ΜΕΤΑΒΟΛΙΚΟ ΣΥΝΔΡΟΜΟ. ΥΠΕΡΤΑΣΗ ΚΑΙ ΔΥΣΛΙΠΙΔΑΙΜΙΑ...
-
Upload
ashly-sculthorpe -
Category
Documents
-
view
220 -
download
0
Transcript of ΜΕΤΑΒΟΛΙΚΟ ΣΥΝΔΡΟΜΟ. ΥΠΕΡΤΑΣΗ ΚΑΙ ΔΥΣΛΙΠΙΔΑΙΜΙΑ...
ΜΕΤΑΒΟΛΙΚΟ ΣΥΝΔΡΟΜΟ. ΥΠΕΡΤΑΣΗ ΚΑΙ ΔΥΣΛΙΠΙΔΑΙΜΙΑ
• Δημήτριος Ρίχτερ, MD, FESC, FAHA
• - Διευθυντής Καρδιολογικής Κλινικής Ευρωκλινικής Αθηνών
• Αντιπρόεδρος ΕΚΟΜΕΝ
• - Γενικός Γραμματέας Ελληνικής Εταιρείας Λιπιδιολογίας.
• - Μέλος ΔΣ ΕΛΙΚΑΡ
NCEP ATP III: The Metabolic SyndromeNCEP ATP III: The Metabolic Syndrome
<40 mg/dL (1.0 mmol/L)<50 mg/dL (1.3 mmol/L)
MenWomen
>102 cm (>40 in)>88 cm (>35 in)
MenWomen
³110 mg/dL (6.0 mmol/L)Fasting glucose
³130/³85 mmHgBlood pressure
HDL-C
³150 mg/dL (1.7 mmol/L)TG
Abdominal obesity (Waist circumference)
Defining LevelRisk Factor
Recommends a diagnosis when ³3 of these risk factors are present
Adapted from NCEP, Adult Treatment Panel III, 2001. JAMA 2001:285;2486–2497.
PREVALENCE OF METS IN GREECEPREVALENCE OF METS IN GREECE
• Mets-Greece study (Athyros et al). 4056 adults.
Prevalence 22.8%. Similar men and women. Increasing with age ( 4,7% 18-29y, 44,2% >60y).
62% 3 components, 28% 4, 10% all 5.
74th EAS Congress, Seville, 17-20 April 2004
ATTICA study (Panagiotakos et al). 2282 adults.
Prevalence 19,8%. Men 25,2%, women 14,6%.
Prevalence increased with age.
Am Heart J 2004; 147: 106-12.
The presence of the Metabolic Syndrome is associated with increased CHD, CVD and
total mortality
The presence of the Metabolic Syndrome is associated with increased CHD, CVD and
total mortality
Unadjusted Kaplan-Meier hazard curves for men with and without the Metabolic Syndrome based on factor analysis. Median follow-up was 11.6 (9.1-13.7) years. Relative risks were determined by age-adjusted Cox proportional hazards regression analysis.
Lakka HM et al, J Am Med Assoc 2002;288:2709-2716
©2004 PPS®
Odds Ratio 95% CI P Value
Metabolic syndrome 2.01 1.53-2.64 <0.0001
Syndrome components
Abdominal obesity 1.15 0.86-1.54 0.3475
High triglycerides 1.51 1.04-2.20 0.0311
Low HDL-C 1.41 1.03-1.95 0.0353
Hypertension 1.42 0.94-2.15 0.0947
Insulin resistance† 1.25 0.92-1.71 0.1461
Ninomiya JK et al. Circulation. 2004;109:42-46.
*Self-reported.†Fasting plasma glucose ³110 mg/dL.
Association of MI* With the Metabolic Syndrome and Individual Components
©2004 PPS®
Ninomiya JK et al. Circulation. 2004;109:42-46.
*Self-reported.†Fasting plasma glucose ³110 mg/dL.
