Global Risk of Cardiovascular

Disease: Assessment and Application

Dadang Hendrawan

PKB Kardiovaskular XVII

Atria Hotel, 7 July 2018
 Atherosclerotic Cardiovascular Disease
• Atherosclerotic cardiovascular disease
(ASCVD)
– Atherosclerosis  thickening of the walls of the
arteries, a process that occurs slowly and ‘silently’
over decades
– Major health issues
– Accounts for mortality worldwide
Sanz J, Fayad, ZA. Nature Imaging Ather Cardiovasc 2008; 451: 953-957
Development of atherosclerotic lesion
Foam Fatty Intermediate Fibrous Complicated
cells streak lesion Atheroma plaque lesion/rupture

Endothelial dysfunction
From first decade From third decade From fourth decade
Smooth muscle Thrombosis,
Growth mainly by lipid accumulation and collagen haematoma

Kiechl S et al. Eradicate Cardiovascular Disease 2008

 CVD mortality in Asia

Ueshima H, et al. Circulation. 2008;118:2702-2709

RISK CATEGORIES
 Natural history of CVD

Natural history of cardiovascular diseases and its correspondence

with some lifestyle and biochemical/physiological characteristics
O’Donnell CJ, Elosua E. Rev Esp Cardiol 2008;61(3):299-310
 CVD Risk Factors
Lipids
Others: Hyperten
genetic sion

Risk
Obesity factors Smoking

Physical
Diabetes
inactivity

O’Donnell CJ, Elosua E. Rev Esp Cardiol 2008;61(3):299-310

 Current guidelines
• The new guidelines simplify the approach to
cholesterol lowering
• Statin therapy is highlighted because there is
less evidence that non-statin drug treatment
reduces the likelihood of cardiovascular
events or stroke
Gorelick PB, et al. Stroke 2014;45:945-947
 Primary prevention: Major role of statin therapy
• Statin therapy is recommended for primary prevention
of ASCVD
• Based on RCTs, statin reduce morbidity and mortality
associated with ASCVD
• Cost-effective: many statins are now generic
• Lifestyle modification also critical to primary
prevention efforts
– Healthy diet: low sweets, high fibers, less sodium
– Regular moderate ro vigorous physical activity
ACC/AHA guidelines 2013
4 primary groups for statin therapy

With elevation of
Clinical ASCVD
LDL-C ≥190 mg/dL

Ages 40 to 75 years who

have an LDL-C 70 to 189 An estimated 10-
mg/dL with a history of
diabetes mellitus year ASCVD risk
regardless of the ≥7.5%
presence of ASCVD

Gorelick PB, et al. Stroke 2014;45:945-947

Lipid Management Recommendation

O’Gara et al. 2013 ACCF/AHA STEMI Guideline. JACC Vol.61.No.4.2013:e78-140

 Lipid management recommendation
• Treatment with statins in patients with stabilized after
ACS (include STEMI) lower the risk of CHD, death,
recurrent MI, stroke, and coronary revascularization
• Only High-Dose Atorvastatin has been shown to reduce
death and ischemic events among patients with ACS
• Statin therapy after ACS is beneficial even in patients
with baseline LDL<70 mg/dL
O’Gara et al. 2013 ACCF/AHA STEMI
Guideline. JACC Vol.61.No.4.2013:e78-140
O’Gara et al. 2013 ACCF/AHA STEMI Guideline. JACC Vol.61.No.4.2013:e78-140
 PROVE-IT TIMI 22: Atorvastatin for
reduction of CV risk in patients with ACS
Study design highlights
Patient population:
 Enrolled at 349 sites in
Double-blind period
eight countries Atorvastatin 80 mg/d
 Men and women,
aged ≥18 years 4162
 Hospitalized for an ACS in the preceding 10 patients
days
 Total-C ≤240 mg/dL or total-C ≤200 mg/dL if
Pravastatin 40 mg/d
receiving lipid-lowering therapy
Mean 2-year follow-up
Primary endpoint: (925 primary events)
 Time to the first occurrence of a major CV event

Cannon CP, et al. N Engl J Med 2004;350:1495–1504

 PROVE-IT: Atorvastatin reduces CV risk in patients with ACS
 PROVE-IT: atorvastatin 80 mg reduced the risk of death or a major CV event by 16%
(p=0.005) compared with pravastatin 40 mg in patients with ACS
Incidence of death or major CV events*
30 16%
Death or major CV event

RRR
25 95% CI,
5 to 26%
20 (p=0.005)
(%)

15 ARR 3.9%
NNT 26
over 2 years
10
Pravastatin 40 mg (n=2063). Median LDL-C 95 mg/dL
5 Atorvastatin 80 mg (n=2099). Median LDL-C 62 mg/dL

0 *Major CV events: MI, unstable

angina requiring hospitalization,
0 0.5 1.0 1.5 2.0 2.5 revascularization, and stroke
Time (years)
Cannon CP, et al. N Engl J Med 2004;350:1495–1504
From New England Journal of Medicine, Cannon CP, et al. Intensive versus
Moderate Lipid Lowering with Statins after Acute Coronary Syndromes, 350, 1495–1504.
Copyright ©(2004) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society
 PROVE-IT: Benefit of atorvastatin over
pravastatin was evident at 30 days
• PROVE-IT: atorvastatin 80 mg reduced the composite triple endpoint (death, MI, or
rehospitalization for ACS) within 30 days of randomization
• This benefit remained stable from 30 days onward
28%
Death, MI, or rehospitalization

5
ARR 1.2% NNT=83 over 30 days RRR
4
for ACS (%)

HR 0.72
3 95% CI,
0.52 to 0.99
(p=0.046)
2

1 Pravastatin 40 mg (n=2063). Mean LDL-C at 30 days=88 mg/dL

Atorvastatin 80 mg (n=2099). Mean LDL-C at 30 days=60 mg/dL

0
0 5 10 15 20 25 30
Time (days following randomization)
Ray K, et al. JACC 2005;46:1405–1410
Reprinted from Journal of the American College of Cardiology, Volume 46, Ray K, et al. Early and Late Benefits of High-Dose Atorvastatin
in Patients With Acute Coronary Syndromes, 1405–1410. Copyright (2005), with permission from Elsevier
 Statins eliminated by hepatic route are preferred →
Atorvastatin is the only high-intensity statin eliminated by
hepatic route
 Summary
• Acknowledgement of ASCVD risk factors may be helpful in preventing CVD
– The first step in this process is the calculation of individual cardiovascular risk
according to risk factor exposure
• The new lipid guideline is moving beyond LDL-C target to ASCVD risk
reduction and recommends
– High-intensive statin treatment is recommended in patients wit ACS and coronary
heart disease
• Safety aspect needs to be considered when choosing moderate to high
intensity statin treatment, especially in special patients population such as
ACS and CKD patients
• Recent clinical trials suggest that atorvastatin shows a significant renal
safety profile