Curiculum Vitae

• Nama : FARIS BASALAMAH

• Tempat/Tanggal Lahir : Tegal, 1 April 1973
• Alamat : Jl. H Mandor 47B, Cilandak.
Jakarta Selatan
• Mobile : +628176661473
• Email : fbslmh@yahoo.com

Riwayat Pendidikan
• 1991 – 1997 S1 Kedokteran Umum FK UNDIP
• 2002 – 2006 S2 Spesialisasi Jantung & Pembuluh darah FK UI
• 2008 – 2009 Intervention Cardiology & Electrophisiology Fellow,PJNHK.
• 2010 Asan Medical Center,Seoul, North Korea
• 2011 CRTD-Device Course IJN, Kualalumpur.

Riwayat Pekerjaan
• Juni 2007 – 2008 Cardiologist @ Klinik Kardiovaskular Hospital Cinere
• Agustus 2009 – Interventional and Electrophysiologist Cardiologist @ Klinik Kardiovaskular Hospital Cinere
• 2010 – Interventional Cardiologist and Electrophysiologist @ RS Mitra Keluarga BekasiTimur
 PERKI Bekasi-Karawang’2018 Workshop

Calcium Channel Blockers in Anti Hypertensive

Treatment : The Role of Lercanidipine

Faris Basalamah, MD FIHA FAPSIC fascc

Cardiologist-Electrophysiologist

PHYSICIAN AND HEAD OF CATHLAB AT RS MITRA KELUARGA BEKASI TIMUR

LECTURER AT UNIVERSITY MUHAMADIYAH JAKARTA
FELLOW OF INDONESIAN HEART ASSOCIATION
FELLOW OF ASIA-PACIFIC SOCIETY OF INTERVENTIONAL CARDIOLOGY
FELLOW of Indonesian Heart RHYTHM SOCIETY
FELLOW OF ASEAN CARDIOLOGY COLLEGE
MEMBER OF ASIA-PACIFIC HEART RHYTHM SOCIETY
 Ny s, 49 tahun

• Hipertensi diketahui sejak 7 tahun lalu

• Mengeluh kaki bengkak
• Rx. Amlodipine 1x5mg, Atenolol 1x50 mg
• Saat ini TD. 160/100 mmHg, Nadi. 55 x/menit
 Hasil pemeriksaan

• EKG: LVH
• Foto Toraks : CTR 53%
• Lab: Ureum 29, Creatinin 0.79, eGFR 89, SGOT/SGPT .
20/23, GD sewaktu 110 mg%, LDL-C. 132 mg%, ACR. 132.6
mg/g, Urin lengkap: albumin (-)
 Burden of Hypertension
 77.9 million (1 in 3) US adults 20 years of
age and older have hypertension.
 69% of people who have a first heart
attack, 77% of those who have a first
stroke, and 74% of those who have heart
failure have a BP >140/90 mmHg.
 Hypertension is associated with shorter
overall life expectancy.

 Poor medication adherence is a major

barrier to effective BP control. only
about 57% remain adherent to their BP
medication at 2 years follow-up.
1. Mozaffarian D et al. Circulation 2015; 131: e29-322.
2. Roger VL, et al. Circulation. 2012;125:e2–e220.
3. Rapsomaniki, E et al. Lancet. 2014;383:1899-1911.
 Direct and indirect costs of CVD and stroke
United States, average annual 2012 to 2013

Direct and Indirect Costs

10%
11%
Heart disease

16% Hypertension
63%
Stroke
Other CVD

A Report From AHA: Heart Disease and Stroke Statistics—2017 Update

 Awareness of Hypertension Status

Normotensive and Hypertensive Unaware Aware No Treated, BP Treated, BP

prehypertensive treatment uncontrolled controlled

Olsen M.H., at al. Lancet. 2016;388;2665-2712.

