# Profoundd archive — Epstein Files
# Bates number: EFTA00447981
# Title:        To: Lesley Groff
# Dataset:      9
# Pages:        3
# Tags:         epstein, doj, dataset-9
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=== SUMMARY ===
From: ' To: Lesley Groff Subject: Fwd: FOURIER: Significant LDL Reduction with Evolocumab Date: Fri, 24 Mar 2017 11:17:36 +0000 Lesley please forward to Jeffrey rs Rony Shimony, M.D. F.A.C.C. Associate Professor of Medicine, Cardiology Icahn School of Medicine at Mount Sinai Director, Clinical Cardiology Mount Sinai West Mount Sinai Heart 425 West 59th Street 9th Floor New York, NY 10019 212-752-2700 212-731-3730 Fax 212-376-3190 Cell 917-922-7391 dictated and sent from an iPhone kindly excuse t


=== EXTRACTED TEXT ===
From: ' 
To: Lesley Groff  
Subject: Fwd: FOURIER: Significant LDL Reduction with Evolocumab 
Date: Fri, 24 Mar 2017 11:17:36 +0000 
Lesley please forward to Jeffrey 
rs 
Rony Shimony, M.D. F.A.C.C. 
Associate Professor of Medicine, Cardiology 
Icahn School of Medicine at Mount Sinai 
Director, Clinical Cardiology 
Mount Sinai West 
Mount Sinai Heart 
425 West 59th Street 
9th Floor 
New York, NY 10019 
212-752-2700 
212-731-3730 
Fax 212-376-3190 
Cell 917-922-7391 
dictated and sent from an iPhone kindly excuse typos 
Begin forwarded message: 
From: Cardiology Alert < 
Date: March 24, 2017 at 7:06:06 AM EDT 
To: <I a 
Subject: FOURIER: Significant  LDL Reduction with Evolocumab 
Reply-To: Cardiology Alert <I 
Email not displaying correctyNiaw it in your browser. 
FOURIER: Significant LDL Reduction with Evolocumab 
New data from the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk 
(FOURIER) study. presented at the 2017 American College of Cardiology Scientific Session in Washington, M. 
suggested that evolocumab was associated with significant reductions in LDL cholesterol in patients with 
atherosclerotic cardiovascular disease and elevated LDL. 
The PCSK9 inhibitor evolocumab was the subject of the study. The research team sought to determine the safety and 
clinical efficacy of the drug when added to statin therapy in patients who have clinically evident atherosclerotic 
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GJ cardiovascular disease. The trial included patients from 1,242 sites 
in 49 countries. 
The double-blind, placebo-controlled study included 27.564 
patients who had clinically evident atherosclerotic cardiovascular 
disease and with a fasting LDL level of 70 mg/dL or higher. All 
patients were on high-intensity or low-intensity statin therapy. 
Patients were randomized 1:1 to subcutaneous evolocumab at 
either 140 mg every two weeks (or 420 mg monthly based on 
patient preference; n = 13,784) or to placebo (n = 13,780). The 
primary efficacy endpoint was major cardiovascular events 
(composite of cardiovascular death. myocardial infarction (MI). 
stroke, hospitalization for unstable angina, or coronary 
revascularization). Key secondary efficacy endpoints included a 
composite of cardiovascular death, MI, or stroke. 
Lower LDL, No Effect on Cardiovascular Mortality 
The researchers reported that the least-squares mean percentage reduction in LDL cholesterol levels was 59% in 
patients assigned to evolocumab. The mean absolute reduction from the media LDL baseline of 92 mg/dL down to 30 
mg/dL in the evolocumab group (P < 0.001). The observed reduction remained steady throughout the trial. For patients 
in the evolocumab group. LDL was reduced to 70 mg/dL or lower in 87% of the patients and 40 mg/dL or less in 67% of 
the group, and down to 25 mg/dL in 42% of the patients. These reductions were significantly more substantial than 
those seen in the placebo group (18%, 0.5% and 0.1% respectively; P < 0.001 for all comparisons). In addition, 
patients in the evolocumab group saw lowered related atherosclerotic lipid measures, such as a 52% reduction in non-
H0L cholesterol levels and a 49% reduction in apolipoprotein E levels (P < 0.001 for both). 
For the primary study endpoint (which occurred in 1,344 patients in the evolocumab group and 1,563 in the placebo 
group: HR, 0.85; 95% CI, .0.79-0.92; P < 0.001), evolocumab was associated with a significant reduction in the risk for 
the primary composite endpoint of cardiovascular death. MI, stroke, hospitalization for unstable angina, or coronary 
revascularization. Also observed was a significant reduction in the risk for the secondary composite endpoint. The key 
secondary endpoint occurred in 816 patients (5.9%) in the evolocumab group versus 1.013 (7.4%) in the placebo group 
(HR, 0.80: 95% CI, 0.73 to 0.88; P < 0.001). The beneficiary effect appeared to increase over time in both groups, and 
were also consistent across quartiles of baseline LDL level (highest, 126 mg/dL to lowest, 74 mg/dL). 
antibodies were reported to develop. 
Some Takeaways from FOURIER "We've never been able to plumb these depths before." lead author 
Marc S. Sabatine, MD, of Brigham and Women's Hospital and 
Harvard Medical School, said in a conference press release. 
"These data strongly suggest that patients benefit from lowering 
LDL cholesterol well below current targets." 
Regarding individual outcomes, no observed effect on 
cardiovascular mortality was reported by the study team. The P 
values, they said, should therefore be considered exploratory. The 
study reported between 21% and 27% reductions in the risk for MI. 
stroke, and coronary revascularization, but there remained no 
observed effects on hospitalization rates for unstable angina, 
cardiovascular death or hospitalization for worsening heart failure, 
or death from any cause. There were no significant differences 
between groups in adverse events, serious adverse events, or 
adverse events thought to be related to the study agent, signaling 
that evolocumab was well-tolerated and safe. No neutralizing 
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One of the issues raised by FOURIER was the issue of decreasing LDL levels to below current recommended target 
levels. 
"These findings show that patients with atherosclerotic cardiovascular disease benefit from the lowering of LDL 
cholesterol levels below current targets," they wrote in their conclusion. 
The major study limitation, the researchers wrote, was the short follow-up period. 
"The major limitation of this trial was a relatively short duration of follow-up as compared with that in other lipid-lowering 
trials, in which follow-up periods have averaged approximately 5 years," the authors wrote. "Although the median 
follow-up period in FOURIER was originally planned to be approximately 4 years, an event rate that was approximately 
50% higher than had been postulated led to a shorter required duration of follow-up to accrue the prespecified number 
of events." 
Dr. Sabatine emphasized the importance of aggressive LDL-lowering treatment in the future. 
"We need to treat LDL cholesterol more aggressively, and now we have a new validated means to do so: he said in the 
press release. "People with atherosclerotic disease should discuss their LDL cholesterol with their physician and 
consider whether they need to lower it further." 
Reference 
Sabatine MS. Giugliano RP, Keech AC, et al. N Engl J Med. 2017;doi:NEJMoa1615664 
http://www.nejm.orq/doUpdf/10.1056/NEJMoa 1615664 
Sabatine M. Primary Results of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects 
With Elevated Risk (FOURIER) Trial. March 17. Presented at: American College of Cardiology 2017 Scientific Session 
in Washington, D.C. 
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