covers all new trails on PCI

1. TRIALS OF PCI VS
FIBRINOLYSIS

2. MYOCARDIAL INFARCTION DEFINITION
• The Joint Task Force of the European Society of Cardiology, American College of Cardiology Foundation,
the American Heart Association, and the World Heart Federation (ESC/ACCF/AHA/WHF)defined acute
MI (2018)

3. • Type 1: MI caused by acute atherothrombotic coronary artery disease and usually precipitated by
atherosclerotic plaque disruption (rupture or erosion).
• Type 2: MI consequent to a mismatch between oxygen supply and demand.
This includes a multiplicity of potential mechanisms including coronary dissection, vasospasm, emboli,
microvascular dysfunction, as well as increases in demand with or without underlying coronary artery
disease.
• Type 3 (MI often resulting in death when biomarker values are unavailable): Patients with a typical
presentation of myocardial ischemia/infarction, such as presumed new ischemic electrocardiographic
(ECG) changes of ventricular fibrillation, with unexpected death before blood samples for biomarkers
could be drawn or before their appearance in the blood.

4. • Type 4a: MI associated with percutaneous coronary intervention (PCI) is arbitrarily defined. Type 4a MI
requires an elevation of cardiac troponin (cTn) values greater than five times the 99th percentile URL in
patients with normal baseline values or, in patients with elevated pre-procedure cTn in whom the cTn
levels are stable (20 percent variation) or falling, the post-procedure cTn must rise >20 percent to an
absolute value more than five times the 99th percentile URL. In addition, there should be evidence of
new myocardial ischemia, either from ECG changes, imaging evidence, or from procedure-related
complications associated with reduced coronary blood flow such as coronary dissection, occlusion of a
major epicardial artery or a side branch occlusion/thrombus,disruption of collateral flow, slow flow or
no-reflow, or distal embolization.
• Type 4b: A subcategory of PCI-related MI is stent/scaffold thrombosis. This is documented by
angiography or autopsy using the same criteria utilized for type 1 MI.

5. • Type 5: Coronary artery bypass graft surgery (CABG) MI is defined as an elevation of cTn values >10
times the 99th percentile URL in patients with normal baseline cTn values. In patients with elevated pre-
procedure cTn in whom cTn levels are stable (20 percent variation) or falling, the post-procedure cTn
must rise by >20 percent. However, the absolute postprocedural value still must be >10 times the
99th percentile URL. In addition, one of the following elements is required:
1. Development of new pathological Q waves
2. Angiographic documented new graft occlusion or new native coronary artery occlusion
3. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern
consistent with an ischemic etiology.

6. PRIOR MI
• According to the Fourth Universal Definition, any one of the following three criteria satisfies the
diagnosis for a prior or silent/unrecognized MI :
• Abnormal Q waves with or without symptoms in the absence of nonischemic causes.
• Imaging evidence of loss of viable myocardium in a pattern consistent with ischemic etiology.
• Pathoanatomical findings of a prior MI.

7. PRIMARY PCI VS FIBRINOLYSIS IN STEMI – CLINICAL
TRIALS
• The benefit of fibrinolysis is greatest when therapy is given within the first four
hours after the onset of symptoms, particularly within the first 70 minutes as the
resistance of cross-linked fibrin to fibrinolysis is time-dependent
• The absolute mortality benefit compared to placebo at five weeks is approximately
3 percent for those presenting within six hours from symptom onset, 2 percent for
those presenting within 7 to 12 hours, and a nonsignificant 1 percent for those
presenting within 13 to 18 hours

8. • Although patency, defined as some antegrade flow through the site of obstruction, is
restored in up to 87 percent of infarct-related arteries, normalization of blood flow (as
assessed by the TIMI flow grade) occurs in only 50 to 60 percent.
• In contrast, TIMI grade 3 flow is achieved in 93 to 96 percent of patients who undergo
primary PCI
• Attainment of TIMI 3 flow is much more common with primary PCI: 93 to 96 percent in
the PAMI and CADILLAC trials of more than 5400 patients

