Deciding the best therapy for chronic stable angina

1. PCI VS OMT IN CHRONIC
STABLE ANGINA
Dr. Lokesh Khandelwal
MD, DM Cardiology

2. WHY THIS DEBATE
In patients with ACS, routine revascularization, in addition to GDMT,
reduces the short- and long-term rates of death and MI compared with a
more conservative approach.
Benefit of revascularization among patients with chronic stable CAD is
debatable
About 80% PCIs are performed in patients with SIHD.
Patients with symptomatic CAD despite GDMT who have significant
coronary stenosis need revascularization.

3. Uncertainties
All patients with significant coronary lesions (i.e., ischemia-producing)
should undergo PCI ?
PCI is required to improve prognosis ?

4. COURAGE TRIAL

5. Courage trial
Randomization to PCI + OMT vs OMT alone
Intensive, guideline-driven medical therapy and lifestyle intervention in
both groups
2.5 to 7 year (mean 4.6 year) follow-up

6. Inclusion Criteria
1, 2, or 3 vessel disease (>70% visual stenosis of proximal coronary
segment)
Anatomy suitable for PCI
CCS Class I-III angina
Objective evidence of ischemia at baseline

7. • Uncontrolled unstable angina
• Revascularization within 6 months
• Ejection fraction <30%
• Cardiogenic shock/severe heart failure
• History of sustained or symptomatic VT/VF
• CCS class IV angina,
• Markedly positive stress test (substantial ST-segment depression
or hypotensive response during stage 1 of the Bruce protocol)
Exclusion Criteria

11. Repeat revascularizations
At a median 4.6 year follow-up, 21.1% of the PCI patients
required an additional revascularization, compared to 32.6% of
the OMT group who required a 1st revascularization

13. Angina free – no. PCI + OMT OMT
Baseline 12% 13%
1 Yr 66% 58%
3 Yr 72% 67%
5 Yr 74% 72%
The comparison between the PCI group and the medical-therapy
group was significant at 1 year ( P<0.001) and 3 years (P=0.02) but
not at 5 years.

14. Freedom from Angina

15. Conclusions
As an initial management strategy, PCI did not reduce the risk of
death, MI, or other major cardiovascular events when added to OMT.
PCI resulted in better angina relief during most of the follow-up period,
but medical therapy was also effective, with no between–group
difference in angina-free status at 5 years.

16. Limitations
Among 70% of patients assigned to PCI who had 2-vessel
disease, only 36% received > 1 stent.
Only 2.7% were treated with a DES.
32% of OMT patients crossed over to PCI.
Excluded high risk patients.

17. BARI 2D TRIAL

18. CABG Stratum (N= 763) PCI Stratum (N= 1605)
OMT alone
(N= 385)
CABG +OMT
(N= 378)
OMT alone
(N= 807)
PCI +OMT (N=
798)
 Study period : January 2001, to March 2005
 Mean follow up : 5.3 yrs
 Primary Endpoint: Death (from any cause)
 Secondary Endpoint: Composite of Death, MI, or Stroke
R R
BARI 2D Study Group, NEJM 2009
2368 pts with mild to moderate CAD and Type 2 diabetes
prior to randomization

19. Inclusion criteria
Diagnosis of both type 2 diabetes & CAD.
CAD diagnosis by documented on angiography ( ≥50% stenosis of a
major epicardial coronary artery associated with a positive stress test
or ≥70% stenosis of a major epicardial coronary artery and classic
angina).

20. Exclusion criteria
Requiring immediate revascularization or had LMCA
disease
Creatinine level > 2.0 mg per deciliter
Glycated Hb > 13.0%
Class III or IV heart failure or hepatic dysfunction
Undergone PCI or CABG within the previous 12 months.

23. Freedom from Angina

24. Conclusion
Prompt coronary revascularization in patients who had been treated
with intensive medical therapy for diabetes and stable ischemic
disease did not significantly reduce rate of death from any cause or
major cardiovascular events.

