ESC Congress 2017 In Review -- Main Edition - 32

Selected Content

Med. 2017]. In addition, data out to 4 years with evolocumab pooled across phase 2 and 3 lipid-lowering studies have raised no safety concerns [Koren MJ et al. JAMA
Cardiol. 2017]. Similarly, pooled data from earlier trials of
alirocumab also indicate no safety concerns (Table 2).

Table 1. Safety Data From the FOURIER Trial
Evolocumab
Placebo
(n = 13,769) (n = 13,756)
Adverse events (%)
Any

77.4

77.4

Serious

24.8

24.7

Allergic reaction

3.1

2.9

Injection-site reaction

2.1

1.6

Treatment-related that led to discontinuation
of study

1.6

1.5

Muscle-related

5.0

4.8

Cataract

1.7

1.8

Diabetes (new onset)

8.1

7.7

Neurocognitive

1.6

1.5

.03

n/a

None

n/a

Laboratory Results (%)
Binding Ab
Neutralizing Ab

Further safety data are pending from the ODYSSEY
Outcomes study with alirocumab [Schwartz GG et al. Am
Heart J. 2014].
Interestingly, PCSK9 may have a variety of functional roles in autocrine and exocrine activities in the liver,
intestinal tract, lung, kidney, pancreas, and arterial wall.
This raises the hope that targeting this protein could
produce benefits beyond the lowering of LDL-C. As
explained by Bertrand Cariou, MD, PhD, Université de
Nantes, Nantes, France, PCSK9 may be directly involved
in atherogenesis independent of the level of LDL-C. In
the intestines, increased PCSK9 may function in the
retention of lipid in the blood following a meal and in the
secretion of apolipoprotein B, the main apolipoprotein
of LDL [Le May C et al. Arterioscl Thromb Vascul Biol.
2009]. PCSK9 may also modulate trans-intestinal cholesterol excretion [Le May C et al. Arterioscl Thromb
Vascul Biol. 2013]. Genetic studies with pancreatic tissue have indicated a possible link between PCSK9 mutations and the increased risk of type 2 diabetes [Ference
BA et al. N Engl J Med. 2016].
The findings highlight the need for more data on the
various actions of PCSK9 in the long-term and more
studies are needed to properly gauge the mode of
action and long-term clinical safety of PCSK9 inhibitors.

Table 2. Pooled Data Fwrom 14 Trials Involving Alirocumab
Pooled Control
(n = 1,894)

Pooled Alirocumab
(n = 3,340)

Pooled Alirocumab
LDL-C < 25 mg/dL
(n = 796)

Pooled Alirocumab
LDL-C < 15 mg/dL
(n = 288)

Infections and infestations

36.3

38.5

34.0

35.4

Musculoskeletal disorders

25.2

24.2

21.1

20.1

Injection-site reaction

3.9

5.7

3.0

3.5

Nervous system disorders

14.9

14.9

10.3

9.0

Diabetes mellitus

1.3

1.2

1.5

2.4

Neoplasms

2.5

2.5

2.8

2.4

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Table of Contents for the Digital Edition of ESC Congress 2017 In Review -- Main Edition