9. • After apparently successful fibrinolysis, evidence of early recurrence of
ischemia (pain or ST segment shifts) has been observed in 20 to 30 percent of
patients - GUSTO-IIb trial , GUSTO-I ST Segment Monitoring Substudy
• Frank fibrinolytic coronary reocclusion in 5 to 15 percent - GUSTO
Angiographic Investigators , TAMI Study Group
• and reinfarction in 3 to 5 percent - (GUSTO I) , (GUSTO III) trials. MITRA, MIR
• PCI is the preferred therapy - TIMI Study Group

10. • Major hemorrhagic complications occur in 2 to 3 percent. The most serious is
intracerebral haemorrhage, which occurs in as many as 1 percent overall , 1.4 percent
of older adults and over 4 percent in patients with multiple risk factors .
• As many as 20 to 30 percent of patients presenting with an acute STEMI, particularly
older adults, are not candidates for fibrinolytic therapy because of contraindications
such as active internal bleeding, a recent stroke, or hypertension
• Efficacy of fibrinolytic therapy has not been demonstrated in patients in cardiogenic
shock (unless coronary perfusion pressure is increased with an Intraaortic balloon
pump [IABP]) or those with prior coronary artery bypass surgery (CABG)

11. • Fibrinolytic therapy does not necessarily involve early angiography, the findings of which
may change treatment.
• In a report from the PAMI trial, 10 percent of patients who underwent angiography were
considered inappropriate candidates for PCI due, in one-half of cases, to lack of residual
stenosis that presumably reflected spontaneous clot lysis
• Other patients have findings, such as severe three-vessel or left main coronary disease, or
anatomic features unfavorable for PCI, that lead to a recommendation for surgical
revascularization.
• Many experts now recommend routine angiography after fibrinolysis for those patients
who have not had it performed for evidence of ongoing or recurrent ischemia.

12. PRIMARY PCI VERSUS FIBRINOLYTIC TRIALS
• Three types of trials
1. Primary PCI with percutaneous transluminal coronary angioplasty compared
to fibrinolysis
2. Primary PCI with stenting compared to fibrinolysis
3. Primary PCI with stenting compared to primary PCI with balloon angioplasty.

13. PRIMARY PCI WITH BALLOON ANGIOPLASTY VERSUS
FIBRINOLYSIS
• The early trials comparing primary PCI with balloon angioplasty to fibrinolysis showed a
significant reduction in mortality
• However, these trials are of limited utility to current practice for the following reasons:
stenting is performed in almost all patients who undergo PCI
 current generation fibrinolytic agents were not used in many of the trials
anticoagulation and antiplatelet protocols differed significantly from contemporary
practice

14. Most of the important studies were included in a 1997 meta-analysis of 10
randomized trials which included 2606 patients randomly assigned to primary PCI
with balloon angioplasty or fibrinolysis
• A significantly lower mortality at 30 days or less (4.4 versus 6.5 percent, odds
ratio 0.66, 95% CI 0.46-0.94); the effect was similar among the different
fibrinolytic regimens used.
• A significantly lower rate of death or nonfatal reinfarction (7.2 versus 11.9
percent, odds ratio 0.58, 95% CI 0.44-0.76).
• A lower rate of total stroke (0.7 versus 2.0 percent) and hemorrhagic stroke
(0.1 versus 1.1 percent).

15. • The Primary Angioplasty in Myocardial Infarction trial (PAMI), published after the
meta-analysis, randomly assigned 395 patients presenting with an acute MI within 12
hours of symptom onset to primary PCI with balloon angioplasty or 100 mg of
intravenous recombinant tissue-type plasminogen activator (alteplase)
• Benefits, similar to those in the meta-analysis, were found with primary PCI with
balloon angioplasty
• An important observation in PAMI was that high-risk groups (age >70, anterior MI,
heart rate >100 on admission) derived the greatest benefit.

