Valsartan based HTN management

1. 여수제일병원
심장내과
이 우 석
2024.3.19 노바티스

2. 노화도 치료가 되나요? 노화도 질병입니다.
아담 930/셋 912/노아 950/셈 600/아브라함 175/이사악 180/야곱147/요셉 110
Treatable disease!!! Imaginable prospect!!!

3. King of CV Medicine
Level A evidence
Anti-thrombotics
(aspirin, P2Y12 inhibitors, low-dose NOAC)
Anti-cholesterol therapies
(statin, ezetimibe, PCSK9 inhibitor)
Antihypertensive drugs
Heart attack & brain attack : 70-80% preventable
업무
승진
육아
시월드
노후대책
내집마련
저축
대출
삶의 무게: 콜레스테롤과 혈압

4. Contents
Hypertension: Current Status in Korea
How to Manage Hypertension: Guideline Update
Valsartan: Choice of ARB Fulfilling Patient’s Needs
Valsartan/Amlodipine: Optimizing Treatment over Monotherapy
Originality of Valsartan with Wealth of Evidence
Case

5. Hypertension:
Current Status in Korea

6. The prevalence of hypertension in Korea has markedly increased
1. Kim HC, et al. Clin Hypertens. 2022;28:1. 2.

7. Over 12 millions have hypertension in Korea,
and more than half of them are uncontrolled

8. The COVID-19 pandemic had a negative influence on hypertension

9. CV mortality risk doubles with each 20/10 mmHg BP increment

10. Cardiovascular Risks of Hypertension
Ettehad D, et al. Lancet 2016;387:957

11. How to Manage Hypertension:
Guideline Update

12. SPRINT study: The game changer for hypertension management
Evidences supporting benefits of intensive BP lowering strategy

13. 2017 ACC Guideline recommended lower BP target than before

14. 2020 ISH Guideline recommends a Treat-to-Target Strategy for
hypertensive patients

15. STEP Study: More advantages of intensive BP treatment for Asian
hypertensive patients than Caucasian people

16. 2022 KSH Guideline: Updates of target BP & recommendations
1. 2022년 고혈압 진료지침. The Korean Society of Hypertension. 2022.
2. 2018년 고혈압 진료지침. The Korean Society of Hypertension. 2018.

17. 2022 KSH Guideline: Algorithm to achieve target BP in Korea
1. 2022년 고혈압 진료지침. The Korean Society of Hypertension. 2022.

18. 2023 ESH Guideline for arterial hypertension
 First < 140/80 mmHg in most patients
 If drug treatment is well tolerated, SBP ≤
130 mmHg
 BP range of 120-129/70-79 mmHg in
patients up to 79 years old
 In patients ≥ 80 yo not frail, first < 150/80
mmHg, then SBP 130-139 mmHg
 In very frail patients, treatment targets
should be individualized
Mancia G, et al. J Hypertens 2023;41:1874

19. Valsartan:
Choice of ARB Fulfilling Patient’s Needs

20. 어떤 ARB 사용해야하나?
Evidence
BP lowering Effect
부가적인 효과

21. There is a large evidence base for ARBs in CV outcomes trials
Volpe M. Expert Rev Cardiovasc Ther 2012;10:1061, Dézsi CA. Am J Cardiovasc Drugs 2016;16:255

22. Valsartan monotherapy: Enough BP control with Once-Daily dosing
1. Neutel J, et al. Clin Ther. 1997;19:447

23. The control your hypertensive patients need:
Superior BP reductions with Valsartan over other ARBs
1. Destro M, et al. Adv Ther. 2005;22:32, 2. Calvo C, et al. J Hypertens. 2004;22:837

24. What is your hypertensive patient’s individual treatment need?
1. Fogari R, et al. Am J Hypertens. 2001;14:27, 2. Aksit E, et al. Cardiovasc J Afr. 2017; 28:14, 3. 디오반필름코팅정. 식품의약
품안전처 의약품상세정보. https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=200108764aupdateTs2023-
01-18%2015:45:05.0b (Accessed at 30 Mar, 2023), 4. Izzo JL, et al. J Clin Hypertens (Greenwich). 2011;13:722, 5.