Association of Stroke* With the Metabolic Syndrome and Individual Components
Odds Ratio 95% CI P Value
Metabolic syndrome 2.16 1.48-3.16 0.0002
Syndrome components
Abdominal obesity 0.97 0.58-1.64 0.9154
High triglycerides 1.87 1.22-2.87 0.0052
Low HDL-C 1.18 0.73-1.90 0.5012
Hypertension 1.56 0.94-2.59 0.0827
Insulin resistance† 1.36 0.93-1.98 0.1119
191418,1 16,6
0
20
40
60
80
100
Smoking Diet and sedentarity
Pe
rce
nta
ge
1990 2000
Major causes of death in USA 1990 and 2000
Mokdad AH et al. JAMA 2004
Risk of AMI associated with risk factors in the overall population
Risk factor % Cont % Cases OR (99% IC) adj age, sex, smoking
OR (99% IC) adj for all
ApoB/ApoA-1 (5 v 1) 20.0 33.5 3.87 (3.39, 4.42) 3.25 (2.81, 3.76)
Smoking 26.8 45.2 2.95 (2.72, 3.20) 2.87 (2.58, 3.19)
Diabetes 7.5 18.4 3.08 (2.77, 3.42) 2.37 (2.07, 2.71)
Hypertension 21.9 39.0 2.48 (2.30, 2.68) 1.91 (1.74, 2.10)
Abd Obesity (3 v 1) 33.3 46.3 2.22 (2.03, 2.42) 1.62 (1.45, 1.80)
Psychosocial - - 2.51 (2.15, 2.93) 2.67 (2.21, 3.22)
Veg et fruits DIE 42.4 35.8 0.70 (0.64, 0.77) 0.70 (0.62, 0.79)
Exercise 19.3 14.3 0.72 (0.65, 0.79) 0.86 (0.76, 0.97)
Alcohol intake 24.5 24.0 0.79 (0.73, 0.86) 0.91 (0.82, 1.02)
Yusuf S et al, Lancet 2004
Declining HDL-C in the Population
>12,000 respondents to a biennial population survey in the Pawtucket Heart Health Program
Between 1981 and 1993, 0.08 mmol/L (3.1 mg/dL) decline
Adjusted for other risk factor changes
Reprinted from Ann Epidemiol, Vol. 8, Derby CA et al., 84-91, copyright 1998, with permission from Elsevier.
HD
L-C
(m
mol/L)
1.5
1.4
1.3
1.2
1.1
0.0
1.3
1.2
1.1
1.0
0.0
1.3
1.2
1.1
1.0
0.0
1.3
1.2
1.1
1.0
0.0
MenWomen
1.5
1.4
1.3
1.2
1.1
0.0
1.5
1.4
1.3
1.2
1.1
0.0
Nonsmokers
Smokers
Nonsmokers
Smokers
Alcohol
No Alcohol
No Alcohol
Alcohol
BMI <22.9 BMI <24.5
BMI 27.6 BMI 27.9
'83-84 '87-89 '92-93
'85-86'81-82 '89-90
'83-84 '87-89 '92-93
'85-86'81-82 '89-90
Treatment of obesity
Modest weight loss can be effective
~250-500 kcal/day restriction energy expenditure as tolerated
Monitor blood pressure with anorectic drugs
Treat CHD, LVH and RVH risk factors aggressivelylipids, blood pressure, diabetes, hypertensionobstructive sleep apnea and respiratory
problems
Poirier et al, Circulation 2006
Finnish Diabetes Prevention Study: Treating the IGT* Patient With Lifestyle Changes
Finnish Diabetes Prevention Study: Treating the IGT* Patient With Lifestyle Changes
Study Design
– 522 middle-aged, overweight† subjects
– 172 men, 350 women with IGT
– BMI 31 kg/m2
– mean age: 55 years
– mean duration: 3.2 years
– intervention group: individualized counseling
• reducing weight, total intake of fat and saturated fat
• increasing intake of fiber, physical activity
*Plasma glucose concentration of 140 to 200 mg/dL. †BMI 25 kg/m2.IGT=impaired glucose tolerance; BMI=body mass index.Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
Finnish Diabetes Prevention Study: Reduction in Risk for Diabetes*
Finnish Diabetes Prevention Study: Reduction in Risk for Diabetes*
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
11%
23%
0
5
10
15
20
25
Intervention Control
(n=265)
(n=257)
*P<0.001; 4-year results
Diabetes (%)
Bariatric surgery and mortality
• Prospective study
• SOS study
• N=4047 patients
• 10.9 yrs follow-up
• Information: 99.9%
Sjostrom L et al, NEJM 2007
SOS: Mortality reduction with weight-loss surgery
Deaths:Control: 129 (6.3%)Surgery: 101 (5.0%)
Unadjusted HR 0.76 (0.59-0.99), P = 0.04
Adjusted HR 0.71*(0.54-0.92), P = 0.01
*Adjusted for age, sex, risk factors Sjöström L et al. N Engl J Med. 2007;357:741-52.
