Individualized Statin Benefit for Determining Statin Eligibility in the Primary Prevention of Cardiovascular Disease

Abstract

Association (ACC/AHA) cholesterol guidelines determined that except for those with diabetes mellitus or low-density lipoprotein (LDL) cholesterol (LDL-C) >190 mg/dL, individuals should be selected for statin therapy for primary prevention of cardiovascular disease on the basis of predicted 10-year cardiovascular risk.1 Such a risk-based approach leads to greater statin eligibility among older individuals with lower levels of LDL-C while limiting eligibility in younger individuals with higher LDL-C because predicted risk is driven primarily by age.2 Defining statin eligibility with the use of a predicted risk threshold also implicitly assumes that the benefit of statins is constant in all eligible individuals, regardless of the factors that contribute to their increased risk such as higher age as opposed to higher LDL-C.Alternative approaches in determining statin eligibility have also been proposed recently, including the use of novel markers for better risk classification 3,4 and the use of entry criteria for randomized, controlled trials (RCTs) to define statin benefit groups. 5,6 Moreover, Pandya et al 7 have shown that statin preventive therapy remains cost-effective even at lower risk thresholds than selected by the ACC/AHA guidelines. Although each of these approaches has advantages and disadvantages, none directly considers the clinical benefits from statin therapy for each individual on the basis of the available clinical trial data. We compared statin eligibilities using 2 separate approaches: a 10-year risk-based approach (≥7.5% 10-year risk) and an individualized benefit approach (ie, based on predicted absolute risk reduction over 10 years [ARR 10 ] ≥2.3% from randomized, controlled trial data). A risk-based approach led to the eligibility of 15.0 million (95% confidence interval, 12.7-17.3 million) Americans, whereas a benefit-based approach identified 24.6 million (95% confidence interval, 21.0-28.1 million). The corresponding numbers needed to treat over 10 years were 21 (range, 9-44) and 25 (range, 9-44). The benefit-based approach identified 9.5 million lower-risk (<7.5% 10-year risk) Americans not currently eligible for statin treatment who had the same or greater expected benefit from statins (≥2.3% ARR 10 ) compared with higher-risk individuals. This lower-risk/acceptable-benefit group includes younger individuals (mean age, 55.2 versus 62.5 years; P<0.001 for benefit based versus risk based) with higher low-density lipoprotein cholesterol (140 versus133 mg/dL; P=0.01). Statin treatment in this group would be expected to prevent an additional 266 508 cardiovascular events over 10 years. Conclusions-An individualized statin benefit approach can identify lower-risk individuals who have equal or greater expected benefit from statins in primary prevention compared with higher-risk individuals. This approach may help develop guideline recommendations that better identify individuals who meaningfully benefit from statin therapy.

Population Impact & Efficiency of Benefit‐Targeted Versus Risk‐Targeted Statin Prescribing for Primary Prevention of Cardiovascular Disease

“…Our results are consistent with previous analyses by Thanassoulis et al,3 who proposed the benefit‐targeting approach, developed an expected ARR estimation algorithm3 using the interaction with baseline risk identified by the CTT,1 and estimated population‐level impact of using benefit‐targeted moderate‐intensity statins with an expected ARR treatment threshold of 2.3% by analyzing NHANES. Our analysis of NHANES, using identical assumptions and a similar approach, augmented by multiple imputation for enhanced generalizability to the US population, produced consistent estimates.…”

“…ARR indicates absolute risk reduction; ASCVD, atherosclerotic cardiovascular disease; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; Max, maximum; Min, minimum; NHANES, National Health and Nutrition Examination Survey; Statin, HMG Co‐A reductase inhibitor.aNHANES participants younger than 40 years, older than 75 years, with LDL ≥190 mg/dL, with diabetes mellitus, with previous cardiovascular disease, or already on a statin are excluded from this analysis.bBaseline risk is defined as 10‐year risk of ASCVD, estimated according to the 2013 Guideline2; expected ARR is the expected absolute risk reduction from moderate‐intensity statin therapy, as formulated by Thanassoulis et al3 see Methods.cUS population estimates are calculated from the Ns in NHANES. Ns for columns 1 to 4 in the 10‐fold imputed data set were 4725, 879, 30, and 2297, respectively; these Ns were divided by 10 to correct for the 10‐fold imputation and then multiplied by the sample weights provided by NHANES.…”

“…Prevention impact‐efficiency curves are provided to illustrated the trade‐offs, labeling thresholds of 7.5% for baseline risk (the 2013 Guideline2), 2.3% for expected ARR (for comparison with previous analyses3), and equivalent‐impact thresholds.…”

Effectiveness of Statins as Primary Prevention in People With Different Cardiovascular Risk: A Population‐Based Cohort Study

“…Although our 5‐year NNT estimate in this risk category was about 20% higher compared to the 10–19.9% category (75 vs. 62), most individuals with an estimated CHD risk 7.5–9.9% could benefit from statin treatment, in line with US guidelines 1, 2. Additional research is needed to define strategies that improve the predictive ability of risk functions by considering new risk factors13 and/or by individualized consideration of LDL cholesterol levels or response to treatment 14, 15…”

Moving Toward the Next Paradigm for Cardiovascular Prevention

“…In this issue of Circulation, Thanassoulis et al 6 have now synthesized the information from these 2 articles, along with the net benefit, a concept first introduced in the 2013 ACC/ AHA cholesterol guideline, to take the next step in refining the estimation of net benefit for an individual patient. The individualized net benefit approach of Thanassoulis et al used an absolute risk reduction (ARR) benefit threshold of ≥2.3% (for a 10-year NNT ≤44), the minimum expected ASCVD risk reduction benefit from the 2013 ACC/AHA cholesterol guideline.…”