azeldipine

1. 1
India’s 1st Azelnidipine –
A Confluence of Cardiology,
Diabetology & Nephrology Perspective

2. Overview
 Hypertension Epidemiology
 Azelnidipine
 Drug Profile
 Cardiac Perspective
 Nephro Perspective
 Diabetic Perspective
 Salient Features
2

3. Hypertension World Wide
3

4. Hypertension – Silent Killer
4
A global brief on Hypertension by WHO

5. ACC/AHA – New Guideline
5
2019 ACC/AHA Guidelines
BP Category SBP DBP
Normal <120 mm Hg and <80 mm Hg
Elevated 120–129 mm Hg and <80 mm Hg
Hypertension
Stage 1 130–139 mm Hg or 80–89 mm Hg
Stage 2 ≥140 mm Hg or ≥90 mm Hg
New Goal for BP Levels

6. Indian Guideline of Hypertension: 2019
6
IGH, 2019

7. Treatment Strategy: Hypertension and CAD
7
2018 ESC/ESH Guidelines for the management of arterial hypertension
Treatment Strategy: Hypertension and CKD

8. CALCIUM CHANNEL BLOCKERS
8

9. Non dihydropridines

10. Fourth generation-Cilnidipine

11. Characteristics of CCB’s
Drugs Blocking activity
L-type N-type T-type
Nifedipine + - -
Amlodipine + - -
Cilnidipine + + -
Efonidipine + - +
Azelnidipine + - +
Keio J Med. September 2010 ; 59 (3) : 84－95.

12. Distribution of L-type and Combined
L-/T-type CCB in Large & Microvessels
12
Hypertension. 2009;53:592-594

14. Azelnidipine – Drug Profile
of A Novel CCB
14

15. Chemical Structure - Azelnidipine
15
• Azelnidipine is a new dihydropyridine calcium channel antagonist
• It is L and T type of calcium channel blocker
• Composed of a racemic mixture containing a 1:1 ratio of the
active R-enantiomer and the inactive S-enantiomer
Drugs 2003; 63 (23): 2613-2621

16. Mechanism of Action of Azelnidipine
 Blocks L-Type calcium channel in blood vessel and T-type Calcium
channel in heart
 Results in vasodilation and reduced heart rate
 Shows 17-folds higher lipophilicity than of amlodipine
16
Drugs 2003; 63 (23): 2613-2621

17. Mechanism of Action
 Azelnidipine acts on SA node
 Inhibits T-type Calcium
channel activation
 It prolongs the late phase-4
depolarization
17
 Azelnidipine block T-type Calcium
channel present on zona glomerulosa
 Inhibit Aldosterone synthesis and
release
Drugs 2003; 63 (23): 2613-2621

18. Mechanism of Action on glomerulus
 Azelnidipine dilates Afferent and Efferent arterioles
 Reduces intra-glomerular pressure
 Offers reno-protective effect
18

19. Pharmacokinetic Profile
19
Parameters Azelnidipine
Protein binding rate (%) ≈90%
Tmax (Hr) 2.3-2.7
Terminal Elimination Half life (Hr) 19.2
Excretion 26 % in urine
63 % in feces
Volume of distribution (L) 403.3 ± 710.4
Metabolism • Undergoes extensive first-pass hepatic
metabolism
• Primarily by cytochrome P450 (CYP) 3A4
AUC (h/ml) 81.6 ng
Cmax (ng/ml) 3-13.1
Drugs 2003; 63 (23): 2613-2621

20. Dosage and Indications
 Azelnidipine tablets 16 mg
 For the treatment of Essential Hypertension.
20
CDSCO site
Approved by
DCGI
USE IN SPECIFIC POPULATION
 Severe renal Impairment: Efficacy have not been established
 Severe hepatic impairment: Efficacy have not been established
 Pediatric Use: Efficacy have not been established
 Elderly Use: Low dose (8 mg once daily) is recommended
 Pregnancy: Not recommended
 Nursing mother: Not recommended

