Perindopril

1. 여수제일병원
심장내과
이 우 석
2022.12.13 세르비에 심포지엄
Rationale for using perindopril
to hypertensive patients with
cardiovascular diseases

2. Global burden of CVD and Risk
Vaduganathan M, et al. J Am Coll Cardiol 2022;80:2361
Top 3 Modifiable #CV Targets:
1) ↑Blood pressure
2) Dietary risk
3) ↑LDL-C

3. The Cardiovascular Continuum
Dzau VJ, et al. Circulation 2006;114:2850

4. The role of vascular endothelial injury or
dysfunction in cardiovascular disease
Dzau VJ, et al. Circulation 2006;114:2850

5. 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

6. Arterial Stiffness: causes and consequences
Dart AM, et al. J Am Coll Cardiol 2001;37:975

7. Deleterious effects of chronic RAAS activation on
cardiovascular and renal system
Ruiz-Hurtado G, et al. Eur Heart J Cardioavsc Pharmacother 2015;1:126

8. Targets of the Renin-Angiotensin-Aldosterone System
Ferrari R, et al. Expert Rev Cardiovasc Ther 2013;11:705

9. ACEi와 ARB의 차이점
Changes in plasma angiotensin II concentrations in
both the perindopril and telmisartan
Changes in bradykinin plasma concentration in
patients
Lévy BI, et al. Am J Hypertens 2022;25:293

10. Are ACEi and ARBs equivalent
at reducing all-cause and CV mortality
in high-risk patients?

11. 고혈압 약제 처방 변화
Korea Hypertension Fact Sheet 2022

12. Divergent data between ACEi and ARB
Strauss MH, et al. Circulation 2017;135:2088, Strauss MH, et al. Prog Cardiovasc Dis 2016;58:473,
Bangalore S, et al. Mayo Clin Proc 2016;91:51, Savarese G, et al. J Am Coll Cardiol 2013;61:131,
Cheng J, et al. JAMA Intern Med 2014;174:773, Thomopoulos C, et al. J Hypertens 2015;33:195

13. KAMIR(Korean Acute Myocardial Infarction Registry)
ACEi vs. ARB in NSTEMI with DM
Byun JK, et al. Atherosclerosis 2018;277:130

14. ACEi reduced the incidence of revascularization and
MACE in NSTEMI with DM
Byun JK, et al. Atherosclerosis 2018;277:130

15. KAMIR NIH (National Institute Health) registry
ACEi vs. ARB in AMI (n=9,722)
Choi IS, et al. J Cardiovasc Pharmacol Ther 2018 Aug 21;1074248418795897

16. ACEi is provided better long-term survival benefits to
patients with AMI than ARB
Choi IS, et al. J Cardiovasc Pharmacol Ther 2018 Aug 21;1074248418795897

17. National Health Insurance claims data
ACEi vs. ARB in AMI (n=21,747)
Ann SH, et al. Int J Cardiol 2020;306:35

18. National Health Insurance claims data
ACEi provided long-term survival benefits to patients with AMI
Ann SH, et al. Int J Cardiol 2020;306:35

19. ARNI vs. ACEi in AMI patients
Jering KS, et al. Eur J Heart Fail 2021;23:1040, Gatto L. Eur Heart J Suppl 2021;23(Suppl E):E87
There were no significant differences between
the two groups even with regard to cardiovascular deaths
[sacubitril/valsartan 5.9% vs. ramipril 6.7%; HR 0.87 (0.71–1.08), P= 0.20]
and new hospitalizations for heart failure [sacubitril/valsartan 6.0% vs. ramipril
6.9%; HR 0.87 (0.70–1.06), P=0.17]2.

20. ACEi vs. ARB on New-onset DM
Shin J, et al. J Clin Pharm Ther 2021;47:97
Without Statin With Statin

21. Position of ACEi and ARB in guidelines of
hypertension, CAD and HF

22. Treatment Strategy for Uncomplicated Hypertension
ESC/ESH Guidelines 2018
The core algorithm is also appropriate for most patients with HMOD, cerebrovascular disease, diabetes, or PAD.
CCB = calcium channel blocker; ESC = European Society of Cardiology; ESH = European Society of Hypertension; HMOD = hypertension-mediated organ damage; MI = myocardial infarction; PAD = peripheral artery disease.
Williams B, et al. J Hypertens 2018;36:2284

23. ACEi vs. ARB in Hypertension
Van Vark LC, et al. Eur Heart J 2012;33:2088
Study selection:
- Prospective, randomized, controlled morbidity-
mortality trials that compared active treatment
(ACEi or ARB) with control, published between
Jan 2000 and Mar 2011.
- Trials including a large majority of hypertensive
patients (>66.7% of studied population, according
to the definition used in these trials).
- Selected total 20 randomized trials (n=158,998)
- 7 ACEi trials (n=76,615)
- 13 ARB trials (n=82,383)

24. Different Effect of ACEi on All-cause Mortality
Van Vark LC, et al. Eur Heart J 2012;33:2088
ACE
Inhibitor
ARB
perindopril
Mortality reduction
10%
(P=0.004)
Mortality reduction
N-S

25. ACEi is recommended (Class I, A)
Knuuti J, et al. Eur Heart J 2020;41:407

26. ACEi is recommended (Class I, A)
Ibanez B, et al. Eur Heart J 2018;39:119

27. ACEi is recommended (Class I, A)
Collet JP, et al. Eur Heart J 2021;42:1289

28. ACEi is the choice of first line
McDoangh TA, et al. Eur Heart J 2021;42:3599

29. 여러 가이드라인에서 고혈압이 동반된 경우
ACE 억제제를 우선 치료제로 권고
Williams B, et al. J Hypertens 2018;36:2284, Cosentino F, et al. Eur Heart J. 2020;41:255, Knuuti J, et al. Eur
Heart J. 2020;41:407, Inabez B, et al. Eur Heart J 2018;39:119, McDonagh TA, et al. Eur Heart J 2021;42:3599

