Journal of Clinical Lipidology (2009) 3, 385–392
Atherosclerosis in a managed care plan: hypercholesterolemia treatment patterns and low-density lipoprotein cholesterol monitoring James McKenney, PharmD, Sanjay K. Gandhi, PhD, Kathleen M. Fox, PhD*, Robert L. Ohsfeldt, PhD National Clinical Research, Richmond, VA, USA (Dr. McKenney); AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA (Dr. Gandhi); Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, P.O. Box 543, Monkton, MD 21111, USA (Dr. Fox); and Department of Health Policy and Management, Texas A&M Health Science Center, College Station, TX, USA (Dr. Ohsfeldt) KEYWORDS: Atherosclerosis; LDL-C; Lipids; Statins
BACKGROUND: Clinical guidelines have recommended a LDL-C goal of ,100 mg/dL for high-risk individuals and lipid-modifying therapy for patients not reaching this goal. OBJECTIVE: This investigation assessed low-density lipoprotein cholesterol (LDL-C) levels and treatment patterns among patients diagnosed with atherosclerosis with or without a previous cardiovascular disease (CVD) event. METHODS: We conducted a retrospective study by using claims data from a national health plan that included patients with $ 1 medical claim for atherosclerosis (ICD-9 of 440.xx, 414.x, 437.0, 437.1, or 437.3) between January 2004 and March 2006. Use of lipid-modifying medications at the time of diagnosis and thereafter, patient demographics, comorbid conditions, baseline, and postdiagnosis LDL-C were assessed. RESULTS: There were 311,567 patients who had an atherosclerosis ICD-9 code, 46% of whom had a previous CVD event. Among patients with an atherosclerosis diagnosis and CVD event, lipid-modifying therapy was received by 50% before diagnosis and 57% after diagnosis, compared with 37% before and 48% after diagnosis for patients with an atherosclerosis diagnosis and no previous CVD event. Of the patients with baseline LDL-C (15%, n 5 46,923), 44% had an LDL-C ,100 mg/dL at diagnosis; of those with LDL-C $ 100 mg/dL, only 54% received lipid-modifying therapy and only 64% achieved an LDL-C ,100 mg/dL in the 12 succeeding months. Among patients with baseline and postdiagnosis LDL-C values (n 5 24,724), 55% had a baseline LDL-C $ 100 mg/dL and 46% had a baseline nonHDL-C $ 130 mg/dL. CONCLUSIONS: In conclusion, many patients in a managed care plan diagnosed with atherosclerosis with or without a previous CVD event present opportunities for better lipid management. Healthcare providers should evaluate more aggressive lipid management interventions for these patients for potential downstream cardiovascular benefits. Ó 2009 National Lipid Association. All rights reserved.
* Corresponding author. E-mail address: [email protected]
Submitted October 14, 2009. Accepted for publication October 16, 2009.
The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) report in 2001 and its update in 2004 recommended a low-density lipoprotein cholesterol (LDL-C) goal of ,100 mg/dL for high-risk
1933-2874/$ -see front matter Ó 2009 National Lipid Association. All rights reserved. doi:10.1016/j.jacl.2009.10.004
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individuals who had experienced a cardiovascular disease (CVD) event (eg, myocardial infarction [MI] or stroke) or had received an intervention for symptomatic atherosclerotic vascular disease (eg, a revascularization procedure).1,2 The Panel further recommended identifying patients who had a .20% 10-year coronary heart disease (CHD) risk as a CHD risk equivalent. These included patients with diabetes, peripheral arterial disease, carotid artery disease, abdominal aortic aneurysm, and multiple risk factors; these patients were also given an LDL-C goal of ,100 mg/dL. For patients with CVD or CHD risk equivalent who had very high risk, an LDL-C goal of ,70 mg/dL was recommended as optional. The evidence