21. Adverse Effects
21
http://www.kegg.jp/medicus- in/japic_med?japic_code=00061591

22. Contraindications
 Hypersensitivity to any of the ingredients
 Pregnant and nursing women
 Concomitant administration of systematic azole antifungal agent (e.g.
fluconazole)
 Concomitant administration of HIV protease inhibitor (e.g atazanavir)
22
Drug / Class Action
Azole anti-fungal agent
These drugs Inhibits CYP3A4 and increases
the concentration of Azelnidipine in body
HIV protease inhibitor
Cimetidine
Erythromycin, Azithromycin
Digoxin Cmax of digoxin increases
http://www.kegg.jp/medicus- in/japic_med?japic_code=00061591
Drug Interactions

23. Effects Proven in Pre-clinical Studies
 Negative chronotropic effect 1
 Inhibit Aldosterone synthesis and secretion 2
 Dilate efferent arterioles 3
 Preserves insulin signaling and glucose uptake 3
23
1. Journal of Hypertension 2014, 32:1898–1904
2. Eur J Pharmacol. 2009 Mar 1;605(1-3):49-52
3. Drugs R D (2013) 13:63–73
4. Endocrine Journal 2015, 62 (8), 741-747

24. Azelnidipine
BP Control & Cardio-protection
24
Clinical Evidences
Azelnidipine
Cardiac Perspective

25. 25

26. Azelnidipine Published Strength of Evidence
Total No. of
research
publications
Total No. of
Review
articles
published
No. of
Clinical
Trials till
date
No of
Randomised
trials till date
No. of
meta
analysis
Year of first
research
publication
236 12 51 42 2 1989
Analysis as of Feb 2020
• Evidences evolved over 3 decades
• 8 out of every 10 trial has been under RCCT setting

27. Study 1: Sustained Blood Pressure-Lowering Effect of Azelnidipine
Guided by Self-Measured Morning and Evening Home Blood
Pressure: Subgroup Analysis of the At-HOME Study
• At-HOME study conducted in Japan
• Objective: To evaluate the sustained BP lowering effect of Azelnidipine,
using mean morning and evening systolic BP [ME average] and morning
systolic BP minus evening systolic BP (ME difference).
• Efficacy analysis- N = 4852
• Safety analysis- N = 5265
27
Drugs R D (2013) 13:75–85

28. Clinical Improvement From Baseline
28
Changes in a morning and evening home blood
pressure (BP)
Changes in morning and evening home pulse
rates after Azelnidipine treatment
*p0.0001 vs. baseline, according to Dunnett’s test. DBP diastolic blood pressure, SBP systolic blood pressure
Changes in morning & evening SBP (ME average) & morning SBP minus evening SBP (ME difference) following
Azelnidipine treatment
Drugs R D (2013) 13:75–85

29. Improvement in Patient Distribution
Drugs R D (2013) 13:75–85
29
Changes in patient distribution according to morning and evening systolic blood pressure (ME average) and morning systolic blood
pressure minus evening systolic blood pressure (ME difference) [n = 2,101; p0.0001 vs. baseline according to the McNemar test].
• Significant reduction in home SBP and DBP
• BP-lowering effect lasted till next day morning
• Useful for patients with morning hypertension, who are at high risk
of cardiovascular events, especially stroke.

30. Study 2: Inhibitory Effects of Azelnidipine Tablets on
Morning Hypertension
Treatment: Azlenidipine 8/16 mg once daily for 16 weeks
30
Drugs R D (2013) 13:63–73
• Objective: To determine the BP- and pulse rate-lowering effects of
Azelnidipine, administered once daily in the morning.
• N=5433 Hypertensive patients
156.9 143 140 138.3 137.1
89.7 82.4 80.8 79.8 78.9
BASELINE4 WEEKS 8 WEEKS12 WEEKS
16 WEEKS
Change in Blood pressure
SBP (mmHg) DBP (mmHg)
72.7
69.6
68.8 68.7 68.7
BASELINE 4 WEEKS 8 WEEKS 12
WEEKS
16
WEEKS
Change in Heart rate
Heart Rate (bpm)
• Azelnidipine offered significant reduction in morning BP
and heart rate within 4 weeks

31. Study 3: Azelnidipine and Amlodipine: A Comparison
of their Pharmacokinetics and Effects on ABPM
To compare the effects of Azelnidipine and Amlodipine on 24-h blood
pressure
 A randomized, double-blind Study in Hypertensive patients
 Azelnidipine 16 mg (23 patients) or amlodipine 5 mg (23 patients)
was administered once daily for 6 weeks
31
Hypertens Res. 2003 Mar;26(3):201-8.

