New cholesterol management guidelines efficient, cost-effective

The 2013 American College of Cardiology and American Heart Association guidelines for cholesterol management improve identification of increased risk for CVD and CAD over prior guidelines, according to data recently published in JAMA.

In a separate study, researchers found that the 10-year ASCVD risk threshold of 7.5% or higher established in the new guidelines is cost-effective, and that an even lower threshold of would reduce the incidence of CVD events while maintaining cost-effectiveness.

ACC/AHA guidelines accurately, efficiently identify CVD, CAD risk

Amit Pursnani, MD, from the cardiac MR PET CT program of the department of radiology at Massachusetts General Hospital, Harvard Medical School, and colleagues compared the ACC/AHA guidelines with the National Cholesterol Education Program’s 2004 Updated Third Report of the Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines. The researchers determined statin eligibility in 2,435 participants aged 40 to 70 years (mean age, 51.3 years; 56% women) who underwent multidetector CT for coronary artery calcification (CAC) between 2002 and 2005. The population included asymptomatic offspring and third-generation cohorts from the Framingham Heart Study.

Patients were followed up annually by telephone for a median of 9.4 years. The primary endpoint was incident CVD, with incident CHD and CAC as secondary endpoints.

Under the ATP III guidelines, participants were considered eligible for statin therapy if they had:

LDL 100 mg/dL and diabetes, peripheral arterial disease or a 10-year Framingham Risk Score (FRS) for CHD 20%;
LDL 130 mg/dL and FRS > 10% and < 20%, in addition to two or more risk factors;
LDL 160 mg/dL and FRS < 10%, as well as two or more risk factors; or
LDL 190 mg/dL and fewer than two risk factors.

Under the ACC/AHA guidelines, based on the Pooled Cohort Equation, participants were eligible for statin therapy if they had:

clinical atherosclerotic CVD (ASCVD);
LDL 190 mg/dL; or
diabetes diagnosed between age 40 and 75 years and LDL of 70 mg/dL to 189 mg/dL; or
no ASCVD or diabetes, with an LDL of 70 mg/dL to 189 mg/dL and an estimated ASCVD risk 7.5%.

Seventy-four CVD events were reported during the observation period, including 40 nonfatal MI events, 31 nonfatal ischemic strokes and three CHD-related mortalities.

According to the results, 39% (n = 941) of participants were eligible for statin therapy under the ACC/AHA guidelines vs. 14% (n = 348) according to the ATP III guidelines (P < .001).

Participants eligible for statin therapy under the ACC/AHA guidelines had a 6.3% incidence rate of CVD vs. 1% among noneligible participants, whereas eligible participants under the ATP III guidelines had a 6.9% incidence rate of CVD vs. 2.4% among noneligible participants (P < .001 for both). The increased likelihood of CVD events in statin-eligible participants under ACC/AHA indicated that the ACC/AHA cholesterol guidelines were more accurate in identifying at-risk patients compared with ATP III guidelines (HR = 6.8; 95% CI, 3.8-11.9 vs. HR = 3.1; 95% CI, 1.9-5). The results were similar for incidence of CHD (HR = 8.6; 95% CI, 3.8-19.3 for ACC/AHA vs. HR = 3.3; 95% CI, 1.8-6.2 for ATP III) and among participants at intermediate CVD risk (HR = 9.3; 95% CI, 1.3-67.8 vs. HR = 0.9; 95% CI, 0.4-1.9).

In addition, ACC/AHA guidelines resulted in higher rates of statin eligibility among participants with CAC scores greater than zero (63% vs. 23%), greater than 100 (80% vs. 32%) and greater than 300 (85% vs. 34%) (P < .001 for all).

Nearly 600 participants were identified as newly eligible for statin therapy under the ACC/AHA guidelines. These patients a CVD incidence rate of 5.7%, which generated a number needed to treat of 39 to 58 to prevent one event over the course of follow-up.

“These findings offer assurance that the 2013 Pooled Cohort Equation can efficiently and appropriately identify those destined to develop a major ASCVD event in the near future,” Philip Greenland, MD, from the departments of medicine and preventive medicine at Northwestern University Feinberg School of Medicine, and Michael S. Lauer, MD, senior editor for JAMA from the division of cardiovascular sciences at NHLBI, wrote in an accompanying editorial. “However, identifying those at risk with reasonable accuracy is only part of the decision-making process. An important consideration involves where to set the threshold for treatment.”

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ASCVD risk threshold set by ACC/AHA cost-effective, potentially “too conservative”

In a separate study, Ankur Pandya, PhD, from the department of health policy and management at Harvard School of Public Health, and colleagues conducted a cost-effectiveness analysis to determine the optimal 10-year ASCVD risk threshold. The researchers used a microsimulation model to estimate ASCVD outcomes and costs per quality-adjusted life-year (QALY) among 1 million hypothetical patients aged 40 to 75 years. The model incorporated data from National Health and Nutrition Examination Surveys, clinical trials and other sources, and was calibrated to 16 age- and sex-specific CHD and stroke targets in cohorts from the Framingham Offspring Study (1980 to 2003) and the Atherosclerosis Risk in Communities study (1987-2001).

Using the ACC/AHA recommended threshold of 7.5%, the model projected that 48% of participants were treated with statins. The incremental cost-effectiveness ratio was $37,000 per QALY, which is below the commonly used cost-effectiveness threshold of $50,000 to $150,000 per QALY, compared with a threshold of at least 10%. However, the researchers wrote, more lenient thresholds of at least 4% and 3% were optimal because they increased the number of participants treated to 61% and 67%, with incremental cost-effectiveness ratios of $81,000 per QALY and $140,000 per QALY, respectively. Lowering the threshold further to at least 3% prevented approximately 161,560 CVD events, the researchers noted.

In a sensitivity analysis, cost-effectiveness was influenced by disutility associated with the need to take a pill every day, price and the risk for diabetes induced by statin therapy. Using a cost-effectiveness threshold of $100,000 per QALY, a probabilistic analysis indicated a 99% chance that the optimal ASCVD threshold was 7.5% or lower and a 93% chance that the optimal threshold was 5% or lower.

Greenland and Lauer wrote that the recommended 7.5% threshold is “justifiable” and cost-effective, and potentially even too conservative.

“Even if risk estimation overestimates risk, widespread use of the Pooled Cohort Equation should be expected to avert a large number of adverse CV events and do so in a manner that is cost-effective without concerns for inappropriate overtreatment,” they wrote. “The next phase of research should be directed at better ways of applying lifestyle and drug treatments to the millions, and possibly billions, worldwide who could potentially benefit from a cost-effective approach to primary prevention of ASCVD.” – by Stephanie Viguers

References :

Greenland P, Lauer MS. JAMA. 2015;doi:10.1001/jama.2015.7434.

Pandya A, et al. JAMA. 2015;doi:10.1001/jama.2015.6822.

Pursnani A, et al. JAMA. 2015;doi:10.1001/jama.2015.7515.

Disclosures: Greenland reports receiving grant funding from the NHLBI. Lauer reports being a full-time employee of the NHLBI. Pandya reports receiving grant funding from the NHLBI and AHA. Pursnani reports no relevant financial disclosures. Please see the full studies for all other authors’ relevant financial disclosures.