25. Limitations
Patients who are at high risk for MI were excluded from the trial.
The broad applicability of BARI 2D is limited by the fact that the patient
population selected represents only a small subset of patients with
diabetes and coronary artery disease

26. FAME 2 TRIAL

27. FAME 2 trial
 FAME TRIAL (2009): Routine measurement of FFR in patients with multivessel
CAD undergoing PCI : significant reduction of MACE events.
 FAME 2 trial: PCI plus OMT vs OMT alone as 1st line t/t for stable angina.
 Short term F/U (2012): FFR-guided PCI group :decreased rate of urgent
revascularization compared to sole medical therapy group.
 Drawback: the follow-up period was probably too short for restenosis to
emerge.

28. HYPOTHESIS
Initial strategy of FFR-guided PCI plus medical therapy would provide
better long-term outcomes than an initial strategy of medical therapy
alone.
• Randomized, multicenter trial: FFR done for 1220
patients.
METHODS

29. Inclusion criteria
 Patients with stable clinical condition and 1/2/3 vessel disease amenable for PCI.
 1. Stable angina pectoris
 2. Atypical or no chest pain but documented ischemia on non-invasive testing
 3. At least one stenosis >/= 50% in at least one major native epicardial coronary artery >/=
2.5mm.
 Note: can include:-
 a) Patients with previous stents and restenosis.
 b) Total occlusion : if this vessel supplies viable myocardium
 c) In total CTO : not mandatory to measure FFR. (FFR value set at an arbitrary value of 0.5)
 d) STEMI or a NSTEMI more than 1 week ago may be included.

30. Exclusion criteria:
 CABG preferable
 LMCA disease
 < 1 week STEMI or NSTEMI
 Prior CABG
 Contraindication to DAPT
 LVEF < 30%
 Extremely tortuous or calcified coronary arteries precluding FFR measurements
 A life expectancy of less than 2 years
 Pregnancy or intention to become pregnant during the course of the trial
 Severe LVH (septal thickness > 13mm)

31. The primary end point :
composite of the 5 year:
• All cause death
• Documented myocardial infarction
• Unplanned hospitalization leading to urgent revascularization
Secondary end points :
• included the components of the primary end point
• death from cardiac causes,
• any revascularization,
• stroke, and
• Stent thrombosis.
TRIAL END POINTS
:

32. BASELINE CHARACTERISTICS
:

34. Primary end-point event :
1. lower in the PCI group (13.9%,n=62) vs. medical-therapy group
(27%,n=119).
2. Insignificant difference between PCI group vs. registry group (15.7%):
good NPV
3. large difference between medical-therapy group vs. registry group
RESULTS

35. Secondary End Points :
• PCI vs Medical therapy: no significant difference in death and MI
although trend to towards lower rate of MI in PCI gr.
• Significant difference between rate of urgent revascularization.
• Revascularisation: At 5 years: 51.0% in the medical-therapy group vs.
PCI gr. : 13.4%
RESULTS

37. DISCUSSION
• Difference in 1⁰ events : driven by a significantly lower rate of urgent
revascularization in the PCI group
• No evidence of convergence of event rates between groups in the long term.
• Present guidelines: revascularize only when signs of reversible ischemia present
• FFR : higher spatial resolution for quantifying the impediment of myocardial flow

38. 1.Non-blinded trial: Selection bias in referring for revascularisation.
2.Enrolment was stopped prematurely
3.No FFR for stenosis </= 50%. , sizable portion have FFR < 0.80 esp. if in proximal
large vessels.
4.Ischemia not assessed by means of non-invasive testing when FFR was 0.8 or less.
5.Increased risk of peri-procedural MI cannot be discounted for.
LIMITATIONS

39. ACCF/AHA/SCAI PCI Guidelines:
Revascularization to Improve Survival

40. Revascularization to Improve Symptoms

41. ESC 2014 guidelines

42. GDMT is a Class I Indication for All SIHD Patients
Diet
If overweight, weight loss
Regular physical activity
If a smoker, smoking cessation
Aspirin 75-162mg daily
High-intensity statin Rx
If hypertensive, Rx to achieve a BP <140/90
If diabetic, appropriate glycemic control
Add anti-anginal medications as needed to control symptoms

