Copyright 2016 American Medical Association. All rights reserved.
Effect of Evolocumab on Progression of Coronary Disease
in Statin-Treated Patients
The GLAGOV Randomized Clinical Trial
Stephen J. Nicholls, MBBS, PhD; Rishi Puri, MBBS, PhD; Todd Anderson, MD; Christie M. Ballantyne, MD; Leslie Cho, MD;
John J. P. Kastelein, MD, PhD; Wolfgang Koenig, MD; Ransi Somaratne, MD; Helina Kassahun, MD; Jingyuan Yang, PhD;
Scott M. Wasserman, MD; Robert Scott, MD; Imre Ungi, MD, PhD; Jakub Podolec, MD, PhD; Antonius Oude Ophuis, MD, PhD;
Jan H. Cornel, MD, PhD; Marilyn Borgman, RN, BSN; Danielle M. Brennan, MS; Steven E. Nissen, MD
IMPORTANCE
Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive
statin therapy reduces progression of coronary atherosclerosis in proportion to achieved
LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce
incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on
coronary atherosclerosis have not been evaluated.
OBJECTIVE To determine the effects of PCSK9 inhibition with evolocumab on progression of
coronary atherosclerosis in statin-treated patients.
DESIGN, SETTING, AND PARTICIPANTS TheGLAGOV multicenter, double-blind, placebo-controlled,
randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197
academic and community hospitals in North America, Europe, South America, Asia, Australia,
and South Africa and enrolling 968 patients presenting for coronary angiography.
INTERVENTIONS Participants with angiographic coronary disease were randomized to receive
monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for
76 weeks, in addition to statins.
MAIN OUTCOMES AND MEASURES The primary efficacy measure was the nominal change in
percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular
ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in
normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque
regression. Safety and tolerability were also evaluated.
RESULTS Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%]
women; mean LDL-C level, 92.5 mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up.
Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C
levels (93.0 vs 36.6 mg/dL; difference, −56.5 mg/dL [95% CI, −59.7 to −53.4]; P < .001). The
primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with
evolocumab (difference, −1.0% [95% CI, −1.8% to −0.64%]; P < .001). The secondary efficacy
parameter, normalized TAV, decreased 0.9 mm
3
with placebo and 5.8 mm
3
with evolocumab
(difference, −4.9 mm
3
[95% CI, −7.3 to −2.5]; P < .001). Evolocumab induced plaque
regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference,
17.0% [95% CI, 10.4% to 23.6%]; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5%
[95% CI, 5.9% to 19.2%]; P < .001 for TAV).
CONCLUSIONS AND RELEVANCE Among patients with angiographic coronary disease treated
with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease
in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of
PCSK9 inhibition on clinical outcomes.
TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01813422
JAMA. 2016;316(22):2373-2384. doi:10.1001/jama.2016.16951
Published online November 15, 2016. Corrected on December 1, 2016.
Supplemental content
CME Quiz at
jamanetworkcme.com and
CME Questions page 2426
Author Affiliations: Author
affiliations are listed at the end of this
article.
Corresponding Author: Stephen
J. Nicholls, MBBS, PhD,
South Australian Health and
Medical Research Institute,
University of Adelaide, PO Box 11060,
Adelaide, SA, 5001, Australia
(stephen.nicholls@sahmri.com).
Research
JAMA | Original Investigation
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R
educing levels of low-density lipoprotein cholesterol
(LDL-C) with inhibitors of 3-hydroxy-3-methyl-
glutaryl coenzyme A reductase (statins) is the corner-
stone of contemporary care for patients with atherosclerotic
cardiovascular disease. Analysis of data within individual
statin trials and through meta-analyses suggests a consistent
relationship between achieving lower LDL-C levels and
reduction in major adverse cardiovascular events.
1,2
In paral-
lel, trials using intravascular ultrasound (IVUS) have studied
the effect of statins on coronary atherosclerosis and demon-
strated a linear relationship between achieved LDL-C levels
and reduction in atheroma burden.
3-6
However, major clini-
cal outcome trials and IVUS studies have explored a range of
achieved LDL-C levels, extending to a mean of approximately
60 mg/dL.
3,5
Proprotein convertase subtilisin kexin type 9 (PCSK9) re-
duces LDL receptor recycling to the hepatic surface, thereby
limiting removal of LDL particles from the circulation.
