benefits of azelnidipine in heart

1. Azelnidipine
Cardiac Perspectives

2. Hypertension is a major public health concern
affecting 26% of adults worldwide
Number of
people with HTN
worldwide in 20001
972 million
Increase in the
number of adults with
HTN globally by 20251
60%
Percent of all global
healthcare spending
attributable to high
blood pressure2
10%
Annual worldwide cost of
hypertension2
$370 billion
1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. Gaziano TA, Asaf B, S Anand, et.al. The
global cost of nonoptimal blood pressure. J Hypertens 2009; 27(7): 1472-1477.
1.6 Billion
HTN patients estimated
by 2025

3. Hypertension
Major risk factor for cardiovascular diseases

4. Number
of
Deaths
233
333
SBP 120-129
1071
SBP 130-139 SBP >140
Category
Hazard
ratio
Normal 1.0
Stage 1, New 1.18
Stage 2, New 1.31
Hypertension Increases cardiovascular mortality
in India
Mumbai Cohort Study - To determine cardiovascular related mortality in
148,173 patients with different grades of hypertension
Even mild to moderate elevation of BP is associated with greater risk of
cardiovascular mortality
Mumbai cohort study. Am J Hypertens.2009;22:1076–1084

5. A small reduction in BP can reduce risk of CV
mortality
Lancet. 2002;360:1903-1913
Smaller
reduction
Higher
benefits

6. Management of hypertension significantly
reduces CV events
Average
reduction
in
events
(%)
35%-40%
20%-25%
>50%
–60
–50
–40
–30
–20
–10
0
Stroke
Myocardial
Infarction Heart failure
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000;355:1955-1964.

7. Role of Calcium Channel Blockers in
Hypertension

8. Classification and effects of CCBs

9. Dihydropyridine CCBs and action on CV system
Strong Vasodilators

10. Calcium channels and their actions on
Cardiovascular system

11. MOA of all CCB in hypertension
Blocks L type Calcium channels in
heart and blood vessels
Int. J. Mol. Sci. 2020, 21, 4709;
Prevents Vasoconstriction

12. Why there is Need of New CCB??

13. Drawbacks of old CCBs
• Blocks only L type channels:
– Rapid and short acting
– Less selectivity to L channels on blood vessels and Heart
• Do not block T channels in heart:
– Increased Heart Rate and Pulse rate
– Causes Reflex tachycardia
– Increased sympathetic nerve activity
Risk of future CV
events

14. Drawbacks of Amlodipine
Increased Reflex Tachycardia
Do not block T channels on SA node in heart
↑ SA node activity
↑ Reflex Tachycardia
↑ Heart Rate &↑ BP variability

15. Azelnidipine
The Dual L and T Calcium Channel Blocker

16. Azelnidipine MOA
Blocks L type Calcium channels in
blood vessels and Heart
Drugs 2003; 63 (23): 2613-2621

17. Azelnidipine blocks cardiac T channels
Reduces Reflex Tachycardia
Drugs 2003; 63 (23): 2613-2621
Blocks T-Calcium channel in SA node
Reduces SA node activity
Also Blocks T- Ca channels in Heart
↓Reflex Tachycardia
↓Heart Rate &↓BP variability

18. Azelnidipine blocks T channels in Brain
Inhibit sympathetic nervous system activity
•Azelnidipine by blocking T channels
in brain exert direct inhibition on the
sympathetic nervous activity
•Reduces central norepinephrine
release
•Better cardioprotection
Norepinephrine
Azelnidipine
blocks T
channels
↓ Arterial stiffness
↑ Endothelial function
vasodilation
↓Renin
↓contractility

19. Whats new about Azelnidipine

20. Azelnidipine Cardioprotective effects

21. Better reduction in morning BP and pulse rate
At HOME study
156.9 143 140 138.3 137.1
89.7
82.4 80.8 79.8 78.9
BASELINE 4 WEEKS 8 WEEKS 12 WEEKS 16 WEEKS
Change in Blood pressure
SBP (mmHg) DBP (mmHg)
-19.3
-10.2
Kario K et al. Drugs R D (2013) 13:63–73
N= 5433 treated with Azelnidipine 16 mg daily for 16 weeks
Early morning BP control reduces risk of CV events

22. Superior 24 hour BP control than Amlodipine
Zhao Xiuli et al. Clinical and Experimental Hypertension, 32(6): 372–376, (2010)
N= 202 Treated wih Azelnidipine 8/16 mg(n=101) and Amlodipine 2.5 and 5 mg(n=101)

