In Reply We thank Falk and Mortensen for their thoughtful comments regarding our article in JAMA Cardiology.1 We agree that the classification of the United States as a high-risk or low-risk country alters the proportion of Americans recommended for cholesterol-lowering therapy, as shown in our sensitivity analysis. However, how to classify a country remains somewhat vague. As the authors of the 2012 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines point out, “any cut-off point is arbitrary and open to debate.”2 As specified in the Methods section, we used country-specific cardiovascular disease mortality data to classify the United States as a high-risk country and included the United States as a low-risk country in our sensitivity analysis.3
In our sensitivity analysis, we found that the proportion of US adults recommended for statins under ESC/EAS guidelines would have been 36.1% if the United States was classified as a low-risk country compared with 39.1% if the United States was considered high risk and 43.8% under the American College of Cardiology/American Heart Association (ACC/AHA) guidelines. As a high-risk country, 3.5 million US adults would meet European Systematic Coronary Risk Evaluation (SCORE) risk criteria for statins compared with 0.6 million if the United States was considered a low-risk country. Because we were interested in the overall proportion of adults affected, our conclusion that the proportional differences were small between the guidelines was unchanged. However, as stated in our conclusion, “This estimate demonstrates the potential for significant differences in recommendations using the high- or low-risk SCORE equations.”1 Thus, we agree with the assessment by Falk and Mortensen that the relative numbers of adults who are recommended for therapy based on risk alone can vary substantially depending on how the risk model is calibrated. This further demonstrates that efforts to calibrate the SCORE risk to country-specific statistics can affect the numbers of adults recommended for statins based on risk alone.
Regarding other factors that affected the comparison of recommendations in our analysis, the authors correctly note that we restricted our analysis to adults aged 40 to 65 years, as specified in the Methods section, as this is the range of age covered by the SCORE risk charts in the ESC/EAS guidelines. How to treat adults at either end of the age spectrum (younger than 40 years or older than 65 years) is not directly addressed in either guideline in large part due to a lack of evidence in these groups.
While both guidelines offer optional recommendations, we chose to evaluate the “major recommendations for statin therapy for ASCVD [atherosclerotic cardiovascular disease] prevention” as highlighted in Figure 2 of the 2013 ACC/AHA guideline4 and the “intervention strategies as a function of total CV [cardiovascular] risk and LDL-C [low-density lipoprotein cholesterol] level” in Table 3 from the ESC/EAS guidelines.2 In the ESC/EAS guidelines, the level of evidence varies between class I and IIa, even within treatment groups. Thus, we chose to focus on those groups where “immediate drug intervention” was recommended and not on level of recommendation. We felt that this approach more likely paralleled the way that clinicians would interpret the guidelines.
Nevertheless, the overall conclusion from our article remains the same. The overall numbers of adults aged 40 to 65 years recommended for statin therapy under the ESC/EAS and the ACC/AHA guidelines are similar when applied to countries that are considered high risk, with differences in guidelines affected by the risk equations used and indications for statin therapy.
Corresponding Author: Ann Marie Navar, MD, PhD, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27705 (email@example.com).
Published Online: January 11, 2017. doi:10.1001/jamacardio.2016.5081
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Navar receives research support from Sanofi and Regeneron and fees for consulting with Sanofi. No other disclosures were reported.
Lee JC, Zdrojewski T, Navar AM. Statin Eligibility Under American and European Cholesterol Guidelines—Reply. JAMA Cardiol. Published online January 11, 2017. doi:10.1001/jamacardio.2016.5081