Meeting NewsPerspective

PCSK9 inhibitors recommended by NLA for certain patient groups

PHILADELPHIA — A National Lipid Association expert panel prepared updated recommendations for the use of PCSK9 antibody therapy at the NLA Scientific Sessions.

The recommendations are an update to the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2.

“We don’t want to ignore that we now have better data and more complete data with regards to PCSK9 inhibitors,” Joyce Ross, MSN, CRNP, CLS, FNLA, past president of the NLA, a retired nurse practitioner in the University of Pennsylvania Health System and an author of the recommendations, told Cardiology Today. “Prior to this, we were recommending them, but we had no proof of anything. We felt strongly that we had to address this, because as specialists in lipidology, people are looking for us to make a statement.”

Joyce Ross

The panel used mechanistic and clinical studies as evidence to update the recommendations for patients with atherosclerotic CVD, Carl E. Orringer, MD, FNLA, associate professor of medicine at University of Miami Miller School of Medicine, said during the presentation.

Carl E. Orringer, MD, FNLA
Carl E. Orringer

One, GLAGOV, studied the effects of evolocumab (Repatha, Amgen) compared with placebo on 968 patients with angiographic coronary disease. At follow-up, evolocumab reduced LDL from 93 mg/dL to 37 mg/dL, lowered percent atheroma volume and total atheroma volume, and was linked to greater plaque regression.

FOURIER was another study that was used, where patients were established CVD and additional risk factors were assigned evolocumab or placebo. Evolocumab was shown to reduce risk for CV death, stroke and MI.

Atherosclerotic CVD recommendations

According to the recommendations, “PCSK9 inhibitor therapy should be considered for atherosclerotic CVD risk reduction in patients with stable [atherosclerotic CVD], particularly in those with additional [atherosclerotic CVD] risk factors, on maximal-tolerated statin therapy [with or without] ezetimibe, with on-treatment LDL ≥ 70 mg/dL or non-HDL ≥ 100 mg/dL. Strength: A. Quality: High.”

The recommendations also state “PCSK9 inhibitor therapy may be considered to further reduce LDL in patients with progressive [atherosclerotic CVD] on maximal-tolerated statin therapy plus ezetimibe, and on-treatment LDL > 70 mg/dL or non-HDL > 100 mg/dL.”

“The strength of evidence there was B and quality is moderate, predominately because GLAGOV and FOURIER did not specifically look at patients with progressive [atherosclerotic] CVD,” Orringer said in the presentation.

Joseph J. Saseen, PharmD, BCPS, BCACP, CLS, FNLA, professor and vice chair of the department of clinical pharmacy and professor in the department of family medicine at University of Colorado, Denver, and an author of the recommendations, told Cardiology Today that the recommendations for patients with atherosclerotic CVD may be the most important part of the document.

Joseph J. Saseen

“For patients with atherosclerotic CVD on maximally tolerated statin therapy with or without ezetimibe, these recommendations alert clinicians that they should consider PCSK9 inhibitors,” he said. “This is where we have the highest level of evidence.”

Patients with FH

Newer studies focusing on patients with familial hypercholesterolemia (FH) phenotype determined that 7% of the U.S. population has a LDL of 190 mg/dL or greater, Orringer said. A pooled cohort study and a Swiss cohort study were also considered, in which researchers found patients with FH have a higher risk for atherosclerotic CVD events, especially in those with documented FH-causing mutations.

Reducing LDL with PCSK9 inhibitors is recommended in “patients aged 40 years to 79 years with phenotypic FH, pre-treatment LDL ≥ 190 mg/dL before treatment, no uncontrolled [atherosclerotic CVD] risk factors or other key additional risk markers, and on-treatment LDL ≥ 100 mg/dL or non-HDL ≥ 130 mg/dL on maximal-tolerated statin therapy [with or without] ezetimibe.”

PCSK9 inhibitor therapy is also recommended for a similar patient population with “the presence of either uncontrolled [atherosclerotic CVD] risk factors, or other key additional high-risk markers, or genetic confirmation of FH and on-treatment LDL ≥ 70 mg/dL or non-HDL ≥100 mg/dL on maximal-tolerated statin therapy [with or without] ezetimibe.”

Younger patient population

The paper addresses younger patients and states “PCSK9 inhibitor therapy may be considered to further reduce LDL in patients aged 18 to 39 years with phenotypic FH, pre-treatment LDL ≥ 190 mg/dL and the presence of either uncontrolled [atherosclerotic CVD] risk factors, key additional high-risk markers or genetic confirmation of FH, and on-treatment LDL ≥ 100 mg/dL or non-HDL ≥ 130 mg/dL on maximal-tolerated statin [with or without] ezetimibe.”

“It’s a little bit tougher to make recommendations on those who meet the criteria with FH phenotype when they’re ages 18 to 39 because the evidence base is very, very shaky in those patients, so we tried to use our best judgment, and there were some patients in those previous studies that did represent individuals in this age group,” Orringer said in the presentation.

