Azelnidipine.pptx

Hypertension is a common medical and social problem leading to cardiovascular diseases worldwide. Antihypertensive drugs are clinically applied to decrease the morbidity and mortality induced by hypertension itself and its complications. The 2014 hypertension guideline of the Eighth Joint National Committee (JNC8) for hypertension therapy in the United States has made several significant changes with respect to the clinical management of hypertension and the initiative medications, as compared with the previous guidelines. In addition to the instructions that pharmacologic treatment should be initiated when blood pressure (BP) is 150/90 mmHg or higher in adults over 60 years, 140/90 mmHg in adults younger than 60 years, or 140/90 mmHg or higher (regardless of age) in patients with hypertension and diabetes, a thiazide-type diuretic, calcium (Ca2+) channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) should be considered to start an initial antihypertensive medication in non-black population. In black population with or without diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. Thus, CCB has become one of the most important initial agents for antihypertensive monotherapy. Furthermore, since CCBs have been proved not to increase the risk of coronary events and stroke,CCBs appear to be a favorable choice for monotherapy as well as for combination with other agent classes in the treatment of hypertension and may provide specific benefits beyond BP lowering.Nowadays, dihydropyridine (DHP) CCBs are one group of most frequently prescribed antihypertensive medications in China and other Eastern Asian countries.

1. AZELNIDIPINE – CCB with a Difference

2. Hypertension Global Prevalence World Health Organization (WHO)-  https://www.who.int/news-room/fact-sheets/detail/hypertension >1.13 billion people worldwide have hypertension 1 in 4 men 1 in 5 women

3. Hypertension Prevalence in India Indian Heart Journal 2019; 71: 309-313 Around 234 million people have hypertension in India One in every 3 adults

4. Hypertension is a gateway for CV diseases

5. Hypertension Trends in India https://www.hindustantimes.com/india-news/6070-indians-with-hypertension-unaware-of-their-condition-study-101629971301949. html (Accessed on 29th July 2022)

6. Drugs for managing Hypertension

7. Hypertension Management Guideline 2018 ESC/ESH Guidelines. European heart journal. 2018;39(33):3021-104.

8. CALCIUM CHANNEL BLOCKERS NON-DIHYDROPYRIDINES DIHYDROPYRIDINES Phenylalkamines Benzothiazipine Eg . Diltiazem Eg : Verapamil 1 st Generation 2 nd Generation 3 rd Generation 4 th Generation Eg : Nifedipine Nicardipine Eg : Manidipine Benidipine Efonidipine Eg : Amlodipine Azelnidipine Felodipine Eg : Cilnidipine Lercanidipine Lacidipine

9. Calcium Channels Blocked & Clinical Significance

10. Limitations of Conventional DHP CCBs Pedal edema Reflex tachycardia Elevated proteinuria

11. Azelnidipine Mechanism of Action Decreases BP & HR Drugs 2003; 63(23): 2613-2621 Azelnidipine acts on SA node  Inhibits T-type Calcium channel activation  Prolongs the late phase-4 depolarization

12. At-HOME Study - Azelnidipine controls morning hypertension and reduces pulse rates significantly 1 . J-CORE Study - Azelnidipine + ARB improved BP variability & arterial stiffness in addition to BP reduction 2 . The AORTA Study - Azelnidipine + ARB causes a greater reduction in central blood pressure and left ventricular mass index than Amlodipine + ARB 3 . Hypertension Research Study - Azelnidipine + ARB is more effective in reducing albuminuria in hypertensive diabetic patients with CKD than Amlodipine + ARB 4 . AGENT Study – Azelnidipine may have beneficial effects on glucose tolerance and the insulin sensitivity in patients with essential hypertension. 1. Drugs R D 2013; 13(1): 63-73.; 2. Hypertension. 2012;59:1132- 1138; 3. Vasc Health Risk Manag . 2011; 7: 383–390. 4. Hypertens Res 34, 935–941 (2011) 5. Cardiovasc Diabetol 10, 79 (2011). . Azelnidipine Major Clinical Trials

13. Changes of ABPM in patients receiving azelnidipine or amlodipine Clinical and Experimental Hypertension 2010; 32(6): 372–376 Azelnidipine effectively controlled blood pressure and had a stable action over 24 h

14. Azelnidipine causes a greater reduction in BP and HR than Amlodipine after 8 weeks of treatment Hypertension research. 2006 Oct;29(10):767-73. Newly diagnosed patients Currently treated patients

15. Azelnidipine + ARB causes a greater reduction in BP as compared to Amlodipine + ARB Takami et al. Vascular health and risk management. 2011;7383. Azelnidipine + ARB Amlodipine + ARB

16. Cardio-protective Effects of Azelnidipine

17. Azelnidipine + ARB causes a reduction in HR while Amlodipine + ARB increases HR Takami et al. Vascular health and risk management. 2011;7383. Azelnidipine + ARB Amlodipine + ARB

18. Azelnidipine lowers BP and improves LV diastolic function in hypertensive patients with diastolic dysfunction Hypertension Research (2009) 32, 895–900; doi:10.1038/hr.2009.119; Azelnidipine reduced systolic and diastolic BP by 26 and 11 mmHg, respectively Azelnidipine increased the e’ velocity, and decreased the E/ e’ratio and BNP level A study evaluated 232 hypertensive patients with diastolic dysfunction Azelnidipine decreased heart rate by 3 beats per minute

