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The contentious American Heart Association and American College of Cardiology guidelines, which stirred controversy when unveiled last year, more accurately matched statin assignment to plaque burden compared with older guidance, researchers said, leading to a "modest" increase in the number of patients who were prescribed statins.

In the single-center, retrospective study of 3,076 adults who underwent undergoing CT angiography, the probability of prescribing statins rose with increasing plaque burden under the 2013 (GACR) compared with the 2001 National Cholesterol Education Program (NCEP) Adult Treatment Panel III recommendations, according to , of Yale School of Medicine, and , of Atlantic Medical Imaging in Galloway, New Jersey.

Under NCEP guidelines, 59% of patients with 50% or more stenosis of the left main coronary artery identified by CT angiogram, and 40% of patients with 50% or more stenosis of other branches would not have been prescribed a statin. The comparable results for the GACR were 19% and 10%, respectively, they wrote online in the .

"The use of low-density lipoprotein targets seriously degraded the accuracy of the NCEP guideline for statin assignment," they wrote. "The proportion of patients assigned to statin therapy was 15% higher under the GACR. The GACR and NCEP methods partition patients into risk groups in similar ways, but the NCEP method then applies LDL targets to decide who gets statin therapy."

Johnson told 麻豆传媒 that when he and Dowe excluded the LDL targets from the 2001 guideline in their analysis, the number of patients assigned to statin therapy was almost identical to the new guidelines.

GACR: A Dramatic Increase in Statin Use?

The decision to do away with LDL targets was widely criticized by opponents of the GACR, with critics predicting that the new guidelines would lead to a dramatic increase of the number of people taking statins.

But in the analysis by Johnson and Dowe, the new guidelines increased the proportion of patients assigned to statin therapy by just 15%, which the researchers characterized as "modestly larger" than under the older recommendations.

"If you are willing to consider coronary plaque burden as a surrogate for risk, then our data clearly show that the new guidelines assign statins to people more accurately than the old guidelines did," Johnson said.

Last week, a group from UT Southwestern Medical Center in Dallas reported similar findings, based on their

They predicted that among participants (ages 30-65) who would have newly qualified for statin use under the new guidelines, 3.6 to 4.9 cardiovascular events would have been prevented for every 1,000 people screened and newly treated.

, of Northwestern University in Chicago, who chaired the , told 麻豆传媒 these studies show the new recommendations to be a very efficient way of finding people who would benefit most from statin therapy.

He said the studies "add confirmation that when the decision is made to give a statin for primary prevention based on risk, we are identifying people who actually benefit."

The 2013 guidelines identify patients (ages 40-75) who have had a heart attack or stroke, those with LDL cholesterol of 190 mg/dL or more, and those with diabetes as high-risk groups who clearly benefit from statin therapy.

"There is strong evidence for treating these three groups and the guidelines make it clear that the best results relate to the intensity of statin therapy," Stone said.

He added that a key feature of the new guidelines which was lost in much of the early controversy: The importance of a clinician-patient discussion when treatment is being considered.

"Some of the original editorials saying statins would be widely overprescribed misinterpreted what was written," he said. "What the guidelines said was that [clinicians and patients] should discuss risk, lifestyle and preferences. They did not say statin treatment should be mandatory."

Study Details

The patients included in the analysis by Johnson and Dowe received CT angiography at a single center between February 2004 and November 2009. They presented for various reasons, including stable atypical chest pain, indeterminate stress test results, multiple risk factors, and a strong family history of cardiovascular disease.

Patients younger than age 40 or older than age 75, without known atherosclerotic cardiovascular disease or LDL cholesterol ≥190 mg/dL were not included in the analysis, because the GACR makes no recommendations for such patients, the researchers noted.

Imaging was performed on the 3,076 patients and 65.3% of the cohort was male, with a mean age at the time of imaging of 55.4. The mean age of the women was 58.9. More than 90% of the cohort was Caucasian.

The median Framingham 10-year risk was 10% for men and 3% for women and the most common reasons for undergoing CT angiography were hypercholesterolemia, family history of coronary heart disease, hypertension, smoking, and nonacute chest pain.

At the time of imaging, 1,362 patients (44.3%) were not on statins or other lipid-lowering therapy; the remaining 1,714 patients (55.7%) were on statins. Patients not taking statins had less disease than patients on statins, the authors stated.

Among the main findings, GACR correlated marginally better with plaque and stenosis burden than the older risk estimation guidelines. For all patients, the correlation of segmental plaque burden scores (SPS) with NCEP guidelines 10-year risk estimate was 0.51 (95% CI 0.48-0.54) compared with 0.56 (95% CI 0.53-0.59) with GACR guidelines.

The GACR assigned fewer patients with no plaque to statins and more patients with heavy plaque to statins.

Among patients with heavy plaque (SPS ≥8), 53% would be assigned to statin therapy under NCEP and 92% under the GACR. Among patients with no or trace plaque, 41% would be assigned to statin therapy under NCEP and 36% under the new.

NCEP was more likely to assign statins to patients with little plaque and less likely to assign statins to those with a great deal of plaque.

"In this study, plaque burden is used as a surrogate for cardiac events, which are the ultimate end point to determine accuracy," Johnson and Dowe wrote. "This hypothesis is partially proved in symptomatic patient but remains unproved in the primary prevention setting."

Other study limitations cited by the researchers included the fact that about half the patients were already taking a statin when they entered the study and homogeneous nature of the cohort.

But they concluded that on the basis of their findings, "it is a reasonable hypothesis that the new guidelines will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis."

'Seminal Findings'

In an accompanying editorial, , from the Department of Veterans Affairs Medical Center in Denver, wore that he could not remember more "groundbreaking ... and controversial" guidelines than GACR.

"They are groundbreaking for using a new race-specific estimator to generate both 10-year and lifetime cardiovascular risk, for considering both stroke and coronary heart disease risk, and especially for [LDL] cholesterol goals with specific drug and dose treatment targets," he explained.

As for the controversy, the guidelines "ignited a firestorm of dissent, ranging from perceived author conflict of interest to overestimation of risk to therapeutic nihilism regarding the benefits of statin treatment."

He said the findings of Johnson and Dowe "strongly support that the 2001 guidelines undertreated especially younger, high-risk patients."

"The major reason for the undertreatment with the 2001 guidelines resulted from their use of LDL cholesterol goals," he wrote. "The new guidelines appear to reduce this critical limitation. The present study suggests that the new guidelines are a major clinical and conceptual improvement over the older ones."

But the study also had some limitations, including a cohort that was "referred for angiography predominately for nonspecific symptoms, indeterminate stress test results, or the presence of multiple risk factors and therefore was at higher than average risk," Vogel pointed out.

Also, total cholesterol and LDL baselines were estimated and not measured in the majority of patients who were already on statin therapy, he added.

Nonetheless, Vogel called the findings "seminal," as it asks the "fundamental question of whether guidelines are really distilled wisdom or simply working hypotheses."

"In a regulatory world in which the quality of medical care, and hence reimbursement, is evaluated by adherence to treatment guidelines, do guidelines need to be prospectively validated?," Vogel concluded. "Do we need fewer comments from experts and medical societies and more science? I would argue the latter. So does the present study."

From the American Heart Association:

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