23. Better Heart Rate reduction compared to
Cilnidipine in Diabetes
-4.6
-5
-2.2
-3.3
-2.6
-1.1
-6
-5
-4
-3
-2
-1
0
24 hr HR Daytime HR Night time HR
Change
in
Heart
Rate
(beats/min)
Change in Heart Rate after 16 weeks
Azelnidipine
Cilnidipine
Azelnidipine blocks T channel on SA node in heart
Reduced Reflex Tachycardia with Azelnidipine shows beneficial CV effects
Abe H. J Diabetes Investig. 2013 Mar;4(2) 202-205
N=19 type 2 diabetics

24. Cardiovascular protection with Azelnidipine

25. Azelnidipine shows Lesser Reflex Tachycardia
than Amlodipine
Inomata Jun-ichiro et al. Journal of Hypertension 2014, 32:1898–1904
N= 14 hypertensive patients without diabetes mellitus or chronic kidney disease treated
with Azelnidipine (16 mg) or amlodipine group (5 mg) daily for 8 weeks
Azelnidipine bocks cardiac T channel and reduces SNS 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

26. Azelnidipine shows Lesser Reflex Tachycardia
than Amlodipine
Reduced catecholamines and improved Baroreceptor sensitivity
Inomata Jun-ichiro et al. Journal of Hypertension 2014, 32:1898–1904
BRSRR, baroreflex control of heart rate; BRSMSNA, baroreflex control of MSNA

27. Azelnidipine reduces sympathetic hyperactivity
in Heart Failure patients after switching from
Cilnidipine
Azelnidipine inhibits cardiac sympathetic nerve hyperactivity of the central system, whereas cilnidipine has
inhibitory action of cardiac sympathetic nerve hyperactivity in the periphery.
42.9
39.6
37
38
39
40
41
42
43
44
Cilnidipine Azelnidipine
Reduced sympathetic overactivity (%)
Kiuchi S. Int Heart J 2018; 59: 120-125
N=24 Heart Failure patients
Azelnidipine bocks cardiac T channel and reduces SNS hyperactivity
Lesser Reflex Tachycardia

28. Azelnidipine shows better Antiatherosclerotic
effect
• 1.Initial treatment with azelnidipine for essential hypertension:
– 18 patients treated with Azelnidipne 16 mg daily
– Blood pressure and pulse rate and inflammatory markers were
measured be-fore and after administration for 3 and 6 months
• 2. Switch from Amlodipine to azelnidipine:
– 17 patients who had been under treatment with amlodipine for 1
month or longer were switched to azelnidipine 16 mg
Nada et al. Arzneimittel-Forschung (Drug Research) 2007;57(11):698–704

29. Azelnidipine shows better Antiatherosclerotic
effect
Nada et al. Arzneimittel-Forschung (Drug Research) 2007;57(11):698–704
Azelnidipine lipophilicity is 17 times higher than amlodipine showing a high
lipoprotein binding activity and stronger antiarteriosclerotic effect

30. Azelnidipine reduces arterial stiffness and
improves Endothelial function
Reduced Arterial stiffness
Reduced Pulse Velocity
Improved Endothelial function
Reduced IMT
Nada et al. Arzneimittel-Forschung (Drug Research) 2007;57(11):698–704

31. Improved LV function with Azelnidipine
Clinical impact of Azelnidipine on Left VentricuLar diastolic
function and OutComes in patients with hypertension
(CALVLOC)
N=232 (1) azelnidipine 16 mg was administered to patients as a first-line therapy (n=160) (2) amlodipine
5 mg was converted to azelnidipine (n=72) for 24 weeks
Ito Hiroshi et al.Hypertension Research (2009) 32, 895–900

32. Azelnidipine has Anti-inflammatory and
Antioxidant effect
Komoda H. Clinical and Experimental Hypertension, 32, 121–128, 2010
Azelnidipine reduces oxidative stress by reducing central and
peripheral sympathetic activity
8-OHdG:8-hydroxy-2-deoxyguanosine
Reduced hsCRP,IL-6,IL-8 and oxidative stress markers
N=16 CAD patients treated with Azelnidipine 16 mg and amlodipine 5 mg for16 weeks

33. Comparison of CCB’s
Keio J Med. September 2010 ; 59 (3) : 84－95.

34. Summary
• Hypertension is one of the key factors for high CV mortality
• CCBs are one the mainstay for tretament of hypertension
• Old generation L type CCBs are devoid of cardiac T channel
blockade thus has potential risk of Reflex tachycardia
• Azelnidipine,a third generation dual L and T CCB shows lesser reflex
tachycardia owing to additional T channel bockade
• Azelnidipine inhibits sympathetic nerve hyperactivity of the central
system by T channel blockade, thus providing better CV protection
• Azelnidipine owing to its additional
antiatherosclerotic ,antioxidant,antiinflammatory action provides
better CV protection than older CCBs
• Based on clinical evidences and dual L/T blockade action
Azelnidipine holds prominent place in hypertension therapy in
future

35. Thank You