43. SYNTAX- Effect of GDMT on Survival
36% relative reduction in mortality at 5 years with OMT
(HR 0.64, 95% CI 0.48-0.85, p=0.002)

44. BARI 2D: Risk Factor Control
Survival and CV Outcomes
1. No smoking
2. non-HDL <130
mg/dL
3. TG <150 mg/dl
4. SBP <130 mm Hg
5. DBP <80 mm Hg
6. HbA1c <7%
Good risk factor control was
associated with half the death rate

45. ACC/AHA : Only Class I Indication for PCI is QoL
>1 significant stenosis amenable to revascularization and
unacceptable angina despite guideline-directed medical
therapy

46. Most Patients Do Not Receive GDMT* before Elective
PCI
COURAGE Published
*GDMT defined as having a prescription for
aspirin + beta blocker + statin
Cath-PCI Registry (N=467,211)
Borden WB, et al JAMA 2011

47. ORBITA TRIAL

48. Symptom relief in stable angina (PCI increases exercise time
more than placebo procedure)
Principal hypothesis
Primary endpoint
Difference in exercise time increment between the arms

49. Secondary endpoints
Components of the primary end point
Death from cardiac causes
Revascularization
Stroke, and stent thrombosis

50. Inclusion criteria
• Stable angina
• One or more ≥ 70% stenosis in a single vessel
• Suitable for PCI

53. PCI
n = 105
Placebo
n = 95
P-value
Area stenosis by QCA(%)
84.6 84.2 0.781
FFR
0.69 0.69
0.778
iFR
0.76 0.76
0.751

56. Primary endpoint result
Change in total exercise time
40
35
30
25
20
15
10
5
0
PCI Placebo
Change
in
exercise
time
(seconds)
28.4
(SD 86.3)
p=0.001
11.8
(SD 93.3)
p=0.235
Error bars are standard errors of the mean
+16.6 sec
(-8.9 to 42.0)
p=0.200

60. Conclusions
• ORBITA is the first placebo-controlled randomized trial of PCI in
stable angina
• Area stenosis QCA 84.4%, FFR 0.69, iFR 0.76
• PCI was safe and physiologically effective
• PCI significantly reduced ischemic burden as assessed by stress
echo
• In this single vessel, angiographically guided trial there was no
difference in exercise time increment between PCI and placebo

61. Limitations
 Small size and shorter duration of follow up
 The medical therapy optimisation phase was intentionally intensive, consisting of one to
three telephone consultations per week with a consultant cardiologist which may not be
possible in real world.
 Patients were up-titrated to an average of three antianginal agents during the initial 6
weeks before randomisation.
 Patients with more extensive territories of coronary disease might receive a larger
physiological benefit from PCI.
 As a result of the limited duration of ORBITA, it cannot address long-term myocardial
infarction and mortality endpoints.

62. Limitations
Ischaemia from non-target vessel or from microvascular disease could
have contributed to angina that the PCI procedure would not have
improved.
Orbita trial using exercise testing as an endpoint might experience a
training effect.

63.  Study Group : Stable CAD with atleast moderate ischemia.
 Primary Aim: to determine whether an initial PCI or CABG +
OMT is superior to a conservative strategy of OMT alone, with
cath reserved for OMT failure.
 Primary Endpoint: CV death or MI
 Secondary Endpoint: angina-related QOL
 Sample size : 8000
 Follow up : Average 4 years.
ISCHEMIA TRIAL

65. CONCLUSIONS
 OMT should be the first preference in patients with stable
angina except those having
 CCS angina grade IV
 markedly positive stress test
 Patients with refractory Angina despite GDMT should be
considered for PCI
 Role of PCI in first place still not established and is not
cost effective
 More RCT’s with newer generation DES need to be
conducted