CAC Screening Is Cost-Effective in Older Men But Not Women

Reed Miller

October 20, 2011

October 19, 2011 (Rotterdam, the Netherlands) — New data from Rotterdam suggests that computed tomography (CT) coronary artery calcium (CAC) screening is cost-effective for older men, but may not be worth it for women [1].

As reported by heartwire , previous analysis from the Rotterdam Coronary Calcification Study showed CAC scoring can reclassify over half the individuals who are considered to be at intermediate risk based on Framingham risk factors alone. The analysis by Bob JH van Kempen (Erasmus Medical Center, Rotterdam, the Netherlands) and colleagues published in the October 11, 2011 issue of the Journal of the American College of Cardiology compares four strategies for managing this patient population: "current practice," "current guidelines," "CT calcium screening" and "statin therapy." The authors explain that "Initiating statins in all individuals is not always considered feasible in all situations, [but] it puts the CT calcium screening strategy into a broader perspective, between the least aggressive strategy ("current practice") and fairly aggressive strategy ("statin therapy"), providing a range of possibilities for an individual at intermediate risk of CHD."

Commenting on the study, Dr James Min (Cedars-Sinai, Los Angeles, CA) told heartwire that the results are "reassuring." "This study really extends prior studies--from both convenience samples and population-based cohorts--that definitively demonstrate the additive utility of calcium scoring beyond traditional clinical risk-factor assessment for risk stratification, discrimination, and reclassification," he said.

But Dr John McEvoy (Johns Hopkins University, Baltimore, MD), the leader of a recent study that found no benefit of coronary computed tomographic angiography (CCTA) in asymptomatic patients, is more skeptical of van Kempen et al's conclusions, because "many presumptions have to be made in the calculations, and the findings represent an educated guess," he told heartwire .

The analysis finds that CAC screening is both more effective and more costly than the other three strategies in men. The picture that emerged for women is more complicated. In women, CAC screening was more effective and more costly than current practice or statin therapy but both less expensive and less effective than the current-guidelines approach. CT screening was not found to be cost-effective in women even after the researchers tried a wide range of different assumptions that would make the model more favorable to the CT calcium screening strategy, such as treating patients in the higher end of "low risk" more aggressively.

Within the low-risk group, women's risk of coronary disease is greater than men's, but more women were reclassified to the low-risk group and therefore got the less aggressive treatment. "So the forgone benefit with less aggressive treatment is higher in women," the authors explain. Most of the benefits of CT screening appear in the high-risk group, who receive more aggressive therapy compared with the people at intermediate risk treated according to the current guidelines. But because fewer women are reclassified to high risk, the potential benefit of CT screening for women is lower than it is for men. Also, aspirin is prescribed in men at high risk but not in women, "due to controversy with regard to its efficacy in primary prevention of CHD," which further shifts the cost/benefit balance, the authors explain.

Probabilistic sensitivity analysis demonstrated that, in men, CAC screening was more cost-effective than current practice in most of the simulations if it is assumed that the "willingness-to-pay threshold" is $50 000 per additional quality-adjusted life-year, but in women, even if the willingness-to-pay thresholds were higher than $50 000, CT calcium screening was cost-effective in fewer than 20% of the simulations.

Four Options for Intermediate-Risk Patients

In the study, patients in the current-practice group were usually treated at baseline with statins, antihypertensive medication, or aspirin by their general practitioners. The current-guidelines patients were given lifestyle advice and statin therapy if their baseline low-density lipoprotein cholesterol exceeded 130 mg/dL. They were given antihypertensive medication if their systolic blood pressure exceeded 140 mm Hg. The patients in the statin-therapy group got a moderate-dose statin and were otherwise managed like the current-practice patients.

The calcium-screening patients underwent CT scans to determine their coronary calcium score. Their 10-year CHD risk was recalculated based on their Framingham risk factors plus the calcium score, so some of these people were reclassified as either high or low risk. The people who ended up in the low-risk group got lifestyle advice and pharmacological treatment if their systolic blood pressure was above 140 mm Hg and/or plasma LDL levels were over 160 mg/dL. The people who stayed in the intermediate-risk category after the CAC score were treated like the people in the current-guidelines group. People moved into the high-risk group received lifestyle advice, statin therapy, and antihypertensive medication. The men in this group were also given low-dose aspirin (80 to 100 mg daily).

Results Depend on Assumptions

Dr Khurram Nasir (Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD), the author of a recent study of plaque-composition differences in men and women, pointed out that the van Kempen et al study enrolled a population over 70, so the conclusions do not apply to younger and middle-aged individuals, who may be more appropriate candidates for CHD screening.