25. Valsartan effectively reduced BP
without compromising sexual function in hypertensive men
Erectile Dysfunction
1. Viigimaa M, et al. World J Cardiol. 2014;6:908, 2. Johannes CB, et al. J Urol. 2000;
163:460, 3. Klocek M, et al. Arterial Hypertens. 2003;7:181, 4. Wang TD, et al. J Clin
Hypertens (Greenwich). 2021;23:481, 5. Fogari R, et al. Am J Hypertens. 2001;14:27

26. Valsartan offers effective BP control
regardless of night-time BP status in hypertensive patients
Non-dipper Patients
1. Hermida RC, et al. J Hypertens. 2005;23:1913, 2. Aksit E, et al. Cardiovasc J Afr. 2017;28: 14, 3. Mahabala C, et
al. Vasc Health Risk Manag. 2013;9:125, 4. Tykarski A, et al. Arterial Hypertens. 2006;10:235

27. Valsartan was as effective as captopril in reducing
cardiovascular events following acute MI patients
Post-MI
1. McMurray JJV, et al. J Am Coll Cardiol. 2006;47:726, 2. Zhang W, et al. Medicine (Baltimore). 2017;96:e7172, 3. 디오반필름코팅정. 식품
의약품안전처 의약품상세정보. https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=200108764aupdateTs2023-01-
18%2015:45:05.0b (Accessed at 30 Mar, 2023)

28. For HF patients, Valsartan reduced incidence rate of deaths
from CV events and non-fatal CV events, similar to captopril
HF
1. Cohn et al. N Engl J Med. 2001;345:1667, 2. 디오반필름코팅정. 식품의약품안전처 의약품상세정보.
https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=200108764aupdateTs2023-01-
18%2015:45:05.0b (Accessed at 30 Mar, 2023)

29. Safety profile of Valsartan Original has been demonstrated
in hypertensive patients including the elderly
Elderly
1. Fogari R, et al. Eur J Clin Pharmacol. 2004;59:863, 2. Izzo JL, et al. J Clin Hypertens (Greenwich). 2011;13:722, 3. Fogari R, et al.
Arch Gerontol Geriatr. 2009;48:401, 4. Malacco E, et al. Clin Ther. 2003;25:2765, 5. Butt DA, et al. J Bone Miner Res. 2014:29:2483

30. Valsartan lowered new-onset diabetes in high-risk CV patients
Diabetes

31. Valsartan reduced BP in hypertensive patients with CKD
Renal Disease

32. Valsartan/Amlodipine:
Optimizing Treatment over Monotherapy

33. BP Begets BP!
Framingham Heart Study Original Cohort
Niiranen TJ, et al. JAMA Cardiol 2018;3:427
변곡점, 그 점
핏줄이 바뀐다
자연의 이치, 선택의 문제
“굵고 짧게 vs. 가늘고 길게“
송골매: resting SBP 200mgHg (심부전증)
펭귄: resting SBP 90mmHg
애완조 (앵무새): 심부전증으로 사망

34. Optimal Intensification of BP med
Xu W, et al. BMJ 2015;350:h158
150mmHg
1.4 months
2.7 months

35. 2023 ESH Guideline for arterial hypertension
Mancia G, et al. J Hypertens 2023;41:1874

36. Combining BP-lowering agents is more effective
than up-titrating the dose of a single agent
1. Wald DS, et al. Am J Med. 2009;122:290, 2. Sood N, et al. Am J Health syst Pharm. 2010;67:885

37. Amlodipine/Valsartan: Choice for hypertensive patients
who were uncontrolled with monotherapy
1. Allemann Y, et al. J Clin Hypertens (Greenwich). 2008;10:185

38. Superior efficacy of Amlodipine/Valsartan 5/80mg over Valsartan
160mg monotherapy for Chinese hypertensive patients
1. Wang KL, et al. J Chin Med Assoc. 2020;83:900