32. 32
 Hypertens Res. 2003 Mar;26(3):201-8.
Differences of Blood Pressure (BP) and Pulse Rate (PR) from the
Baseline Values after 6 Weeks of Treatment with Azelnidipine or
Amlodipine
• Both drugs offered 24h BP reduction and have similar antihypertensive effect
• Azelnidipine decrease pulse rate
• Amlodipine significantly increased pulse rate

33. Study 4: Azelnidipine and Amlodipine: A Comparison of Their Effects
and Safety in a Randomized Double-Blinded Clinical Trial in Chinese
Essential Hypertensive Patients
 N=220
 Treatment Azelnidipine 8 and 16 mg. Amlodipine 2.5 and 5 mg
 Duration: 8 Weeks
 ABPM was monitored at baseline and at 8 weeks (N=40)
33
 Clinical and Experimental Hypertension, 32(6): 372–376, (2010)
Changes of blood pressure and pulse rate in azelnidipine or amlodipine group

34. Conclusion
 Azelnidipine significantly reduced BP, and was greater than amlodipine.
34
 Clinical and Experimental Hypertension, 32(6): 372–376, (2010)
Differences of Δ BP after treatment with Azelnidipine or
Amlodipine

35. Study 5: Clinical use of Azelnidipine in
Treatment of Hypertension in Chinese Patients
• Relevant literature identified by from PubMed and CNKI (China
National Knowledge Infrastructure)
• Total of 23 articles selected from 54 articles
35
Therapeutics and Clinical Risk Management 2015:11
Azelnidipine and BP Reduction
• Significant reduction in BP mild-to moderate hypertension, similar to amlodipine and nifedipine
• Showed CV protective effects, anti-oxidative action, reduction in heart rate and improved systolic and
diastolic function
• Well tolerated and no severe adverse events were observed

36. Study 6: Impact of Azelnidipine and Amlodipine on Left
Ventricular Mass & Longitudinal Function in Hypertensive
Patients with LVH
 The study conducted to compare the effects of Azelnidipine & amlodipine on
LV function
 N= 32 hypertensive patients
 Intervention- 5 mg of amlodipine/day and16 mg of Azelnidipine/day.
 LV function and morphology was examined by conventional and speckle
tracking echocardiography at baseline and at 1, 3, 6,and 12 months after
treatment initiation
36
DOI: 10.1111/echo.12548 Echocardiography

37. Study 7: Effects Of Azelnidipine Plus Olmesartan Vs Amlodipine
Plus Olmesartan on Central BP and LVMI: The AORTA Study
 Effects of olmesartan combined with either Azelnidipine or
amlodipine on central blood pressure (CBP) and left ventricular mass
index (LVMI) in hypertensive patients was tested.
 Patients with SBP > 140 mmHg and/or DBP >90 mmHg received
olmesartan monotherapy (20 mg daily) for 12 weeks.
 The patients were then randomly assigned to fixed-dose add-on
therapy with Azelnidipine (16 mg daily) or amlodipine (5 mg daily) (25
patients/group) for a further 24 weeks.
 CBP and LVMI were measured at baseline and at the end of study
37
Vascular Health and Risk Management 2011:7

38. Changes in CBP and LVMI
38
Vascular Health and Risk Management 2011:7 AIx@75: Heart Rate-corrected Augmentation Index
• 24 weeks of combination therapy, olmesartan/Azelnidipine
showed significantly greater decreases in CBP than
olmesartan/amlodipine
• AIx@75, baPWV, & HR showed significantly greater reduction
with olmesartan/Azelnidipine than with olmesartan/amlodipine.