Years
14
12
0
0 2
Cumulativemortality
(%)
Control
Surgery
4 1614121086
10
8
6
4
2
Surgery(n)
Controls(n)
Cardiovascular condition 43 53
Cardiac Myocardial infarction Heart failure Sudden death
13 220
25 5 14
Stroke 6 6
Other 2 3
Noncardiovascular condition 58 76
Cancer/meningioma 29/0 47/1
Infection 12 3
Thromboembolic disease 5 7
Other 12 18
Total mortality 101 129
SOS: Causes of death
Sjöström L et al. N Engl J Med. 2007;357:741-52.
2007 Guidelines for the Management of
Arterial Hypertension
Journal of Hypertension 2007;25:1105-1187
European Society of Hypertension European Society of Cardiology
Initiation of antihypertensive treatmentOther risk factors, OD or disease
Normal SBP 120-129 or DBP 80-84
High normal SBP 130-139 or DBP 85-89
Grade 1 HTSBP 140-159 or DBP 90-99
Grade 2 HTSBP 160-179 or DBP 100-109
Grade 3 HT SBP ≥180 or DBP ≥110
No other risk factors
No BP intervention
No BP intervention
Lifestyle changes for several months then drug treatment if BP uncontrolled
Lifestyle changes for several weeks then drug treatment if BP uncontrolled
Lifestyle changes + immediate drug treatment
1-2 risk factors Lifestyle changes Lifestyle changes
Lifestyle changes for several weeks then drug treatment if BP uncontrolled
Lifestyle changes for several weeks then drug treatment if BP uncontrolled
Lifestyle changes + immediate drug treatment
3 or more risk factors, MS, OD or diabetes
Lifestyle changesLifestyle changes and consider drug treatment Lifestyle changes
+ drug treatmentLifestyle changes + drug treatment
Lifestyle changes + immediate drug treatmentDiabetes Lifestyle changes Lifestyle changes
+ drug treatment
Established CV or renal disease
Lifestyle changes + immediate drug treatment
Lifestyle changes + immediate drug treatment
Lifestyle changes + immediate drug treatment
Lifestyle changes + immediate drug treatment
Lifestyle changes + immediate drug treatment
The Metabolic Syndrome
• Subjects with the metabolic syndrome also have a higher prevalence of microalbuminuria, left ventricular hypertrophy and arterial stiffness than those without the metabolic syndrome. Their cardiovascular risk is high and the chance of developing diabetes markedly increased
• In patients with a metabolic syndrome diagnostic procedures should include a more in-depth assessment of subclinical organ damage. Measuring ambulatory and home BP is also desirable
The Metabolic Syndrome• In all individuals with metabolic syndrome individuals intense
lifestyle measures should be adopted. When there is hypertension drug treatment should start with a drug unlikely to facilitate onset to diabetes. Therefore, a blocker of the renin-angiotensin system should be used followed, if needed, by the addition of a calcium antagonist or a low-dose thiazide diuretic. It appears desirable to bring BP to the normal range
