ROME (FRONTLINE MEDICAL NEWS) – An estimated 14% of Americans with atherosclerotic cardiovascular disease can’t reach the LDL cholesterol goal of less than 70 mg/dL on maximal intensified oral lipid-lowering therapy and thus are candidates for a PCSK9 inhibitor such as alirocumab, Christopher P. Cannon, MD, reported at the annual congress of the European Society of Cardiology.

After adding alirocumab (Praluent) at 75 mg by subcutaneous injection every 2 weeks, that figure drops to 2%. And by increasing the alirocumab dose to 150 mg in that 2%, the result is that fewer than 1% of patients with atherosclerotic cardiovascular disease (ASCVD) will have an LDL cholesterol level of 70 mg/dL or more, assuming no tolerability issues along the way, added Dr. Cannon , professor of medicine at Harvard Medical School, Boston.

He presented a Monte Carlo simulation model based upon the real-world lipid-lowering treatment experiences of 105,289 individuals with ASCVD drawn from the MarketScan Research Database, a large database of U.S. patients enrolled in employer-based health plans. A Monte Carlo simulation model is a computerized mathematical technique that extrapolates from real-world outcomes in a population to create a realistic range of possible outcomes in a much larger hypothetical population, in this case 1 million imaginary but representative Americans with ASCVD.

This Monte Carlo simulation relies on lipid-lowering treatment outcome rates from published landmark clinical trials such as IMPROVE-IT ( N Engl J Med. 2015 Jun 18;372[25]:2387-97 ), for which Dr. Cannon was a lead investigator, as well as data from the ongoing ODYSSEY program of alirocumab studies. Importantly, the model doesn’t factor in drug intolerance.

In this model, the average age of the hypothetical 1 million ASCVD patients was 66.5 years and 54.6% were men. The distribution of ASCVD diagnoses was representative of the real-world experience: 70% had coronary heart disease, 25% had ischemic cerebrovascular disease, 35% had peripheral artery disease, and 5% had experienced an acute coronary syndrome within the past 12 months.

Current guidelines would strongly recommend that all of these patients be on lipid-lowering therapy, yet only 53% were at baseline. Guideline-recommended lipid-lowering strategies would suggest that those patients not on a lipid-lowering drug be placed on atorvastatin at 20 mg/day; by that step, 50% of the 1 million ASCVD patients would be at the goal of an LDL cholesterol level below 70 mg/dL.

For the other 50%, a reasonable next step would be a high-intensity statin: say, atorvastatin at 80 mg/day instead of 20. That would leave only 21% of the original ASCVD population with an LDL cholesterol level of 70 mg/dL or higher. The next step for those patients, as established in IMPROVE-IT, would be to add ezetimibe (Zetia). That constitutes maximal oral lipid-lowering therapy, and 14% of the original ASCVD population would still have an LDL cholesterol level of 70 mg/dL or more on that multidrug regimen.

On the basis of the results of the ODYSSEY trials, adding alirocumab at 75 mg would drop that figure from 14% down to 2%. And by switching to alirocumab at 150 mg every 2 weeks in those outliers, less than 1% of the 1 million patients with ASCVD would still have an LDL cholesterol level of 70 mg/dL or more. The mean LDL cholesterol level would be 52.0 mg/dL in patients on full treatment intensification with a high-dose statin, ezetimibe, and alirocumab.

If future studies were to establish that the new LDL cholesterol level goal for patients with known ASCVD was less than 55 mg/dL, the simulation indicates that just under 59% of patients on full-on treatment intensification including alirocumab would achieve it, according to Dr. Cannon.

He reported receiving research grants from and/or serving as a consultant to well over a dozen pharmaceutical companies, including Sanofi and Regeneron, which sponsored this analysis.