In one study that informed the recommendations, when evolocumab was added to stable lipid-lowering therapy in patients with FH aged 13 to 57 years, LDL was lowered by a mean of 30.9% (P < .0001) with no serious adverse events or anti-evolocumab antibodies.

Patients with homozygous FH may be considered for PSCK9 inhibitor therapy if they are LDL-receptor defective, the diagnosis is of unknown genotype or if the patient has LDL above 70 or non-HDL above 100 mg/dL despite maximally tolerated statin therapy with or without ezetimibe.

The recommendations also cover a population Orringer said is underserved: very high-risk patients with statin intolerance. “PCSK9 inhibitor therapy may be considered to further reduce LDL in selected very high-risk patients who meet the definition of intolerance (as previously defined by the NLA Statin Expert Panel) and who require substantial atherogenic cholesterol lowering despite the use of other lipid-lowering therapies,” the document stated.

“This definitely requires clinical judgment for you to make that decision whether therapy might be considered in those patients,” Orringer said in the presentation.

Patient-provider discussion

“We’ve advocated the importance of continuing to emphasize lifestyle and evidence-based lipid therapy to your patients,” Orringer said. “No patient who starts on PCSK9 inhibitor therapy should feel that they should stop their drugs because they’re on PCSK9 inhibitor.”

Orringer added that topics like cost, delays in therapy due to prior authorization process, follow-up lipoprotein monitoring and need for subcutaneous injection should be reviewed in a patient-provider discussion.

“We ask that you carefully consider the impact of patient characteristics, concomitant medical conditions and patient preferences,” Orringer said.

Ross said she hopes the recommendations “clear the way for [clinicians] to make better decisions about when to implement [PCSK9 inhibition], particularly in young patients with FH. We need to treat them as aggressively as possible, as early as possible, to prevent disease.”

The recommendations may “set the stage” for a new American College of Cardiology clinical decision pathway, due to be completed in 2018, Saseen said. – by Darlene Dobkowski and Erik Swain

References:

Orringer CE, et al. NLA Updated PCSK9 Inhibitor Recommendations. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.

Orringer CE, et al. J Clin Lipidol. 2017;doi:10.1016/j.jacl.2017.05.001.

Disclosure: Orringer and Ross are former presidents of the National Lipid Association. Saseen reports no relevant financial disclosures.

 

PHILADELPHIA — A National Lipid Association expert panel prepared updated recommendations for the use of PCSK9 antibody therapy at the NLA Scientific Sessions.

The recommendations are an update to the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2.

“We don’t want to ignore that we now have better data and more complete data with regards to PCSK9 inhibitors,” Joyce Ross, MSN, CRNP, CLS, FNLA, past president of the NLA, a retired nurse practitioner in the University of Pennsylvania Health System and an author of the recommendations, told Cardiology Today. “Prior to this, we were recommending them, but we had no proof of anything. We felt strongly that we had to address this, because as specialists in lipidology, people are looking for us to make a statement.”

Joyce Ross

The panel used mechanistic and clinical studies as evidence to update the recommendations for patients with atherosclerotic CVD, Carl E. Orringer, MD, FNLA, associate professor of medicine at University of Miami Miller School of Medicine, said during the presentation.

Carl E. Orringer, MD, FNLA
Carl E. Orringer

One, GLAGOV, studied the effects of evolocumab (Repatha, Amgen) compared with placebo on 968 patients with angiographic coronary disease. At follow-up, evolocumab reduced LDL from 93 mg/dL to 37 mg/dL, lowered percent atheroma volume and total atheroma volume, and was linked to greater plaque regression.

FOURIER was another study that was used, where patients were established CVD and additional risk factors were assigned evolocumab or placebo. Evolocumab was shown to reduce risk for CV death, stroke and MI.

Atherosclerotic CVD recommendations

According to the recommendations, “PCSK9 inhibitor therapy should be considered for atherosclerotic CVD risk reduction in patients with stable [atherosclerotic CVD], particularly in those with additional [atherosclerotic CVD] risk factors, on maximal-tolerated statin therapy [with or without] ezetimibe, with on-treatment LDL ≥ 70 mg/dL or non-HDL ≥ 100 mg/dL. Strength: A. Quality: High.”

PAGE BREAK

The recommendations also state “PCSK9 inhibitor therapy may be considered to further reduce LDL in patients with progressive [atherosclerotic CVD] on maximal-tolerated statin therapy plus ezetimibe, and on-treatment LDL > 70 mg/dL or non-HDL > 100 mg/dL.”

“The strength of evidence there was B and quality is moderate, predominately because GLAGOV and FOURIER did not specifically look at patients with progressive [atherosclerotic] CVD,” Orringer said in the presentation.

Joseph J. Saseen, PharmD, BCPS, BCACP, CLS, FNLA, professor and vice chair of the department of clinical pharmacy and professor in the department of family medicine at University of Colorado, Denver, and an author of the recommendations, told Cardiology Today that the recommendations for patients with atherosclerotic CVD may be the most important part of the document.

Joseph J. Saseen

“For patients with atherosclerotic CVD on maximally tolerated statin therapy with or without ezetimibe, these recommendations alert clinicians that they should consider PCSK9 inhibitors,” he said. “This is where we have the highest level of evidence.”

