Transcript Treatment of stable coronary artery disease

Treatment of stable coronary artery
disease: Pharmacotherapy or
Intervention
Nurcan Arat, MD,
Istanbul Bilim University, Department of Cardiology
Coronary Artery Disease
 CAD has decreased by more than 40% during the
last two decades.
 Half of this decline resulted from prevention and
reduction in major risk factors, whereas the other
half has been attributed to medical treatment and
revascularization.
N Engl J Med 2007;356:2388-2398.
Mortality from stable CAD has not changed significantly over
the last decades
 Aims
Medical management of atherosclerosis ;
 Alleviate symptoms,
 Delay or prevent the progression of coronary disease,
 Prevent adverse outcomes such as death or myocardial infarction retardation
of progression of plaque formation,
 Prevention of plaque rupture, and subsequent events
 Treatment of the sequelae of the disease.

Revascularization (PCI or CABG)
 Treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia
and its manifestations.
Stable CAD. Pharmacotheraphy
Treatments aimed at Improving Prognosis
Stable CAD. Pharmacotheraphy
Treatments aimed at Symptom Relief
Lifestyle Modifications for Patients with CAD
 Tobacco cessation
 Body mass index goal of 18.5 to 24.9 kg per m2
 Moderate-intensity activity for 30 to 60 minutes seven days a
week
 Alcohol consumption in moderation
 Low-sodium diet
 Two to three servings of fruit and vegetables each day
 Saturated fat less than 10 percent of daily calories
Stable CAD. Pharmacotheraphy
 Patients with stable CAD included in the recent ACTION or
EUROPA trials, who already received different preventive drugs,
had an annual risk of cardiovascular death or MI of about 2.5%.
Revascularization by PCI or CABG
 Acute coronary syndrome
 Clearly shown to improve survival
 Chronic stable Angina
 The role of revascularization of in stable CAD remains
controversial
Randomized trials comparing revascularization with
medical treatment
 >30 randomized trials, 44 -2368.pts
 CABG -13 trials,
 6 were performed more than 2 decades ago using predominantly saphenous
vein grafts.
 Balloon angioplasty alone 8 studies,
 use of stents in 9–100%
 Drug-eluting stent implantation was negligible
 except for BARI-2D (35% of patients).
 Several trials failed to specify the implemented medical treatment.
 Currently recommended aggressive risk factor reduction was not
performed
BYPASS SURGERY VS. MEDICAL THERAPY
Relief of angina
95 % of patients have an improvement in
or complete relief of angina immediately
after CABG.
 CASS –(1970s -1980s)
•
More patients remained symptom-free after CABG compared to medical therapy
at one year (66 vs 30 %) and five years (63 vs 38 %)
•
By 10 years, this difference had disappeared (47 vs 42 %).
•
The reoperation rate for recurrent symptoms was 6 to 8 % per year
CABG
Survival Benefit?
 Better than medical
therapy for
 LM disease ( VA Coop Study)
 3 vessel disease
 involves proximal LAD
(European Coronary Surgery Study)
 3 vessel CAD with low EF
(CASS)
Revascularization for Stable CAD.
BYPASS SURGERY VS. MEDICAL THERAPY
 Survival advantage as well as a reduced need for repeat
intervention at two years
 For more severe CAD, SYNTAX scores > 22 for 3-vessel disease
and
 SYNTAX scores > 32 for left main disease
With the exception of left main disease, the survival benefit from CABG
compared to medical therapy tends to disappear with prolonged follow-up in
these groups
SYNTAX trial
CABG
Survival Benefit?
 One year after CABG or PCI
 25 to 60% of patients still have ongoing angina
 Many patiens are deemed “inoperable”
 Anatomy not suitable for PCI or CABG
 Co-morbidities make procedure too high risk
The impact of Revascularization on
Clinical Outcome
Revascularization, more effectively relieves myocardial
ischaemia than medical treatment alone
 ACIP study, 2 years follow-up
 lower risk of death and MI
 SWISSI II trial
 lower rates of ischaemia
 improved left-ventricular ejection fraction
 absolute reduction in clinical events

(cardiac death, MI, and
revascularization) of 6.3% per year in
favour of PCI.
The Impact of Revascularization
on Clinical Outcome
 DANAMI study
• Better prognosis after revascularization vs.medical therapy alone
 COURAGE
• Greater absolute reduction in myocardial ischaemia and
more patients exhibited a relevant reduction in ischaemia
among those with moderate to severe ischaemia
• Improved event-free survival in patients with significant
reduction of ischaemia.
Survival benefit is proportional to the amount of ischaemia
Myocardial perfusion study ,10 627 pts, without prior CAD