"It is hard to argue for screening for subclinical atherosclerosis among the very elderly, the majority of whom are harboring coronary atherosclerosis," Nasir told heartwire . "The main cost-beneficial downstream effect of CAC testing lies in the 'power of zero.' . . . The absence of CAC is seen in nearly half of middle-aged individuals [and] confers such a low risk--about a 1% 10-year rate--that physicians can safely withhold statin therapy, limit lipid-lowering pharmacotherapy, and focus on lifestyle-modification strategies."

Nasir also suggests that statin therapy might have been more cost-effective in the trial if the study had set the threshold at LDL >190 mg/dL instead of 160 mg/dL. This could have made an especially big difference in the elderly women with absent to mild atherosclerosis because that group had so few adverse events. "This conservative strategy would have provided more bang for the buck," Nasir said. "From a societal standpoint, there is little utility in trying to treat a lot of very low-risk individuals as appropriately identified by CAC testing to prevent few events; this approach will never be cost-effective."

A recent study led by Dr John Nance (Medical University of South Carolina, Charleston) showed that women have more noncalcified plaques than males, but these plaques presented a lower risk in women. Nance told heartwire that his group's study, which used CCTA instead of CAC scoring, showed that noncalcified plaque is more common in women and predicts adverse events independent of clinical risk factors; coronary CT angiography may be better than CAC scoring for risk stratification in women. Meanwhile, noncalcified plaques are less common in men but portend a higher risk in men than women, so CCTA may be better than CAC scoring for risk stratification in men, too, he said.

"Noncalcified plaque posed a higher risk in men than in women, which may, at first glance, seem incongruent with [van Kempen et al's] postulation, since CAC scoring, which does not evaluate noncalcified plaque, seemed not to underestimate risk as badly in men," Nance explained. "However, men had significantly more calcified plaque, and noncalcified plaque and calcified plaque are not mutually exclusive, suggesting that while noncalcified plaque may still be more dangerous in men, underestimation of plaque burden by CAC scoring is not as likely."

"This is really an exploratory study. I would think of this as a type of medical 'weather forecasting,' " McEvoy said.  "For now, I would have healthy skepticism for the true accuracy of the results, especially as minor changes to the model led to different strategies winning out as the most cost-effective . . . and simply implementing the current prevention guidelines fully is nearly, if not just, as effective as using a CAC-testing-based strategy in primary prevention."

Forget the Tests and Treat Them All?

The authors of the study note that the differences in quality-adjusted life-years between the various strategies tested were small, and the sensitivity analysis suggests that an optimal strategy could either be routine CAC testing or perhaps moderate-dose statin therapy for almost every one of these intermediate-risk patients.

In an accompanying editorial [2], Dr Philip Greenland (Northwestern University, Chicago, IL) and Dr Tamar Polonsky (University of Chicago, IL) point out that if the guidelines are eventually updated to expand the indications for statins, they might be used more in clinical practice, which would make CAC testing less valuable for selecting patients for statin treatment [2].

"All of these scenarios lead to the conclusion that additional information beyond that available from the cost-effective analysis by van Kempen et al might be needed before a convincing and definitive change in clinical-practice guidelines would be justified," Greenland and Polonsky explain. They cite a 2009 editorial by Dr Aroon Hingorani (University College London, UK) and Dr Bruce Psaty (University of Washington, Seattle) that suggests that giving generic statins to all adults on the basis of an age threshold, regardless of the level of LDL cholesterol, C-reactive protein, or absolute risk, would be easier and more effective than expecting doctors and patients to sort out how the complex lipid-lowering guidelines apply to their case [3]. None of the risk-prediction models are highly sensitive or highly specific, so a "treat-all" approach, perhaps with a polypill, may turn out to be the best approach for all patients above a certain level of risk, the editorialists suggest.

Calls for a More Definitive Trial Grow Louder

"With the residual uncertainty in this important area of preventive medicine, we believe that the only way to determine the 'best' strategy is to conduct a clinical trial with CAC testing to select patients for more or less intensive treatments," Greenland and Polonsky argue. "Such a trial would need to enroll a large number of patients who were followed for at least four to five years. The study would be challenging logistically as well as costly. However, in the absence of such a trial, the options seem to be so close to one another on careful analysis that reasonable errors in the assumptions can lead to very different conclusions."

The need for a definitive trial was also stressed by the experts who commented on the study for heartwire . "It would be wonderful to see such a trial get off the ground,” Min said.

"This study provides significant food for thought as far as designing a comparative strategy trial that includes CAC testing is concerned. The proposed clinical trial should strongly consider appropriate age groups . . . [and focus] on a small subgroup of individuals (CAC >100) among whom a majority of coronary events occur," Nasir said.

McEvoy agreed. "A prospective and randomized outcomes study of CAC testing would answer many of the outstanding questions."

The study was funded by ZonMw, the Netherlands Organization for Health Research and Development. Study coauthor Dr Gabriel Krestin (Erasmus Medical Center) has served as a consultant to GE Healthcare. All other authors have reported that they have no relevant relationships to disclose.

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