The document discusses stable ischemic heart disease and new approaches for its treatment. It summarizes several studies comparing different drug combinations for treating angina, finding that combining multiple hemodynamic drugs provides no additional benefit over monotherapy. Newer drugs like ivabradine, ranolazine, and trimetazidine are discussed as alternatives for treating angina by non-hemodynamic mechanisms like metabolic modulation. Trimetazidine in particular is highlighted for its efficacy in reducing angina symptoms and improving quality of life in real-world clinical studies. The document advocates for more personalized treatment approaches combining different drug classes tailored to individual patient characteristics and comorbidities.

1. Stable Ischemic Heart Disease
Is This the Beginning of a New Era?

3. Spectrum of IHD
Guidelines relevant to the spectrum of IHD are in parentheses

4. Aetiology of chest pain without obstructive coronary artery disease
Ferrari, R. et al. (2017) A ‘diamond’ approach to personalized treatment of angina
Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.131

5. Different manifestations of myocardial ischaemia
Ferrari, R. et al. (2017) A ‘diamond’ approach to personalized treatment of angina
Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.131

6. Myocardial ischemia is multifactorial
The benefits of adding Trimetazidine MR to beta-blockers in angina patients
By Professor F. Pinto. President-Elect of the European Society of Cardiology,
Department of Cardiology, University Hospital Santa Maria, Lisboa, Portugal
ATP deficiency

7. New mechanistic approaches to myocardial
ischemia
Metabolic modulation (trimetazidine)
Sinus node inhibition (ivabradine)
Late Na+ current inhibition (ranolazine)
Preconditioning (nicorandil)

8. Correlation – doctor’s demands and
patient expectations
I have this new
operative approach
that will help you Why don’t we
ask him what
he wants?
How about EECP &
angiogenesis?
Thanks Doc; but
once is enough.
Any new
medicines?
The patient-centered approach

9. TIBET, Dargie et al. IMAGE, Savonitto et al. CESAR, Knight et al.
Eur Heart J, 1996;17:96–103 JACC, 1996;27:311–316 Am J Cardiol, 1998;81:133–136
Atenolol, nifedipine SR & its combination Metoprolol, nifedipine SR & its combination Amlo + atenolol vs diltiazem + atenolol
No additive benefit from combination purported benefit of 2 drugs is due to
addition of new drug in resistant patients
Exercise test parameters don’t improve
when adding second hemodynamic drug
Akhras et al. Meyer et al. Madjlessi-Simon et al.
Lancet, 1991;338:1036–1039 Cardiovasc drugs ther, 1993;7:909–913 Eur Heart J, 1995;16:1780–1788
Atenolol, nifedipine SR, ISMN & its
combination
Atenolol, nifedipine SR & its combination Beta blockers, amlodipine & its
combination
No substantial benefit to any
combination over beta blocker
monotherapy
Combination therapy is no better
than atenolol alone
Combination provides no additional
benefits in patients resistant to beta
blockers
All of these studies agree:
Combination of hemodynamic
agents is
NOT ENOUGH

10. Glucose
Lactate Pyruvate
Fatty Acids
Reduced
ATP
production
• Pyruvate to Lactate
• Cell Acidosis
• Calcium Overload
Increased Fatty Acid
Oxidation Rate
Need more
ATP Trimetazidine MR
partially inhibits
Fatty Acid pathway
Increased
ATP
production
More Effective

11. In Patients with Diabetes Mellitus and Chronic Stable Angina

12. Antianginal Drug
Relief of symptoms Improving prognosis
(Prevent cardiovascular events)
Feel better Live longer
European guidelines on the management of
stable coronary artery disease
Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery
disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

13. “We recommend the old drugs as first
line treatment because they are cheap,
effective and available everywhere.”
“We have roughly the same level of evidence for all of the second line drugs and we
recommend that physicians also choose according to what is available in their
country.”
Angina relief Event prevention
• β-blockers and/or CCB
 Ivabradine
 Long-acting nitrates
 Nicorandil
 Ranolazine
 Trimetazidine
• Lifestyle management
• Control of risk factors
• Aspirin (if intolerance, consider clopidogrel)
• Statins
• Consider ACE inhibitors or ARBs
+ consider angio → PCI-stenting or
CABG
Short-acting nitrates, plus
1st line
2nd line
Medical management of SCAD patients
Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary
artery disease: the task force on the management of stable coronary artery disease of the European Society of
Cardiology. Eur Heart J. 2013;34(38):2949-3003.
Chairmen opinion:*
Educate the patient