7-9
Monoclonal antibodies against PCSK9 reduce LDL-C
levels when administered alone or in combination with
statins.
10,11
Initial studies have demonstrated the fea-
sibility of using the combination of statins and PCSK9 inhibi-
tors to achieve LDL-C levels much lower than achieved
previously.
10,11
However, to our knowledge, no trials to date
have explored whether LDL-C lowering with a PCSK9 in-
hibitor reduces the rate of progression of coronary athero-
sclerosis, and no data exist assessing whether achieving very
low LDL-C levels via combination therapy results in incre-
mental benefits in reducing disease progression compared
with statins alone. The GLAGOV (Global Assessment of
Plaque Regression With a PCSK9 Antibody as Measured by
Intravascular Ultrasound) trial was designed to assess
whether PCSK9 inhibition reduces progression of atheroscle-
rosis as measured by IVUS.
Methods
Study Design
The GLAGOV trial was a multicenter, double-blind, placebo-
controlled, randomized clinical trial. Randomization was strati-
fied according to geographic region. The trial was designed by
the Cleveland Clinic Coordinating Center for Clinical Re-
search (C5Research) in collaboration with the sponsor. Insti-
tutional review boards at each site approved the protocol, and
patients provided written informed consent. The study pro-
tocol and statistical analysis plan are available in Supplement
1 and Supplement 2, respectively, and the design of the trial
has been described.
12
Patients 18 years or older were eligible if they demon-
strated at least 1 epicardial coronary stenosis of 20% or
greater on clinically indicated coronary angiography and had
a target vessel suitable for imaging with 50% or less visual
obstruction. Patients were required to have been treated with
a stable statin dose for at least 4 weeks and to have an LDL-C
level of 80 mg/dL or higher or between 60 and 80 mg/dL
(to convert LDL-C values to mmol/L, multiply by 0.0259)
with 1 major or 3 minor cardiovascular risk factors. Major risk
factors included noncoronary atherosclerotic vascular dis-
ease, myocardial infarction or hospitalization for unstable
angina in the preceding 2 years, or type 2 diabetes mellitus.
Minor risk factors included current cigarette smoking, hyper-
tension, low levels of high-density lipoprotein cholesterol,
family history of premature coronary heart disease, high-
sensitivity C-reactive protein (hsCRP) level of 2 mg/L or
higher (to convert hsCRP values to nmol/L, multiply by
9.524), or age 50 years or older for men and 55 years or older
for women.
By design, patients with an entry LDL-C level between
60 and 80 mg/dL were limited to 25% of the total patient
cohort. A 4-week lipid stabilization period was included for
patients not currently taking lipid-modifying therapy at
screening. Inclusion of patients intolerant to statins was lim-
ited to 10% of the total cohort. Patients were excluded if they
had uncontrolled diabetes or hypertension, heart failure,
renal dysfunction, or liver disease. Patients were asked to
identify race/ethnicity according to fixed categories deter-
mined by the study protocol, to evaluate potential differ-
ences in concomitant treatment and disease progression.
Patients underwent randomization in a 1:1 allocation
ratio with a block size of 4 using an interactive voice response
system to treatment with evolocumab (420 mg) or placebo
administered monthly via subcutaneous injection for 76
weeks. During the treatment period, patients underwent
clinic visits at weeks 4, 12, 24, 36, 52, 64, and 76 and repeat
IVUS imaging at week 78. A clinical events committee,
blinded to treatment assignment, adjudicated cardiovascular
events. An independent, unblinded data monitoring commit-
tee led by an academic cardiologist reviewed clinical trial
safety during the study.
Acquisition and Analysis of Ultrasound Images
After coronary angiography, baseline intravascular ultraso-
nography was performed. Previous reports have described
the methods of image acquisition and analysis.
3,5,6,13-18
Imaging was performed in a single artery and screened by a
core laboratory. Patients meeting prespecified requirements
for image quality were eligible for randomization. At week
Key Points
Question Does treatment with a PCSK9 inhibitor modify coronary
atherosclerosis disease progression?