Increasing survival benefit of revascularization over medical treatment in patients with
moderate to severe ischaemia,

No benefit was apparent in patients with only mild or absence of ischaemia
Benefit of revascularization in terms of survival is proportional to the
amount of ischaemia as assessed by single photon emission computed
tomography imaging prior to revascularization.
Circulation 2003;107:2900-2907
24 studies, 3088 pts.
LV dysfunction
(mean LVEF = 32 ±
8%)
Viability assessment,
25 months follow up
Mortality reduction is related to viability
 In patients with myocardial
viability, revascularization was
associated with an 80% reduction
of risk-adjusted mortality
compared with medical
treatment (16%/year vs. 3%/year).
 This benefit was most apparent in
patients with impaired leftventricular function.
 No benefit was observed in
patients without viability at any
level of left-ventricular function.
J Am Coll Cardiol 2002; 39: 1151-1158
FAME
FFR was compared with angiography for guiding PCI in a
large-scale randomized trial with 1005 patients
 At 1 year, routine measurement of FFR to select lesions requiring PCI
(FFR < 80%) was associated with lower rates of death or MI than PCI
guided by angiography alone. (7.3 vs. 11.1%, P = 0.04)
 Similarly, deferring revascularization in patients with non-significant
lesions as determined by FFR appeared safe as shown during the 5
year follow-up of the randomized DEFER study with similar rates of
death or MI (<1%/year) among patients treated medically and those
undergoing PCI.
The Impact of Revascularization
on Prognosis
 These findings imply that part of the patients enrolled in
previous trials were unlikely to benefit from PCI or CABG if
they had no, or limited myocardial ischaemia and
suggest that functional assessment of lesions (ischaemia
or none) may help to identify those who benefit from
revascularization.
LIMITATIONS OF CLINICAL TRIALS
Before the COURAGE
The number of patients entered into the trials was only a small
percentage of the number screened and is therefore not reflective of
the general population.





Predominantly male patients
relatively young
preserved left ventricular function
focal atherosclerotic coronary disease
had not undergone previous revascularization by CABG or PCI.
The majority of patients underwent PTCA alone, without stenting.
For patients in later trials who received a bare-metal stent, current
antithrombotic regimens (eg, klopidogrel and glycoprotein IIb/IIIa
inhibitors) were not employed.
LIMITATIONS OF CLINICAL TRIALS
 Patients were highly selected as randomization was performed
following delineation of coronary anatomy by angiography in
the vast majority of studies.
 The ‘cross-over’ from medical treatment to revascularization
was observed in up to half of patients during follow-up.
 Accordingly the proportion of patients without revascularization
progressively diminished during follow-up, potentially blunting
differences between the two strategies.
COURAGE
The largest study comparing PCI with current medical treatment

2287pts, 5 year , minimal or no symptoms

nuclear imaging in a subset of patients was not severe.
The rate of death was
similar in the PCI
(7.6%) and medical
therapy group (8.3%)
Kaplan-Meier survival curves.
P = 0.38
Optimal medical therapy was not used in any of
the trials prior to COURAGE.
 Secondary prevention has proved its worth, with lipidmodulating therapy, lifestyle modification, and the use of
aspirin, beta-blockers, and ACE inhibitors.
 Patients who are clinically unstable, who have left main CAD, or
in whom OMT has failed to control symptoms remain
candidates for revascularization.
 In the courage trial,, drug-eluting stents that markedly reduce the
rate of restenosis and therefore repeat revascularization were used
in only 15 percent of patients
Prior meta-analyses were based on PCI and medical therapy that do not
reflect current interventional practice.
Meta-Analysis
The impact of PCI on survival of patients with stable CAD
 Recent meta-analyses have yielded conflicting results
 Studies; 1980s - 1990s, balloon angioplasty
 Interventional practice has evolved toward the placement of
coronary stents
 Medical therapy has advanced over the last 20 years as well.
Circulation. 2005;111(22):2906-2912
J Am Coll Cardiol. 2008;52(11):894-904.
A META-ANALYSIS
11 randomized trials
Comparison of PCI vs conservative medical treatment for (A) death, (B) cardiac death or any
MI, (C) nonfatal MI, (D) CABG, and (E) PCI during follow-up.
In patients with chronic stable CAD, in the
absence of a recent myocardial infarction, PCI
does not offer any benefit in terms of death,
myocardial infarction, or the need for subsequent
revascularization compared with conservative
medical treatment.
Circulation 2005;111:2906-2912
New Meta analysis
Arch Intern Med. 2012;172(4):312-319
INCLUSION CRITERIA

MEDLINE from 1970 to September 2011

Prospective studies, randomized trials

PCI plus medical therapy vs medical therapy alone

Stable CAD

Minimum follow-up of 1 year.