supporting these recommendations and the benefit of lipid–modifying therapy to reduce CVD risk in these patients is substantial. The NCEP ATP III also recognized that patients with advanced subclinical (ie, asymptomatic) atherosclerotic vascular disease may also have a substantial CVD risk and should be considered for lipid-modifying therapy. Patients with subclinical atherosclerosis include those with an ankle brachial blood pressure index of ,0.9, a positive exercise electrocardiogram, myocardial perfusion imaging or echocardiographic stress test indicating the presence of ischemia, carotid intima-media thickening, or a high coronary calcium score. In this group of patients, studies have shown that lipid-modifying therapy can alter the progression of atherosclerosis.3–6 Angiographic studies in which the investigators administered statins and other agents that lower LDL-C demonstrate slowing of the progression of atherosclerotic plaque and, in some cases, regression.7–9 In fact, the greater the LDL-C reduction, the greater the chance that regression was demonstrated.9,10 More recently, through the use of computed tomography, high-resolution magnetic resonance imaging (MRI), and ultrasonographic measurement, investigators have shown the beneficial effects of lipid-modifying therapy on vessel wall thickness, endothelial dysfunction, and arterial stiffness of atherosclerotic lesions. Cases in point are the ASTEROID and METEOR trials.11,12 By administering rosuvastatin 40 mg/d to achieve a mean LDL-C of 60.8 mg/dL and to increase HDL-C by 14.7%, the ASTERIOD trial investigators demonstrated significant regression of atheroma volume as measured by intravascular ultrasound11 and coronary stenosis as measured by quantitative coronary angiography.9 The METEOR trial also reported that rosuvastatin, compared with placebo therapy, was associated with a significant reduction in the progression of carotid intima-media thickness among patients with a low Framingham risk score and evidence of subclinical atherosclerosis (maximum carotid intima-media thickness of 1.2 to ,3.5 mm).12 Studies of how well the NCEP treatment guidelines have been implemented and whether patients at high risk of CVD events are being effectively treated to recommended goal levels have generally reported disappointing results. One of the first and most widely publicized reports was the L-TAP study, which was reported before the release of the ATP III guidelines.13 The investigators of this study
found that among patients being managed by high-statin2 prescribing physicians who acknowledged awareness of the guidelines, 85% were prescribed lipid-modifying drug therapy but only 38% were at their LDL-C goal. Among the highestrisk patients, those with documented CHD, only 18% were at their LDL-C goal.13 Five years later, after the release of the ATP III guidelines, the researchers of the NEPTUNE project14 also evaluated the status of patients being managed by high-prescribing physicians who were aware of treatment guidelines and found that although 87% of patients received lipid-modifying treatment, only 67% achieved their LDL-C goal. Among patients with hypertriglyceridemia, only 39% achieved both their LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) goals. Among patients with CHD or a CHD risk equivalent, only 60% were at their LDL-C goal.14 No information was available on the pattern of treatment of patients with asymptomatic, subclinical atherosclerosis. The present study was undertaken to assess treatment patterns among patients with a high CVD risk in a usualcare setting from evidence gathered in the administrative claims database of a large national managed care plan. The question addressed was: Are patients with atherosclerosis with and without clinical evidence of CVD being identified and effectively treated?
