patients did not receive treatment at time of discharge.

Key Words: myocardial infarction • risk factors • hypercholesterolemia • lipids

	Introduction

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Compelling scientific evidence suggests that lipid-lowering therapy reduces the risk of recurrent coronary events and improves survival in patients after myocardial infarction (MI).^{1 2 3 4 5} Benefits of lipid-lowering medications apply to both men and women, to patients older and younger than 65 years of age, and to diabetics.^{6 7 8 9} The magnitude of benefit with lipid-lowering medications matches or exceeds benefits with other secondary prevention medications, such as aspirin, ß-blockers, and angiotensin-converting enzyme (ACE) inhibitors, in the patient after MI.^{3 10}

Despite the effectiveness of lipid-lowering therapy in altering subsequent cardiovascular mortality, several prior studies have documented low treatment rates in patients with established coronary artery disease (CAD).^{11 12 13 14 15 16} Many of these studies involved patients from a single or a limited number of centers, enrolled in randomized clinical trials, or treated before dissemination of the most convincing clinical trial evidence. Use of lipid-lowering medications in the post-MI setting represents a major clinical practice and public health issue, with factors predicting use not previously studied in a large national patient data set. The purpose of the present study was to evaluate recent physician practice patterns of prescription of lipid-lowering medications to patients hospitalized for acute MI (AMI) and the clinical characteristics, practices, and institutional factors associated with such use.

	Methods

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The National Registry of Myocardial Infarction (NRMI) 3 is a prospective, observational study of patients admitted to the hospital with AMI that was initiated April 1998. Hospitals participating in the registry enroll consecutive patients with AMI as previously described.¹⁷ Methods used for AMI diagnosis, case ascertainment, and data acquisition by the NRMI 3 are similar to the ones used by the NRMI 2 registry, which were validated previously.¹⁸

Measurements
Detailed demographic data were collected and included age, sex, race, and past medical history (history of stroke, history of heart failure, prior coronary angioplasty, prior CABG, history of congestive heart failure, history of angina, and previous MI). Risk factors for CAD were assessed, including history of diabetes mellitus, history of hypertension, history of hypercholesterolemia, and current tobacco usage. Initial diagnosis of the patient on presentation and location and type of AMI were recorded. Primary medical insurance of the patient was classified as commercial/preferred provider organization (PPO), Medicare, health maintenance organization (HMO), medicaid, self-pay/uninsured, or other. Because patients with Medicare may have additional primary or secondary insurance and this affects prescription medication benefits, patients with Medicare alone and Medicare with commercial/PPO (Medicare–non-HMO) were compared with patients with Medicare-HMO. Hospital characteristics classified by bed size, type (urban versus rural, teaching versus nonteaching, and noninvasive versus cardiac catheterization without cardiac surgery versus with cardiac surgery), and geographic location were also recorded. Use of the following cardiac procedures were reported: echocardiography, coronary angiography, PTCA, and in-hospital CABG. Use of the following medications within 24 hours of diagnosis was collected: aspirin, thrombolytic agent, ß-blocker, ACE inhibitor, heparin, and calcium channel blocker. Medications prescribed at hospital discharge were ascertained: aspirin, ß-blockers, calcium blockers, nitrates, and prescription lipid-lowering medications. Smoking cessation counseling in current smokers was also abstracted from the medical record.

Statistical Analysis
Baseline demographics, use of medications, institutional variables, and use of cardiac procedures were compared with the outcome of interest, lipid-lowering medication prescribed at discharge. ² and Student’s t tests were performed to determine whether significant associations existed. A stepwise logistic regression model was developed to identify predictors of receiving lipid-lowering medical therapy at discharge. Variables included in the model were chosen on the basis of univariate statistical significance and clinical importance. The model included all variables shown in Tables 1 to 3. Adequacy of fit and discriminatory power of the model were assessed according to standard methods. Odds ratios and 95% confidence intervals are reported for the model. All tests of statistical significance were 2-tailed. All statistical calculations were performed with SAS software version 6.12 (SAS Institute Inc).