Findings In this clinical trial in which 968 patients with coronary
disease were treated with the PCSK9 inhibitor evolocumab or
placebo monthly for 76 weeks and underwent serial intravascular
ultrasound determination of coronary atheroma volume, lower
low-density lipoprotein cholesterol levels were observed in the
evolocumab group (36.6 vs 93.0 mg/dL), which also was
associated with a reduction in percent atheroma volume for
evolocumab (−0.95%) but not placebo (+0.05%) and a greater
percentage of patients demonstrating plaque regression (64.3%
vs 47.3%).
Meaning Addition of the PCSK9 inhibitor evolocumab to statin
therapy produced greater low-density lipoprotein cholesterol
lowering and atheroma regression.
Research Original Investigation Evolocumab and Coronary Disease Progression in Statin-Treated Patients
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78, patients underwent a second ultrasonographic examina-
tion within the same artery. Using digitized images, person-
nel unaware of treatment status performed measurements of
the lumen and external elastic membrane in images within
a matched artery segment. Measurement personnel were
blinded to the sequence of imaging studies (baseline vs
follow-up). The accuracy and reproducibility of this method
have been reported.
3,5,6,13-18
Figure 1. Flow of Patients Through the GLAGOV Randomized Clinical Trial
2628 Patients screened
1246 Enrolled
1382 Excluded
a
845 Did not meet inclusion criteria
562 Met exclusion criteria
275 Medical or laboratory
c
166 Baseline IVUS (poor image quality or
stented vessel)
81 Unavailable for study visits or procedures
21 Participant unreliable
10 Unable to give informed consent or adhere
to study requirements
3 Known sensitivity to treatment
6 Other
74 Ineligible screening LDL-C level
b
629 Not statin intolerant
102 Did not meet IVUS criteria
5 No clinical indication for coronary angiography
24 Prior lipid-regulating therapy
11 No informed consent
276 Excluded (enrolled but not randomized)
235 Did not meet inclusion criteria or met exclusion criteria
32 Withdrew informed consent
9 Other
175 LDL-C value during or at end of lipid stabilization
period did not meet inclusion criteria
21 Ineligible laboratory value at end of lipid
stabilization period
21 IVUS did not meet core laboratory requirements
10 Did not tolerate statin during lipid stabilization
8 Not titrated to optimal dose of statin within 1 mo
970 Randomized
486 Randomized to receive placebo
484 Received placebo as randomized
2 Never received study drug
35 Discontinued treatment
2 Lost to follow-up
1 Physician decision
2 Other
19 Patient preference
11 Adverse event
61 Did not complete end point assessment
16 Final IVUS not analyzable
1 Died before final IVUS obtained
44 Final IVUS not obtained
423 Included in primary analysis
2 Did not receive study drug
484 Included in safety analysis
63 Excluded
61 Did not complete end point
assessment
484 Randomized to receive evolocumab
484 Received evolocumab as
randomized
38 Discontinued treatment
3 Lost to follow-up
1 Died
1 Physician decision
3 Other
12 Patient preference
18 Adverse event
61 Did not complete end point assessment
15 Final IVUS not analyzable
3 Died before final IVUS obtained
43 Final IVUS not obtained
423 Included in primary analysis
484 Included in safety analysis
61 Excluded (did not complete
end point assessment)
a
Patients could be excluded for
more than 1 reason; therefore,
the sum of the criteria may be
greater than the number of
patients. CETP indicates
cholesterylester transfer protein;
GLAGOV, Global Assessment of
Plaque Regression With a PCSK9
Antibody as Measured by
Intravascular Ultrasound;
IVUS, intravascular ultrasonography;
LDL-C, low-density lipoprotein
cholesterol.
b
LDL-C level 80 mg/dL
(2.07 mmol/L) or greater, with or
without risk factors; less than
60 mg/dL (1.55 mmol/L);
or 60 mg/dL or greater to
less than 80 mg/dL.
c
Clinically significant heart disease
(154), hyperthyroidism or
hypothyroidism (38), type 1
diabetes (27), history of malignancy
(16), fasting triglyceride level
greater than 400 mg/dL
(4.52 mmol/L) (15), active liver
disease or hepatic dysfunction (11),
uncontrolled cardiac arrhythmia (4),
creatine kinase level greater than 3
times upper limit of normal (2),
history of hereditary muscular
disorders (2), known active
infection or systemic dysfunctions
(2), New York Heart Association III
or IV heart failure or left ventricular
ejection fraction less than 30% (2),
severe renal dysfunction (1),
uncontrolled hypertension (1).