Stent implantation >50% of PCI procedures

ACS were excluded

Stable patients following a completed MI were included.

included regardless of the presence of documented ischemia or any functional
assessment of the hemodynamic significance of a coronary stenosis.

only the comparison of medical therapy vs stent implantation was extracted.
Stergiopoulos and Brown. Arch Intern Med. 2012;172(4):312-319.
Randomized Trials of Stent
Implantation vs Medical
Therapy
in Patients With Stable CAD
Patient Characteristics
Comparison of initial stent implantation vs
medical management for ;
1.
Death
2.
Death with 0.5 added to cells with no
mortality events reported in the study
by hambrecht et al.
3.
Nonfatal myocardial infarction;
4.
Unplanned revascularization;
5.
Persistent angina during follow-up.
Effect of initial stent implantation vs medical management for persistent
angina during follow-up
Implantation of a stent for the treatment of stable coronary artery disease
(CAD) does not lower the risk of death, nor does PCI reduce the risk of
nonfatal MI or angina when compared with optimal medical therapy.
non fatal MI
angina
Meta-analysis of eight contemporary trials (7229 patients, 4.3 years follow-up)
Stergiopoulos and Brown. Arch Intern Med. 2012;172(4):312-319.
Implications
•
The failure of stent implantation to reduce the risk of death or MI
compared with medical therapy reinforces current concepts of the
underlying pathophysiologic characteristics of atherosclerosis as a
diffuse process leading to vulnerable plaque disruption and subsequent
coronary thrombosis, MI, and death.
•
The findings support recommendations that stable CAD patients should
be treated with medical therapy rather than first undergoing stent
implantation.
Chronic Ischemic Heart Disease
Treatment Gaps
 Many patients have relative intolerans to maximum doses of
traditional antianginal agents (BB, CCBs, and nitrates)
 Patients continue to experience myocardial ischemia
 B blockers and many CCBs have similar depressive hemodynamic
and electrophysiologic effects
 Antianginal drugs without these limitation are needed
Cost efficiency
 Secondary prevention of Stable CAD
 Statin: 780 $ / year
 By treating 1000 patients with statins 32 death, 59 revascularization can be
prevented
 Beta blocker : 127 $ / year
 Aspirin: 30 $ / year
 Average cost/ year for a patient with stable angina: 990 $ / year
 PCI cost depent on the institution: 2100- 4500 $ / year
J Am Coll Cardiol 2002; 40:603-609
Lancet 2005İ 365-1779
Circulation 2005; 111: 2906-2911
Revascularization vs Medical Therapy
 Initial pharmacological approach to symptom control
may be taken in patients not at high risk
 Revascularization may be recommended for patients
with suitable anatomy who don’t respond adequately to
medical therapy, or for the patient who wishes to remain
physically active
 Optimal secondary preventive medical therapy should
be continued in patient after revascularization
irrespective of the need for anti-anginal therapy
2006 ESC Guideline
Revascularization to Improve Survival
Compared With Medical Therapy
Revascularization to Improve Survival
Compared With Medical Therapy
SUMMARY
 The basic evidence for CABG and PCI is derived from
RCTs and large propensity-matched observational
registries; both have important strengths, but also
limitations.
 By eliminating bias, individual RCTs and their subsequent
meta-analyses constitute the highest hierarchical form of
evidence-based medicine.
 However, their extrapolation to routine clinical practice is
complicated by the fact that their patient populations
are often not representative of those encountered in
normal clinical practice
CONCLUSION

Patients with no or mild symptoms and little
ischaemia can safely be treated with medical
treatment alone.

Non-invasive (MS-CT, perfusion scintigraphy, or
PET-CT) or invasive (FFR) identification of lesions
giving rise to extensive ischaemia may further
improve outcome in patients submitted to
revascularization.

Finally, patient preference must be carefully
weighed in the overall treatment selection.
Thank you for your attention
CONCLUSION

Patients with no or mild symptoms and little
ischaemia can safely be treated with medical
treatment alone.

Non-invasive (MS-CT, perfusion scintigraphy, or
PET-CT) or invasive (FFR) identification of lesions
giving rise to ischaemia may further improve
outcome in patients submitted to
revascularization.