16. PRIMARY PCI WITH STENTING VERSUS PRIMARY PCI
WITH BALLOON ANGIOPLASTY
• The clinical efficacy of primary PCI with balloon angioplasty in acute STEMI is limited by
the risks of early reocclusion and late restenosis, providing the rationale for the use of
intracoronary stents.
• Initial nonrandomized studies suggesting that primary stenting was more effective than
primary percutaneous transluminal coronary angioplasty (PTCA) - (PAMI) stent pilot trial.
• Primary stent implantation without coumadin in acute myocardial infarction ,
• Effects of coronary stenting on restenosis and occlusion after angioplasty of the culprit vessel in
patients with recent myocardial infarction .
• Randomized trials, including Stent PAMI and CADILLAC, confirmed the greater efficacy
of stenting compared with balloon angioplasty for patients with STEMI.

17. META-ANALYSIS - 2005
• Evaluated nine randomized trials with a total of 4433 patients
• Stenting (predominantly with bare metal stents), compared to balloon angioplasty,
was associated with significant reductions in reinfarction (odds ratio [OR] 0.52, 95% CI
0.31-0.87 at 30 days, and OR 0.67, 95% CI 0.45-0.98 at one year)
• target vessel revascularization (OR 0.45, 95% CI 0.34-0.60 at 30 days, and OR 0.47,
95% CI 0.38-0.57 at one year).
• There was no significant difference in mortality (OR 1.06 at one year).

18. PRIMARY PCI WITH STENTING VERSUS FIBRINOLYSIS
• Several randomized trials (DANAMI-2, PRAGUE-2, AIR PAMI, STAT, STOPAMI-1,
and STOPAMI-2) have demonstrated a better outcome with primary PCI with
stenting compared to fibrinolysis.
• In the two largest trials, DANAMI-2 and PRAGUE-2, most of the patients
presented to hospitals without PCI facilities. Bare-metal stents were used in
these trials.

19. DANAMI-2 TRIAL
• Randomly assigned 1572 patients to front-loaded alteplase or to primary PCI with
stenting (93 percent with stenting)
• The majority of patients were initially evaluated in referral hospitals, and then
transferred to a PCI center if randomized to primary PCI
• Inclusion criteria included STEMI, duration of symptoms less than 12 hours (median
105 minutes), and ability to complete transfer to a PCI center within three hours of
randomization
• For those patients enrolled in referral centers, the median time between
randomization and arrival in the catheterization laboratory was 67 minutes, with 96
percent arriving within 120 minutes.

20. • The study was discontinued prematurely because of a significant reduction in the
primary end point of mortality, reinfarction, or stroke at 30 days with primary PCI
(8.0 versus 13.7 percent).
• The mortality benefit was noted only in the subgroup of high-risk patients with a
TIMI risk score ≥5 at presentation
• The benefit remained significant at three years (19.5 versus 25.2 percent) and was
primarily due to less clinical reinfarction (8.9 versus 12.3 percent)
• At median follow-up of 7.8 years, the combined end point of death or reinfarction
was significantly lower in the primary PCI group (34.8 versus 41.3 percent),
attributable to a significantly lower reinfarction rate (11.7 versus 18.5 percent)

21. POTENTIAL LIMITATIONS TO DANAMI-2 INCLUDED
THE FOLLOWING:
• Repeat fibrinolysis in the alteplase group as opposed to rescue PCI, which is
the preferred approach.
• Absence of protocol mandated clopidogrel in all patients and
glycoprotein IIb/IIIa inhibitors in most patients undergoing primary PCI, both
of which are recommended in most major guidelines