Evolocumab and Coronary Disease Progression in Statin-Treated Patients Original Investigation Research
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The primary efficacy measure, percent atheroma volume
(PAV), was calculated using the following equation:
PAV = Σ(EEM
area
− Lumen
area
)/ΣEEM
area
× 100,
where EEM
area
is the cross-sectional area of the external elas-
tic membrane and Lumen
area
is the cross-sectional area of the
lumen. The change in PAV was calculated as the PAV at 78
weeks minus the PAV at baseline. A secondary measure of
efficacy, normalized total atheroma volume (TAV), was calcu-
lated using the following equation:
TAV
normalized
= (EEM
area
− Lumen
area
)/Number of Images in
Pullback × Median Number of Images in Cohort,
where the average plaque area in each image was multiplied
by the median number of images analyzed in the entire co-
hort to compensate for differences in segment length be-
tween patients. Change in normalized TAV was calculated as
the TAV at 78 weeks minus the TAV at baseline. Regression was
defined as any decrease in PAV or TAV from baseline.
Efficacy End Points
The primary efficacy end point was the nominal change in PAV
from baseline to week 78 as described above. Secondary effi-
cacy end points included, in sequential order of testing, nomi-
nal change in TAV from baseline to week 78 as described above
and the proportion of patients demonstrating any reduction
of PAV from baseline and any reduction of TAV from baseline.
Exploratory end points included the incidence of adjudi-
cated events (all-cause mortality, cardiovascular death, myo-
cardial infarction, hospitalization for unstable angina, coro-
nary revascularization, stroke, transient ischemic attack, and
hospitalization for heart failure) and change in lipid param-
eters. Additional exploratory post hoc analyses included com-
parison of the change in PAV and percentage of patients un-
dergoing regression of PAV in those with an LDL-C level less
than or greater than 70 mg/dL at baseline. Locally weighted
polynomial regression (LOESS) curve fitting was performed to
examine the association between achieved LDL-C levels and
disease progression.
Statistical Analysis
All statistical analyses were performed using SAS version 9.4
(SAS Inc). For continuous variables with an approximately nor-
mal distribution, means and standard deviations are re-
ported. For variables not normally distributed, medians and
interquartile ranges (IQRs) are reported. IVUS efficacy para-
meters are reported as least squares means (95% CIs) and treat-
ment groups compared using analysis of covariance on rank-
transformed data with adjustment for baseline value and
geographic region. On-treatment lipoprotein levels are re-
ported as time-weighted means (95% CIs) and compared using
analysis of covariance, with adjustment for treatment group
and geographic region. Time-weighted averages for each labo-
ratory parameter were created by the summation of the prod-
uct between each measurement and time interval between
each visit divided by the total time.
A step-down statistical approach was applied to investi-
gate the primary and secondary end points. First, the pri-
mary end point was tested at the .05 significance level, then
the secondary end points were tested at the .05 significance
level in the sequential order as listed in section 4.1.2 in the sta-
tistical analysis plan (Supplement 2). A sensitivity analysis
using multiple imputation was performed to impute missing
primary end point data. The imputation model included vari-
ables for treatment group, background statin therapy inten-
sity, region, baseline LDL-C level, baseline PAV, age, and sex
Table 1. Baseline Characteristics of Patients in the Randomized
Population Who Received Study Drug (N = 968)
a
Parameter
No. (%)
Placebo
(n = 484)
Evolocumab
(n = 484)
Age, mean (SD), y 59.8 (8.8) 59.8 (9.6)
Men 350 (72.3) 349 (72.1)
Race/ethnicity
White 452 (93.4) 456 (94.2)
Black or African American 5 (1.0) 4 (0.8)
Asian 16 (3.3) 14 (2.9)
Native Hawaiian
or other Pacific islander
0 1 (0.2)
American Indian
or Alaska native
2 (0.4) 0
Multiple 6 (1.2) 7 (1.4)
Other 3 (0.6) 2 (0.4)
BMI, mean (SD)
b
29.5 (5.0) 29.4 (5.0)
Hypertension 405 (83.7) 398 (82.2)
Previous PCI 188 (38.8) 189 (39.0)
Previous MI 171 (35.3) 169 (34.9)
Smoking 113 (23.3) 124 (25.6)
Diabetes 104 (21.5) 98 (20.2)
Baseline statin use
c
476 (98.3) 478 (98.8)
Intensity
d
High 290 (59.9) 280 (57.9)
Moderate 185 (38.2) 196 (40.5)
Low 1 (0.2) 2 (0.4)
Baseline ezetimibe use
c
9 (2.1) 9 (2.1)
Baseline medications
Antiplatelet therapy 465 (96.1) 454 (93.8)
β-Blocker 370 (76.4) 362 (74.8)
ACE inhibitor 264 (54.5) 260 (53.7)
ARB 92 (19.0) 87 (18.0)
Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor
blocker; BMI, body mass index; MI, myocardial infarction; PCI, percutaneous
coronary intervention.