View this table: [in this window] [in a new window]   Table 1. Baseline Demographics and Clinical Characteristics by Lipid-Lowering Medication Treatment at Discharge

View this table: [in this window] [in a new window]   Table 2. Patient and Hospital Characteristics by Lipid-Lowering Medication Treatment at Discharge

View this table: [in this window] [in a new window]   Table 3. In-Hospital Therapy by Lipid-Lowering Medication Treatment at Discharge

	Results

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From July 1, 1998, to June 30, 1999, a total of 199 450 patients from 1470 US hospitals registered in NRMI 3 had been enrolled. In the current analysis, 42 830 (21.5%) patients that were transferred from a participating registry hospital to another acute-care institution were excluded because medication at discharge information was not available. In addition, 18 619 (9.3%) patients who died during the hospital period were excluded from the analysis. The final study cohort consisted of 138 001 patients.

Univariate Analysis
Baseline demographic and clinical characteristics by lipid-lowering medication treatment at discharge are shown in Table 1. In this cohort of patients being discharged from the hospital after AMI, only 31.7% were prescribed lipid-lowering medications. Patients prescribed lipid-lowering medications at discharge were significantly younger (average age, 63.4 years) than patients not treated with lipid-lowering medications (average age, 70.1 years; P<0.0001). There was a marked decline in prescription of therapy with advancing age. Lipid-lowering treatment rates were 43.6% in patients age <55 years, 33.4% in patients ages 65 to 75 years, 22.8% in patients ages 75 to 84 years, and 9.7% in patients age 85+ years. Women were less likely to be treated with lipid-lowering medications: 34.8% of men were discharged on lipid-lowering therapy compared with 26.8% of women. This difference was not entirely due to differences in age of presentation with AMI (Figure).

View larger version (18K): [in this window] [in a new window]   Figure 1. Association of patient age and sex with prescription of lipid-lowering medications at hospital discharge for AMI.

Patient and hospital characteristics are shown in Table 2. Although patients with documented prior history of CAD were more likely to be discharged on lipid-lowering therapy than those without previous cardiac history, substantial proportions of these patients were still not treated. In patients with previous history of AMI, 65.1% were discharged without lipid-lowering therapy after having 2 MIs. In patients with previous CABG, 57.4% were sent home without treatment, as were 54.6% of patients with previous PTCA.

In this AMI patient population, 32.2% of patients were documented as having a medical history of hypercholesterolemia. Patients with a history of hypercholesterolemia were more likely to be discharged on lipid-lowering medications. Still, 41.7% of these patients were discharged without documented treatment. Despite being at higher risk and standing to receive greater benefit from treatment, patients with diabetes mellitus were not more likely to be treated with lipid-lowering medications: treatment use occurred in only 31.6% of diabetes versus 31.7% of nondiabetics (P=NS). Patients with history of stroke and heart failure were less likely to be treated.

Patients with Medicare–non-HMO insurance were substantially less likely to be treated than patients with Medicare-HMO. Interestingly, no significant differences were seen between commercial/PPO, HMO, Medicaid, and self-pay/uninsured patient treatment rates. Teaching hospitals had a significantly higher rate of providing lipid treatment than did nonteaching hospitals (39.4% versus 30.3%; P<0.0001).

Patients undergoing coronary angiography and PTCA during the AMI hospitalization were more likely to receive lipid-lowering medications, whereas patients undergoing CABG were significantly less likely (Table 3). Patients who received other secondary medications at discharge (aspirin, ß-blocker, or ACE inhibitors) were more likely to be treated with lipid-lowering medications. Only 40.6% of current smokers received documented smoking cessation counseling, but these patients were more likely to receive lipid treatment than current smokers that did not receive counseling (45.7% versus 28.0%; P<0.0001).