39. Study 8: Effects of Azelnidipine on The Autonomic Functions And
its Influence on Arterial Stiffness and Endothelial Functions
 Azelnidipine on autonomic functions and vascular functions (i.e., arterial
stiffness and endothelial function) were tested
 N= 21 patients (65±9 years old) treated with CCBs
 Patients were switched to Azelnidipine 16 mg/day and benidipine 4
mg/day, alternately for 8 weeks each
 Heart rate variability, baro-receptor sensitivity (BRS), brachial-ankle pulse
wave velocity (baPWV) and flow-mediated vasodilatation (FMD) in the
brachial artery were measured
39
Journal of Cardiology (2008) 51, 114—120

40. BRS and P-R interval – Azelnidipine vs Benidipine
40
*p < 0.05 vs. benidipine treatment; †p < 0.01 vs. benidipine treatment BRS – baroreceptor sensitivity, P-R interval
• Azelnidpine has greater beneficial effects on autonomic
functions than benidipine
• Reduction of the BP was similar
• Azelnidipine improves BRS better than benidipine
• Reduction of heart rate by Azelnidipine might be mediated by
the parasympathetic-dominant state

41. Study 9: Effects of Azelnidipine on Reflex Tachycardia
 95 patients with mild-to-moderate hypertension were treated with
Azelnidipine for 1 year
41
Drugs. 2003;63(23):2613-21; discussion 2623-4.
165.7
95.4
138.2
79.9
SBP(MMHG) DBP (MMHG)
Change in BP (mmHg)
Baseline Series 2
• Azelnidipine significantly reduced BP
• Its use was not associated with reflex tachycardia

42. Study 10: Effect on Sympathetic Nerve Activity
35.1
52.7
30.6
44.1
44.1
61.5
BURST FREQUENCY (BURSTS/MIN) BURST INCIDENCE (BURSTS/100
BEATS)
Change in sympathetic response
Baseline Azelnidipine Amlodipine
42
Journal of Hypertension 2014, 32:1898–1904
• Cross over study in 14 patients with primary hypertension
• Azelnidipine 16 mg and Amlodipine 5 mg
• Azelnidipine offered favorable effect on sympathetic nerve activity
as compare to amlodipine
• Useful for treating hypertensive patients, when hypertension is
associated with HF and IHD

43. Effect of Azelnidipine on muscle sympathetic nerve activity
Journal of Hypertension 2014, 32:1898–1904
Distinctiveness of Azneldipine (3rd Generation CCB)
• Long-acting
• Highly lipid-soluble, hence- Vasodilatory action maintained in vascular wall after
clearance from blood
• Reduces sympathetic nerve activity, contributing to a decreased HR, via a central
inhibitory effect
• Significantly reduces serum noradrenaline levels and the low frequency and high
frequency ratio (indirect surrogate markers of sympathetic nerve activity)
Decreases HR and lowers BP

44. The heart-rate-lowering effect of Azelnidipine
Journal of Hypertension 2014, 32:1898–1904
Underlying mechanisms
• Associated with enhanced vagal efferent effects
• Direct negative chronotropic effect on sinoatrial node contribute to HR
reduction- Negative chronotropic actions on the sinoatrial node are induced by
L-type and T-type CCBs through the prolongation of phase 4 depolarization of
the sinus node action potential
HR reduction caused by azelnidipine may be attributable not only to
sympathetic inhibition, but also to a direct effect on the sinoatrial node

45. Effects of Azelnidipine and amlodipine on
Journal of Hypertension 2014, 32:1898–1904
1. Sympathetic nerve activity
2. Baroreflex function
3. Heart-rate-lowering effect of azelnidipine
Azelnidipine Vs amlodipine, exerts added favorable
effect on sympathetic nerve activity, with lowering of the HR,
in hypertensive patients

46. 46

47. 1. Mean hemispheric CBF was maintained for 6 months,
although systemic BP was significantly lowered
2. Hemispheric CBF was maintained regardless of the
presence of infracted and/or peri-infarcted tissues
3. Regional CBF was also maintained for 6 months
Safely decrease systemic BP without decreasing cerebral
blood flow (CBF) in the chronic stage of ischemic stroke
CCB-SPECT study Hypertension Research (2010) 33, 43–48

