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A Prospective Randomized Trial of Triage Angiography in Suspected Acute Myocardial Infarction Patients who are Considered Ineligible for Reperfusion Therapy.

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Presentation on theme: "A Prospective Randomized Trial of Triage Angiography in Suspected Acute Myocardial Infarction Patients who are Considered Ineligible for Reperfusion Therapy."— Presentation transcript:

1 A Prospective Randomized Trial of Triage Angiography in Suspected Acute Myocardial Infarction Patients who are Considered Ineligible for Reperfusion Therapy Peter A. McCullough, MD, MPH, William W. O’Neill, MD, Mariann Graham, BSN, Shukri David, MD, Robert Stomel, DO, Felix Rogers DO, Cindy L. Grines, MD William Beaumont Hospital, Royal Oak, MI Providence Hospital, Southfield, MI Botsford Hospital, Farmington Hills, MI Riverside Hospital, Trenton, MI McCullough PA, O’Neill WW, Graham M, David S, Stomel R, Rogers F, Grines CL. A Prospective Randomized Trial of Triage Angiography in Suspected Acute Myocardial Infarction Patients Who are Considered Ineligible for Reperfusion Therapy. Circulation 1996;94:I-570 [oral].

2 MATE Medicine vs Angiography in Thrombolytic (Reperfusion) Exclusion Patients

3 Background u Only 15-20% of Acute MI (AMI) patients are considered eligible for reperfusion therapy by conventional criteria u Previous studies have shown high cardiac event rates (recurrent ischemic events and death) for those patients with AMI who are ineligible for reperfusion therapy* * Cragg, D.R., Friedman, H.Z., Bonema, J.D., Jaiyesimi, I.A., Ramos, R.G., Timmis, G.C., O'Neill, W.W., and Schreiber, T.L. Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy. Ann.Intern.Med. 115:173-177, 1991.

4 Purpose To prospectively test the hypothesis that triage angiography and subsequent revascularization, if indicated, is superior to conservative therapy in those patients who have suspected AMI but do not meet eligibility criteria for reperfusion therapy.

5 Methods u Randomized, prospective, multicenter trial u Subjects: those patients ages 18 and up who had suspected AMI (< 24 hours of pain) and were considered ineligible for reperfusion therapy due to excessive bleeding risks or uncertain benefit u Randomized 201 subjects to conservative care (ASA, beta-blockers, heparin, and nitrates), observation and non-invasive evaluation vs initial triage angiography upon admission with subsequent therapy guided by the angiogram u Major endpoint: composite of recurrent ischemic events and in-hospital death

6 Southeast Michigan Participating Centers u William Beaumont Hospital, Royal Oak, Drs. Peter McCullough and Cindy Grines u Botsford Hospital, Farmington Hills, Dr. Robert Stomel u Providence Hospital, Southfield, Dr. Shukri David u Riverside Hospital, Trenton, Dr. Felix Rogers

7 Analysis u Interim analysis performed at 200 patients u Randomization tested for control of confounders u Major endpoint assessed as the percent risk reduction of recurrent ischemia and death u LOS and true hospital costs calculated

8 Baseline Characteristics Characteristic ConservativeTriage Angiogram P-value Mean Age6157ns Female:Male38:4934:79ns Hx Angina27 (31%)30 (27%)ns Hx MI18 (21%)25 (22%)ns Hx CABG8 (9%)11 (10%)ns Hx PTCA15 (17%)14 (12%)ns Diabetes24 (28%)12 (11%).002 HTN57 (66%)59 (53%)ns Dyslipidemia41 (47%)41 (37%)ns Tobacco Use47 (54%)52 (46%)ns Fhx of CAD29 (33%)39 (35%)ns

9 Presentation Duration of Sx8.6 hrs9.2 hrsns ECG ST Elevation23 (26%)37 (33%)ns ST Depression22 (25%)25 (22%)ns T-wave Changes37 (43%)49 (43%)ns Q-waves21 (24%)27 (24%)ns LBBB5 (6%)4 (4%)ns RBBB4 (5%)5 (4%)ns Normal18 (21%)22 (20%)ns Feature ConservativeTriage Angiogram P-value

10 Reasons for Reperfusion Ineligibility Reason ConservativeTriage Angiogram P-value Non-dx ECG71 (83%)87 (77%)ns Past 6 hours38 (44%)55 (49%)ns Bleeding risks10 (12%)15 (13%) ns Too elderly7 (8%)7 (6%) ns Hx of Stroke6 (7%)7 (6%)ns Pain free7 (8%)17 (15%) ns Miscellaneous13 (15%)15 (13%) ns