Methods A retrospective observational database study that used administrative claims data from a national health plan with a commercial and Medicare Advantage benefit was conducted. The database included approximately 16 million covered lives across the United States. Patients 18 years of age or older with at least one medical claim for a diagnosis of atherosclerosis (coronary, cerebral, or general, ICD-9 codes of 440.x, 414.x, 437.0, 437.1, or 437.3) during the 27-month period of January 1, 2004, to March 31, 2006, were identified from medical and pharmacy claims data. New cases of diagnosed atherosclerosis were defined as those patients with no recorded atherosclerosis diagnostic code in the preceding 12 months and the recording of at least one of the following ICD-9 codes by the physician during the observation period: 414.x for coronary atherosclerosis; 437.0, 437.1, and 437.3 for cerebral atherosclerosis; and 440.x for general atherosclerosis (see Appendix for full list). Patients with a diagnosis of a CVD event or intervention, including those with ischemic heart disease requiring hospitalization or peripheral vascular disease with intermittent claudication, but without a diagnosis specifically for atherosclerosis, were not included in the study population, even though they may have atherosclerosis. Patients with a diagnosis of atherosclerosis during the 27-month study window were included and further stratified as to whether they had experienced a previous CVD event or intervention (eg, MI, stroke/transient ischemic attack, or revascularization). The objective of the study was to determine the monitoring and treatment patterns among patients with
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clinically documented and coded atherosclerosis, with or without a CVD event. The date of the diagnosis of atherosclerosis was the index date. To assess lipid monitoring and hypercholesterolemia treatment patterns, LDL-C measures were selected based on the date of diagnosis of atherosclerosis. The claims data did not record whether the lipid sample was collected while patients were in a fasting state. Baseline LDL-C was defined as the LDL-C measure at the date of diagnosis of atherosclerosis or up to 6 months before the diagnosis. Postdiagnosis LDL-C was defined as the LDL-C measure after the diagnosis date and within 12 months of the diagnosis. Lipidmodifying therapy at the time of the diagnosis was defined as at least one prescription claim within the 4 months before or up to the date of the diagnosis of atherosclerosis. Lipidmodifying therapy after the diagnosis was defined as at least one prescription claim in the 12 months after diagnosis. Lipidmodifying therapy was recorded as any prescription claim for a statin, fibrate, bile acid sequestrant, niacin, or cholesterol absorption inhibitor during the observation period. The proportion of patients prescribed statin therapy alone or any lipid-modifying therapy before and/or after the diagnosis was computed. The distribution of LDL-C levels at the time of diagnosis and after the diagnosis was computed for patients with diagnosed atherosclerosis as well as for those prescribed lipid-modifying therapy and stratified based on previous history of CVD events in the 12 months preceding the atherosclerosis diagnosis recording. Categorical variables were described by the use of frequencies, and continuous variables were reported as means with standard deviations. Comparison of differences between patients with and without previous CVD events in categorical variables were tested by the use of chi-square tests, and continuous variables were tested by the use of t tests. Analyses were performed with SAS software, version 9.1 (SAS Institute Inc., Cary, NC). De-identified information was analyzed in compliance with the Health Insurance Portability and Accountability Act. Because of the retrospective claims approach, institutional review board approval was not required.
387 Table 1 Characteristics of patients diagnosed with atherosclerosis between January 2004 and March 2006 Characteristics Age, years, mean (SD) Men, % Hypertension, % Diabetes, % Prior cardiovascular disease event, % Myocardial infarction, % Stroke, % Angina, % Coronary atherosclerosis, % Cerebral atherosclerosis, %
Total atherosclerosis population (n 5 311,567) 58.3 (12.3) 65 82 30 46 16 9 16 90 5
did not differ from patients without a previous event with regard to age, sex, or the prevalence of hypertension, diabetes, or coronary versus cerebral atherosclerosis (P . .50).
Hypercholesterolemia treatment patterns Among patients with an atherosclerosis diagnosis and a previous CVD event (n 5 144,567), 50% were receiving lipid-modifying therapy at the time atherosclerosis was diagnosed; after this diagnosis, the proportion of patients who received lipid-modifying therapy increased slightly to 57% (Table 2). Among patients with an atherosclerosis diagnosis and no evidence of a previous CVD event, 37% were receiving lipid-modifying therapy at the time atherosclerosis was diagnosed; after the diagnosis, the proportion of patients who received lipid-modifying therapy increased to 48%. Significantly more patients with previous CVD events (47%) received lipid-modifying therapy at diagnosis and afterward compared with patients without an event (36%; P , .001; Table 2). A similar pattern of limited therapy utilization was observed when only statin therapy prescription claims were tabulated (Table 2).