• Lack of evidence from specific clinical trials prevents firm recommendations on use of antihypertensive drugs in all metabolic syndrome subjects with a high normal BP. There is some evidence that blocking the renin-angiotensin system may also delay incident hypertension
Hypertension Guidelines: ESH/ESC 2013
Definitions and classification of office blood pressure levels (mmHg)
Category Systolic Diastolic
Optimal < 120 And < 80
Normal 120-129 And/or 80-84
High normal 130-139 And/or 85-89
Grade 1 hypertension
140-159 And/or 90-99
Grade 2 hypertension
160-179 And/or 100-109
Grade 3 hypertension
> = 180 And/or > = 110
Isolated systolic hypertension
>= 140 and < 90
BP Goals
• all be treated to <140/90 mm Hg
• Except : diabetes (<85 mm Hg diastolic)
• In patients near 80 years age, the systolic blood-
pressure target should be 140 to 150 mm Hg, but
physicians can go lower than 140 mm Hg if the
patient is fit and healthy-mentally & physically
Life style changes
Salt
• A reduction to 5 g per day can decrease systolic blood pressure
about 1 to 2 mm Hg in normotensive individuals and 4 to 5
mm Hg in hypertensive patients, he said.
Wt loss
• Losing about 5 kg can reduce systolic blood pressure by as
much as 4 mm Hg, aerobic endurance training
• can reduce systolic blood pressure 7 mm Hg
When to start drug Rx
Consider BP level and correlate with overall risk:
• cardiovascular risk factors
• overt cardiovascular disease
• asymptomatic organ damage
• diabetes
• chronic kidney disease.
Asymptomatic Target Organ Damage (TOD)
√
√
Pulse pressure ( in the elderly) >= 60 mmHg
Electrocardiograhic LVH( Sokolow-Lyon index > 3.5 mV; RaVL > 1.` mV; Cornell voltage duration product> 244 mV* ms), or
Echocardiographic LVH [ LVM index: men > 115 g/m2; women > 95 g/m2 (BSA)]a
Carotid wall thickening (IMT > 0.9 mm) or plaque
Carotid- femoral PWV > 10 m/s
Ankle- brachial index < 0.9
CKD with Egfr 30-60 ml/min/1.73 m2 (BSA)
Microalbuminuria (30-300 mg/24 h), or albumin- creatinine ratio(30-300 mg/g; 3.4-34 mg/mmol) (preferentially on morning spot urine)
Combination Rx
• For patients at high risk for cardiovascular events or those
with a markedly high baseline blood pressure
• In those at low or moderate risk for cardiovascular events or
with mildly elevated blood pressure, a single starting agent is
preferred.
• For a high-risk individual, you can't play around with one drug
after another, trying to control blood pressure
Drugs to be preferred in specific conditions
Compelling and possible contra-indications to the use of antihypertensive drugs
Effects of lipid-lowering therapy on CHD events in statin trials
25
20
15
10
5
0
Pat
ient
s w
ith C
HD
eve
nt (
%)
90 110 130 150 170 190 210
S=statin treated P=placebo treated
*Extrapolated to 5 years
4S-P
CARE-P
LIPID-P4S-S
WOSCOPS-SWOSCOPS-P
AFCAPS-PAFCAPS-S
LIPID-S
CARE-S
Primary Prevention
Simvastatin
Pravastatin
Lovastatin
Modified from Kastelein JJP. Atherosclerosis. 1999;143(Suppl 1): S17-S21.