11 Results Outcome ConservativeTriage Angiogram Percent Risk Reduction with Triage Angiogram (95% CI) P-value Mean Peak CPK461562-ns Ruled in for MI49 (56%)66 (58%)-ns Chest Pain with ECG or Hemodynamic changes 10 (12%)4 (4%)42% (16%-60%).03 Chest Pain without ECG changes 21 (24%)9 (8%)45% (25%-59%).002 Reinfarction0 (0%)2 (2%)-ns Death2 (2%)1 (1%)35% (-46%-71%)ns Aggregate Recurrent Ischemic Events or Death 30 (34%)15 (13%)45% (26%-59%)0.0004

12 Infarction Subgroup Outcome Conservative (n=49) Triage Angiogram (n=66) Percent Risk Reduction with Triage Angiogram (95% CI) P-value Peak CPK728887-ns Ischemic Events or Death Chest Pain with ECG or Hemodynamic changes 8 (16%)3 (5%)46% (16%-65%)0.05 Chest Pain without ECG changes 14 (29%)2 (13%)60% (44%-71%)0.0001 Reinfarction0 (0%)1 (2%)-ns Death1 (2%)0 (0%)-ns Aggregate Recurrent21 (43%)6 (9%)59% (41%-72%)0.00003

13 ST Elevation or LBBB Subgroup Outcome Conservative (n=28) Triage Angiogram (n=40) Percent Risk Reduction with Triage Angiogram (95% CI) P-value Mean Peak CPK490847-ns Ruled in for MI19 (68%)32 (80%)-ns Chest Pain with ECG or Hemodynamic Changes 5 (18%)2 (5%)47% (7%-70%)ns Chest Pain without ECG Changes 12 (45%)5 (15%)56% (26%-73%)0.004 Reinfarction0 (0%)2 (5%)-ns Death1 (4%)0 (0%)-ns Aggregate Recurrent Ischemic Events or Death 15 (54%)9 (23%)53% (18%-73%)0.009

14 ST Depression or T-wave Inversion Subgroup Outcome Conservative (n=28) Triage Angiogram (n=40) Percent Risk Reduction with Triage Angiogram (95% CI) P-value Mean Peak CPK546505-ns Ruled in for MI20 (54%)27 (56%)-ns Chest Pain with ECG or Hemodynamic Changes 3 (8%)1 (2%)44 (-4%-70%)ns Chest Pain without ECG Changes 4 (11%)3 (6%)26% (-48%-63%)ns Reinfarction0 (0%) -ns Death1 (3%)1 (2%)13% (-254%-79%)ns Aggregate Recurrent Ischemic Events or Death 8 (22%)4 (8%)60 (3%-63%)ns

15 Female Subgroup Outcome Conservative (n=38) Triage Angiogram (n=34) Percent Risk Reduction with Triage Angiogram (95% CI) P-value Mean Peak CPK403456-ns Ruled in for MI21 (55%)19 (56%)-ns Chest Pain with ECG or Hemodynamic Changes 3 (8%)1 (3%)31% (-26%-63%)ns Chest Pain without ECG Changes13 (34%)3 (9%)45% (20%-62%)0.01 Reinfarction0 (0%) -ns Death0 (0%)1 (2.9%)-ns Aggregate Recurrent Ischemic Events or Death 16 (42%)4 (12%)47% (22%-64%)0.004

16 Death or Recurrent Ischemia null = 1 ST Elevation or LBBB Definite MI Entire Group RR = 0.47 RR = 0.41 RR = 0.55 RR = 0.40ST Depression or TWI Conservative care better Triage Angiography better -------><-------

17 Early Discharge LOS < 2 daysLOS < 5 days p=0.00007 p=0.03 Triage Angiogram Conservative Care

18 Hospital Costs p=0.04 True hospital costs after adjustment for outliers

19 Safety of Triage Angiography Adverse Event Conservative Triage Angiogram P-value Stroke2 (2%) ns Transient Azotemia3 (3%)2 (1.8%)ns Transfusion4 (5%)11 (10%)ns Vascular Complications 0 (0%)1 (1%)ns

20 Conclusions Early Triage Angiography in those patients with suspected AMI who are reperfusion ineligible: u Can be done safely u Leads to more efficient referral for revascularization with overall increased cost u Reduces in-hospital combined recurrent ischemic events and death (45% risk reduction) u Provides for more effective early discharge to home

21 Importance of Recurrent Ischemia u PAMI-1: recurrent ischemia occurred in 19% and led to re-infarction in 4% and death in 3% (Stone,JACC,1996) u TIMI-3 Registry: recurrent ischemia occurred in 48% and led to MI, death, or stroke in 4% at 10 days (Kleiman,AJC,1996) u TAMI-1+TAMI-3: recurrent ischemia occurred in 17% and led to MI in 4%, and death in 3% (Ellis,Circulation,1989)

