INTENSITY OF

CHOLESTEROL
LOWERING WITH STATIN IN
PATIENTS WITH CAD
Dr. Henry A. P. Pakpahan, SpJP, FIHA, FAsCC
SMF Jantung dan Pembuluh Darah Primaya Bekasi Barat
PERKI JAYA
Key Facts of Cardiovascular Disease
– CVD are the number 1 cause of death globally: more people die annually from
CVDs than from any other cause
– + 17.9 million people died from CVDs in 2016, representing 31% of all global
deaths. Of these deaths, 85% are due to heart attacks and stroke.
– Most CVD can be prevented by addressing behavioural risk factors such as
tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of
alcohol using population-wide strategies.
– People with CVD or who are at high CV risk (hypertension, diabetes,
hyperlipidaemia or already established disease) need early detection and
management using counselling and medicines, as appropriate.
https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
Faktor Risiko “Dapat dimodifikasi” vs
“Tidak Dapat dimodifikasi”

www.obesityaction.org
 Dyslipidemia: Strong CVD Risk Factor

• With the decline of cigarette smoking, dyslipidemia has become

the number one modifiable risk factor for vascular disease.
• In the INTERHEART case-control study (27.098 participants; 52
countries)  dyslipidemia (elevated ApoB/ApoA1) had the
highest mortality odd ratio (3.25), followed by smoking (2.87),
psychosocial factors (2.67), and history of diabetes (2.37), and
hypertension (1.91).
• In a prospective study of 27673 women, in addition to Apos, CVD
risk was also strongly related to nuclear magnetic resonance
measures of dyslipidemia and standard lipids (TC/HDL-C).
Hendrani AD, et al. World J Cardiol 2016;8(2):201-210
INTERHEART Study
Risk factors for AMI in
South Asians in the
INTERHEART Study. The
population attributable
risks show that certain risk
factors such as high Apo
B/A1 ratio, smoking or
tobacco use, high waist-
hip ration, lack of exercise
and low consumptin of
fruits and vegetables are
more important risk
factors
INTERHEART Study
 Patofisiologi Aterosklerosis:
Peranan Lipid dan Lipoprotein
• Semua lipoprotein mengandung Apo-B dengan <70nm dapat
melewati endothelial barriers, apalagi bila terdapat disfungsi
endotel.
• Bila lipoprotein berinteraksi dengan
materi ekstraselular seperti proteoglikan,
lipoprotein terperangkap di subendotel.
• Interaksi lipoprotein dan proteoglikan
menimbulkan proses kompleks yang
menginisiasi deposisi lipid dan pembentukan
www.lifelinecelltech.com
ateroma.
2019 ESC-EAS Guidelines for the Management of Dyslipidaemias
 Patofisiologi Aterosklerosis:
Peranan Lipid, Lipoprotein, Inflamasi

PROSES YANG
SANGAT KOMPLEKS!!

Raggi P, et al. Atherosclerosis 2018;276:98-108

 Patofisiologi Aterosklerosis:
Peranan Lipid dan Lipoprotein
Konsentrasi kolesterol LDL

Konsentrasi lipoprotein lain

yang juga mengandung ApoB

Durasi pajanan

– Ketiga hal di atas menjadi penentu beban plak aterosklerotik. Pentingnya

durasi pajanan menjadi sebuah argumen kuat pentingnya pola hidup sehat
untuk menekan kedua faktor lain untuk menghambat proses
aterosklerosis.
2019 ESC-EAS Guidelines for the Management of Dyslipidaemias
 Treating Dyslipidemia Offers
Significant CV Protection
CHOLESTEROL TREATMENT TRIALISTS (CTT)
– More than 170 000 pts in 26 RCT
– For each 1 mmol/L reduction in LDL-C, statin reduced:
– major vascular events (MI, CAD death, or any stroke or coronary revasc)
by ~22%;
– major coronary events by 23%;
– CAD death by 20%;
– total stroke by 17%; and
– total mortality by 10% over 5 years
The relative benefits were half as large in the 1st year as compared with
subsequent years. 2019 ESC-EAS Guidelines for the Management of Dyslipidaemias
 Guidelines identify four statin benefit groups

Group 1 Group 2

Clinical ASCVD LDL-C ≥190 mg/dL

CHD, stroke, and
peripheral arterial
disease, all of presumed
atherosclerotic origin