39. Amlodipine/Valsartan 5/160mg was more efficacious to amlodipine 10mg
monotherapy in Korean hypertensive patients with inadequate response
1. Sung JD, et al. Korean Circ J. 2016;46:222

40. With Amlodipine/Valsartan, significant BP reduction was also observed in
subgroups with different CV risk factors
CHINA STATUS II

41. Amlodipine/Valsartan demonstrated meaningful BP reductions from
baseline across all hypertension severities
EXCITE

42. Amlodipine/Valsartan has well-established tolerability and safety profile

43. In a real-world setting, Amlodipine/Valsartan showed
favorable tolerability for most of the hypertensive patients
1. Huo Y, et al. Curr Med Res Opin. 2019;35:1441, 2. Sison J, et al. Curr Med Res Opin. 2014;30:1937

44. Originality of Valsartan
with Wealth of Evidence

45. KR2307177380
References 1. IQVIA Data Disclosure. 3Q MAT, 2022.Source:Internal calculations by Novartis Korea based on IQVIA database. 2. Diovan US Prescribing Information. 2021. Novartis Pharma AG. https://www.novartis.com/us-en/sites/novartis_us/files/diovan.pdf. 3.
디오반필름코팅정. 식품의약품안전처 의약품상세정보. https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=200108764aupdateTs2023-01-18%2015:45:05.0b (Accessed at 30 Mar, 2023). 4. Novartis ESG Report. 2020.
https://www.novartis.com/sites/www.novartis.com/files/novartis-in-society-report-2020.pdf.
Originality of Valsartan Family:
Keeps No.1* Position in Worldwide Market1
46
LONG HISTORY
• Diovan, among Valsartan
Family, was first launched
in 1996 by Novartis2
• Used for over 20 years
in Korea
(Approved in 2001)3
RELIABLE QUALITY
• Maintaining a robust
quality system in
compliance with external
regulatory requirements
and standards4
• Closely monitoring
every step of
manufacturing process4
KR2307177380