Finally, patient preference must be carefully
weighed in the overall treatment selection.
Revascularization to Improve Survival
Compared With Medical Therapy
Revascularization to Improve Survival
Compared With Medical Therapy
While recommendations for coronary intervention by PCI or CABG
should be mainly evidence-based, the overall clinical picture (e.g.
advanced age, significant co-morbidities, need for dual
antiplatelet medication) as well as patient preferences should also
be considered.
 Myocardial revascularisation in chronic heart failure
 Patients with (CHF) and systolic (LV) dysfunction, presenting
predominantly with anginal symptoms and regardless of
ventricular volumes.
 Patients with CHF and no or mild angina
 Only in the presence of viability and left ventricular endsystolic volume index (LVESVI) ≤ 60 mL/m2.
Medical Therapy
 The numbers needed to treat with drugs depend on the risk for future events
of a specific patient group.
 To avoid one such event,





175 patients should be treated during 1 year with aspirin (relative risk reduction 23%),
120 patients with a ‘standard dose’ statin (RRR 30%),
200 with an ACE inhibitor or AT2 receptor blocker (RRR 20%),
200 patients with clopidogrel in the first year after ACS (RRR 20%),
240 with high dose statin (RRR 15% when compared with lower statin dose).
 In patients at higher risk, the numbers needed to treat are obviously lower,
and treatment is more cost-effective.
Chronic Ischemic Heart Disease
Treatment Gaps
 Patients with peripheral artery disease are at increased risk for periprocedural
complications after PCI and CABG.
 Higher incidence of a major complication (death, MI, stroke, coma, or emergency,
revascularization) after
 PCI (12 versus 8 % for those without PAD)
 CABG (21 versus 3 %)
 A higher five-year mortality after CABG (14 vs.3 %)
 Higher rate of neurologic complications after CABG
ACC/AHA Class I Recommendation for PCI in
Stable Chronic Angina
A review compared medical treatment with surgical or
percutaneous revascularization
•
13 121 pts. 17 PCI, 6 CABG, and 5 trials using either revascularization strategy
 Mortality was lower after revascularization than in the medical therapy group
 (7.9 vs. 9.8%, OR = 0.74, 95% CI 0.63–0.88).
 These findings remained consistent following exclusion of studies in patients with
recent MI
 (OR = 0.77, 95% CI 0.65–0.91).
The treatment effect appeared more pronounced in early studies comparing
CABG with medical treatment than in the more recent studies comparing PCI
with medical treatment
Am J Med 2009;122:152-161

Coronary Angiography for Risk Stratification in Patients With Chronic Stable Angina

Recommendations Class I

Patients with disabling (Canadian Cardiovascular Society [CCS] classes III and IV) chronic stable angina despite medical therapy. (Level of Evidence: B)

Patients with high-risk criteria on noninvasive testing regardless of anginal severity. (Level of Evidence: B)

Patients with angina who have survived sudden cardiac death or serious ventricular arrhythmia. (Level of Evidence: B)

Patients with angina and symptoms and signs of congestive heart failure. (Level of Evidence: C)

Patients with clinical characteristics that indicate a high likelihood of severe CAD. (Level of Evidence: C)

Class IIa

Patients with significant LV dysfunction (ejection fraction <45%), CCS class I or II angina, and demonstrable ischemia but less than high-risk criteria on
noninvasive testing. (Level of Evidence: C)

Patients with inadequate prognostic information after noninvasive testing. (Level of Evidence: C)

Class IIb

Patients with CCS class I or II angina, preserved LV function (ejection fraction >45%), and less than high-risk criteria on noninvasive testing. (Level of Evidence:
C)

Class III

Patients with CCS class I or II angina who respond to medical therapy and have no evidence of ischemia on noninvasive testing. (Level of Evidence: C)

Patients who prefer to avoid revascularization. (Level of Evidence: C)
Circulation.1999; 99: 2829-2848

IV. Treatment

Recommendations for Pharmacotherapy to Prevent MI and Death and Reduce Symptoms Class I

Aspirin in the absence of contraindications. (Level of Evidence: A)

ß-Blockers as initial therapy in the absence of contraindications in patients with prior MI. (Level of Evidence: A)

ß-Blockers as initial therapy in the absence of contraindications in patients without prior MI. (Level of Evidence: B)

Calcium antagonists* and/or long-acting nitrates as initial therapy when ß-blockers are contraindicated. (Level of Evidence: B)