HPS-S
HPS-P
Atorvastatin
ASCOT-S*ASCOT-P*
Secondary Prevention
LDL-C (mg/dL)
Metabolic syndrome was based on the updated NCEP ATP III definition,1
and was defined as 3 of the following prior to open-label run-in: Waist circumference: Men 40 inches (102 cm); Women 35 inches (88 cm)* Triglycerides 150 mg/dL (1.7 mmol/L) HDL-C: Men <40 mg/dL (<1.0 mmol/L); Women <50 mg/dL (<1.3 mmol/L) Blood pressure 130/85 mm Hg Fasting glucose 100 mg/dL (5.6 mmol/L)
TNT Study Design: Post-Hoc Analysis of Patients With Metabolic Syndrome
Atorvastatin 10 mg
Open-label run-in
8 weeks1-8 weeks
Screening and wash-out
Atorvastatin 10 mg
LDL-C target: 100 mg/dL (2.6 mmol/L)
Median follow-up = 4.9 years
Atorvastatin 80 mg
LDL-C target: 75 mg/dL (1.9 mmol/L)
Double-blind periodn=5584
n=2764
n=2820
Baseline
1Grundy SM et al. Circulation. 2005;112:2735-2752.
Metabolic Syndrome Subgroup
*BMI 28 substituted for waist circumference
0 1 2 3 4 5 60
2
4
6
8
10
12
14
16
18
20
Time to First Major Cardiovascular Event in Patients with Metabolic Syndrome (MetS)
Time (years)
Metabolic Syndrome Subgroup
Cu
mu
lati
ve i
nci
den
ce o
f m
ajo
r ca
rdio
vasc
ula
r ev
ents
*
*Coronary heart disease death, nonfatal non–procedure-related myocardial infarction, resuscitated cardiac arrest, fatal or nonfatal stroke Deedwania P et al. Lancet. 2006;368:919-928.
Metabolic syndrome, no diabetesAtorvastatin 10 mg (n=2191)Atorvastatin 80 mg (n=2162)
HR = 0.70 (95% CI: 0.57, 0.84) P=.0002
All metabolic syndromeAtorvastatin 10 mg (n=2820)Atorvastatin 80 mg (n=2764)
HR = 0.71 (95% CI: 0.61, 0.84) P<.0001
First Major Cardiovascular Event in Patients With Metabolic Syndrome: Summary
End point No. of patients (%)
Atorvastatin 10 mg (n=2820)
Atorvastatin 80 mg (n=2764)
Major cardiovascular event* 367 (13.0) 262 (9.5)
CHD death 66 (2.3) 46 (1.7)
Nonfatal non–PR MI 201 (7.1) 139 (5.0)
Resuscitated cardiac arrest
6 (0.2) 10 (0.4)
Fatal/Nonfatal stroke 94 (3.3) 67 (2.4)
*HR = 0.71 (95% CI: 0.61, 0.84)P<.0001
*HR = 0.71 (95% CI: 0.61, 0.84)P<.0001
Metabolic Syndrome Subgroup
Data on file, Pfizer Inc, New York, NY.
Secondary Event Rates in Patients With Metabolic Syndrome (MetS) and Overall
Major coronary 9.9% 7.3%
Cerebrovascular 6.0% 4.5%
PAD 6.5% 6.3%
CHF with hosp. 4.2% 3.1%
All-cause mortality 6.3% 6.2%
Any coronary 29.8% 23.3%
Any CV event 37.6% 30.9%
Event rate (MetS) 10 mg 80 mg
26.5% 21.6%
5.0% 3.9%
3.3% 2.4%
5.6% 5.5%
5.6% 5.7%
8.3% 6.7%
33.5% 28.1%
Event rate (overall) 10 mg 80 mg
Atorvastatin 80 mg better Atorvastatin 10 mg better
Metabolic Syndrome Subgroup
Deedwania P et al. Lancet. 2006;368:919-928.