46. KR2307177380
In large number of clinical trials,
Valsartan family has
proven efficacy
for >140,000 patients1-34
BP reduction
has been demonstrated
in >60,000 patients35-46
Valsartan family has established
tolerability and safety profile,
with overall adverse reaction incidence
comparable with placebo47-51
BP Reduction Safety Profile
Well-established
3 Indications Efficient
Proven
Valsartan family has proven efficacy and safety profile
in many hypertensive patients1-51
47
CV, cardiovascular; BP, blood pressure
Reference 1. Julius S, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022-31. 2. Wong M, et al. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002;40:970-5. 3. Cohn JN, et al. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. NEJM. 2001;345:1667-
75. 4. Pfeffer MA, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. NEJM. 2003;349:1893-906. 5. Califf RM, et al. Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. Am Heart J. 2008;156:623-32. 6. Ogilhara T, et al. Target blood pressure for treatment of
isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study. Hypertension. 2010;56:196-202. 7. Muramatsu T, et al. Comparison between valsartan and amlodipine regarding cardiovascular morbidity and mortality in hypertensive patients with glucose intolerance: NAGOYA HEART Study. Hypertension. 2012;59(3):580-6. 8. Ogawa H, et al. https://clinicaltrials.gov/ct2/show/NCT00140790. Accessed on Mar 2023. 9. Ridker PM, et al. Valsartan, blood pressure
reduction, and C-reactive protein: primary report of the Val-MARC trial. Hypertension. 2006;48:73-9. 10. Zapper DH, et al. Metabolic and antihypertensive effects of combined angiotensin receptor blocker and diuretic therapy in prediabetic hypertensive patients with the cardiometabolic syndrome. J Clin Hypertens (Greenwich). 2008;10:894-903. 11. Ruilope LM, et al. Efficacy and tolerability of combination therapy with valsartan plus hydrochlorothiazide compared with amlodipine monotherapy in
hypertensive patients with other cardiovascular risk factors: the VAST study. Clin Ther. 2005; 27: 578-87. 12. Cuocolo A, et al. Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril. J Hypertens. 1999;17:1759-66. 13. Yasunari K, et al. Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular
hypertrophy. J Am Coll Cardiol. 2004;43(11):2116-23. 14. Thümann PA, et al. Influence of the angiotensin II antagonist valsartan on left ventricular hypertrophy in patients with essential hypertension. Circulation. 1998;98:2037-42. 15. Mutlu H, et al. The efficacy of valsartan in essential hypertension and its effects on left ventricular hypertrophy. Blood Press. 2002;11(1):53-5. 16. Duprez DA, et al. Beneficial effects of valsartan in asymptomatic individuals with vascular or cardiac abnormalities: the
DETECTIV Pilot Study. J Am Coll Cardiol. 2007;50(9):835-9. 17. White HD, et al. Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Circulation. 2005;112(22):3391-9. 18. Solomon SD, et al. Changes in ventricular size and function in patients treated with valsartan, captopril, or both after
myocardial infarction. Circulation. 2005;111(25):3411-9. 19. Delea TE, et al. Valsartan versus lisinopril or extended-release metoprolol in preventing cardiovascular and renal events in patients with hypertension. Am J Health syst Pharm. 2007;64(11):1187-96. 20. Peters S, et al. Valsartan for prevention of restenosis after stenting of type B2/C lesions: the VAL-PREST trial. J Invasive Cardiol. 2001;13(2):93-7. 21. Peters S, et al. Valsartan versus ACE inhibition after bare metal stent implantation--
results of the VALVACE trial. Int J Cardiol. 2005;98(2):331-5. 22. Julius S, et al. The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy. Hypertension. 2006;48:385-91. 23. Hudson M, et al. Angiotensin II receptor blockers for the treatment of heart failure: a class effect? Pharmacotherapy. 2007;27(4):526-34. 24. Cohn JN, et al. Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with
chronic heart failure: results from the Valsartan Heart Failure Trial. Circulation. 2003;108(11):1306-9. 25. Anand IS, et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation. 2005;112(10):1428-34. 26. Latini R, et al. Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: the Valsartan Heart Failure Trial (Val-HeFT). Circulation. 2002;106(19):2454-8. 27. Krum H, et al. Effect of valsartan added to
background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT. Eur J Heart Fail. 2004;6(7):937-45. 28. Weber MA, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004;363(9426):2049-51. 29. Mazayev VP, et al. Valsartan in heart failure patients previously untreated with an ACE inhibitor. Int J Cardiol. 1998;65(3):239-46. 30. Maggioni AP, et al. Effects of valsartan on morbidity and mortality in
patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol. 2002;40(8):1414-21. 31. Majahalme SK, et al. Comparison of treatment benefit and outcome in women versus men with chronic heart failure (from the Valsartan Heart Failure Trial). Am J Cardiol. 2005; 95(4):529-32. 32. Baruch L, et al. Morbidity, mortality, physiologic and functional parameters in elderly and non-elderly patients in the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J.
2004;148(6):951-7. 33. Solomon SD, et al. Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet. 2007;369(9579):2079-87. 34. Zhang W, et al. Effectiveness and safety of valsartan/amlodipine in hypertensive patients with stroke: China Status II subanalysis. Medicine (Baltimore). 2017;96(26):e7172. 35. Kızılırmak P, et al. Efficacy and safety of valsartan and amlodipine single-pill
combination in hypertensive patients (PEAK study). Turk Kardiyol Dern Ars. 2013;41(5):406-17. 36. Kızılırmak P, et al. Efficacy and safety of valsartan/amlodipine single-pill combination in patients with essential hypertension (PEAK LOW). Turk Kardiyol Dern Ars. 2014;42(4):339-48. 37. Hu D, et al. Efficacy and safety of valsartan/amlodipine single-pill combination in 11,422 Chinese patients with hypertension: an observational study. Adv Ther. 2014;31(7):762-75. 38. Sison J, et al. Real-world clinical
experience of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide in hypertension: the EXCITE study. Curr Med Res Opin. 2014;30(10):1937-45. 39. Eckert S, et al. Meta-analysis of three observational studies of amlodipine/valsartan in hypertensive patients with additional risk factors. Blood Press. 2013;22 Suppl 1:11-21. 40. Karpov Y, et al. Amlodipine/valsartan single-pill combination: a prospective, observational evaluation of the real-life safety and effectiveness in the routine
treatment of hypertension. Adv Ther. 2012;29(2):134-47. 41. Chazova IE and Martynyuk TV. [On the way to achieve hypertension treatment goals: results of the open observational program AESCULAP (exforge--clinical safety and efficiency of using a double combination of antihypertensive drugs in patients with uncontrolled blood pressure)]. Ter Arkh. 2013;85(9):35-45. 42. Lins R, et al. Effectiveness of amlodipine-valsartan single-pill combinations: hierarchical modeling of blood pressure and total
cardiovascular disease risk outcomes (the EXCELLENT study). Ann Pharmacother. 2011;45(6):727-39. 43. Chazova IE, et al. Real-life safety and effectiveness of amlodipine/valsartan combination in the treatment of hypertension. Adv Ther. 2011;28(2):134-49. 44. Kafrawy NE, et al. Effectiveness and tolerability of fixed dose combination of amlodipine/valsartan in treatment of hypertension in the real-life setting among Egyptian patients. Egypt Heart J. 2014;66:30-5. 45. Vilela GC and Villanueva ART.
Observational study to evaluate the safety and effectiveness of a fixed dose combination of amlodipine and valsartan in the treatment of hypertension. Philippine J I Med. 2012;50:40-6. 46. Cheng SM, et al. Post-marketing surveillance study of valsartan/amlodipine combination in Taiwanese hypertensive patients. Blood Press. 2012;21(Suppl 1):11-9. 47. Diovan US Prescribing Information. 2021. Novartis Pharma AG. https://www.novartis.com/us-en/sites/novartis_us/files/diovan_hct.pdf. 48. 식약처 허
가사항. 49. Novartis ESG Report. 2020. https://www.novartis.com/sites/www.novartis.com/files/novartis-in-society-report-2020.pdf. Accessed on Mar 2023. 50. Novartis Pharmaceuticals Corporation (Novartis). 2018. https://www.novartis.com/us-en/news/novartis-pharmaceuticals-corporation-novartis-statement-recall-outside-united-states-sandoz-generic-valsartan-and-sandoz-valsartan-and-hydrochlorothiazide-film-coated-tablets. Accessed on Mar 2023. 51. Diovan core data sheet. Novartis Pharma
AG.

