Abstract Background It is unclear to what extent the 2019 European Society of Cardiology (ESC), 2018 American College of Cardiology/ American Heart Association (ACC/AHA), 2016 US Preventive Services Task Force (USPSTF), and 2016 Canadian Cardiovascular Society (CCS) guidelines differ in assigning levels of evidence and classes of recommendations (LOE/class) to lipid-lowering treatment recommendations in primary prevention of cardiovascular disease (CVD). Purpose To compare LOE/class from four commonly used guidelines at population level. Methods A total of 7262 participants, aged 45–75 years of age and without history of CVD, from the prospective population-based Rotterdam Study were included. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity, and numbers needed to treat at 10 years (NNT10y) were calculated. Results Mean age was 61.1 (SD 6.9) years, and 58.2% were women. ESC, ACC/AHA, USPSTF and CCS strongly recommended statin use for a respective 33.8%, 48.1%, and 40.2% and 73.0% of the eligible population based on high-quality evidence, while in an additional 55.3%, 7.1%, 8.4% and 9.2% of participants statins use could or should be considered based on varying LOE/class. The sensitivity for treatment recommendations supported with strong, high quality evidence was 61.6% for ESC (“IA”), 74.6% for ACC/AHA (“IA or IB”), 69.4% for USPSTF (“USPSTF-B”) and 92.5% for CCS (“strong”). Specificity was highest for the ACC/AHA at 46.8% and lowest for ESC at 11.4%. Estimated NNT10y for those with the strongest LOE/class were comparable across all guidelines, ranging from 18 to 26 for moderate-intensity statin use, and 11 to 16 for high-intensity statin use. NNT10y reflective of recommendations supported with moderate strength of LOE/class varied substantially among guidelines for both moderate-intensity and high-intensity statin use, ranging from 33 for ESC and USPSTF to 91 for CCS. Conclusions Assigned LOE/class varied greatly among four clinical practice guidelines for primary prevention of CVD. Efforts for harmonized and comparable evidence grading system for clinical practice guidelines in primary prevention of CVD may reduce ambiguity, and reinforce updated evidence-based recommendations for appropriate treatment of populations for whom clear evidence for benefit of statin use is available. Funding Acknowledgement Type of funding source: None
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