Calcium antagonists* and/or long-acting nitrates in combination with ß-blockers when initial treatment with ß-blockers is not successful. (Level of Evidence: B)

Calcium antagonists* and/or long-acting nitrates as a substitute for ß-blockers if initial treatment with ß-blockers leads to unacceptable side effects. (Level of Evidence: C)

Sublingual nitroglycerin or nitroglycerin spray for the immediate relief of angina. (Level of Evidence: C)

Lipid-lowering therapy in patients with documented or suspected CAD and LDL cholesterol >130 mg/dL with a target LDL of <100 mg/dL. (Level of Evidence: A)

*Short-acting dihydropyridine calcium antagonists should be avoided.
 IV. Treatment
 Class IIa
 Clopidogrel when aspirin is absolutely contraindicated. (Level of Evidence: B)
 Long-acting nondihydropyridine calcium antagonists* instead of ß-blockers as initial
therapy. (Level of Evidence: B)
 Lipid-lowering therapy in patients with documented or suspected CAD and LDL
cholesterol 100 to 129 mg/dL, with a target LDL of 100 mg/dL. (Level of Evidence: B)
 *Short-acting dihydropyridine calcium antagonists should be avoided.
 Class IIb Low-intensity anticoagulation with warfarin in addition to aspirin. (Level of
Evidence: B)
 Class III
 Dipyridamole. (Level of Evidence: B)
 Chelation therapy. (Level of Evidence: B)

E. Revascularization for Chronic Stable Angina Recommendations for Revascularization With PTCA (or
Other Catheter-Based Techniques) and CABG in Patients With Stable Angina

Class I

CABG for patients with significant left main coronary disease. (Level of Evidence: A)

CABG for patients with 3-vessel disease. The survival benefit is greater in patients with abnormal LV
function (ejection fraction <50%). (Level of Evidence: A)

CABG for patients with 2-vessel disease with significant proximal left anterior descending CAD and either
abnormal LV function (ejection fraction <50%) or demonstrable ischemia on noninvasive testing. (Level
of Evidence: A)

PTCA for patients with 2- or 3-vessel disease with significant proximal left anterior descending CAD, who
have anatomy suitable for catheter-based therapy, normal LV function, and who do not have treated
diabetes. (Level of Evidence: B)

PTCA or CABG for patients with 1- or 2-vessel CAD without significant proximal left anterior descending
CAD but with a large area of viable myocardium and high-risk criteria on noninvasive testing. (Level of
Evidence: B)

CABG for patients with 1- or 2-vessel CAD without significant proximal left anterior descending CAD who
have survived sudden cardiac death or sustained ventricular tachycardia. (Level of Evidence: C)

In patients with prior PTCA, CABG or PTCA for recurrent stenosis associated with a large area of viable
myocardium and/or high-risk criteria on noninvasive testing. (Level of Evidence: C)

PTCA or CABG for patients who have not been successfully treated (see text) by medical therapy and
can undergo revascularization with acceptable risk. (Level of Evidence: B)

lass IIa

Repeat CABG for patients with multiple saphenous vein graft stenoses, especially when
there is significant stenosis of a graft supplying the left anterior descending coronary
artery. PTCA may be appropriate for focal saphenous vein graft lesions or multiple
stenoses in poor candidates for reoperative surgery. (Level of Evidence: C)

PTCA or CABG for patients with 1- or 2-vessel CAD without significant proximal left anterior
descending CAD but with a moderate area of viable myocardium and demonstrable
ischemia on noninvasive testing. (Level of Evidence: B)

PTCA or CABG for patients with 1-vessel disease with significant proximal left anterior
descending CAD. (Level of Evidence: B)

Class IIb

Compared with CABG, PTCA for patients with 3- or 2-vessel disease with significant
proximal left anterior descending CAD who have anatomy suitable for catheter-based
therapy and who have treated diabetes or abnormal LV function. (Level of Evidence: B)

PTCA for patients with significant left main coronary disease who are not candidates for
CABG. (Level of Evidence: C)

PTCA for patients with 1- or 2-vessel CAD without significant proximal left anterior
descending CAD who have survived sudden cardiac death or sustained ventricular
tachycardia. (Level of Evidence: C)
 Class III
 PTCA or CABG for patients with 1- or 2-vessel CAD without significant proximal
left anterior descending CAD who a. Have mild symptoms that are unlikely
due to myocardial ischemia or have not received an adequate trial of
medical therapy and
 1) Have only a small area of viable myocardium or 2) Have no demonstrable
ischemia on noninvasive testing. (Level of Evidence: C)
 PTCA or CABG for patients with borderline coronary stenoses (50% to 60%
diameter in locations other than the left main) and no demonstrable ischemia
on noninvasive testing. (Level of Evidence: C)
 PTCA or CABG for patients with insignificant coronary stenosis (<50%
diameter). (Level of Evidence: C)
 PTCA in patients with significant left main CAD who are candidates for CABG.
(Level of Evidence: B)
 Note: PTCA is used in these recommendations to indicate PTCA and/or other
catheter-based techniques such as stents, atherectomy, and laser therapy.
OMT versus PCI