0.4 0.6 0.8 1.0 1.2 1.4
All-cause mortality
MetS
PAD
MetS
CHF with hospitalization
MetS
Cerebrovascular event
MetS
Any coronary event
MetS
Major coronary event
MetS
Any CV event
MetS
Hazard ratio (95% CI)
Slide SourceLipidsOnline
www.lipidsonline.org
Couillard C et al. Arterioscler Thromb Vasc Biol 2001;21:1226-1232. | Kraus WE et al. N Engl J Med 2002;347:1483-1492. Copyright 2002 Massachusetts Medical Society. All rights reserved.
Treating HDL:Nonpharmacologic Methods Exercise overrated
HDL only when TG high
HDL only with intense, frequent exercise
Alcohol
Raises TG
Affects CETP activity
Modest HDL changes
Smoking cessation
Weight loss
Ch
an
ges
in H
DL-
CC
on
cen
trati
on
(m
g/d
L)
7
4
1
0
-2
P=0.015
Intense
Control
Moderate
Infrequent exercise
Frequent, intense exercise
HDL-C Response to Exercise
Lipids and Exercise Duration of exercise effect on lipids TG increase delays for several hours after exercise and this effect
can persist for 24-48 hours or several days when exercise is prolonged and intense.
Usually HDL begins to rise after >10 weeks of exercise
Single exercise sessions reduce postprandial hyperlipidemia but have no other effect on lipids.
After exercise cessation lipids return on original values
The longer the exercise program lasted the longer the favorable lipid profile remains after exercise cessation.
Smoking Cessation Increases HDL-C Level
• In study by Moffatt, smokers had HDL-C levels 15–20% lower than nonsmokers (P < 0.05).1
– PROCAM showed less of an effect of smoking on HDL-C (7% lower than nonsmokers).2
• HDL-C levels returned to normal within 30–60 days after smoking cessation.1
• In eight women who smoked > 1 packs per day for 5 years, HDL-C levels increased from 51 to 64 mg/dL after quitting for 60 days.1
1. Moffatt RJ. Atherosclerosis 1988;74:85–892. Cullen P et al. Eur Heart J 1998;19:1632–1641
Weight and HDL-C
• Inverse correlation between body weight and HDL-C is consistently observed in both men and women.
• For every 3 kg of weight loss, HDL-C levels increase 1 mg/dL.
Dattilo AM, Kris-Etherton PM. Am J Clin Nutr 1992;56:320–328
Caloric Restriction Acutely Lowers HDL-C Level
• Trials of very-low-calorie diets show that HDL-C levels decrease by 2–12 mg/dL during acute caloric restriction.
• After 12 wks, HDL-C returned to pretreatment range, and this trend was still apparent after 1 year.
• Therefore, benefits of weight-loss programs should not be assessed during acute caloric restriction.
Rössner S et al. Atherosclerosis 1987;64:125–130
Alcohol Increases HDL-C Level
• Alcohol increases HDL-C level in a dose-dependent manner.
• Half bottle of wine per day (39 g alcohol) for 6 weeks significantly increased mean HDL-C level by 7 mg/dL in 12 healthy subjects.1
– Wine intake did not significantly affect Total-C, Total-TG, or LDL-C.1
• One beer per day (13.5 g alcohol) for 6 weeks significantly increased mean HDL-C level by 2 mg/dL in 20 healthy subjects.2
– Beer intake did not significantly affect LDL-C, VLDL-C, TG, or apolipoproteins.
1. Thornton J et al. Lancet 1983;ii:819–8222. McConnell MV et al. Am J Cardiol 1997;80:1226–1228
HDL-C Response to Pharmacological Intervention
ACCORD Study Design
• Overall ACCORD Glycemia Trial: 10,251 participants
• Lipid Trial: 5,518 in Lipid Trial • 2765 randomized to fenofibrate• 2753 randomized to placebo
• Primary Outcome: First occurrence of a major cardiovascular event (nonfatal MI, nonfatal stroke, cardiovascular death)
• 87% power to detect a 20% reduction in event rate, assuming placebo rate of 2.4%/yr and 5.6 yrs follow-up in participants without events.
