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FOURIER: Evolocumab reduces CV events regardless of baseline LDL, statin intensity

PHILADELPHIA — A subanalysis of the FOURIER trial presented at the National Lipid Association Scientific Sessions found that evolocumab was linked to reduction in CV events regardless of a patient’s LDL or intensity of statin therapy at baseline.

Marc S. Sabatine, MD, MPH, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group and the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, and colleagues evaluated the safety and efficacy of the PCSK9 inhibitor evolocumab (Repatha, Amgen) in patients with LDL < 70 mg/dL at baseline and in those on maximum-intensity statin therapy, defined as atorvastatin 80 mg per day or rosuvastatin 40 mg per day.

In the FOURIER cohort, there were 2,034 patients with baseline LDL < 70 mg/dL (mean age, 62 years; 80% men). In those patients, evolocumab was associated with a 66% mean reduction in LDL (95% CI, 62-69; P < .00001), Sabatine said.

Marc S. Sabatine, MD, MPH
Marc S. Sabatine

For the primary endpoint of CV death, MI, stroke, unstable angina or coronary revascularization, the reduced risk associated with evolocumab was similar in those with baseline LDL < 70 mg/dL (HR = 0.8; 95% CI, 0.6-1.07) and in those with baseline LDL 70 mg/dL or greater (HR = 0.86; 95% CI, 0.79-0.92; P for interaction = .65), Sabatine said.

A similar pattern was observed for the key secondary outcome of CV death, MI or stroke (HR for LDL < 70 mg/dL = 0.7; 95% CI, 0.48-1.01; HR for LDL 70 mg/dL or greater = 0.81; 95% CI, 0.73-0.89; P for interaction = .44).

Among patients with baseline LDL < 70 mg/dL, safety outcomes were similar between the evolocumab group and the placebo group, Sabatine said.

Out of all the patients in FOURIER, 7,533 (27%) were on a maximum-intensity statin at baseline (mean age, 61 years; 76% men), according to the researchers.

In that cohort, evolocumab was associated with a 58% mean reduction in LDL (95% CI, 57-59; P < .00001), Sabatine said.

There was no significant difference in treatment effect for the primary outcome in patients on a maximum-intensity statin (HR = 0.86; 95% CI, 0.75-0.98) and those taking a lesser-intensity statin (HR = 0.85; 95% CI, 0.78-0.93; P for interaction = .88), and the same was true for the key secondary outcome (HR for maximum-intensity = 0.78; 95% CI, 0.66-0.92; HR for lesser-intensity = 0.81; 95% CI, 0.72-0.9; P for interaction = .71), he said.

The groups did not display any difference in safety outcomes, according to the researchers.

“Evolocumab safely lowers CV events in patients with stable [atherosclerotic CVD] to a similar degree whether the baseline LDL was less than 70 mg/dL or at least 70 mg/dL, and regardless of whether the backrground statin was maximal intensity or not,” Sabatine said. “These findings support using evolocumab go beyond what is recommended in current guidelines to lower CV risk in well-treated patients.”

In the newly issued National Lipid Association recommendations for PCSK9 inhibitors, “the threshold for treatment was 70 mg/dL,” Sabatine said. “When we do the math, patients at 70 mg/dL should have ... achieved LDL somewhere in the mid to high twenties. I think that makes sense; that’s the level at which data are pointing to a consistent benefit. by Erik Swain

Reference:

Sabatine MS, et al. Late Breakers. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.

Disclosure: The study was funded by Amgen. Sabatine reports receiving grants from Abbott Laboratories, Critical Diagnostics, Daiichi Sankyo, Eisai, Genzyme, Gilead, GlaxoSmithKline, Janssen Research Development, Novartis, Poxel, Roche Diagnostics and Takeda; grants and personal fees from Amgen, AstraZeneca, Intarcia, MedImmune and Merck; and personal fees from Alnylam, Cubist, CVS Caremark, Esperion, Ionis, MyoKardia, The Medicines Company and Zeus Scientific.