The COURAGE trial16 randomised 2287 patients

with known stable CAD and objective findings

of myocardial ischaemia to OMT alone, or in

combination with PCI. Over a 4.6-year follow up,

there was no significant difference in the primary

composite endpoint of death, myocardial infarction,

stroke, or rehospitalisation for unstable angina. At

one year, freedom from angina was greater by 12%

in the PCI group; however, at 5 years this benefit had

disappeared, while 21% of the PCI group and 33% of

the OMT group underwent repeat revascularisation

(p<0.001). Thus, this study showed that, in patients
The effectiveness of PCI (with or without stenting) versus
OMT has been evaluated in many meta-analyses10-15
and in the large, randomised COURAGE trial.16
Most of the meta-analyses reported no difference
in total and cardiovascular mortality, a greater incidence
of non-fatal peri-procedural myocardial infarction,
a reduced need for repeat revascularisation, and

no difference in angina relief in the PCI arm. Only

the meta-analysis of Schömig et al,12 which included

with chronic stable CAD, OMT is comparable to PCI

17 RCTs, showed a survival benefit for PCI compared

as regards the risk of death, myocardial infarction or

with OMT alone (respective mortalities 7.4% versus

major adverse cardiovascular events (MACE).

8.7% over 51 months’ follow up), but this study included

However, in the COURAGE trial16 the severity

in the revascularisation group patients with a

of the coronary artery disease was rather moderate—

the incidences of 1-, 2- and 3-vessel disease

being 31%, 39% and 30%, respectively—while only
Hellenic J Cardiol 2011; 52: 516-524

recent myocardial infarction, as well as patients who

underwent CABG. However, a meta-analysis by Jeremias
Balloon angioplasty versus bare-metal stents versus
drug-eluting stents

Brophy et al,17 in a meta-analysis of 29 studies that

However, after multivariable adjustment, the

included a total of 9918 patients, found no difference

benefits of DES decreased significantly, and the possibility

between bare-metal stents (BMS) and PTCA

cannot be ruled out that their benefit was partly

as regards death, myocardial infarction, or need for

due to the simultaneous prolonged dual antiplatelet

CABG, although there was an absolute reduction of

therapy.

5% in restenosis rate in the stented group.

The above findings are reflected in the recent

Subsequent meta-analyses18 of RCTs that compared

network meta-analysis by Trikalinos et al13 that in518

drug-eluting stents (DES) with BMS reported

• HJC (Hellenic Journal of Cardiology)

no differences in the rates of death, cardiac death, or

E.I. Chatzistamatiou et al

non-fatal myocardial infarction, although there was a

cluded 61 studies, involving a total of 25,388 patients

significantly reduced need for target vessel revascularisation

with chronic CAD, from the earliest use of balloon

with the use of DES. In contrast, Kirtane et

angioplasty to the present era of BMS and DES. The

al,19 in an unadjusted analysis of 182,901 patients in

researchers found no difference in terms of risk of

34 observational studies of BMS and DES, reported

death or myocardial infarction between drug therapy,

significantly lower rates of mortality (HR 0.78, 95%

PTCA, and PCI with BMS or DES, although there
Hellenic J Cardiol 2011; 52: 516-524

CABG versus drug therapy

The superiority of CABG over medical therapy in

treating certain subgroups of patients with stable

CAD was confirmed persuasively by Jusuf et al20 in





However, the recent meta-analysis by Jeremias

et al3 reported a lower risk of death for CABG compared

to OMT (HR 0.63, 95% CI: 0.50-0.77). Moreover,

these findings were confirmed in the recent

BARI-2D trial,24 which included 2368 diabetic type

2 patients (31% with 3-vessel disease). Patients were

stratified as being eligible for either PCI or CABG

and were then randomised to contemporary OMT or

revascularisation. After an average of 5.3 years’ follow

up, rates of all-cause mortality (the primary end

point) were similar for the medical and revascularisation

groups, but in the CABG stratum, patients assigned

to revascularisation had lower cardiovascular

event rates (death, myocardial infarction or stroke)