Treating Hypertension: The Importance of Achieving
Target Blood Pressure
10 mmHg reduction in SBP is associated with
Coronary
All-cause heart disease Heart Renal
mortality Stroke failure failure
0
Relative Risk Reduction (%)

-5
-10

-13

-17
-20

-27
-30 -28

SBP= Systolic Blood Pressure

Ettehad D, at al. Lancet. 2016;387;957-367.

 Optimal Therapy Regimen in Hypertension

Lowering Blood Pressure

1

Reducing Cardiovascular Risk

2

Adherence on treatment
3

Kjeldsen S.E., et al. Drugs R D. 2014;14:31–43.

Peacock E., et al. Med Clin N Am. 2017;101:229–245.
 Blood Pressure Target and Stroke Prevention
in The ONTARGET Study
3
Visit with BP <130/80 mmHg
2,4
2,2 <25%
2 25-49%
50-74%
Stroke
≥75%
Incidence 1,2
(%) 1,1
1

0
N= 9141 4288 2282 1032
SBP 145 133 125 116
DBP 82 76 72 68

Mancia G et al. Circulation 2011; 124: 1727-1736.

 Initial Medications For
The Management of Hypertension (JNC 8)
Lifestyle Modification—
Especially Diet and Exercise

Thiazide-type
diuretic

-blockers should be included in the regimen if there is a

compelling indication for a -blocker

ACE-I
or ARB CCB

James P. A. et al: JAMA. 2014;311(5):507–20.

 Absolute Risk Reduction of Various Outcomes Based on
Various Antihypertensive Drugs
Diuretics ACE Inhibitors ARBs CCBs
0

-2
-5
-5
-7 -7 -7
-10 -9 -9 -9
Absolute -12
Risk Reduction -15
(%) -15
-17
-20

-25
-26
-30
Stroke CHD Heart Failure

Adapted from Thomopoulos C, et al. J Hypertens 2015;33:195-211.

 Common Reasons for Non-adherence

Side
effect
Not
understand Costly
instruction medication

Forgot to Drugs Taking to

Refill Rx Adherence many meds

Rx not Transportation
covered issues
Lack of
communi-
cation

Rx Outcomes Adviser - WordPress.com

 Prognostic of Poor Adherence to
Antihypertensive Therapy
p<0.001

1,00 0.87
1,0 (0.73-1.03)

0,8
0.50
0,6 (0.35-0.69)

0,4

0,2

0,0
Low (<40%) Medium (40-70%) High (≥80%)
Adherence within 6 months after diagnosis
Estimated by Cox proportional models

Mazzaglia et al. Circulation 2009;120:1598-605.

 Evolution of Dihydropyridine CCBs
Short-acting DHP
1st generation
eg, nifedipine

Modified formulation
2nd generation
eg, nifedipine GITS

Long plasma half-life

3rd generation
eg, amlodipine

Long receptor half-life

eg, lercanidipine

Borghi C. Vascular Health and Risk Management 2005:1(3) 173–182.

 Pharmacological Characteristics of
Lercanidipine

1 Ca2+
Extra-Cellular Space
1 Highly selectivity on
vascular

Highly lipophilic, better

2 penetration in cell
2 5 membranes

3 Gradually diffuses into

the calcium channels
3
4 Binding on calcium
channel receptors
4
5 Continuous and ascending
inhibition of the calcium
channel
Calcium Channel (VOC) Intra-Cellular Space

Burnier M, et al. Expert Opin Drug Metab Toxicol, 2009;5(8):981-987.

 24-hour Antihypertensive Efficacy:
Trough-to-Peak Ratio
Telmisartan

Irbesartan

Valsartan

Lisinopril

Captopril

Felodipine

Nifedipine GITS

Amlodipine

Lercanidipine

0 20 40 60 80 100
T/P Ratio (%)

1. Hernandez RH et al. Blood Press Monit. 2001;6(1):47-57. 4. Zannad F et al. Am J Hypertens. 1996;9(7):633-643.
2. McClellan KJ et al. Drugs. 2000;60(5):1123-1140. 5. Gradman AH, et al. Circulation. 2005;111:1012-1018.
3. Diamant M et al. J Hum Hypertens. 1999;13(6):405-412. 6. Hermida RC et al. Hypertens. 2003;42(3):283-290.
 Lercanidipine: Controlling BP over 24 hours
160
SYSTOLIC
140
BP (mmHg)

120

100
DIASTOLIC

80

60 Clock time (h)

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 1 2 3 4 5 6 7 8

Placebo Lercanidipine 20 mg OD Amlodipine 10 mg OD

BP= Blood Pressure

De Giorgio, et al. Curr Ther Res 1999; 60:511-520.