Multivariate Analysis
To evaluate which clinical, demographic, hospital, and process-of-care–related factors independently influenced use of lipid-lowering medications at the time of discharge, a multivariate logistic regression model was constructed with all variables in Tables 1 to 3. Independent predictors of use of lipid-lowering therapy included younger age, previous MI, previous PTCA or CABG, and history of hypercholesterolemia, as shown in Table 4. Odds of receipt of lipid-lowering treatment in patients ages 75 to 84 was 0.59 (95% CI 0.56 to 0.62) compared with patients age <55 years. Hypertension was associated with an 0.92 (95% CI 0.89 to 0.95) odds ratio of being discharged on lipid therapy, and a current history of smoking was associated with one of 0.79 (95% CI 0.76 to 0.82).

View this table: [in this window] [in a new window]   Table 4. Predictors of Discharge Lipid-Lowering Medication Use

Receiving cardiac catheterization or PTCA during hospitalization for AMI was an independent predictor for receiving lipid-lowering medications. Administration of thrombolytic therapy was not predictive, and receiving CABG during AMI hospitalization was associated with a substantially lower likelihood of receiving lipid therapy (odds ratio 0.58). Receiving smoking cessation counseling during hospitalization with AMI among current smokers was associated with an odds ratio of 1.51 (95% CI 1.44 to 1.59), which indicates a strong association between use of these 2 secondary prevention measures.

	Discussion

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Despite widespread dissemination of national treatment guidelines and publicized results of major clinical trials on the value of lipid-lowering medications in the secondary prevention of coronary heart disease, the present study found that only one third of patients hospitalized with AMI were discharged on lipid-lowering medications as recorded in the medical record. A variety of clinical, demographic, treatment, and process-of-care factors that significantly influenced treatment use of lipid-lowering medications were identified.

Elderly patients, independent of associated comorbidities, were at increased risk of being discharged without lipid-lowering therapy. Elderly patients face a higher risk of recurrent MI and death than younger patients.⁷ Although some question has arisen regarding the association between elevated cholesterol and cardiovascular risk in the elderly, individual clinical trials and meta-analysis have supported that patients age 65 years with established CAD derive substantial benefit from lipid-lowering medications.⁷ Young women were less likely to be treated with lipid-lowering medications than young men, but after adjustment of other variables, sex of the patient was only a minor independent predictor of not receiving lipid treatment.

As expected, patients with prior medical history of hypercholesterolemia were more likely to be discharged on lipid-lowering therapy. Still, 41.7% of patients who had a previously documented history of hypercholesterolemia and had sustained an AMI, were discharged without medical treatment. The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial demonstrated that in patients after MI or unstable angina with baseline cholesterol levels of 155 to 271 mg/dL, a substantial reduction occurs in all-cause mortality when a lipid-lowering medication (HMG-CoA reductase inhibitor) is added to modified diet alone.⁵ This trial and other studies clearly demonstrate that post-MI patients with lipid levels that would not be classified as hypercholesterolemic derive significant benefit from lipid-lowering medical treatment.

Patients undergoing cardiac catheterization and PTCA were more likely to be discharged on lipid-lowering medications. This result was independent of other patient and hospital characteristics and suggests that the extra medical personnel and attention that these patients were exposed to favorably affected treatment rates. Patients at teaching hospitals had a greater likelihood of receiving treatment. Patients discharged on other evidence-based therapies of aspirin, ß-blockers, or ACE inhibitors also were more likely to be discharged on a lipid-lowering medication. Likewise, current smokers treated by physicians and nurses that provided smoking cessation counseling during hospitalization were more likely to be discharged on lipid-lowering medication. These associations indicate that administration of lipid-lowering medications is affected by physician education and the process of care in place within the hospital and could be favorably affected by educational initiatives and quality-improvement projects. Prior studies have demonstrated improvements in hospital treatment use rates for other secondary prevention measures such as aspirin or ß-blockers in AMI patients through use of educational programs.¹⁹

Patients enrolled in managed care were slightly more likely to receive lipid-lowering therapy than patients with other insurance, a result that is similar to those of previous studies.¹⁵ Patients enrolled in Medicare alone or combined with commercial/PPO insurance were less likely to receive lipid-lowering therapy. Even after adjusting for differences in age, comorbidity, and other factors, this effect was apparent. These data suggest that prescription drug coverage may significantly improve lipid-lowering medication treatment rates in the Medicare patient population.