22. PRAGUE-2 TRIAL
• Randomly assigned 850 patients with an STEMI who had had symptoms for less than
12 hours to immediate fibrinolysis with streptokinase at the presenting community
hospital or transfer to a PCI center
• Primary PCI was associated with a nonsignificant trend toward lower mortality at 30
days (6.8 versus 10.0 percent with fibrinolysis).
• At five years, the cumulative incidence of the composite end point (death from any
cause, recurrent infarction, stroke, or revascularization) was significantly lower in the
primary PCI group (40 versus 50 percent), driven principally by a lower rate of
recurrent infarction

23. HIGH- VERSUS LOW-RISK PATIENTS
• DANAMI-2 trial cited above stratified patients according to the TIMI risk score for
STEMI in an attempt to assess whether all patients with STEMI benefit from primary
PCI
• In a three-year follow-up from the DANAMI-2 cohort, primary PCI was associated
with a significant reduction in mortality at three years compared to fibrinolysis in
high-risk patients with a TIMI risk score ≥5 (25.3 versus 36.2 percent)
• In contrast, there was no mortality benefit from primary PCI in the 74 percent of
patients who were at low risk with a score of 0 to 4 (8.0 versus 5.6 percent), and only
a nonsignificant trend toward a reduction in the composite end point of death,
reinfarction, and disabling stroke (13.7 versus 15.7 percent), which was due to a
significant reduction in reinfarction (6.6 versus 10.4 percent).

25. • The mortality findings are consistent with a community-based sample of 1058 patients,
which found that the added benefit from primary PCI increased with overall risk, that 87
percent of the benefit could be attained by treating patients in the upper half of risk
• In meta-regression analysis of 10 randomized trials of primary PTCA, a mortality benefit
was unlikely in patients with a 30-day mortality risk of about 2 percent or less, which is
seen with a TIMI risk score of 0 to 2
• The low-risk patients in DANAMI-2 had a 30-day mortality of 2.5 percent with
fibrinolysis .

26. META-ANALYSIS — A LARGE 2009 META-ANALYSIS
• Randomized controlled trials (RCT) and observational studies (OS), which compared
primary PCI (with balloon angioplasty or stenting) to fibrinolysis, came to the
following conclusions :
1. Primary PCI was associated with significant reductions in short-term (≤6 weeks) mortality of 34
percent in RCT and 23 percent in OS.
2. Primary PCI was associated with significant reductions in long-term (>1 year) mortality of 24
percent and reinfarction of 51 percent in RCT.
3. No significant benefit of primary PCI compared to fibrinolytic therapy was seen for either
mortality or reinfarction in the observational studies.

27. SPECIFIC SETTINGS
• The above trials do not provide data on the efficacy of primary percutaneous
coronary intervention (PCI) in a number of specific settings
• Mostly nonrandomized data are available for patients with anterior wall myocardial
infarction (MI) and prior coronary artery bypass graft surgery (CABG), as well as
following noncardiac surgery.
• The role of primary PCI in cardiogenic shock was evaluated in the randomized SHOCK
trial.

28. ANTERIOR WALL MI
• There is substantial evidence of benefit of primary PCI for anterior wall in subgroup
analyses from randomized trials
• As examples, the benefit of primary percutaneous transluminal coronary
angioplasty (PTCA) compared to fibrinolysis in PAMI was limited to patients with
anterior wall ST elevation myocardial infarction (STEMI) , the benefit of primary
stenting compared to fibrinolysis was similar with anterior and nonanterior acute
MI in DANAMI-2 and the benefit of primary stenting compared to primary PTCA was
significant with left anterior descending disease, which is responsible for anterior
infarctions

29. • Efficacy in anterior wall MI was directly addressed in a study in which 220 such
patients were randomly assigned to primary PCI or alteplase
• Primary PCI was associated with significant reductions in in-hospital mortality (2.8
versus 10.8 percent), postinfarction angina or positive exercise test (11.9 versus 25.2
percent), repeat revascularization (22 versus 47.7 percent) and, at six months,
mortality (4.6 versus 11.7) and revascularization (31.2 versus 55.9 percent).