a
Clinical characteristics and concomitant medications of patients treated with
placebo or evolocumab with evaluable imaging at baseline and follow-up.
b
Calculated as weight in kilograms divided by height in meters squared.
c
Baseline statin and ezetimibe use is defined as patient treated with statin or
ezetimibe therapy at the end of the lipid stabilization period at randomization.
d
High intensity: atorvastatin (ⱖ40 mg), rosuvastatin (ⱖ20 mg), simvastatin
(ⱖ80 mg). Moderate intensity: atorvastatin (10-40 mg), rosuvastatin
(5-20 mg), simvastatin (20-80 mg), pravastatin (ⱖ40 mg), lovastatin
(ⱖ40 mg), fluvastatin (80 mg), pitavastatin (ⱖ2 mg). Low intensity:
atorvastatin (<10 mg), rosuvastatin (<5 mg), simvastatin (<20 mg), pravastatin
(<40 mg), lovastatin (<40 mg).
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Table 2. Baseline and On-Treatment Biochemical Measures and Blood Pressure in the Randomized Population Who Received Study Drug
a
Parameter
Baseline On-Treatment
P Value
b
Absolute Change (95% CI)
P Value
b
Placebo
(n = 484)
Evolocumab
(n = 484)
Placebo
(n = 484)
Evolocumab
(n = 484)
Placebo
(n = 484)
Evolocumab
(n = 484)
Cholesterol,
mean (95% CI), mg/dL
TC 166.2 (163.1 to 169.2) 166.1 (163.0 to 169.2) 169.1 (166.3 to 172.0) 108.6 (106.0 to 111.3) <.001 1.8 (−2.0 to 5.6) −59.0 (−62.8 to −55.2) <.001
LDL-C
c
92.4 (90.0 to 94.8) 92.6 (90.1 to 95.0) 93.0 (90.5 to 95.4) 36.6 (34.5 to 38.8) <.001 0.2 (−2.9 to 3.4) −56.3 (−59.4 to −53.1) <.001
HDL-C 45.4 (44.2 to 46.5) 46.7 (45.5 to 47.8) 47.1 (46.0 to 48.2) 51.0 (49.8 to 52.1) <.001 0.7 (−0.1 to 1.6) 3.3 (2.4 to 4.1) <.001
Triglycerides,
median (IQR), mg/dL
d
124.5 (90.0 to 173.0) 117.0 (88.0 to 155.0) 130.5 (100.3 to 177.2) 105.1 (82.5 to 141.6) <.001 8.1 (−0.4 to 16.6) −10.9 (−19.4 − 2.5) <.001
non–HDL-C,
mean (95% CI), mg/dL
120.8 (117.9 to 123.7) 119.4 (116.5 to 122.3) 122.0 (119.3 to 124.7) 57.7 (55.2 to 60.2) <.001 1.1 (−2.7 to 4.8) −62.3 (−66.0 to −58.5) <.001
TC:HDL-C, mean (95% CI) 3.9 (3.8 to 4.0) 3.7 (3.6 to 3.9) 3.8 (3.7 to 3.9) 2.3 (2.2 to 2.3) <.001 −0.1 (−0.2 to 0.04) –1.5 (−1.6 to −1.4) <.001
Apolipoprotein,
mean (95% CI), mg/dL
B 81.9 (80.1 to 83.6) 81.1 (79.3 to 82.9) 83.5 (81.8 to 85.2) 42.4 (40.8 to 44.0) <.001 0.3 (−2.0 to 2.6) −40.3 (−42.6 to −38.0) <.001
A-I 139.5 (137.2 to 141.9) 140.5 (138.3 to 142.8) 145.4 (143.4 to 147.4) 151.6 (149.5 to 153.7) <.001 3.5 (1.5 to 5.5) 8.5 (6.5 to 10.5) <.001
B:A-I 0.60 (0.59 to 0.62) 0.59 (0.58 to 0.61) 0.59 (0.57 to 0.60) 0.29 (0.28 to 0.30) <.001 −0.02 (−0.04 to −0.001) −0.3 (−0.33 to −0.29) <.001
hsCRP, median (IQR), mg/L
d,e
1.6 (0.8 to 3.4) 1.6 (0.8 to 3.4) 1.4 (0.7 to 3.0) 1.4 (0.7 to 3.0) .47 −0.3 (−1.3 to 0.6) −0.4 (−1.3 to 0.6) .35