 ELYPSE Study:
Lercanidipine in Daily Clinical Practice
9,059 patients with a 3-month follow-up
80
70 68
Symptoms/adverse events (%)

60 Baseline
49
50 Lercanidipine 10 mg/day
40
30
21 19
20
12 11
10 6,6
3.0 0,6 0,3 1,2 1,2
0
Overall Headache Palpitations Asthenia Ankle edema Flushing

The ELYPSE study. Blood Pressure 2002; 11: 95–100.

 Incidence of Edema with Dihydropyridine CCBs

35 32,8 Amlodipine
30 28,9 Felodipine
Isradipine
25
22.0 Lacidipine
20 Nifedipine
17,6
15,1
16,2 Nitrendipine
15 13,8 14,2
Lercanidipine
9,3
10 8,6 8,2
5,7
5 3,9
2,2

0
Drop outs due to AEs Edema

Adapted from Papavassiliou MV, et al. Am J Hypertens. 2001;14:114A.

 Lercanidipine in Stable Effort Angina Patients
23 patients in a randomized, double-blind, parallel trial. Exercise was performed before (run-in placebo
period) & after 2-week treatment with lercanidipine 10 or 20 mg once daily.

Lercanidipine Lercanidipine Patients with angina during ETT

10 mg/day 20 mg/day Day 0 Day 14
0 100
ST segment depression (mm)

-0,15
-0,3 75
-0,3

% of Patients
-0,6
50
-0,9
25
9
-1,2 -1,1
1
-1,25 0
Lercanidipine Lercanidipine
-1,5
Day 0 Day 14 10 mg/day 20 mg/day

ETT= Exercise Treadmill Test

D. Acanfora D, et al. Am J Ther 2002;9:444-453.

 Lercanidipine in Type II Diabetic Patients
with Hypertension
8-week double-blind study, receiving lercanidipine 10 mg, up-titrated to 20 mg if
sufficient BP control was not achieved after 4 weeks.
Fasting blood glucose HbA1C
170 6,2
Baseline W4 W8 Baseline W4 W8

160
5,9 * *
*
150 * *
*
mg/dl

5,6

%
* *
140
5,3
130

5
120 Lercanidipine Lercanidipine
Lercanidipine Lercanidipine 10 mg/day 20 mg/day
10 mg/day 20 mg/day
N = 38 patients
*p < 0.001 vs. baseline.

Adapted from Viviani G.L. J Cardiovasc Pharmacol 2002; 40: 133-139.

 The DIAL Study:
Renal Protection with Lercanidipine
N=180, mild-to-moderate hypertension, type 2 diabetes, persistent microalbuminuria.
Mean blood pressure reduction Albumin excretion rate reduction
Lercanidipine Ramipril Lercanidipine Ramipril
0 0

-3
-5
-6

mg/day
mmHg

-9 -10

-12
-11,9 -15
-12,7
-15
-14,8
-17,4
-16,2 -20
-18
-19,7
SBP DBP
follow-up range was 9–12 months

Adapted from Dalla Vestra et al. Diabetes Nutr Metab 2004;17:259–66.

Antiproteinuria Effect of Lercanidipine in Patients Previously
Treated with ACE-I or ARB
1 month 3 month 6 month
0
-5
-10 -7,4
-10,4 -10,8
-15
-20
% -25
-30 -29
-35 -33
-40 Changes in mean SBP -37
-45 Changes on proteinuria N=68
-50

ACE-I = Angiotensin Converting Enzyme inhibitor, ARB = Angiotensin II Receptor Blocker

Robles NR, et al. Renal Failure 2010;32:192–197.