47. KR2307177380
BP, blood pressure; KSH, Korean Society of Hypertension; HTN, hypertension; CVD, cardiovascular disease
References 1. 2022년 고혈압 진료지침. The Korean Society of Hypertension. 2022. 2. Lee HY, et al. 2018 Korean Society of Hypertension Guidelines for the management of hypertension: part II-diagnosis and treatment of hypertension. Clin Hypertens. 2019;25:20. 3. 식품의약품안전처, 통
합정보시스템 (nedrug.mfds.go.kr)
Treatment options in a variety of formulations within Valsartan family3
48
Products Strengths3
Amlodipine/Valsartan
5/80 mg 5/160 mg 10/160 mg
Valsartan + HCTZ
80/12.5 mg 160/12.5 mg
Valsartan
40 mg 80 mg 160 mg 320 mg
In patients with BP >160/100 mmHg or
20/10 mmHg higher than target BP,
≥2 classes of antihypertensive
medication can be used to maximize BP
reduction and rapidly control BP
2022 KSH Recommendation1
Benefits of Single Pill Combination2
Maximizing reduction of BP
Increasing adherence
Preventing CVD and target organ damage
Minimizing adverse effects
Valsartan Family: Flexible Choice to Get Patient’s BP Under Control!

48. CASE

49. 73/F 전 O O
Office BP : 192/102 mmHg
ABPM : Mean – 169/105 mmHg
아타칸 8mg 다이크로짇 12.5mg
엑스포지 160/5mg

50. 73/F 전 O O
엑스포지정 5/160mg

51. Thank you for your attention