Lipid monitoring and LDL-C distribution
A total of 311,567 patients were found to be newly diagnosed with coronary, cerebral, or general atherosclerosis (based on a diagnostic code for atherosclerosis) between January 2004 and March 2006. Most (83%) were diagnosed with coronary atherosclerosis. The next most frequent atherosclerosis diagnostic codes were chronic ischemic heart disease, renal artery atherosclerosis, atherosclerosis in peripheral vessels, or unspecified atherosclerosis. Of the patients receiving a diagnosis of atherosclerosis, 46% (n 5 144,567) had a previous CVD event in the 12 months preceding diagnosis. Patients diagnosed with atherosclerosis were, on average, 58 years of age, hypertensive (.80%), and frequently diabetic (30%; Table 1). A large proportion (65%) of the patients was men. Patients with a previous CVD event
The majority (85%) of patients with a diagnosis of atherosclerosis did not have an LDL-C measurement recorded around the time of their diagnosis (up to 4 months before or at the time of the diagnosis), leaving 46,923 patients (15% of 311,567 patients) with a baseline LDL-C measure. Patients with baseline LDL-C measures were similar in age, sex, and prevalence of hypertension and diabetes to the total atherosclerosis population (Table 3). At the time atherosclerosis was diagnosed, the mean lipid panel values for these patients were LDL-C 110.0 mg/dL, total cholesterol 189.7 mg/dL, high-density lipoprotein cholesterol (HDL-C) 50.1 mg/dL, and triglycerides 259.1 mg/dL (Table 3). Newly diagnosed atherosclerotic patients with previous CVD events had significantly higher
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Lipid-modifying therapy patterns among patients with clinical atherosclerosis
Hypercholesterolemia treatment patterns
Total atherosclerosis group (n 5 311,567)
Atherosclerosis patients with previous CVD event (n 5 144,567)
Atherosclerosis patients without previous CVD event (n 5 167,000)
Any lipid-modifying therapy (statins and/or fibrates, niacin, bile acid sequestrants, or cholesterol absorption inhibitor), n (%) No therapy at diagnosis and after diagnosis 142,982 (45.9) 58,169 (40.2) 84,813 (50.8) Therapy started after diagnosis only 35,191 (11.3) 14,601 (10.1) 20,590 (12.3) Therapy at diagnosis only and not after diagnosis 5395 (1.7) 3416 (2.4) 1979 (1.2) Therapy at diagnosis and after diagnosis 127,999 (41.1) 68,381 (47.3) 59,618 (35.7) Statin therapy alone, n (%) No therapy at diagnosis and after diagnosis 145,616 (46.7) 59,660 (41.3) 85,956 (51.4) Therapy started after diagnosis only 35,463 (11.4) 14,510 (10.0) 20,953 (12.5) Therapy at diagnosis only and not after diagnosis 5294 (1.7) 3376 (2.3) 1918 (1.1) Therapy at diagnosis and after diagnosis 125,194 (40.2) 67,021 (46.6) 58,173 (34.8) P , .001 for comparison of with and without previous CVD event for both any lipid therapy and statin therapy alone.
LDL-C, total cholesterol, and triglyceride levels, compared with patients without prior events (P , .05; Table 3). The proportion of all patients with an LDL-C ,100 mg/dL at the time atherosclerosis was diagnosed was 44% (Fig. 1). The same proportions were observed for atherosclerotic patients with and without a prior CVD event (P . .10). Comparing patients at the time of the diagnosis of atherosclerosis whose LDL-C was $100 mg/dL (n 5 25,935) with those whose LDL-C was ,100 mg/dL (n 5 20,988), a greater proportion of the former did not receive lipid-modifying therapy either within 4 months before the diagnosis or within 12 months after diagnosis—45% versus 25% (Table 4). Moreover, 43% of patients with baseline LDL-C $100 mg/dL versus 62% of patients with LDL-C ,100 mg/dL had received lipid-modifying therapy after the atherosclerosis diagnosis. Data on statin therapy utilization were similar, with 26% of patients with LDL-C ,100 mg/dL not prescribed a statin after diagnosis compared with 46% of patients with LDL-C $100 mg/dL not receiving statin therapy (Table 4). Treatment patterns that used the optional LDL-C goal of ,70 mg/dL for intensive management of very-high-risk patients were similar to the observations noted previously for
the LDL-C ,100 mg/dL goal. The proportion of all patients with LDL-C ,70 mg/dL at the time atherosclerosis was diagnosed was 11% (Fig. 1). The same proportions were observed for atherosclerotic patients with and without a prior CVD event (P . .10). Among those with LDL-C ,70 mg/dL at the time atherosclerosis was diagnosed, 67% were receiving lipid-modifying therapy both at diagnosis and within 12 months of diagnosis. Approximately 50% of patients with LDL-C $70 mg/dL at the time of diagnosis were prescribed lipid-modifying therapy both at diagnosis and within the 12 months after the diagnosis. Statin therapy utilization was similar.
