Primary prevention of CVD likely superior with guideline-based approach

For primary prevention with statins of atherosclerotic CVD, an approach based on the latest American College of Cardiology/American Heart Association guidelines outperformed two other approaches, according to new findings.

To compare the approaches, researchers included 37,892 adults aged 40 to 75 years (16,398 men; 100% white) recruited into the Copenhagen General Population Study from 2003 to 2008 who were free of atherosclerotic CVD and diabetes and were not assigned statins at baseline.

The approaches defined eligibility for statin therapy using these criteria:

• risk-based approach from ACC/AHA guidelines: aged 40 to 75 years with 10-year risk for atherosclerotic CVD of at least 7.5% or LDL at least 190 mg/dL;
• trial-based approach: men aged 45 to 64 years with total cholesterol at least 252 mg/dL and LDL at least 155 mg/dL; men aged 45 to 73 years and women aged 55 to 73 years with total cholesterol 180 mg/dL to 264 mg/dL, LDL 130 mg/dL to 190 mg/dL, and HDL up to 45 mg/dL in men and up to 47 mg/dL in women; men and women aged 40 to 79 years with untreated systolic BP at least 160 mm Hg or untreated diastolic BP at least 100 mm Hg or treated systolic BP at least 140 mm Hg or treated diastolic BP at least 90 mm Hg and total cholesterol up to 251 mg/dL and at least three risk factors aside from hypertension; men and women aged 40 to 70 years with total cholesterol 220 mg/dL to 270 mg/dL; or men aged at least 50 years and women aged at least 60 years with LDL less than 130 mg/dL and high-sensitivity C-reactive protein at least 2 mg/L; and
• hybrid approach: aged 45 to 79 years with 10-year risk for atherosclerotic CVD of at least 7.5% plus LDL at least 160 mg/dL or LDL 130 mg/dL to 160 mg/dL and HDL up to 45 mg/dL or LDL less than 130 mg/dL and high-sensitivity CRP at least 2 mg/L.

The researchers calculated the number and percentage of participants eligible for statin therapy based on each of the three approaches and calculated the observed event rate per 1,000 patient-years in participants eligible for statin therapy according to each approach.

Predicted vs. observed

Martin B. Mortensen, MD, PhD, from the atherosclerosis research unit, department of cardiology, Aarhus University Hospital, Denmark, and colleagues determined that 42% of participants were eligible for statin therapy using the risk-based approach, 56% were eligible using the trial-based approach and 21% were eligible using the hybrid approach.

The event rate of atherosclerotic CVD was 9.8 per 1,000 person-years (95% CI, 9.1-10.6) in statin-eligible participants using the risk-based approach, 6.8 per 1,000 person-years (95% CI, 6.3-7.4) in statin-eligible participants using the trial-based approach and 11.2 per 1,000 person-years (95% CI, 10.1-12.5) in statin-eligible participants using the hybrid approach, according to the researchers.

Predicted 10-year risk for atherosclerotic CVD was 15.5% (95% CI, 10.8-22.8) in men and 12% (95% CI, 8.8-17.5) in women using the risk-based approach, 11.5% (95% CI, 6-19.1) in men and 4.5% (95% CI, 2-9.1) in women using the trial-based approach and 16.9% (95% CI, 11.9-24.4) in men and 13.3% (95% CI, 9.8-18.7) in women using the hybrid approach, they found.

For the risk-based approach, predicted/observed ratios for atherosclerotic CVD were 0.8 for those with less than 5% predicted 10-year risk, 1.1 for those with 5% to less than 7.5% predicted 10-year risk, 1.2 for those with 7.5% to less than 10% predicted 10-year risk and 1.4 for those with at least 10% predicted 10-year risk, Mortensen and colleagues wrote.

Compared with the risk-based approach, the net reclassification index for statin eligibility was –0.21 for the trial-based approach and –0.13 for the hybrid approach, they found.

Discrimination was higher for the risk-based approach (area under the receiver-operating characteristic [ROC] curve, 0.676) than for the trial-based approach (ROC curve, 0.572) or the hybrid approach (ROC curve, 0.613).

“Our results indicate that the ACC/AHA guidelines will prevent more [atherosclerotic CVD] events than the trial-based and hybrid approaches; compared with the trial-based approach, it will prevent more [atherosclerotic CVD] events by treating fewer people,” Mortensen and colleagues wrote.

Best tool for now

In a related editorial, Vera Bittner, MD, MSPH, from the University of Alabama-Birmingham and a Cardiology Today Editorial Board member, wrote: “Quantification of risk is just a first step. For now, the 2013 ACC/AHA risk calculator is our best tool to accomplish this goal and, in the absence of contraindications or patient wishes, we should treat those who fall into the primary prevention statin benefit groups. However … we have no data confirming that subjects who fall outside the age and lipid thresholds that define the statin benefit groups would not benefit from treatment.” – by Erik Swain

Disclosure: The researchers report no relevant financial disclosures. Bittner reports receiving research support from Amgen, AstraZeneca, Bayer, Janssen Pharmaceuticals, Pfizer and Sanofi, and serving on advisory panels for Amgen and Eli Lilly.