19. Azelnidipine + ARB causes a greater reduction in augmention index than Amlodipine + ARB Takami et al. Vascular health and risk management. 2011;7383. Azelnidipine + ARB Amlodipine + ARB A decrease in augmentation index indicates a decrease in arterial stiffness

20. Azelnidipine + ARB causes a greater reduction in brachial-ankle pulse wave velocity than Amlodipine + ARB Takami et al. Vascular health and risk management. 2011;7383. Azelnidipine + ARB Amlodipine + ARB A decrease in baPWV indicates a decrease in arterial stiffness

21. Azelnidipine + ARB causes a greater reduction in left ventricular mass index than Amlodipine + ARB Takami et al. Vascular health and risk management. 2011;7383. Azelnidipine + ARB Amlodipine + ARB A decrease in LVMI indicates a decrease risk of CV events

22. Azelnidipine Decreases Aldosterone Secretion Drugs 2003; 63(23): 2613-2621 Mechanism of Action Azelnidipine block T-type calcium channel present on zona glomerulosa. Inhibit Aldosterone synthesis and release.

23. Azelnidipine + ARB causes a greater reduction in plasma aldosterone as compared to Amlodipine + ARB Hypertension Research (2011) 34, 935–941 Azelnidipine + ARB significantly reduced Aldosterone level from 91.9 to 74.1 pg /ml (P<0.01) 20% Reduction

24. Azelnidipine improves insulin resistance in hypertensive patients Therapeutic Research 2008; 29(7):1175-1181 Azelnidipine treatment significantly lowered blood pressure and heart rate. Azelnidpine also significantly lowered fasting serum immunoreactive insulin (F-IRI) and homeostasis model assessment (HOMA-R). 12 months of treatment with Azelnidpine in hypertensive patients

25. Azelnidipine treatment significantly decreased levels of glucose and insulin 120 min after the 75 g oral glucose tolerance test compared with amlodipine treatment. Expert Review of Cardiovascular Therapy 2014; 13(1): 23–31 Comparison of 75 g oral glucose tolerance test between treatment with azelnidipine and amlodipine

26. Azelnidipine Reno-protective effect Hypertension Research (2011) 34, 910–912; Drugs 2003; 63(23): 2613-2621 Mechanism of Action Azelnidipine dilates afferent & efferent arterioles Reduces intra-glomerular pressure Reduces proteinuria Retards the progression of CKD

27. Azelnidipine + ARB causes a greater reduction in UACR as compared to Amlodipine + ARB UACR (%) Hypertension Research (2011) 34, 935–941

28. Azelnidipine delays the progression of urinary albumin excretion as compared to Amlodipine Diabetol Metab Syndr (2015) 7:80 DOI 10.1186/s13098-015-0073-9 Closed bar , amlodipine (n = 19); O pen bar , azelnidipine (n = 19 *p < 0.05

29. Azelnidipine – Robust Clinical Evidence BP & HR Reduction At-HOME Study (n= 5,433) OSCAR (n=1164) COAT RCT (n=240) OLCA study (n=236) Reno-Protection Hypertension Research Study (n=67) OLCA study (n=236) Cardio-Protection OSCAR (n=1164) J-CORE Study (n=207) The AORTA Study (n=95) ↑ Insulin Sensitivity AGENT Study (n=18) OLCA study (n=236) Aldosterone Reduction Keri Wellington et al Masanori Abe et al (n=67)

30. Azelnidipine Clinical Trials Summary Reduces blood pressure Reduced heart rate Reduces proteinuria Prevents insulin resistance Azelnidipine has also been confirmed to have cardio-protective, neuroprotective, and anti-atherosclerotic properties Journal of Drug Delivery & Therapeutics. 2019; 9(3-s):1002-1005

31. Azelnidipine Safety and Tolerability Azelnidipine do not cause pedal edema. Azelnidipine does not induce reflex tachycardia , probably since it elicits a gradual fall in BP. Azelnidipine considerably reduces heart rate . Azelnidipine considerably reduces proteinuria . Journal of Drug Delivery & Therapeutics. 2019; 9(3-s):1002-1005

32. Nifedipine XL Amlodipine Cilnidipine Azelnidipine BP control + + + + + + + + + + + + + + Heart Rate  ↑  ↑  ↓  ↓ Proteinuria ↑ ↑ ↓ ↓ ↓ Edema risk ↑ ↑ ↓ ↓ Glomerular Pressure ↑ ↑ ↓ ↓ Aldosterone secretion ↔ ↔ ↔ ↓↓ AZELNIDIPINE – CCB with a Difference

33. O ffers gradual and smooth BP control Minimal risk of pedal edema D ecreases heart rate (minimal risk of reflex tachycardia) Decreases the aldosterone secretion Increases Insulin Sensitivity Reduces UACR Improves LV diastolic function in hypertensive patients with diastolic dysfunction Reduces augmention index & brachial-ankle pulse wave velocity Why Azelnidipine – PRACTICE PEARLS