than patients assigned to OMT.
a meta-analysis of seven RCTs that is still the main
legacy for modern CABG. The study revealed a survival
benefit for CABG in patients with main stem or
3-vessel CAD, especially when the proximal segment

of the anterior descending artery was involved. The

benefits were greater in patients with severe symptoms,

with early positive stress tests, and with impaired

left ventricular performance, as well as in diabetic

patients, as shown by the BARI trial.21 The relevance

of these findings to modern practice is being

increasingly questioned, since the medications used

in those studies were significantly inferior to modern

Isolated disease of the proximal anterior descending

artery

Aziz et al25 and Kapoor et al26 reported two metaanalyses

of more than 3000 patients over a 5-year follow

up, both of which reported no significant differences

in safety endpoints (mortality, myocardial infarction,

stroke) between PCI and CABG. However,

they observed a threefold higher rate of recurrence of

angina and a fivefold higher rate of target vessel revascularisation

in the PCI patients. Similar findings

were reported from a smaller study of 711 patients,

who were treated with minimally invasive direct aortocoronary

bypass or with stenting (predominantly

BMS) and were followed for more than 2 years. The
Hellenic J Cardiol 2011; 52: 516-524
Multi-vessel coronary artery disease

There are more than 15 studies of PCI versus CABG

terior descending artery, 58% had 3-vessel disease

in multi-vessel CAD,28 and only one study of OMT

and 42% 2-vessel disease. All the patients had a normal

versus CABG (MASS II).29 Most of the patients in

ejection fraction and about 30% were diabetics.

these RCTs had essentially normal left ventricular systolic

The primary endpoint of the study (a composite

performance, with 1- or 2-vessel CAD and without

of total deaths, Q-wave myocardial infarction, or refractory

involvement of the anterior descending artery.

angina requiring revascularisation) occurred

The meta-analysis of these RCTs carried out by

more often in the drug group than in the CABG

Hlatky et al2 reported that CABG resulted in a fivefold

group (RR 2.35, 95% CI: 1.78-3.11) and more often

reduction in the need for re-intervention, with no

in the PCI group than in the CABG group (RR 1.85,

or moderate benefit in terms of survival, or a survival

95% CI: 1.39-2.47). In addition, the 10-year anginafree

benefit only in patients aged >65 years (HR 0.82)

rates were 64% for CABG, 59% for PCI, and

and in diabetic patients (HR 0.7).

43% for drug therapy (p<0.001). The researchers

Hueb et al30 recently reported the results from

determined that, compared to CABG, drug therapy

a 10-year follow up of patients in the MASS II randomised

trial. The unique feature of that study was
Hellenic J Cardiol 2011; 52: 516-524

was associated with a higher incidence of myocardial

infarction, higher rates of repeat revascularisation, a

In addition, CABG proved to be superior to drug

Coronary main stem disease

therapy in eliminating anginal symptoms. No statistically

CABG is conventionally considered to be the standard

significant difference was found as regards

therapeutic strategy in patients with significant

total mortality among the three therapeutic strategies,

main stem disease who are eligible for surgery, and

although the study was not designed to show

the CASS registry reported a mean survival advantage

differences in mortality. The superiority of revascularisation

of 7 years in 912 patients who were treated with

compared with drug therapy in the MASS

CABG versus medication.34 However, the latest data

II trial is in conflict with the findings of the COURAGE

from the large SYNTAX trial,35 two more recent

trial referred to above. Of course, the difference

RCTs36,37 and a meta-analysis,38 indicate that PCI offers

could probably be explained by the different patient

equivalent results to CABG, at least in more simple

populations in the two studies. Indeed, the anatomical

lesions. None of these trials showed significant

complexity of the CAD was much greater in

mortality differences between the two revascularisation

the MASS II trial and came close to the anatomical

strategies, making PCI an option for those patients

characteristics of the patients in the SYNTAX trial,


which will be analysed below. In the COURAGE

unwilling to undergo surgery and prepared to
Hellenic J Cardiol 2011; 52: 516-524
accept further interventional procedures as necessary.
Hellenic J Cardiol 2011; 52: 516-524
Hellenic J Cardiol 2011; 52: 516-524

Recent ESC guidelines

In patients with chronic stable CAD the choice of the

most appropriate therapeutic strategy should be the

result of two components:42

1. Eligibility for revascularisation (Table 1).

2. Relative advantages of CABG and PCI in the

various anatomical and clinical forms of the

disease (Table 2).