48. Azelnidipine useful in hypertensives with post-ischemic stroke
CCB-SPECT study Hypertension Research (2010) 33, 43–48
62-year-old male suffered from
lacunar infarction in left basal
ganglia
(a) MRI image
(b) IMP SPECT image at basal
ganglia at pretreatment
(c) 3 months after azelnidipine
(d) 6 months after
Significant CBF increase in
bilateral hemispheres

49. 1
Azelnidipine
Diabetic Perspective

50. Azelnidipine and Amlodipine on Glucose Tolerance and
Endothelial function (AGENT Trial)
 N=17 non-diabetic patients with essential hypertension, controlled BP with
amlodipine (5 mg/day) were enrolled
 Either Azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a
crossover design for 12-weeks
 At baseline and the end of each CCB therapy, OGTT was performed
50
Cardiovascular Diabetology 2011 10:79.

51. Comparison of 75 g Oral Glucose Tolerance Test
Between Treatment with Azelnidipine and Amlodipine
Cardiovascular Diabetology 2011 10:79.
51

52. Comparison of Laboratory Data and PAT Ratio Between
Treatment with Azelnidipine and Amlodipine
Cardiovascular Diabetology 2011 10:79.
52
Data are mean ± SD. TC; total cholesterol, LDL-C; low-density lipoprotein cholesterol, HDL-C; high-density lipoprotein cholesterol, Hb; hemoglobin, hs-CRP; high
sensitivity C-reactive protein, BNP; brain natriuretic peptide, eGFR; estimated glomerular filtration ratio, GFR(ml/min/1.73 m2) L-FABP, L-type fatty acid binding
protein, alb; albuminuria, U-Cre; urine creatinine, HPC; hematopoietic progenitor cell, PAT: peripheral arterial tonometry. * P < 0.05 vs. baseline. ** Azelnidipine vs.
amlodipine.
Azelnidipine treatment have beneficial effects against glucose intolerance, insulin
sensitivity, inflammatory state in non-diabetic patients with hypertension.

53. Blood pressure control with olmesartan & Azelnidipine
in Type 2 diabetes (BOAT2 study)
To evaluate the efficacy of Azelnidipine and amlodipine on diabetic nephropathy and
atherosclerosis
 A prospective, two-arm, randomized controlled clinical study
 38 hypertensive subjects with type 2 diabetes
 Treatment: Azelnidipine 16 mg/day or amlodipine 5mg/day for 32 weeks
Endpoints:
 Change in BP and heart rate
53
Diabetol Metab Syndr. 2015; 7: 80.

54. BOAT2 Study- Efficacy in Reduction of BP and HR
54
Reduction in BP was similar between both groups
Azelnidipine offered significant reduction in HR than Amlodipine
(p < 0.05)
Diabetol Metab Syndr. 2015; 7: 80.

55. BOAT2 Study- Efficacy In Urinary Albumin Excretion
55
• Azelnidipine offered significant reduction in Urinary albumin
excretion (p < 0.05), amlodipine was not effective
• Urinary albumin excretion in Azelnidipine group was
significantly lowered compared to amlodipine group (p < 0.05)
Diabetol Metab Syndr. 2015; 7: 80.

56. BOAT2 Study- Carotid Intima Media Thickness And
Inflammatory Markers
IMT: Carotid intima-media thickness
MCP -1: monocyte chemoattractant protein 1 (type of cytokine)
TNF: Tumor necrosis factor
56
• Azelnidipine offered significant reduction in Max IMT,
MCP-1and TNF -α compared to amlodipine
• Azelnidipine but not amlodipine, delayed the progression
of urinary albumin excretion and carotid atherosclerosis
(p < 0.05)
(p < 0.05) (p =0.05)

57. Changes in Left Ventricular Relaxation After Azelnidipine
Treatment in Hypertensive Patients With Diabetes: Sub Analysis
of Prospective Single-arm Multicentre Study
57
BMJ Open 2014;4:e006136
• The e-velocity is a marker of the
function of the left ventricle of
the heart.
 Sub analysis of a prospective single-arm multicentre
study
 228 hypertensive patients with normal ejection
fraction and impaired left ventricular relaxation
(septal e-velocity <8 cm/s on echocardiography)
enrolled for CALVLOC trial.
 They were divided into two groups based on
presence or absence of diabetes.
 Administered Administration of 16 mg of
Azelnidipine for 8 months
 Septal e-velocity before and at the end of the study.