Postdiagnosis LDL-C levels Of the 46,923 patients with a baseline LDL-C measure, 24,724 (52.7%) had a LDL-C measure after the diagnosis. Among these 24,724 patients, 59% had an LDL-C ,100 mg/dL and 17% had an LDL-C ,70 mg/dL after diagnosis (Fig. 2). This constitutes a modest improvement from the 45% of patients who had an LDL-C ,100 mg/dL and an LDL-C ,70 mg/dL at baseline. For patients with LDL-C values at and after the diagnosis, 17,207 (69.6%) were prescribed
Characteristics of patients diagnosed with atherosclerosis who had a baseline LDL-C level Atherosclerosis patients with baseline LDL-C level
Total sample (n 5 46,923)
Age, years, mean (SD) 58.1 Men, % 63 Hypertension, % 84 Diabetes, % 34 Baseline lipid, mg/dL, mean (SD) LDL-C 110.0 Total cholesterol 189.7 HDL-C 50.1 Triglycerides 259.1
(37.0) (70.3) (17.1) (98.9)
*P , .05 for comparison of with and without previous CVD events.
Patients with previous CVD event (n 5 21,350) 58.2 (11.2) 63 84 35 111.8 190.7 49.1 260.2
(36.8) (70.1) (16.9) (98.5)
Patients without previous CVD event (n 5 25,537) 58.0 (11.2) 63 84 34 108.5 188.8 51.0 258.1
(36.6)* (70.0)* (16.9)* (98.7)*
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Figure 1 Distribution of LDL-C at time of diagnosis for patients diagnosed with atherosclerosis (n 5 46,923). P . 0.10 for comparison of with and without previous CVD event.
lipid-modifying therapy, and 16,858 (68.2%) were prescribed statin therapy alone. Among patients who were prescribed lipid-modifying therapy, 52% had a LDL-C ,100 mg/dL at baseline and 64% had an LDL-C ,100 mg/dL in the 12 months after the diagnosis (Fig. 3). Statin therapy alone provided similar LDL-C improvements. The majority of patients in this study had high triglycerides at baseline (mean triglyceride level of 259 mg/dL), suggesting the presence of triglyceride-rich remnant lipoproteins and an increased CV risk. NCEP ATP III guidelines recommended that a secondary target level, defined by a non-HDL-C level 30 mg/dL above the LDL-C level, be established for these patients. Approximately 54% of patients had non-HDL-C levels ,130 mg/dL at baseline; 57% had levels ,130 mg/dL after diagnosis of atherosclerosis. Similarly, 20% of patients achieved the more rigorous non-HDL-C level of ,100 mg/dL at baseline, compared with 25% after diagnosis (Fig. 4).
