Intensifying Lipid-Lowering Therapy May Curb Need for PCSK9 Inhibitors

By Marilynn Larkin

NEW YORK (Reuters Health) – Most patients with atherosclerotic cardiovascular disease (ASCVD) can achieve low-density lipoprotein (LDL) concentrations <70 mg/dL with oral lipid-lowering therapy, with only a modest percentage requiring a proprotein convertase subilisin/kexin type 9 (PCSK9) inhibitor, researchers say.

The 2013 American College of Cardiology and American Heart Association guidelines on lipid-lowering therapy recommend optimizing statin treatment in ASCVD patients, and then using ezetimibe and PCSK9 inhibitors in patients with persistently elevated LDL levels despite statin use.

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Dr. Christopher Cannon of the Baim Institute for Clinical Research, in Boston, and colleagues sought to determine the percentage of ASCVD patients who would need a PCSK9 inhibitor when lipid-lowering therapy is intensified first.

To do so, they created a simulation model based on a cohort of 105,269 ASCVD patients with data available from 2012 to 2013.

The study did not enroll human participants. All findings are based on the simulation cohort, of 1 million people, whose characteristics were similar to those of the database cohort.

For example, in the database cohort, the mean age was 65, including 23% who were 75 or older; 46% were on Medicare; 30% had peripheral artery disease (PAD); 25% had ischemic cerebrovascular disease; and 68% had another coronary heart disease (CHD) diagnosis. In the simulation cohort, the mean age was 66, including 27% who were 75 or older; 53% were on Medicare; 31% had PAD; 27% had ischemic cerebrovascular disease; and 66% had another CHD diagnosis.

Overall, due to various analytic strategies, “the simulation model is representative of the overall U.S. population with ASCVD,” the authors state.

All patients not initially receiving a statin were given 20-mg atorvastatin, followed by lipid-lowering intensification as needed to achieve LDL <70 mg/dL: up-titration to 80-mg atorvastatin; add-on ezetimibe therapy; add-on 75-mg alirocumab (a PCSK9 inhibitor); and up-titration to 150-mg alirocumab.

Before treatment intensification, 51.5% of the cohort used statin monotherapy and 1.7% used statins plus ezetimibe. In that scenario, only 25.2% achieved LDL cholesterol concentrations <70 mg/dL, according to the report in JAMA Cardiology, online August 2.

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After as-needed treatment intensification, 99.3% could attain LDL concentrations <70 mg/dL: 67.3% with statin monotherapy, 18.7% with statins plus ezetimibe, and 14% with an add-on PCSK9 inhibitor. The findings assume full adherence and no tolerability issues, according to the authors.

“With important new medical therapies, especially if they are expensive, we want to make sure the most appropriate patients get them,” Dr. Cannon told Reuters Health by email. Although PCSK9 inhibitors “are very strong in lowering LDL, (given) the expense, we want to use them only when other less expensive treatments have not been enough.”

“Our model should help allay fears that this new class (of drugs) will bankrupt the health system,” he stressed. “If we use them appropriately, the costs will be more moderate.”

“Our study is also a call to action,” he added. “We need to do a better job using the therapies we have. Many patients can benefit from more-intensive lowering of cholesterol with the low-cost medications we have now. Then, for the remaining who need (further) treatment, the newer agents can help.”

Editorialist Dr. Sidney Smith of the University of North Carolina, Chapel Hill told Reuters Health, “Unfortunately, many patients who might benefit from intensive statin therapies do not receive these medications, and the non-statin drugs are expensive. Although it is clear that a certain number of patients will benefit, there will be significant additive cost.”

“Major efforts are needed to be sure that patients who are candidates receive intensive statin therapy,” he said by email.

“New guidelines are now being developed to determine which patients are candidates for the addition of non-statin therapies,” he added. “Implementation of these recommendations by physicians will be critical if we are to achieve the cost-effective benefits of non-statin therapy for patients with ASCVD.”

Dr. Gregg Fonarow, co-chief of the University of California, Los Angeles Division of Cardiology, told Reuters Health by email, “This study provides further data highlighting that PCSK9 inhibitors may be needed in only one in seven patients with ASCVD, assuming high-intensity statin and ezetimibe therapy is well tolerated.”

“While this study utilized an LDL cholesterol goal level of less than 70 mg/dL, there is emerging data that greater cardiovascular event reductions may be attained by aiming for greater percent LDL cholesterol reduction and lower goal levels (e.g. <50 mg/dL) in high-risk patients,” he observed.

“These findings were based on a simulation of LDL cholesterol goal attainment in a representative population of patients,” Dr. Fonarow said. “Demonstrating that a similar proportion of patients can achieve and maintain LDL cholesterol goals with this approach would augment the evidence-base.”

Sanofi and Regeneron Pharmaceuticals, which make PCSK9 inhibitors, funded the study.

SOURCES: https://bit.ly/2vPeUAE and https://bit.ly/2uqqfDW

JAMA Cardiol 2017.

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