Patients with FH

Newer studies focusing on patients with familial hypercholesterolemia (FH) phenotype determined that 7% of the U.S. population has a LDL of 190 mg/dL or greater, Orringer said. A pooled cohort study and a Swiss cohort study were also considered, in which researchers found patients with FH have a higher risk for atherosclerotic CVD events, especially in those with documented FH-causing mutations.

Reducing LDL with PCSK9 inhibitors is recommended in “patients aged 40 years to 79 years with phenotypic FH, pre-treatment LDL ≥ 190 mg/dL before treatment, no uncontrolled [atherosclerotic CVD] risk factors or other key additional risk markers, and on-treatment LDL ≥ 100 mg/dL or non-HDL ≥ 130 mg/dL on maximal-tolerated statin therapy [with or without] ezetimibe.”

PCSK9 inhibitor therapy is also recommended for a similar patient population with “the presence of either uncontrolled [atherosclerotic CVD] risk factors, or other key additional high-risk markers, or genetic confirmation of FH and on-treatment LDL ≥ 70 mg/dL or non-HDL ≥100 mg/dL on maximal-tolerated statin therapy [with or without] ezetimibe.”

PAGE BREAK

Younger patient population

The paper addresses younger patients and states “PCSK9 inhibitor therapy may be considered to further reduce LDL in patients aged 18 to 39 years with phenotypic FH, pre-treatment LDL ≥ 190 mg/dL and the presence of either uncontrolled [atherosclerotic CVD] risk factors, key additional high-risk markers or genetic confirmation of FH, and on-treatment LDL ≥ 100 mg/dL or non-HDL ≥ 130 mg/dL on maximal-tolerated statin [with or without] ezetimibe.”

“It’s a little bit tougher to make recommendations on those who meet the criteria with FH phenotype when they’re ages 18 to 39 because the evidence base is very, very shaky in those patients, so we tried to use our best judgment, and there were some patients in those previous studies that did represent individuals in this age group,” Orringer said in the presentation.

In one study that informed the recommendations, when evolocumab was added to stable lipid-lowering therapy in patients with FH aged 13 to 57 years, LDL was lowered by a mean of 30.9% (P < .0001) with no serious adverse events or anti-evolocumab antibodies.

Patients with homozygous FH may be considered for PSCK9 inhibitor therapy if they are LDL-receptor defective, the diagnosis is of unknown genotype or if the patient has LDL above 70 or non-HDL above 100 mg/dL despite maximally tolerated statin therapy with or without ezetimibe.

The recommendations also cover a population Orringer said is underserved: very high-risk patients with statin intolerance. “PCSK9 inhibitor therapy may be considered to further reduce LDL in selected very high-risk patients who meet the definition of intolerance (as previously defined by the NLA Statin Expert Panel) and who require substantial atherogenic cholesterol lowering despite the use of other lipid-lowering therapies,” the document stated.

“This definitely requires clinical judgment for you to make that decision whether therapy might be considered in those patients,” Orringer said in the presentation.

Patient-provider discussion

“We’ve advocated the importance of continuing to emphasize lifestyle and evidence-based lipid therapy to your patients,” Orringer said. “No patient who starts on PCSK9 inhibitor therapy should feel that they should stop their drugs because they’re on PCSK9 inhibitor.”

Orringer added that topics like cost, delays in therapy due to prior authorization process, follow-up lipoprotein monitoring and need for subcutaneous injection should be reviewed in a patient-provider discussion.

“We ask that you carefully consider the impact of patient characteristics, concomitant medical conditions and patient preferences,” Orringer said.

Ross said she hopes the recommendations “clear the way for [clinicians] to make better decisions about when to implement [PCSK9 inhibition], particularly in young patients with FH. We need to treat them as aggressively as possible, as early as possible, to prevent disease.”

The recommendations may “set the stage” for a new American College of Cardiology clinical decision pathway, due to be completed in 2018, Saseen said. – by Darlene Dobkowski and Erik Swain

References:

Orringer CE, et al. NLA Updated PCSK9 Inhibitor Recommendations. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.

Orringer CE, et al. J Clin Lipidol. 2017;doi:10.1016/j.jacl.2017.05.001.

Disclosure: Orringer and Ross are former presidents of the National Lipid Association. Saseen reports no relevant financial disclosures.

 

    Perspective
    Roger S. Blumenthal

    Roger S. Blumenthal

    Clinicians need to remember that to achieve reasonable cost-effectiveness, the yearly cost of a PCSK9 inhibitor needs to be less than $4,500. Currently, the cost is nearly 2.5 times that amount. Thus, patients should generally go on ezetimibe and/or colesevelam (Welchol, Daiichi Sankyo) in addition to the highest tolerated dose of a statin before a PCSK9 inhibitor is begun. Insurance companies vary greatly in granting approval for such therapy.

    • Roger S. Blumenthal, MD
    • CARDIOLOGY TODAY Section Editor Johns Hopkins Ciccarone Center for the Prevention of Heart Disease

    Disclosures: Blumenthal reports no relevant financial disclosures.

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