Group 3 Group 4

Diabetes mellitus ASCVD risk ≥7.5%

using Pooled
+ age of 40–75 years Cohort Equations
+ LDL-C 70–189 mg/dL
No diabetes
+ age of 40–75 years
+ LDL-C 70–189 mg/dL
ASCVD, atherosclerotic cardiovascular disease
CHD, coronary heart disease
LDL-C, low density lipoprotein-cholesterol Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print11
 Specific statin for specified
intensity
High-intensity Moderate-intensity ↓ Low-intensity
↓ LDL-C by ≥50% LDL-C by 30–50% ↓ LDL-C by <30%*
Atorvastatin (40)–80 mg 10–20 mg –
Rosuvastatin 20–40 mg 5–10 mg –
Simvastatin – 20–40 mg 10 mg
Pravastatin – 40–80 mg 10–20 mg
Lovastatin – 40 mg 20 mg

Fluvastatin XL – 80 mg –
Fluvastatin – 40 mg bid 20–40 mg
Pitavastatin – 2–4 mg 1 mg
Bold: Statins and doses evaluated in RCTs
Italics: Statins and doses approved by US FDA but not tested in RCTs reviewed
*Should be used in patients unable to tolerate moderate-to high-intensity therapy
Asian ancestry may modify the statin dose prescribed

Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print
Reproduced with kind permission from American College of Cardiology Jan 201412
 A Randomized Trial of Rosuvastatin in the Prevention
of Cardiovascular Events Among 17,802 Apparently Healthy
Men and Women With Elevated Levels
of C-Reactive Protein (hsCRP):
The JUPITER Trial
• 17,802 apparently healthy men and women with LDL-C <130 mg/dL,
hsCRP ≥2.0 mg/L to rosuvastatin 20 mg daily or placebo
• Combined primary end point of MI, stroke, arterial revascularization,
hospitalization for unstable angina, or death from CV causes.

Ridker PM, et al. JUPITER Trial. N Engl J Med 2008;359:2195-207

Lipid and hsCRP Levels during the follow-up period

Ridker PM, et al. JUPITER Trial. N Engl J Med 2008;359:2195-207

Outcomes according to study group

Ridker PM, et al. JUPITER Trial. N Engl J Med 2008;359:2195-207

Outcomes according to study group

Ridker PM, et al. JUPITER Trial. N Engl J Med 2008;359:2195-207

Outcomes according to study group

Ridker PM, et al. JUPITER Trial. N Engl J Med 2008;359:2195-207

 Safety

Ridker PM, et al. JUPITER Trial. N Engl J Med 2008;359:2195-207

Clinical Importance of Achieving LDL-C < 70 mg/dL and hsCRP < 2 mg/L
Following Initiation of Statin Therapy

PROVE IT – TIMI 22 A to Z
NEJM 2005;352:20-28. Circulation 2006;114:281-8
 NICE lipid guidelines: statin intensity categories
are based on LDL-cholesterol reduction
Statin LDL-cholesterol reduction
Dose (mg/day) 5 10 20 40 80
Fluvastatin – – 21%1 27%1 33%2
Pravastatin – 20%1 24%1 29%1 –
Simvastatin – 27%1 32%2 37%2 42%3§
Atorvastatin – 37%2 43%3 49%3 55%3
Rosuvastatin 38%2 43%3 48%3 53%3 –

1
20–30% reduction in LDL-C: low-intensity statin
2
31–40% reduction in LDL-C: medium-intensity statin
3
>40% reduction in LDL-C: high-intensity statin
§ Advice from UK Medicines and Healthcare products Regulatory Agency (MHRA). There is an increased risk of myopathy associated with high-dose (80
mg) simvastatin. The 80 mg dose should be considered only in patients with severe hypercholesterolemia and high risk of cardiovascular complications
who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks

The information used to make the table is from Law MR et al BMJ 2003;326:1423
National Institute for Health and Care Excellence
Lipid modification July 2014 http://www.nice.org.uk/Guidance/CG181
Treatment targets and goals for CVD prevention

2019 ESC-EAS Guidelines for the Management of Dyslipidaemias

Recommendations for pharmacological
LDL–C Lowering

2019 ESC-EAS Guidelines for the Management of Dyslipidaemias

 SIMPULAN
 LDL-C merupakan faktor risiko kuat kejadian kardiovaskular
 Kontribusi LDL-C terhadap aterosklerosis melibatkan sebuah proses
yang kompleks, termasuk proses inflamasi dalam dinding vaskular.
 Manfaat terbesar diperoleh pada penurunan LDL-C paling besar.
 Pemilihan statin didasarkan pada kekuatannya untuk menurunkan LDL-
C, dengan manfaat terbesar ada pada “high-intensity statin.”
 Sebagian besar CVD dapat dicegah dengan penguatan perilaku yang
positif terhadap pencegahan faktor risiko. Karena itu, perilaku sehat
harus tetap menjadi prioritas pengobatan dislipidemia.