Polypill for Primary Prevention: Where Does CAC Score Fit in?

JACC in a Flash | The concept of using a single polypill as primary prevention in people with "average" risk factor levels for cardiovascular disease has recently gained popularity. While a combination of aspirin, beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor has been shown to prevent a large portion of CVD events, the polypill strategy has far-reaching health care and economic implications, and opens up the possibility of over-treating millions of asymptomatic men and women. Use of the coronary artery calcium (CAC) scoring algorithm has been suggested as a way to narrow down patients who would benefit from pharmacotherapy and those who would be treated unnecessarily.

Marcio Sommer Bittencourt, MD, and colleagues evaluated how well CAC score (measured by cardiac computed tomography [CCT]) for identifying subclinical coronary atherosclerosis could help guide more selective application of polypill therapy. Using patient data from the Multi-Ethnic Study of Atherosclerosis (MESA) study, investigators stratified participants according to criteria of four polypill studies that analyzed different polypill regimens: TIPS (n = 2,238), Poly-Iran (n = 2,278), Wald's (n = 4,416), and the PILL collaboration (n = 3,911).

TABLE. CAC Scores in Four Analyses of Polypill Regimens
Number of events per 1,000 person-years
  CHD Events CVD Events
TIPS
 CAC = 0
 CAC = 1-100
 CAC = >100

1.2
4.6
13.3

2.5
6.1
18.4
Poly-Iran
 CAC = 0
 CAC = 1-100
 CAC = >100

1.9
5.1
11.6

2.5
6.0
15.8
Wald
 CAC = 0
 CAC = 1-100
 CAC = >100

1.7
5.5
12.5

3.7
8.3
16.5
PILL Collaboration
 CAC = 0
 CAC = 1-100
 CAC = >100

1.7
5.5
12.5

4.0
8.5
17.2

Rates of CVD and coronary heart disease (CHD) events were stratified by the presence or absence of CAC for each study population. Overall, the rates of events for patients with a CAC score of zero was low in all four groups, with the risk increased up to 11-fold in higher CAC-scoring patients (TABLE).

These associations persisted even after adjustment for age, gender, race, education, and MESA site from which the patient was recruited. Hazard ratios for CAC score of 1–100 to predict CHD and CVD ranged from 2.3–2.8 and 1.7–1.9, respectively. This further increased with higher CAC score (CAC >100: 4.7–6.4 [CHD] and 3.3–4.4 [CVD]).

Using the estimates of events from the survival model at median follow-up, and assuming the proposed benefit of 62% event reduction found in the TIPS study, the number-needed-to-treat (NNT) for 5 years to prevent one CVD event would range from 84 to 134 for patients with a CAC = 0; from 40 to 55 for patients with CAC of 1–100; and from 19 to 21 for patients with a CAC >100.

Importantly, Dr. Bittencourt and colleagues pointed out, the current analysis did not address the potential adverse effects of any of the polypill regimen's individual components, which is of particular concern when considering treatment of individuals with a CAC = 0 who have very low CVD rates, and are thus more likely to be harmed by therapy.

"A simple test with a high negative predictive value could be used to identify individuals with an extremely low event rate, in whom indiscriminate polypill therapy might be safely deferred," Dr. Bittencourt and colleagues concluded. "Such an approach would significantly reduce the number of individuals requiring treatment, thus reducing important side effects and cost, but still ensure treatment to the majority of individuals who are likely to experience CHD and CVD events."


Bittencourt MS, Blaha MJ, Blankstein R, et al. J Am Coll Cardiol. 2013 October 10. [Epub ahead of print]


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