58. Changes in LV Relaxation After Azelnidipine Treatment in
Hypertensive Patients With Diabetes
Whereas patients with diabetes (n=53, 23.2%) had lower SBP than Patients
without diabetes (155±17 vs 161±16 mm Hg, p=0.03).
They had lower e’ velocity (5.7±1.5 vs 6.1±1.4 cm/s, p=0.04) at baseline.
Azelnidipine decreased BP and heart rate, and increased e’ velocity similarly
in patients with diabetes (5.7±1.5 to .3±1.5 cm/s, p=0.0003) and without
diabetes (6.1±1.4 to 6.9 ±1.4 cm/s, p<0.0001).
•LV relaxation was more impaired in hypertensive patients with
diabetes than in those without diabetes,
•Azelnidipine improved LV relaxation in both groups to the same
degree
58
BMJ Open 2014;4:e006136

59. Azelnidipine Decreased Plasma Aldosterone & Plasminogen
Activator lnhibitor Type l Levels in Hypertensive Patients
with T2DM
59
 Azelnidipine in treatment of hypertension lead to decrease of Plasma
Aldosterone (PAC) and Plasminogen Activator lnhibitor Type l (PAI-1)
 PAC and PAI-1 involved in the pathogenesis of cardiovascular diseases and
metabolic syndrome
 Azelnidipine decrease PAC independent to plasma renin activity as
compare to Amlodipine, Nifedipine, Benidipine, Cilnidipine and
Felodipine; in the patients with type 2 diabetes mellitus and hypertension
 Based on these results, Azelnidipine exert additional beneficial actions
beyond the antihypertensive action
 One of the suitable CCBs in the treatment of hypertension in the patients
with type 2 diabetes mellitus.
59
Therapeutic Research vol 32 no. 3 2011

60. Effects of Long-term Administration of Azelnidipine
on Insulin Resistance and Adrenal Androgens
 Azelnidipine, on insulin resistance and adrenal androgens in 16 hypertensive
patients with insulin resistance.
 All subjects were treated with Azelnidipine for 12 months
 Azelnidipine treatment lowered BP, HR, F-IRI and HOMA-R significantly.
 Serum levels of DHEA, DHEA-S and adiponectin increased significantly.
 No clinically significant changes in BMI, FPG, HbA1c, ACTH, Cortisol and
aldosterone were observed during treatment
60
https://www.researchgate.net/publication/287525677
BP: Blood Pressure; HR: Heart Rate; F-IRI: Fair Insulin Resistance Index; HOMA-R: Homeostatic model assessment; DHEA:
Dehydroepiandrosterone; DHEA-S: Dehydroepiandrosterone-Sulfate; ACTH: Adrenocorticotropic hormone

61. 6190
Clinical Evidences
Azelnidipine and Kidney
Protection

62. Azelnidipine Reduces Urinary Protein Excretion and
Urinary Liver-Type Fatty Acid Binding Protein in
Patients with Hypertensive Chronic Kidney Disease
 A randomized study
 N= 30 Hypertensive CKD patients
 Azelnidipine 16 mg once daily or amlodipine 5 mg once daily
 Duration 6 months
 Endpoints:
 Change in BP and HR
 Urinary protein excretion and urinary levels of 8-OHdG and urinary
L-FABP measured before 3 and 6 months post treatment
62
Am J Med Sci 2007;333(6):321–326.