Discussion This study found a significant gap in the management of patients who were diagnosed with atherosclerosis in the usual-care setting. Patients diagnosed with atherosclerosis
based on ICD-9 codes were not optimally managed at the time of diagnosis or within the 12 months after diagnosis. Only 37% of patients diagnosed with atherosclerosis who did not have a previous CVD event received lipid-modifying therapy, and only 50% of those with a previous CVD event, where the indication for therapy is arguably strongest, received lipid-modifying therapy. Five of every 6 patients did not have a lipid profile recorded at the time of or 6 months before their diagnosis of atherosclerosis. Of the 15% of patients who did have a baseline LDL-C, only 53% had another lipid profile within the 12 months after diagnosis. Forty-four percent of patients with atherosclerosis had an LDL-C ,100 mg/dL at the time of the diagnosis; of those with an LDL-C $100 mg/dL, only 54% received lipid-modifying therapy after the diagnosis, and only 64% of these had an LDL-C ,100 mg/dL in the 12 months after the diagnosis. Only 54% had a nonHDL-C ,130 mg/dL at baseline, and only 57% achieved this goal after their diagnosis of atherosclerosis. Despite the publication of new landmark trials during the period of study assessment, ongoing medical education about the ATP III guidelines, and release of more efficacious lipid-modifying therapies since the release of the ATP III treatment guidelines, our results suggest that there has
Lipid-modifying therapy patterns stratified by baseline LDL-C among patients with clinical atherosclerosis
Hypercholesterolemia treatment patterns
Atherosclerosis patients with baseline LDL-C ,100 mg/dL (n 5 20,988)
Atherosclerosis patients with baseline LDL-C $100 mg/dL (n 5 25,935)
Any lipid-modifying therapy (statins and/or fibrates, niacin, bile acid sequestrants, cholesterol absorption inhibitor), n (%) No therapy at diagnosis and after diagnosis 5204 (24.8) 11,583 (44.7) Therapy started after diagnosis only 2466 (11.8) 2723 (10.5) Therapy at diagnosis only and not after diagnosis 230 (1.1) 381 (1.5) Therapy at diagnosis and after diagnosis 13,088 (62.4) 11,248 (43.4) Statin therapy alone, n (%) No therapy at diagnosis and after diagnosis 5365 (25.6) 12,013 (46.3) Therapy started after diagnosis only 2483 (11.8) 2778 (10.7) Therapy at diagnosis only and not after diagnosis 234 (1.1) 386 (1.5) Therapy at diagnosis and after diagnosis 12,906 (61.5) 10,758 (41.5)
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Distribution of baseline and post-diagnosis LDL-C for patients diagnosed with atherosclerosis (n 5 24,724).
been little or no progress in identifying and treating highrisk CVD patients in the past decade. Compared with the LTAP and NEPTUNE studies,13,14 fewer of the patients in our study received lipid-modifying therapies and a similar number achieved the LDL-C goal of ,100 mg/dL after diagnosis. Only slightly more than half of these high-risk patients achieved a non-HDL-C ,130 mg/dL. The previous studies reported that $85% of patients received lipidmodifying therapy, compared with 52% of our patients after the diagnosis of atherosclerosis, but this may be attributable in part to the fact that in the previous studies, only patients who were managed by high-prescribing physicians with professed knowledge of treatment guidelines were included, whereas in our study patients managed by all medical providers in a general-care setting were included. In the NEPTUNE study,14 60% of CHD and CHD risk-equivalent patients achieved their LDL-C goal of ,100 mg/dL, and in the present study, 64% of patients receiving lipid-modifying therapy after their diagnosis were at this goal. Given the efficacy of currently available therapies and evidence base supporting current goals, these results suggest significant opportunity for improvement.
Figure 3 Distribution of baseline and postdiagnosis LDL-C for patients diagnosed with atherosclerosis and prescribed lipid-modifying therapy (fibrates, bile acid sequestrants, niacin, cholesterol absorption inhibitor, and/or statins; n 5 17,207).
Our study has examined, for the first time, the treatment pattern of patients with the diagnosis of ostensibly subclinical, asymptomatic atherosclerosis and found that treatment patterns are similar to the suboptimal treatment of patients who had experienced a CVD event. Among the patients with atherosclerosis and a prior CVD event, 57% received lipid-modifying therapy after the diagnosis, compared with 48% of patients with a diagnosis of atherosclerosis but without a CVD event history. In both groups of patients, the diagnosis of atherosclerosis prompted a small increase of 7–11% in the proportion of patients who received lipidmodifying therapy. The mean lipid levels of the two groups were similar and above the LDL-C ,100 mg/dL and nonHDL-C ,130 mg/dL goals. These data call for a greater effort to identify patients with subclinical atherosclerosis and to appropriately consider effective lipid-modifying therapy, especially in patients with evidence of advanced subclinical disease. The recent publication of the JUPITER study15 underscores this recommendation. The study examined 17,802 men and women with no evidence of CVD, a mean LDL-C of 108 mg/dL, a low Framingham risk score, and an hsCRP of .2.0 mg/L, which is a marker of increased cardiovascular disease risk, likely associated with vascular atherosclerosis. In this study, patients achieved LDL-C levels of 55 mg/dL after median reductions of 50%. After 1.9 years of follow-up, treatment with rosuvastatin significantly reduced cardiovascular events by 44% compared with placebo. This primary end point was a composite of cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina, and revascularization. Rosuvastatin also significantly reduced total mortality by 20%,15 a new finding in patients without documented CVD. Given the treatment gap identified in the present study, closer attention to high-risk patients who have experienced a CVD event or have advanced atherosclerosis is needed. There may be a lack of awareness among clinicians regarding the level of CVD risk in these patients and the benefit of lipid-modifying therapy. Clinical trials have demonstrated very positive effects of statin therapy on the
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Distribution of baseline and postdiagnosis non-HDL-C for patients diagnosed with atherosclerosis (n 5 24,724).