Lp(a), median (IQR), mg/dL 10.9 (3.9 to 50.7) 12.1 (4.6 to 57.1) 8.9 (3.9 to 48.1) 7.1 (2.5 to 46.7) .07 −1.0 (−2.2 to 0.2) −7.8 (−9.0 to −6.6) <.001
PCSK9, mean (95% CI), ng/mL 322.5 (313.6 to 331.5) 325.4 (316.8 to 334.1) 307.8 (301.7 to 313.9) 146.9 (140.8 to 152.9) <.001 −7.2 (−19.4 to 5.0) −172.8 (−184.9 to −160.7) <.001
Glucose, mean (95% CI), mg/dL
d,e
107.3 (104.6 to 110.1) 104.0 (101.8 to 106.2) 109.4 (106.9 to 112.0) 110.1 (107.8 to 112.3) .72 3.9 (1.3 to 6.5) 7.8 (5.3 to 10.4) .02
HbA
1c
, mean (95% CI), %
e
5.9 (5.8 to 6.0) 5.8 (5.8 to 5.9) 6.0 (5.9 to 6.1) 6.0 (5.9 to 6.1) .85 0.2 (0.1 to 0.2) 0.2 (0.15 to 0.25) .09
Blood pressure,
mean (95% CI), mm Hg
Systolic 129.6 (128.2 to 131.0) 131.4 (130.1 to 132.7) 131.9 (130.8 to 133.1) 131.5 (130.4 to 132.5) .55 0.9 (−0.7 to 2.5) −1.3 (−2.9 to 0.4) .007
Diastolic 76.7 (75.8 to 77.6) 78.0 (77.2 to 78.9) 78.5 (77.8 to 79.2) 78.6 (77.9 to 79.2) .94 2.2 (1.0 to 3.3) 0.9 (−0.2 to 1.99) .01
Abbreviations: Apo, apolipoprotein; HbA
1c
, hemoglobin A
1c
; HDL-C, high-density lipoprotein cholesterol;
hsCRP, high-sensitivity C-reactive protein; IQR, interquartile range; LD-CL, low-density lipoprotein cholesterol;
Lp(a), lipoprotein(a); non–HDL-C, non–high-density lipoprotein cholesterol; PCSK9, proprotein convertase
subtilisin kexin type 9; TC, total cholesterol.
SI conversion factors: To convert total cholesterol, LDL-C, HDL-C, and non–HDL-C values to mmol/L,
multiply by 0.0259; to convert triglyceride values to mmol/L, multiply by 0.0113; to convert hsCRP values
to nmol/L, multiply by 9.524; to convert Lp(a) values to μmol/L, multiply by 0.0357; to convert glucose
values to mmol/L, multiply by 0.0555.
a
On-treatment laboratory parameters are the time-weighted averages (95% CIs) of all postbaseline values, and
estimates are derived from an analysis of variance model with factors for treatment group and region. Baseline
and time-weighted average on-treatment values and absolute changes of laboratory measures and blood
pressure of patients who were randomized and received at least 1 dose of study drug. Results expressed as mean
(95% CI) at baseline and least squares mean (95% CI) for on-treatment values.
b
P value for between–treatment group comparison.
c
When the calculated LDL-C level is less than 40 mg/dL or triglyceride level is greater than 400 mg/dL,
ultracentrifugation LDL-C was determined from the same blood sample.
d
Tested using Wilcoxon rank-sum test.
e
Final measurements are used for on-treatment values. Absolute changes are presented as least squares means
(95% CIs).
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