22 Late Outcomes in the Medicine vs. Angiography for Thrombolytic Exclusion Study Peter A. McCullough, MD, MPH*, William W. O’Neill, MD, Mariann Graham, BSN, Shukri David, MD, Robert Stomel, DO, Felix Rogers, DO, Ali Farhat, MD, Rasa Kazlauskaite, MD, Cindy L. Grines, MD William Beaumont Hospital, Royal Oak, Michigan *Current Institution: Henry Ford Heart and Vascular Institute, Detroit, Michigan McCullough PA, O’Neill WW, Graham M, David S, Stomel R, Rogers F, Farhat A, Kazlauskaite R, Grines CL. Late Outcomes in the Medicine vs. Angiography for Thrombolytic Exclusion (MATE) Study. Circulation, 1997;96:I-595-596 [oral].

23 Background u The majority of patients with acute ischemic syndromes are not considered candidates for thrombolysis* u The Medicine vs. Angiography for Thrombolytic Exclusion (MATE) Study was a randomized, prospective, multicenter trial of triage angiography performed in the first 24 hours of admission vs. conventional medical care in 201 patients with acute ischemic syndromes considered ineligible for thrombolysis *Cragg, D.R., Friedman, H.Z., Bonema, J.D., Jaiyesimi, I.A., Ramos, R.G., Timmis, G.C., O'Neill, W.W., Schreiber, T.L. Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy. Ann.Intern.Med. 115:173-177, 1991.

24 M.A.T.E. Southeast Michigan Participating Centers William Beaumont Hospital, n=168 Botsford Hospital, n=15 Riverside Hospital, n=10 Providence Hospital, n=8

25 Baseline Characteristics Triage Angiography Conservative Care Triage Angiography Conservative Care Mean age 57 61 Females:Males 34:77 38:52 Prior AMI 23 (21%) 20 (22%) Prior CABG 10 (9%) 9 (10%) ST  36 (22%) 25 (28%) ST  24 (22%) 23 (26%) T wave  49 (44%) 37 (41%) ECG ineligible 85 (77%) 74 (83%) Sx > 6 hours 55 (50%) 38 (43%)

26 Treatment Triage Angiography Conservative Care Triage Angiography Conservative Care Sx onset to ED 9 ± 6 hrs 9 ± 7 hrs Sx onset to angio 16 ± 14 hrs (n=109) 84 ± 92 hrs (n=54)* Aspirin 109 (98%) 88 (98%) Heparin IV 106 (96%) 89 (99%) Beta Blockers IV/PO 63 (57%) 63 (70%)  NTG IV 106 (96%) 86 (96%) PTCA performed 48 (43%) 27 (30%)  CABG 18 (16%) 7 (8%)  *non-protocol angiography  p=.05  p=.07 *non-protocol angiography  p=.05  p=.07

27 In-Hospital Clinical Endpoints Triage Angiography Conservative Care P-value Triage Angiography Conservative Care P-value Confirmed AMI 57 (51%) 49 (54%) 0.81 CP + ECG/HD  ’s 3 (3%) 12 (13%) 0.004 CP - ECG/HD  ’s 9 (8%) 21 (23%) 0.003 Reinfarction 2 (2%) 0 (0%) 0.5 In-hospital death 1 (1%) 3 (3%) 0.3 Composite 14 (13%) 31 (34%) 0.0002 (All recurrent ischemic events or death)

28 Clinical Benefit of Triage Angiography Reduction of Recurrent Ischemic Events and Death RR=1 P<0.001 P<0.001 P=0.002 P=0.03 Definite AMI by CK ST  or LBBB ST  or TWI All Patients RR=0.55 (95% CI.41-.63) Number needed to treat (NNT) = 5

29 Translation of Benefit u Does a reduction of in-hospital recurrent ischemic events by early angiography and revascularization, when indicated, translate into a benefit after discharge with respect to rates of re-hospitalization, later angiography and revascularization, and recurrent AMI, development of CHF, or death?

30 Follow-up Protocol u Subjects underwent a structured phone interview at a median time of 22 months after the index event u Interviewers were blinded to the randomization arm u Endpoints were confirmed by medical record abstraction and personal physician contact u 12 subjects, unable to be tracked, were submitted to the National Death Registry which confirmed vital status for complete follow-up on all 201 subjects

31 Late Results Triage Angiography Conservative Care P-value Triage Angiography Conservative Care P-value Hospitalization 25 (23%) 20 (22.2%) 0.87 Recurrent AMI 2 (2%) 2 (2%) 0.86 Developed CHF 9 (8%) 5 (6%) 0.45 Late Angiography 14 (13%) 18 (20%) 0.20 Late PTCA 13 (12%) 9 (10%) 0.66 Late CABG 2 (2%) 3 (3%) 0.51 Death 11 (10%) 6 (7%) 0.44 Composite Endpoint* 32 (29%) 20 (22%) 0.29 *AMI, CHF, PTCA, CABG or death