30. CARDIOGENIC SHOCK
• Observational data from the GUSTO-I trial and the controlled SHOCK trial
suggest benefit from an early invasive strategy with revascularization by
either PCI or CABG
• Fibrinolysis is generally not effective for these patients. However it may be of
benefit when a significant delay before PCI is anticipated.

31. PRIOR CABG
• There has been an increase in the number of patients presenting with an acute MI
who have had a previous CABG.
• In the National Registry of Myocardial Infarction-2 (NRMI-2), a prior CABG was an
independent predictor of mortality (odds ratio 1.23)
• There was no difference in outcome between reperfusion therapy with primary PTCA
or a fibrinolytic agent. However, higher-risk patients were more likely to be referred
for primary PTCA.

32. ACUTE SAPHENOUS VEIN GRAFT OCCLUSION
• Although uncommon, an acute MI may result from acute saphenous vein graft
occlusion.
• There is little high-quality evidence upon which to recommend either fibrinolysis or
primary PCI over the other.
• In those patients who undergo PCI with stenting, drug-eluting stents (DES) have not
been shown to be better than bare metal stents (BMS) in preventing restenosis

33. ELDERLY PATIENTS
• There are no trials that specifically compare primary PCI with fibrinolysis in
older adults.
• The available data from subset analyses of major trials and nonrandomized
retrospective analyses support a benefit from primary PCI.

34. DIABETIC PATIENTS
• The limited data available on the effect of diabetes on the outcome after
primary PCI suggest that the relative benefit compared to fibrinolytic therapy
may be similar to nondiabetics.
• However, diabetics remain at increased risk, perhaps due in part to
microvascular disease

35. WOMEN
• Women tend to be at higher risk with an acute MI than men because they are
usually older and have more comorbidities
• Nevertheless, women with an STEMI have improved outcomes with primary
PCI compared to fibrinolysis and the degree of benefit may actually be greater
than in men

36. CULPRIT SHOCK TRIAL
BACKGROUND
• Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery
disease, the risk of a composite of death from any cause or severe renal failure leading to renal-
replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of
the culprit lesion only than with immediate multivessel PCI. We evaluated clinical outcomes at 1 year.

38. METHODS
• We randomly assigned 706 patients to either culprit-lesion-only PCI or immediate multivessel PCI. The results
for the primary end point of death or renal-replacement therapy at 30 days have been reported previously.
Prespecified secondary end points at 1 year included death from any cause, recurrent myocardial infarction,
repeat revascularization, rehospitalization for congestive heart failure, the composite of death or recurrent
infarction, and the composite of death, recurrent infarction, or rehospitalization for heart failure.

39. RESULTS
• As reported previously, at 30 days, the primary end point had occurred in 45.9% of the patients in the
culprit-lesion-only PCI group and in 55.4% in the multivessel PCI group (P=0.01). At 1 year, death had
occurred in 172 of 344 patients (50.0%) in the culprit-lesion-only PCI group and in 194 of 341 patients
(56.9%) in the multivessel PCI group (relative risk, 0.88; 95% confidence interval [CI], 0.76 to 1.01). The
rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI (relative
risk, 0.85; 95% CI, 0.29 to 2.50), and the rate of a composite of death or recurrent infarction was 50.9%
and 58.4%, respectively (relative risk, 0.87; 95% CI, 0.76 to 1.00). Repeat revascularization occurred
more frequently with culprit-lesion-only PCI than with multivessel PCI (in 32.3% of the patients vs. 9.4%;
relative risk, 3.44; 95% CI, 2.39 to 4.95), as did rehospitalization for heart failure (5.2% vs. 1.2%; relative
risk, 4.46; 95% CI, 1.53 to 13.04).

40. CONCLUSIONS
• Among patients with acute myocardial infarction and cardiogenic shock, the risk of death or renal-
replacement therapy at 30 days was lower with culprit-lesion-only PCI than with immediate multivessel
PCI, and mortality did not differ significantly between the two groups at 1 year of follow-up.