progression of atherosclerosis11,16,17 and on CVD events,15 even in those at low risk with early signs of the disease.12 The findings from these and other clinical trials and their implications for patient care need to be communicated to clinicians treating patients with atherosclerosis. These study findings should be interpreted in light of several limitations. Patients included in the study were required to have an ICD-9 diagnosis of atherosclerosis but this could not be confirmed by imaging studies because the results of the imaging tests were not available in the administrative claims database. Furthermore, we could not confirm whether each diagnosis of atherosclerosis was advanced and thus indicated for lipid-modifying therapy. Patients with clinical atherosclerosis who did not receive one of the specific diagnostic codes for atherosclerosis (ICD-9 code 5 414, 440, 437) used in our study were not included in this study. Clinicians may have recorded the CVD event (eg, MI or stroke) without recording an atherosclerosis diagnosis code. These patients were not included in the current study as the focus was on patients with explicit atherosclerosis diagnosis. Opportunities to improve dyslipidemia therapy in patients with documented CVD events have been reported elsewhere.18 Although selection bias was possible because of the observational nature of the study, the data used for this study were derived from a national health plan for patients receiving care in a usual-care setting, which should make the findings generalizable to other large managed care plans. Additionally, the benefit of claims data arises from its high external validity and real-world applicability. The results from our usual-care study approximate the management and treatment patterns in real-world clinical practice. Quantification of differential risk of CVD events (MI or stroke) among patients with atherosclerosis receiving lipidmodifying therapy, compared with those receiving no therapy, was beyond the scope of the present study. Cardiovascular disease is the leading cause of morbidity, disability, and mortality in Western countries, and atherosclerosis is the main underlying pathology.19 Given the gap in lipid monitoring and treatment of CVD risk among
patients with atherosclerosis in this study, there is a need to raise awareness of the importance of monitoring and treating lipids in patients with atherosclerosis, whether or not it has produced symptoms. Improvement in evaluation and control of hypercholesterolemia is needed, particularly in this segment of the population with increased risk of CVD events. Also, a more aggressive therapeutic approach that helps patients reach treatment goals may be needed among patients with atherosclerosis.
Financial disclosures This research was supported by AstraZeneca Pharmaceuticals LP. The sponsor did not have any involvement in the study design, data collection, data analysis, manuscript preparation, or publication decision except through the author, Dr. Gandhi, who is an employee of AstraZeneca Pharmaceuticals LP. Dr. McKenney is a clinical investigator and advisor for AstraZeneca Pharmaceuticals LP. Dr. Gandhi is an employee and stockholder of AstraZeneca Pharmaceuticals LP. Drs. Fox and Ohsfeldt received research funds from AstraZeneca Pharmaceuticals LP to conduct the study.
References 1. 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. 2. Grundy SM, Cleeman JI, Merz CN, et al. Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004;44:720–732. 3. Corti R, Fuster V, Fayad ZA, et al. Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol. 2005;46:106–112. 4. Yonemura A, Momiyama Y, Fayad ZA, et al. Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging. J Am Coll Cardiol. 2005;45:733–742.