32 Conservatively Treated Subgroup N = 38, 36 from the conservative arm and 2 from the invasive arm who ultimately did not undergo angiography during the hospitalization 38 cases 23 (60%) managed on meds on meds median 26 mo.. F/U median 26 mo.. F/U 4 (11%) late deaths median 12 mo.. 12 (32%) Caths 6 PTCA’s 1 CABG 2 MI’s 3 CHF

33 Freedom from Hospitalization P>0.05 by log rank Conservative Care Triage Angiography

34 Freedom from Late PTCA P>0.05 by log rank Conservative Care Triage Angiography

35 Composite Endpoint AMI, CHF, Late Revascularization, or Death Triage Angiography Conservative Care P>0.05 by log rank

36 Long-term Survival Triage Angiography Conservative Care P>0.05 by log rank

37 Power and Sample Size u This follow-up study had a 80% power to detect a 100% effect size in the crude composite endpoint between the two groups (  =.05, two-tailed) u A future study would need ~1100 patients in each group to detect an effect size of 20% (ß=.20,  =.05) in the composite endpoint u Similarly, ~7700 patients in each arm would be needed to detect a 20% effect size in mortality between the two strategies

38 Conclusions In Patients with Acute Ischemic Syndromes Ineligible for Thrombolysis u A strategy of triage angiography reduces in-hospital recurrent ischemic events u Follow-up revealed equivalent event rates in each randomization arm u The choice of early angiography and revascularization versus conservative medical therapy presents a trade-off resulting in similar long-term outcomes u Large randomized trials are needed to formally test for a mortality difference between these two strategies

39 Pre-empting Ischemic Events Index Event Stabilize Persistent Ischemia Medically Manage Recurrent Ischemia Troponin Elevation Reinfarction by CPK Late death or MI 90% 10% 30%

40 Timing of Intervention

41 MATE Resources McCullough PA, O’Neill WW, Graham M, David S, Stomel R, Rogers F, Farhat A, Kazlauskaite R, Grines CL. Late Outcomes in the Medicine vs. Angiography for Thrombolytic Exclusion (MATE) Study. Circulation, 1997;96:I-595-596 [oral]. McCullough PA, Al-Zagoum M, Graham M, David S, Stomel R, Rogers F, Farhat A, Kazlauskaite R, Grines CL, O’Neill WW. A Time to Treatment Analysis in the Medicine vs. Angiography for Thrombolytic Exclusion Trial. Cathet Cardiovasc Diag 1998;44:105 [oral]. McCullough PA, Al-Zagoum M, O’Neill WW, Graham M, David S, Stomel R, Rogers F, Farhat A, Kazlauskaite R, Grines CL. A Program of Triage Angiography in Acute Coronary Syndromes Ineligible for Thrombolysis: An Efficacy Analysis. Cathet Cardiovasc Diag 1998;44:105[poster]. McCullough PA, O’Neill WW, Graham M, Stomel RJ, Rogers F, David S, Farhat A, Kazlauskaite R, Al-Zagoum M, Grines CL. A Prospective Randomized Trial of Triage Angiography in Acute Coronary Syndromes Ineligible for Thrombolytic Therapy: Results of the Medicine versus Angiography in Thrombolytic Exclusion (MATE) Trial. J Am Coll Cardiol 1998;32:596-605. NLM CIT. ID: 98412530. McCullough PA, O'Neill WW. Unstable Angina: Early Use of Coronary Angiography and Intervention. Cardiol Clin 1999;17(2):373-386. NLM CIT. ID: 10384833. McCullough PA, O’Neill WW, Graham M, Stomel RJ, Rogers F, David S, Farhat A, Kazlauskaite R, Al-Zagoum M, Grines CL. Impaired Culprit Vessel Flow in Acute Coronary Syndromes Ineligible for Thrombolysis. J Thromb Thrombolysis 2000;00:000-000 McCullough PA, O’Neill WW, Graham M, Stomel RJ, Rogers F, David S, Farhat A, Kazlauskaite R, Al-Zagoum M, Grines CL. A Time to Treatment Analysis in the Medicine versus Angiography in Thrombolytic Exclusion (MATE) Trial. J Inv Card 2000;00:000-000. McCullough PA, O’Neill WW, Graham M, David S, Stomel R, Rogers F, Grines CL. A Prospective Randomized Trial of Triage Angiography in Suspected Acute Myocardial Infarction Patients Who are Considered Ineligible for Reperfusion Therapy. Circulation 1996;94:I-570 [oral].


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