Appeal type: Experimental
Decision: Overturned

Summary Reviewer 2 
A 48-year-old male enrollee has requested reimbursement for laboratory testing on 12/2/22. The Health 
Insurer has denied this request and reported that services at issue were investigational for the 
evaluation of the enrollees premature coronary artery disease and hyperlipidemia. The physician 
reviewer found that in this clinical setting, lipoprotein(a) testing was likely to have been more beneficial 
for the assessment and management of dyslipidemia compared to standard lipid panel testing alone. 
Despite the proven clinical utility of standard lipid testing for risk management, there remains a 
significant risk of atherosclerotic cardiovascular disease (ASCVD) events. In a meta-analysis of statin 
trials examining major cardiovascular disease (CVD) events during five years of follow-up, Nacimento 
Harada and colleagues report that this residual risk is noted to be as high as 21.7% in secondary 
prevention patients and 9.5% in primary prevention patients. Advanced lipoprotein assays have been 
proposed for improving the assessment of cardiovascular risk and guiding lipid-modifying therapy. 
Wilson and colleagues explain that lipoprotein(a) is a form of low-density lipoprotein (LDL) associated 
with apolipoprotein(a), a unique protein attached to the apolipoprotein B segment of LDL. The authors 
further noted, Numerous studies provide strong evidence of a causal link between elevated 
lipoprotein(a) and myocardial infarction, ischemic stroke, valvular aortic stenosis (VAS), coronary artery 
stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause 
mortality. The relationships are independent of LDL cholesterol (LDL-C) or other lipid concentrations. 
The American Heart Association (AHA) and American College of Cardiology (ACC) guidelines on the 
management of blood cholesterol state that measuring lipoprotein(a) is reasonable in patients with a 
family history of premature ASCVD or personal history of ASCVD not explained by major risk factors, as it 
can provide more detailed risk assessment. The ACC/AHA guidelines on the primary prevention of 
cardiovascular disease note that lipoprotein(a) increases ASCVD risk, especially at higher levels. Thus, in 
patients with a lipoprotein(a) equal to or greater than 50 mg/dL or 125 nmol/L, lipoprotein(a) may be 
considered a risk-enhancing factor. The importance of clinical risk enhancers lies in their potential 
influence on the threshold for pharmacologic therapy initiation or intensification. Mach and colleagues  note that while there are currently no targeted treatments to lower lipoprotein(a) that have 
demonstrated impact on CVD outcomes or disease progression, there are phase II trials that have shown 
that treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy may lead to 
a lipoprotein(a) reduction of about 30% to 40%. Therefore, patients on statin therapy who have elevated 
lipoprotein(a) are the most likely to receive benefit from more aggressive LDL-C lowering therapy, 
including ezetimibe or PCSK9 inhibitors. In these select groups, lipoprotein(a) levels may be useful in 
reclassifying ASCVD risk and in aiding in decisions regarding pharmacotherapy. Overall, there is sufficient 
support in peer-reviewed literature for the use of advanced lipoprotein testing with lipoprotein(a) in 
certain patients in whom the results may refine risk assessment. The additional insights provided by the 
measurement of lipoprotein(a) have the potential to further clarify estimations of ASCVD risk and alter 
medical management in this select group of patients. As such, the service at issue was likely to have 
been more beneficial for the enhanced risk stratification and aid in therapeutic decision-making than 
standard lipid panel testing alone in this patient with SLE, hyperlipidemia, and severe premature 
coronary artery disease status post coronary artery bypass grafting, on high-intensity statin therapy. 
Therefore, laboratory testing on 12/2/22 was likely to have been more beneficial for the evaluation of 
the patients condition than any available standard therapy.