30. Perindopril

31. Perindopril
Perindopril is highly lipophilic and has strong
tissue enzyme-binding capabilities.
Lipophilic ACE inhibitor probably leads to
regression of atherosclerotic plaque thanks to
tissue ACE inhibition.
Ferrari R, et al. Am J Hypertens 2005;18:142S, Veltmar A, et al. Am J Hypertens 1991;4:263S,
Unger T, et al. J Cardiovasc Pharmacol 1986;8:276, Candido R, et al. Circulation 2002;106:246

32. Higher Bradykinin/angiotensin selectivity ratio
Ceconi C, et al. Eur J Pharmacol 2007;577:1

33. Restores bradykinin level as normal range
Ceconi C, et al. Cardiovasc Res 2007;73:237

34. Presumed differences in mechanisms of
action of ACEi & ARB
De´zsi CA, et al. Am J Cardiovasc Drugs 2016;16:399

35. 24 hrs Therapeutic Coverage with Perindopril
Flack JM, et al. Vasc Health Risk Manag 2011;7:777
Perindopril:
High Trough-to-Peak ratio

36. 24 hrs BP lowering efficacy
Nedogoda SV, et al. Clin Drug Investig 2013;33:553

37. Superior BP control of perindopril
Tsoukas G, et al. Am J Cardiovasc Drugs 2011;11:45, Telejko E. Curr Med Res Opin 2007;23:953

38. ADVANCE trial: Efficacy of perindopril on
macro/microvascular outcomes in patients with type 2 DM
Patel A, et al. Lancet 2007;370:829

39. Effect of Perindopril in Type 2 DM with Hypertension
Patel A, et al. Lancet 2007;370:829

40. Perindopril significantly reduced cardiovascular and renal
outcomes in patients with type 2 DM with hypertension
Patel A, et al. Lancet 2007;370:829

41. ADVANCE ON, 6 years follow-up

42. Persistent benefit on Reducing mortality

43. EUROPA trial: Efficacy of perindopril to reduce
CV risk in stable coronary artery disease

44. Perindopril significantly reduced primary end point

45. Perindopril significantly reduced MI risks in
revascularized patients
EUROPA연구의 하위분석
• 대 상 : 전체 CAD환자 12,218명 중, 심근경색 기왕력과는 관계 없이 혈관재생술을 받은 6,709명 환자
• 시험기간 : 평균 4.2년
• 시험약물 : 표준치료+Perindopril 8mg vs. 표준치료+Placebo
• Primary endpoint : Composite of cardiovascular mortality / non-fatal MI / Cardiac arrests
*Results from the revascularized patients without previous MI(n=3047)

46. Perindopril significantly reduced primary end
points in MI patients with LVD

47. Is practical management of cough in
patients on ACEi possible?

48. Frequency of cough by gender in Japan
Sato A, et al. Clin Exp Hypertens 2015;37:563

49. Incidence of Cough in Patients on Monotherapy
and With Concomitant Therapies
Sato A, et al. Clin Exp Hypertens 2015;37:563

50. Managing an ACEi induced cough
Fogari R, et al. Curr Ther Res 1999;60:121

51. Calcium Channels and Cough
Pinto B, et al. Indian Heart J 2020;72:345

52. Cough and ACEi: Practical Evidence
Cough is a very common symptom
• Can be elicited by many different conditions not directly involving the lung
Before definitely discontinuing treatment with an ACEi
• Any patient complaining of cough should undergo a challenge and rechallenge period
to verify whether the onset of cough is concurrent with the treatment schedule
Cardioprotective effect of ACEi
• Discontinuation of ACEi can have a negative impact on clinical outcomes in patients
with CVD
Borghi C, et al. Clin Pharmacol Ther 2019;105:550

53. Summary
ACE 억제제는 이론적으로 ARB에 비해 약리적으로 이득이 있는 약제이나 부작용의 우려
로 ARB에 비해 덜 사용된다.
ACE 억제제는 고혈압, high risk 동반 환자의 심혈관 사고 위험과 사망의 위험 감소를 입
증
고혈압, 심근경색, CAD, 심부전 가이드라인에서 ACE 억제제를 우선 치료제로 권고
Perindopril은 고혈압 및 당뇨병 동반 환자에서 사망의 위험 감소를 입증했으며, CAD 환
자의 심근경색, 심부전 입원 위험을 낮춤
Strauss MH, et al. Circulation 2017;135:2088, Strauss MH, et al. Prog Cardiovasc Dis 2016;58:473, Byun JK, et al.
Atherosclerosis 2018;277:130, Choi IS, et al. J Cardiovasc Pharmacol Ther 2018:074248418795897, Ann SH, et al.
Int J Cardiol 2019;306:35, Cosentino F, et al. Eur Heart J 2020;41:255, Knuuti J, et al. Eur Heart J 2020;41:407,
Inabez B, et al. Eur Heart J 2018;39:119, Roffi M et al. Eur Heart J 2016;37:267, McDonagh TA, et al. Eur Heart J
2021;42:3599, Patel A, et al; ADVANCE Collaborative Group. Lancet. 2007;370:829, Zoungas S, et al; ADVANCE-
ON Collaborative Group. N Engl J Med. 2014;;371:1392, Fox KM, et al; EUROPA Investigators. Lancet 2003;362:782

54. Thank you for your attention