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5. Zhao XQ, Yuan C, Hatsukami TS, et al. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study. Arterioscler Thromb Vasc Biol. 2001;21:1623–1629. 6. Dilaveris P, Giannopoulos G, Riga M, Synetos A, Stefanadis C. Beneficial effects of statins on endothelial dysfunction and vascular stiffness. Curr Vasc Pharmacol. 2007;5:227–237. 7. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289–1298. 8. Brown BG, Hillger L, Zhao XQ, Poulin D, Albers JJ. Types of change in coronary stenosis severity and their relative importance in overall progression and regression of coronary disease. Observations from the FATS trial. Familial Atherosclerosis Treatment Study. Ann NY Acad Sci. 1995;748:407–417. 9. Ballantyne CM, Raichlen JS, Nicholls SJ, et al., ASTEROID Investigators. Effect of rosuvastatin therapy on coronary artery stenosis assessed by quantitative coronary angiography: a study to evaluate the effect of rosuvastatin on intravascular ultrasound-derived atheroma burden. Circulation. 2008;117:2458–2466. 10. Thompson GR. What targets should lipid-modulating therapy achieve to optimise the prevention of coronary heart disease? Atherosclerosis. 1997;131:1–5. 11. Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, for the ASTEROID Investigators. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis. The ASTEROID Trial. JAMA. 2006;295:1556–1565. 12. Crouse JR III, Raichlen JS, Riley WA, et al., for the METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media
thickness in low-risk individuals with subclinical atherosclerosis: the METEOR trial. JAMA. 2007;297:1344–1353. Pearson TA, Laurora I, Chu H, Kafonek S. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160:459–467. Davidson MH, Maki KC, Pearson TA, et al. Results of the National Cholesterol Education (NCEP) Program Evaluation Project Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations. Am J Cardiol. 2005;96:556–563. Ridker PM, Danielson E, Fonseca FA, et al., JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207. Jensen LO, Thayssen P, Pedersen KE, et al. Regression of coronary atherosclerosis by simvastatin: a serial intravascular ultrasound study. Circulation. 2004;110:265–270. Okazaki S, Yokoyama T, Miyauchi K, et al. Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH study. Circulation. 2004;110:1061–1068. Fox KM, Gandhi SK, Ohsfeldt RL, Blasetto JW, Davidson MH. Effectiveness of statins in Medicare-eligible patients and patients ,65 years using clinical practice data. Int J Clin Pract. 2007;61:1634–1642. Kiechl S, Willeit J, for the Bruneck Study Group. The natural course of atherosclerosis. Part I: incidence and progression. Arterioscler Thromb Vasc Biol. 1999;19:1484–1490.
Appendix Atherosclerosis ICD-9 codes used to identify eligible patients and number of patients with each code
Number of patients
414.00 414.01 414.02 414.03 414.04 414.05 414.06 414.07 414.10 414.11 414.12 414.19 414.8 414.9 437.0 437.1 437.3 440.0 440.1 440.2x 440.3 440.8 440.9
Coronary atherosclerosis of unspecified type of vessel, native or graft Coronary atherosclerosis of native coronary artery Coronary atherosclerosis of autologous biological bypass graft Coronary atherosclerosis of nonautologous biological bypass graft Coronary atherosclerosis of artery bypass graft Coronary atherosclerosis of unspecified type of bypass graft Coronary atherosclerosis of native artery of transplanted heart Coronary atherosclerosis of bypass graft of transplanted heart Aneurysm of heart, of heart (wall) Aneurysm of heart, of coronary vessels Dissection of coronary artery Aneurysm of heart, other aneurysm of heart Chronic ischemic heart disease Chronic ischemic heart disease, unspecified Cerebral atherosclerosis Generalized ischemic cerebrovascular disease Cerebral aneurysm, nonruptured Atherosclerosis of aorta Atherosclerosis of renal artery Atherosclerosis of native arteries of the extremities Atherosclerosis of bypass graft of extremities Atherosclerosis of other specified arteries Atherosclerosis, general and unspecified
205,329 38,664 2,050 29 10,545 820 25 59 498 29 30 293 14,499 30,375 1,289 1,494 2,841 1,816 5,858 4,950 440 234 5,624