The findings we have to hand show that revascularisation

is chosen:

• On an symptomatic basis: in patients with persistent

symptoms (angina or equivalent) despite OMT,

and/or

• On a prognostic basis: in specific anatomical forms

of the disease or if there is a confirmed significant

myocardial mass at risk (even in asymptomatic
The impact of revascularization on
clinical outcomes
(ACIP) study, 57% of patients treated with revascularization
were free of ischaemia at 1 year compared with 31 and
36% in the ischaemia-guided and angina-guided
strategies, respectively (P < 0.0001).


at 2 years follow-up, the risk of death and MI was
significantly lower among patients undergoing
revascularization (4.7%) compared with those receiving
ischaemia-guided (8.8%) or angina-guided medical
treatment (12.1%, P < 0.04).

SWISSI II trial, patients with silent ischaemia after recent MI



lower rates of ischaemia when allocated to PCI (12%) than
medical treatment (29%, P = 0.03),
a beneficial effect accompanied by improved leftventricular ejection fraction (57 vs. 49%, P < 0.001)
an absolute reduction in clinical events (cardiac death, MI,
and revascularization) of 6.3% per year in favour of PCI.

DANAMI study, Patients with angina or exercise-induced ischaemia early after MI had a better prognosis after revascularization
than with medical therapy alone

COURAGE, PCI compared with medical treatment showed a greater absolute reduction in myocardial ischaemia (−2.7 vs. −0.5%, P
< 0.0001), and more patients exhibited a relevant reduction in ischaemia (33 vs. 19%, P = 0.0004), particularly among those with
moderate to severe ischaemia (78 vs. 52%, P = 0.007)

There was a graded relationship between reduction of ischaemia and subsequent risk of death or MI with
improved event-free survival in patients with significant reduction of ischaemia.
Impact of revascularization on mortality in patients with chronic stable coronary artery
disease.
There was no difference in the risk of MI between both groups.
•
CI overlapped widely and an analysis of variance
revealed
no significant difference between the two
Simoons M L , Windecker S Eur Heart J 2010;31:530-541
revascularization
strategies (P = 0.33)
CABG
Effects on survival
 CABG offered no significant overall mortality benefits
compared to medical therapy alone in trials from the 1970s
 However, survival was improved in selected patients with
severe CAD who were at high risk because a large amount of
myocardium was supplied by the diseased vessel or because
of significant underlying left ventricular dysfunction.
All patients with stable CAD require medical therapy to prevent
disease progression and recurrent cardiovascular events
2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina:
J. Am. Coll. Cardiol. 2007;50;2264-2274
All patients with stable CAD require medical therapy to prevent
disease progression and recurrent cardiovascular events
An annual influenza vaccination is recommended for patients with cardiovascular disease
2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina:
J. Am. Coll. Cardiol. 2007;50;2264-2274
What is the definitive role of PCI in chronic angina
and stable CAD?
 PCI improves angina and exercise capacity
 However, compared to optimal medical therapy,
does PCI





Prolong survival?
Reduce risk of subsequent MI?
Reduce hospitalization for unstable angina?
Decrease need for subsequent CABG?
Improve quality of life?
Courtesy of WE Boden, MD
Early Meta-analysis
J Am Coll Cardiol 2008 ;52:894-904
•
•
•
•
17 randomized trials
7513 pts.
51 months follow up
PCI 92%
•
•
•
43% balloon angioplasty,
41% stents,
8% CABG
 Overall mortality was significantly reduced by 20% in favour of PCI
 MI was similar among both groups
 The benefit of revascularization became more pronounced with follow-up
periods beyond 5 years.
Meta-analysis
 No significant reduction in mortality or MI for PTCA
compared with medical therapy,
 Bare-metal stents compared with PTCA
 Drug-eluting stents compared with bare-metal stents
 The different results of these meta-analyses reflect
differences in the analytic methodology and trial
selection, but also illustrate that any mortality benefits of
PCI are modest at best.
Lancet 2009;373:911-918
Chronic stable coronary artery disease: drugs vs. revascularization
Revascularization and quality of life
Freedom from angina in trials comparing a routine
invasive with an initial non-invasive strategy in
patients with stable coronary artery disease
Proportion of patients requiring anti-angina drugs in
trials comparing a routine invasive with an initial
non-invasive strategy in patients with stable
coronary artery disease
 Compared with medical therapy, revascularization by PCI or
CABG has been consistently shown to more effectively relieve
angina, reduce the use of anti-angina drugs, improve exercise
capacity and quality of life