ACCORD Lipid Trial Eligibility• Stable Type 2 Diabetes >3 months
• HbA1c 7.5% to 11%
• High risk of CVD events = clinical or subclinical disease or 2+ risk factors
• Age (limited to <80 years after Vanguard)• ≥ 40 yrs with history of clinical CVD (secondary prevention)• ≥ 55 yrs otherwise
• Lipids• 60 < LDL-C < 180 mg/dl• HDL-C < 55 mg/dl for women/Blacks; < 50 mg/dl otherwise• Triglycerides < 750 mg/dl if on no therapy; < 400 mg/dl
otherwise
• No contraindication to either fenofibrate or simvastatin
Characteristic Mean or % Characteristic Mean or %
Age (yrs) 62 Total Cholesterol (mg/dl)
175
Women % 31 LDL-C (mg/dl) 101
Race / Ethnicity HDL-C (mg/dl) 38
White % 68 Triglyceride (mg/dl)* 162
Black % 15 Blood pressure (mm Hg)
134/74
Hispanic % 7 Serum creatinine (mg/dl)
0.9
Secondary prevent %
37 Current smoking % 15
DM duration (yrs)* 9 On a statin % 60
A1c (%) * 8.3 On another LLA % 8
BMI (kg/m2) 32 On Insulin % 33
Baseline Characteristics
* Median values
140
150
160
170
180
190
200
0 1 2 3 4 5 6 7
mg
/dl
Years Post-Randomization
Mean Total Cholesterol
Feno
Placebo
N = 5483 5180 4988 4783 5250 3377 1668 491
60
70
80
90
100
110
120
0 1 2 3 4 5 6 7
mg
/dl
Years Post-Randomization
Mean LDL-C
Feno
Placebo
N = 5483 5180 4988 4783 5250 3377 1668 491 N = 5483 5180 4988 4783 5250 3377 1668 491 N = 5483 5180 4988 4783 5250 3377 1668 491
37
38
39
40
41
42
0 1 2 3 4 5 6 7
mg
/dl
Years Post-Randomization
Mean HDL-C
Feno
Placebo
N = 5483 5180 4988 4783 5250 3377 1668 491 N = 5483 5180 4988 4783 5250 3377 1668 491
110
120
130
140
150
160
170
0 1 2 3 4 5 6 7
mg
/dl
Years Post-Randomization
Median Triglycerides
Feno
Placebo
N = 5432 5180 4988 4783 5250 3377 1668 491
Primary Outcome
Rate Rate(%/yr) (%/yr) HR (95% CI) P Value
Primary Outcome: Major Fatal or Nonfatal Cardiovascular Event
291 2.24 310 2.41 0.92 (0.79 - 1.08)
0.32
Fenofibrate Placebo(N=2765) (N=2753)
N of Events
N of Events
Prespecified Secondary Outcomes
Rate Rate(%/yr) (%/yr) HR (95% CI) P Value
Primary + Revasc + hospitalized CHF
641 5.35 667 5.64 0.94 (0.85-1.05) 0.30
Major Coronary Event 332 2.58 353 2.79 0.92 (0.79-1.07) 0.26
Nonfatal MI 173 1.32 186 1.44 0.91 (0.74 - 1.12) 0.39
Total Stroke 51 0.38 48 0.36 1.05 (0.71 - 1.56) 0.80
Nonfatal Stroke 47 0.35 40 0.30 1.17 (0.76 - 1.78) 0.48
Total Mortality 203 1.47 221 1.61 0.91 (0.75 - 1.10) 0.33
Cardiovascular Death 99 0.72 114 0.83 0.86 (0.66 - 1.12) 0.26
Fatal/Nonfatal CHF 120 0.90 143 1.09 0.82 (0.65 - 1.05) 0.10
Fenofibrate Placebo
Outcome
(N=2765) (N=2753)N of
EventsN of
Events