NRMI 3 collected data on use of lipid-lowering medications at the time of hospital discharge, and it is not possible to determine the frequency at which therapy was begun after hospital discharge. Many patients may have been started on lipid-lowering medications after discharge. However, numerous studies have demonstrated a significant failure to implement treatment in the outpatient setting in patients with coronary heart disease.^{11 12 13 14 15 16} Approximately one half of the patients in the present study had established CAD before admission for AMI and would have been previously eligible for lipid-lowering medication. Admission for AMI may be associated with previous failure to implement secondary prevention measures. Other studies of a more limited scope have demonstrated low treatment rates in patients after MI. In a study at a single university hospital in 1996, Frolkis et al¹² demonstrated that 36% of patients were treated with lipid-lowering medications at the time of discharge after being hospitalized with CAD. An analysis of elderly patients hospitalized for AMI in 37 community hospitals in Minnesota from 1995–1996 showed a treatment rate of 37% at time of discharge in patients with cholesterol levels >200 mg/dL.¹⁵

Treatment guidelines and algorithms such as the NCEP have recommended delaying baseline lipid assessment and treatment until 6 weeks after acute presentation in recognition that the acute-phase response triggered by AMI can substantially lower total and LDL cholesterol.²⁰ As a result, the first opportunity for beginning treatment is delayed to a time at which the patient may no longer be focused on their underlying atherosclerotic disease process and to a setting with less resources. It has been suggested that evidence of CAD alone is sufficient to begin administration of lipid-lowering medications with or without baseline lipid levels.^{21 22} The fact that lipid panels obtained in the first 24 hours of hospital admission have been shown to accurately reflect steady-state lipid levels at 6 weeks removes a substantial perceived barrier to initiating lipid-lowering therapy in the hospital setting.²³ Diet alone is unlikely to result in LDL <100 mg/dL in this patient population.^{24 25} One study of post-MI patients showed 93% of the study patients required lipid-lowering medications, given that their LDL level remained >100 mg/dL at 90 days after discharge, despite intensive diet, exercise counseling, and monitoring.²⁴ A 1997 AHA Science Advisory on when to start cholesterol-lowering therapy in patients with coronary heart disease²³ recommended that cholesterol-reducing medication be considered for institution simultaneously with nonpharmacologic therapy at time of hospital discharge in patients with coronary heart disease and LDL 130 mg/dL. Institution of lipid-lowering therapy in the in-patient setting has a number of potential advantages. A Cardiac Hospitalization Atherosclerosis Management Program (CHAMP) that focused on initiating lipid-lowering medications before hospital discharge preliminarily was reported to be associated with a marked increase in treatment rates, improved patient compliance, and a greater number of patients achieving LDL 100 mg/dL.²²

Study Limitations
Although the data collected were not independently validated, methods of case ascertainment and acquisition of other data from NRMI have been found to be valid.¹⁸ Data on lipid levels in individual patients are not available. Thus, it is not possible to determine for a given patient the appropriateness of prescribing or not prescribing lipid-lowering medications. However, on the basis of prior studies in post-MI patients, in aggregate this population would be expected to consist of a large proportion of patients that would qualify for and derive substantial benefit from lipid-lowering medications.^{11 12 15} Specific medications prescribed and doses and extent of dietary and exercise counseling were not available in the present study. Use of a lipid-lowering medication does not necessarily indicate that the patient was treated with the most appropriate agent or dosage or that the patient had achieved LDL 100 mg/dL. Prior studies have shown that only 30% to 40% of outpatients with CAD who received lipid-lowering medications have achieved LDL 100 mg/dL.^{11 15}

Conclusions
Despite compelling scientific evidence of the benefits of lipid-lowering medications in patients with clinically evident CAD, the present study documents that a substantial proportion of patients after AMI are not discharged on treatment. A variety of clinical, demographic, hospital, and process-of-care characteristics appear to influence physician use of lipid-lowering treatment, which suggests that educational programs and hospital-based treatment algorithms may be effective for improvement of use of lipid-lowering medications in patients after MI.