 Ny s, 49 tahun

• Hipertensi diketahui sejak 7 tahun lalu

• Mengeluh kaki bengkak
• Rx. Amlodipine 1x5mg, Atenolol 1x50 mg
• Saat ini TD. 160/100 mmHg, Nadi. 56 x/menit
 Hasil pemeriksaan

• EKG: LVH
• Foto Toraks : CTR 53%
• Lab: Ureum 29, Creatinin 0.79, eGFR 89, SGOT/SGPT . 20/23,
GD sewaktu 110 mg%, LDL-C. 132 mg%, ACR. 132.6 mg/g,
Urin lengkap.albumin (-)
 Apa yang akan diberikan?

1. Amlodipine 1x10mg, Irbesaran 1x150mg

2. Amlodipine 1x5mg, Irbesartan 1x300mg
3. Lercanidipine 1x10mg, Irbesartan 1x300mg
4. Lercaridipine 1x 20mg, Irbesartan 1x300mg
5. Atenolol 1x50mg, Irbesartan 1x 150mg
 Follow up

• Lercanidipine 1x20mg, Irbesartan 1x 300mg

• 2 bulan kemudian: kaki bengkak (-)
• TD. 130/80 mmHg, Nadi 62 x/menit, ACR 53 mg/g
• 5 bulan kemudian:
• TD. 120/80 mmHg, Nadi 63 x/menit, ACR 28 mg/g
 Summary
Hypertension is a disease needing life-long lifestyle modifications and
drug therapy.
Despite of many effective antihypertensive drugs, target blood
pressures are reached in only a minority of patients in clinical practice.
Excellent adherence to drug therapy is necessary to achieve blood
pressure control.
The use of antihypertensive agents with a high efficacy in a broad
range of patient categories and a favorable tolerability profile is
important to improve adherence.
Lercanidipine is a third-generation calcium antagonist with a proven
antihypertensive efficacy and lower incidence of adverse effects, in
particular peripheral edema.
T hanks
 BP Goals for Treatment of Hypertension

Chobanian AV. JAMA. 2017;317(6):579-580.

Prevalence of Hypertension and BP Control in
UK between 2005 and 2014
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0% Year
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Normotensive Hypertensive controlled

Hypertensive uncontrolled Hypertensive untreated

Vrijens B, et al. Front Pharmacol. 2017; 8:100.

 Awareness, Treatment, and Control of HBP by
Race/Ethnicity - NHANES: 2011–2014
90 84,1 85,1 85,5
79,8
% of Population with hypertension

77,9 75,8
80 76
69
70
60 57
54,4
49,1 48,3
50
40
30
20
10
0
Awareness Treatment Control
Total population White Black Hispanic

HBP= High Blood Pressure

Benjamin E.J, et al. Circulation. 2017;135: e1-458.

 Comparisons of BP-lowering Treatment Based on
CCB with All Other Drug Classes
Difference
Calcium antagonist Trial RR RR
Outcome SBP/DBP
vs (n) (95% CI) (95% CI)
(mmHg)
All other drug Stroke 27 -0.29/-0.72 0.88 (0.84-0.93)
CHD 27 -0.29/-0.72 1.00 (0.93-1.08)
HF 23 -0.30/-0.74 1.19 (1.09-1.30)
Stroke + CHD 28 -0.28/-0.71 0.95 (0.90-1.01)
Stroke + CHD + HF 23 -0.30/-0.74 1.04 (0.98-1.10)

CV Death 24 -0.23/-0.72 0.96 (0.92-1.01)

All cause Death 28 -0.30/-0.71 0.97 (0.94-0.99)

0.5 1.0 2.0

CCB better Control
better

CHD= Coronary Heart Disease,

HF= Heart Failure,
CV= cardiovascular
CCB= Calcium Channel Blocker, Thomopoulos C, et al. J Hypertens 2015;33:195-211
RR= Relative Risk
Lercanidipine