14. Alessandra Giavarini & Ranil de Silva. Cardiovasc Drugs Ther. DOI 10.1007/s10557-016-6678-x
Effect of ivabradine on symptoms
(angina population: CCS class≥ II, n=12 049)

15. Werdan K et al. Clin Res Cardiol. 2012;101:365-373.
- 82 % weekly angina attacks
P < 0.0001
(2300 patients from Germany)
β-Blockers Ivabradine + β-Blockers
ADDITIONS (prActical Daily efficacy anD safety of Procoralan® In combinaTION
with betablockerS)

16. Hidalgo FJ et al. Int J Cardiol. 2016;217:7-11
During hospitalization
• Beta-Blockers
on BBs: not stop after admission, with reduction in doses if necessary (based on clinical
and hemodynamic condition of patients). BBs were uptitrated every 48 h in both groups
No BBs before admission: BBs were started at low doses (carv: 3125 mg/12 h or 6.25
mg/12 h, bisop: 1.25 to 2.5mg/day) once the patient was stabilized, in both groups.
• Ivabradine: added to BBs at initial dose of 5 mg bid after and uptitrated every 48 h until
a dose of 7.5 mg bid based on HR
After discharge
• BBs: up-titration continued at the 14 and 28 days visits in both groups
• Ivabradine: up-titration to target dose of 7, 5 mg bid at 14 days

19. Cardioprotective effects of ivabradine administration in the setting of acute coronary syndromes
and myocardial infarction.
Juan Carlos Kaski et al. Open Heart 2018;5:e000725
©2018 by British Cardiovascular Society

20. Reduction in mean weekly angina attacks (a) and short-acting
nitrate use (b) before and during trimetazidine administration.
Trimetazidine effect on change in CCS angina
class at 6 months
Real-world Evidence for the Antianginal Efficacy of Trimetazidine
from the Russian Observational CHOICE-2 Study
Maria Glezer; Adv Ther. 2017 Apr;34(4):915-924. doi: 10.1007/s12325-017-0490-2. Epub 2017 Feb 20.

21. Angina attacks/week at baseline and after 2 weeks and 2, 4 and 6 months of trimetazidine administration in the four first-line therapy group
Real-world Evidence for the Antianginal Efficacy of Trimetazidine
from the Russian Observational CHOICE-2 Study
Maria Glezer; Adv Ther. 2017 Apr;34(4):915-924. doi: 10.1007/s12325-017-0490-2. Epub 2017 Feb 20.

22. Mean walking distance eliciting angina
before and during trimetazidine
administration
Mean self-rated well-being (visual
analogue scale, 0–100) before and during
trimetazidine administration
Real-world Evidence for the Antianginal Efficacy of Trimetazidine
from the Russian Observational CHOICE-2 Study
Maria Glezer; Adv Ther. 2017 Apr;34(4):915-924. doi: 10.1007/s12325-017-0490-2. Epub 2017 Feb 20.

23. Rethinking Stable Ischemic Heart Disease:
Is This the Beginning of a New Era?

26. Possible combinations of different classes of antianginal drugs
Ferrari, R. et al. (2017) A ‘diamond’ approach to personalized treatment of angina
Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.131

28. Ferrari, R. et al. (2017) A ‘diamond’ approach to
personalized treatment of angina
Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.131
Possible combinations of classes of antianginal drugs according to different comorbidities
A ‘diamond’ approach to personalized treatment of angina

29. Possible combinations of classes of antianginal drugs according to different comorbidities
Ferrari, R. et al. (2017) A ‘diamond’ approach to personalized treatment of angina
Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.131
A ‘diamond’ approach to personalized treatment of angina

30. Sir William Osler

31. "People don't want to hear the truth
because they don't want their illusions destroyed."
- Friedrich Nietzsche

32. The efficAcy and safety of Trimetazidine in Patients with angina pectoris
having been treated by percutaneous Coronary Intervention. ATPCI study
in the future…

34. Grading of angina pectoris

35. Clinical Classification of Chest Pain

36. Pretest Likelihood of CAD in Symptomatic Patients
According to Age and Sex* (Combined Diamond/Forrester
and CASS Data)
*Each value represents the percent with significant CAD on
catheterization.

37. Comparing Pretest Likelihood of CAD in Low-Risk
Symptomatic Patients With High-Risk Symptomatic
Patients (Duke Database)
Each value represents the percentage with significant CAD. The first is the percentage for a
low-risk, mid-decade patient without diabetes mellitus, smoking, or hyperlipidemia. The second
is that of a patient of the same age with diabetes mellitus, smoking, and hyperlipidemia. Both
high- and low-risk patients have normal resting ECGs. If ST-T-wave changes or Q waves had
been present, the likelihood of CAD would be higher in each entry of the table.