	Acknowledgments

 
The National Registry of Myocardial Infarction 3 is supported by Genentech, Inc, South San Francisco, Calif.

	Footnotes

 
Dr French serves as an advisory board member of The National Registry of Myocardial Infarction (NRMI). In addition, Dr Fonarow serves as a consultant and speaker for Merck and Bristol-Myers Squibb.

A complete list of the participating hospitals is available from ClinTrials Research, 1100 Weston Pkwy, Cary, NC 27513.

Received June 8, 2000; revision received August 11, 2000; accepted August 14, 2000.

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				K. A. LaBresh, A. G. Ellrodt, R. Gliklich, J. Liljestrand, and R. Peto Get With the Guidelines for Cardiovascular Secondary Prevention: Pilot Results Arch Intern Med, January 26, 2004; 164(2): 203 - 209. [Abstract] [Full Text] [PDF]

				V. G. Athyros, A. A. Papageorgiou, A. N. Symeonidis, T. P. Didangelos, A. N. Pehlivanidis, V. I. Bouloukos, and D. P. Mikhailidis Early Benefit from Structured Care with Atorvastatin in Patients with Coronary Heart Disease and Diabetes Mellitus: A Subgroup Analysis of the GREek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study Angiology, November 1, 2003; 54(6): 679 - 690. [Abstract] [PDF]

				L. L. Carr Summary of the Role of Statins in the Treatment of Dyslipidemia J Am Osteopath Assoc, July 1, 2003; 103(7_suppl_3): S1 - S3. [Full Text] [PDF]

				R. O. Bonow The Challenge of Balancing Scientific Discovery and Translation Circulation, January 28, 2003; 107(3): 358 - 362. [Full Text] [PDF]

				W. Lalouschek, W. Lang, S. Greisenegger, and M. Mullner Determination of Lipid Profiles and Use of Statins in Patients With Ischemic Stroke or Transient Ischemic Attack Stroke, January 1, 2003; 34(1): 105 - 110. [Abstract] [Full Text] [PDF]

				J. Muntwyler, G. Abetel, C. Gruner, and F. Follath One-year mortality among unselected outpatients with heart failure Eur. Heart J., December 1, 2002; 23(23): 1861 - 1866. [Abstract] [Full Text] [PDF]

				S. H. Rahimtoola Bilateral internal mammary artery grafting for coronary artery bypass grafting: why men versus women? Ann. Thorac. Surg., November 1, 2002; 74(5): 1435 - 1437. [Full Text] [PDF]

				L Wei, J Wang, P Thompson, S Wong, A D Struthers, and T M MacDonald Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study Heart, September 1, 2002; 88(3): 229 - 233. [Abstract] [Full Text] [PDF]

				E. J. Benjamin, S. C. Smith Jr, R. S. Cooper, M. N. Hill, and R. V. Luepker Task Force #1--magnitude of the prevention problem: opportunities and challenges J. Am. Coll. Cardiol., August 21, 2002; 40(4): 588 - 603. [Full Text] [PDF]

				P. A. Ades, T. E. Kottke, N. Houston Miller, J. C. McGrath, N. B. Record, and S. S. Record Task Force #3--getting results: who, where, and how? J. Am. Coll. Cardiol., August 21, 2002; 40(4): 615 - 630. [Full Text] [PDF]

				G. C Fonarow Treating to goal: new strategies for initiating and optimizing lipid-lowering therapy in patients with atherosclerosis Vascular Medicine, August 1, 2002; 7(3): 187 - 194. [Abstract] [PDF]