Methods

This analysis used projected clinical outcomes to test the utility of reclassification based on CAC score in the Multi-Ethnic Study of Atherosclerosis (MESA). In MESA, subjects were first categorized into 3 groups of cardiovascular risk based on age, gender, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol levels, and race/ethnicity. These groups were conventional low risk (LR; <3% 5-year risk of cardiovascular event), conventional intermediate risk (IR; 3% to 10% 5-year risk of cardiovascular event), and conventional high risk (HR; >10% 5-year risk of cardiovascular event). After their CAC scores were included in the risk algorithm, subjects were reclassified as to their cardiovascular risk.

Because the America College of Cardiology Foundation/American Heart Association guideline panel has recommended only CAC scoring as a screening test in subject at conventional IR, we focused on the impacts of reclassification of these subjects. Subjects with conventional IR could remain at IR (reclassified IR) or be reclassified as LR (reclassified LR) or HR (reclassified HR). In the original report by Polonsky et al, the clinical outcomes in reclassified subjects in MESA were shown to correspond to their observed 5-year cardiovascular risk groups and net reclassification was judged a success. Nevertheless, it remains an assumption that more accurate risk classification will result in better clinical outcomes when the impact of therapy is taken into account. Moreover, reclassification does not consider costs and improvement in risk reclassification does not guarantee a favorable cost–benefit profile.

Accordingly, we examined the impact on outcome of 2 strategies of statin-induced LDL-lowering therapy. In strategy 1, we labeled the broad statin prevention approach in which all those at conventional IR are treated with moderate doses of statins; in strategy 2, using the reclassification prevention approach in which those reclassified to LR are not treated, those remaining at IR receive a moderate dose of a statin and those reclassified to HR receive intensive statin treatment. We chose to model statin therapy because the clinical pattern of benefit from statin therapy has been remarkably robust and consistent in a wide variety of clinical trials. Furthermore, the percent lowering of LDL cholesterol by different doses of different statins has been well documented.

For the 2 treatment scenarios, we made the following assumptions. (1) The relative effect of treatment on events would be the same regardless of other risk factors across all risk categories. (2) The relative risk decrease would be 22% for simvastatin 40 mg and the risk decreases for different doses of atorvastatin would be proportionate to their decrease of LDL cholesterol compared to simvastatin 40 mg. (3) Compliance with treatment would be 100%. (4) There would be no significant adverse effects of statin therapy or CAC study within the treatment period of 5 years.

We also calculated the cost savings associated with the 2 scenarios. This was done by first retrieving the coronary heart disease events noted in participants in the MESA study. In total 209 coronary heart disease events were observed over a median follow-up of 5.8 years (interquartile range 5.6 to 5.9). Of these, 96 patients developed a myocardial infarction, 14 died of coronary heart disease, 12 had a resuscitated cardiac arrest, and 87 had angina, 73 of whom underwent coronary revascularization. Costs were determined from published estimates: $55,400 for myocardial infarction, $15,400 for death from myocardial infarction or cardiac arrest, $72,200 for nonfatal resuscitated cardiac arrest, $40,200 for patients admitted with angina undergoing revascularization, and $32,700 for those admitted with angina not undergoing revascularization. We then determined the average cost “per coronary heart disease event” in MESA, weighted by the proportions of patients developing these events in MESA ($46,855.50 per coronary heart disease event).

Statin costs were estimated at $4 per month based on current generic dose-independent estimates. Statin costs were determined for the mean MESA follow-up of 5.8 years ($278.40 spent on statins per patient during mean time in the study). CAC screening was estimated at $340 per scan based on the charge at the Cleveland Clinic. This translated into $627,980 spent in scenario 2 on CAC scoring for risk assessment of the 1,847 subjects at IR.

Results

The results of reclassification based on CAC score in the MESA study as reported by Polonsky et al are presented in Table 1 . Subjects in the IR group before classification had a mean age ± SD of 68 ± 9 years, 70% were men, systolic blood pressure was 134 ± 21 mm Hg, 62% were current smokers, 51% were on antihypertensive treatment, and total cholesterol and high-density lipoprotein cholesterol levels were 197 ± 37 mg/dl and 47 ± 12 mg/dl, respectively. Over 5 years, 115 cardiovascular events occurred in 1,847 subjects who were classified as IR by conventional criteria. Of the total, 292 (13.2%) were reclassified as HR by coronary calcification; within this group, 48 (16.5%) had clinical events. Of 712 who were reclassified as LR, 15 (2.1%) had clinical events. Accordingly, at least in the short term, reclassification based on CAC did appear to accurately allocate subjects based on risk. Clinical outcomes of the 2 treatment scenarios are presented in Table 2 .

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