63. Effects of Azelnidipine and Amlodipine on BP
Both drugs exhibited similar effects on systolic and diastolic blood
pressure. Azelnidipine exhibited reduction in HR
63
Am J Med Sci 2007;333(6):321–326
74
71 71
76
79 79
66
68
70
72
74
76
78
80
Baseline 3 months 6 months
Change in Heart rate (bpm)
Azelnidipine Amlodipine

64. Effects of Azelnidipine and Amlodipine on Urinary Protein
Excretion (UPE)
64
1.5
1.6
0.9
1.7
0.8
1.7
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
Azelnidpine Amlodipine
Change in UPE (g/day)
Baseline 3 months 6 months
Azelnidipine offered significant reduction in urinary protein
excretion, amlodipine was ineffective in reducing UPE
Am J Med Sci 2007;333(6):321–326.

65. Changes in UPE , Urinary 8-OHdG and Urinary L-FABP
Am J Med Sci 2007;333(6):321–326.
65
Changes of Urinary Protein Excretion (g/day), Urinary 8-OHdG (ng/mg crea tinine), Urinary L-FABP (I¨-g/g crea tinine), Serum
Creatinine (mg/dl) and 24h Ccr (ml/min). Before and 3 and 6 Months After Treatment
L FABP – liver type fatty acid binding protein, 8- OHdG-8-hydroxydeoxyguanosine (8-OHdG), an oxidized nucleoside of DNA

66. Conclusion From Study
 Baseline proteinuria was correlated with baseline urinary L-FABP
levels,
 Azelnidipine ameliorated markers of glomerular and tubule interstitial
injury in hypertensive patients with CKD
 Urinary 8-OHdG is a sensitive biomarker of oxidative DNA damage,
 Excretion of urinary 8-OHdG is significantly correlated with severity of
tubule interstitial lesions
 Azelnidipine but not amlodipine, has potent anti-oxidant effect
 Provide additive clinical benefit in addition to long-lasting
antihypertensive action.
66
Am J Med Sci 2007;333(6):321–326

67. Effects of Azelnidipine on Uric Acid Metabolism
in Patients with Essential Hypertension
 N= 72
 Azelnidipine 8 or 16 mg
 In 22 cases out of the 72 patients, a different CCB was switched
to Azelnidipine
 BP measured and biochemical parameters of blood and urine
were evaluated before and 2–3 months after the administration
67
Clin Exp Hypertens, 2014; 36(7): 447–453

68. Effects of Azelnidipine on Uric Acid Metabolism
in patients with Essential Hypertension
68
Clin Exp Hypertens, 2014; 36(7): 447–453
SBP: systolic blood pressure, DBP: diastolic blood pressure, Cr: creatinine, eGFR: estimated glomerular filtration rate, LDL:
low density lipoprotein, HDL: high-density lipoprotein

69. Effects of Azelnidipine on Uric Acid Metabolism in Patients With
Hypertension
69
Clin Exp Hypertens, 2014; 36(7): 447–453
7.25
6.42
6
6.2
6.4
6.6
6.8
7
7.2
7.4
Change in Uric acid mg/dL
Baseline Aft. Azelnidipine
 Azelnidipine reduces uric acid levels, more in patients with high
serum urate levels
 Azelnidipine is a promising antihypertensive agent for treating
hypertensive patients with hyperuricemia

70. Salient Features
 Azelnidipine offers double digit BP control
 Offers 24 hr. smooth BP control including morning surge, does not cause reflex
tachycardia with noted reduction in heart rate
 Superior sympathetic nerve activity reduction compared to amlodipine –
sympathomodulating CCB
 Reduces proteinuria, reduces glomerular hypertension
 Delays progression of urinary albumin excretion & improves LV relaxation in DM
with hypertension
 Exhibits anti oxidant property, improves endothelial function and arterial stiffness
70

71. Salient Features
 Reduction in B type natriuretic peptide, can be beneficial in improving prognosis
of HF patients
 Preserves insulin signaling and glucose uptake in hypertensive patients with
insulin resistance
 In the chronic stage of ischemic stroke, Azelnidipine could safely decrease
systemic blood pressure without decreasing CBF
 Reduces serum uric acid in hypertensive patients with hyperuricemia
 Exhibits -Cardio-protection, Neuro-protection and renal protection & Lesser
incidences of pedal edema
 Well tolerated
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72. Thank You
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