 

PHILADELPHIA — A subanalysis of the FOURIER trial presented at the National Lipid Association Scientific Sessions found that evolocumab was linked to reduction in CV events regardless of a patient’s LDL or intensity of statin therapy at baseline.

Marc S. Sabatine, MD, MPH, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group and the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, and colleagues evaluated the safety and efficacy of the PCSK9 inhibitor evolocumab (Repatha, Amgen) in patients with LDL < 70 mg/dL at baseline and in those on maximum-intensity statin therapy, defined as atorvastatin 80 mg per day or rosuvastatin 40 mg per day.

In the FOURIER cohort, there were 2,034 patients with baseline LDL < 70 mg/dL (mean age, 62 years; 80% men). In those patients, evolocumab was associated with a 66% mean reduction in LDL (95% CI, 62-69; P < .00001), Sabatine said.

Marc S. Sabatine, MD, MPH
Marc S. Sabatine

For the primary endpoint of CV death, MI, stroke, unstable angina or coronary revascularization, the reduced risk associated with evolocumab was similar in those with baseline LDL < 70 mg/dL (HR = 0.8; 95% CI, 0.6-1.07) and in those with baseline LDL 70 mg/dL or greater (HR = 0.86; 95% CI, 0.79-0.92; P for interaction = .65), Sabatine said.

A similar pattern was observed for the key secondary outcome of CV death, MI or stroke (HR for LDL < 70 mg/dL = 0.7; 95% CI, 0.48-1.01; HR for LDL 70 mg/dL or greater = 0.81; 95% CI, 0.73-0.89; P for interaction = .44).

Among patients with baseline LDL < 70 mg/dL, safety outcomes were similar between the evolocumab group and the placebo group, Sabatine said.

Out of all the patients in FOURIER, 7,533 (27%) were on a maximum-intensity statin at baseline (mean age, 61 years; 76% men), according to the researchers.

In that cohort, evolocumab was associated with a 58% mean reduction in LDL (95% CI, 57-59; P < .00001), Sabatine said.

There was no significant difference in treatment effect for the primary outcome in patients on a maximum-intensity statin (HR = 0.86; 95% CI, 0.75-0.98) and those taking a lesser-intensity statin (HR = 0.85; 95% CI, 0.78-0.93; P for interaction = .88), and the same was true for the key secondary outcome (HR for maximum-intensity = 0.78; 95% CI, 0.66-0.92; HR for lesser-intensity = 0.81; 95% CI, 0.72-0.9; P for interaction = .71), he said.

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The groups did not display any difference in safety outcomes, according to the researchers.

“Evolocumab safely lowers CV events in patients with stable [atherosclerotic CVD] to a similar degree whether the baseline LDL was less than 70 mg/dL or at least 70 mg/dL, and regardless of whether the backrground statin was maximal intensity or not,” Sabatine said. “These findings support using evolocumab go beyond what is recommended in current guidelines to lower CV risk in well-treated patients.”

In the newly issued National Lipid Association recommendations for PCSK9 inhibitors, “the threshold for treatment was 70 mg/dL,” Sabatine said. “When we do the math, patients at 70 mg/dL should have ... achieved LDL somewhere in the mid to high twenties. I think that makes sense; that’s the level at which data are pointing to a consistent benefit. by Erik Swain

Reference:

Sabatine MS, et al. Late Breakers. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.

Disclosure: The study was funded by Amgen. Sabatine reports receiving grants from Abbott Laboratories, Critical Diagnostics, Daiichi Sankyo, Eisai, Genzyme, Gilead, GlaxoSmithKline, Janssen Research Development, Novartis, Poxel, Roche Diagnostics and Takeda; grants and personal fees from Amgen, AstraZeneca, Intarcia, MedImmune and Merck; and personal fees from Alnylam, Cubist, CVS Caremark, Esperion, Ionis, MyoKardia, The Medicines Company and Zeus Scientific.

 

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