Primary Angioplasty versus Fibrinolysis in the Very Elderly



        TRatamiento del Infarto Agudo de miocardio eN Ancia...
Study Organization

Sponsor: Spanish Society of Cardiology
           WG on Ischemic Heart Disease & CCUs
           WG on...
Background
•              Increasing population aging
•              Very old patients with STEMI more frequently admitted...
Background
•   Increasing population aging
•   Very old patients with STEMI more frequently admitted to CCUs
•   Primary P...
Study Rationale




Ayanian JZ, Braunwald E. Circulation 2000;101:2224-6.




                                            ...
Study Objective



To compare the efficacy and safety of
primary angioplasty and fibrinolytic treatment
in patients 75 ye...
Study Design
                                       Patients ≥75 years                 No contraindications for TT
       ...
Study Design
                               Patients ≥75 years               No contraindications for TT
                 ...
Analysis


Sample size: 570 patients needed to detect with 80% power
             a 40% RRR (8.9% absolute risk difference...
Endpoints

Primary
Incidence of the composite all-cause death, re-infartion or
disabling stroke at 30 days
Secondary
•   R...
Inclusion Criteria


1. Subjects ≥ 75 years of age or older
2. Diagnosis of STEMI: chest pain or any symptom of
   myocard...
Exclusion Criteria

1. Documented contraindication to the use of thrombolytics
     • Internal active bleeding or known hi...
Exclusion Criteria
1.    .




2.    Cardiogenic shock
3.    Estimated door-to-balloon time 120 minutes
4.    Administrat...
Results: Recruitment




• Study initiated in March 2005
• 23 hospitals participated
• 266 patients were recruited
• Study...
Results: Baseline Characteristics

                         Thrombolysis   Primary PCI
                            n=134  ...
Results: Baseline Characteristics

                                Thrombolysis       Primary PCI
                        ...
Results: Management

                            Thrombolysis       Primary PCI
                               n=134      ...
Results: Angiographic results and
              management
                                 Thrombolysis   Primary PCI
   ...
Results: In-hospital treatments

                            Thrombolysis   Primary PCI
                               n=1...
Results: Primary Endpoint
Death, reinfarction or disabling stroke incidence at 30 days


% 30                    OR 1.46 (...
Results: Primary Endpoint components
 Death, reinfarction or disabling stroke incidence at 30 days

                      ...
Results: Other outcomes


% 20                                                              Primary Angioplasty
          ...
Results: Safety outcomes


% 20                                                                       Primary Angioplasty
...
Results: 12-month outcomes


                                           Composite endpoint                                ...
Results: 12-month outcomes


                           Thrombolysis Primary PCI        OR (95%CI)
                       ...
Conclusions

• TRIANA did not prove (due to lack of power), but is
  consistent with, a superiority of primary angioplasty...
Participating Investigators and Centers

Hospital - City                                   PI Cath Lab                PI C...
Definitions (1)

Reinfarction
   Within first 24 hours: Recurrent symptoms of ischemia at rest accompanied
   by new or re...
Definitions (2)

Shock: presence of hypotension (systolic blood pressure < 90 mmHg without
body fluids response accompanie...
Upcoming SlideShare
Loading in...5
×

Triana

916

Published on

Tratamiento del infarto agudo de miocardio en ancianos

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
916
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
18
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Triana

  1. 1. Primary Angioplasty versus Fibrinolysis in the Very Elderly TRatamiento del Infarto Agudo de miocardio eN Ancianos Héctor Bueno, MD, PhD, FESC on behalf of the Working Group on Ischemic Heart Disease and CCUs Working Group on Interventional Cardiology Spanish Society of Cardiology Funded by the Fondo de Investigaciones Sanitarias - Instituto de Salud Carlos III, Ministry of Health, Spain, and additional support from Sanofi-Aventis, Boston Scientific, Guidant, Johnson & Johnson, Medtronic
  2. 2. Study Organization Sponsor: Spanish Society of Cardiology WG on Ischemic Heart Disease & CCUs WG on interventional Cardiology Steering Committee: Héctor Bueno (chair), Rosana Hernández-Antolín (co-chair), Joaquín J. Alonso, Amadeo Betriu, Angel Cequier, Eulogio J. Garcia, Magda Heras, Jose L. Lopez-Sendon, Carlos Macaya DSMB: José Azpitarte (chair) Adjudication Committee: Ginés Sanz (chair), Angel Chamorro, Ramón López-Palop, Alex Sionis, Fernando Arós Funding: Fondo de Investigación Sanitaria (grant # PI042122) Instituto Carlos III, Ministry of Health, Spain and unrestricted grants from: • Sanofi-Aventis • Boston Scientific • Guidant • Johnson & Johnson • Medtronic
  3. 3. Background • Increasing population aging • Very old patients with STEMI more frequently admitted to CCUs • Primary PCI preferred therapy for STEMI patients in general • Scarce direct evidence for both reperfusion strategies in patients >75 years old Zwolle RCT in patients ≥75 years old Senior PAMI – Subgroup Age ≥80 years PA SK 1.00 PA n = 87 patients 25 n=131 SK 77 excluded 0.95 1996-1999 20 0.90 Survival 15 0.85 % 10 0.80 P=0.04 P=0.96 P=0.72 P=0.57 0.75 5 0.70 0 0 0,5 1 1,5 2 Death Death / Dis. Death / Stroke Follow up (years) Stroke / ReMI De Boer MJ. J Am Coll Cardiol 2002;39:1723-28. Grines C. Personal Communication. TCT, Washington, 2005
  4. 4. Background • Increasing population aging • Very old patients with STEMI more frequently admitted to CCUs • Primary PCI preferred therapy for STEMI patients in general • Scarce direct evidence for both reperfusion strategies in patients >75 years old • Thrombolysis still the most frequently reperfusion therapy used over the world, including older patients 100% TRIANA Pilot Study 22.4 Primary Angioplasty Spanish Survey 80% 26 Hospitals with active PA program 35.6 Thrombolysis March – July 2002 50% 410 consecutive patients ≥75 years 25% 42.0 No reperfusion 0% Bardají A. Rev Esp Cardiol 2005;58:351-8.
  5. 5. Study Rationale Ayanian JZ, Braunwald E. Circulation 2000;101:2224-6. Thiemann DR. J Am Coll Cardiol 2002;39:1729–32. Keeley EC, de Lemos JA. Eur Heart J 2005;26:1693–4.
  6. 6. Study Objective To compare the efficacy and safety of primary angioplasty and fibrinolytic treatment in patients 75 years-old with STEMI who are eligible for thrombolytic therapy in Spanish medical centres with an active program of primary angioplasty
  7. 7. Study Design Patients ≥75 years No contraindications for TT STEMI / LBBB < 6 hours • No shock on admission “optimal” candidates for TT • No single BP measured + >180/110 mmHg • Never stroke / TIA TNK + UFH Primary Weight adjusted Angioplasty Tenecteplase (TNK): Single weight-adjusted bolus UFH 60 U/Kg (maximum 4000 IU) Anticoagulation with UFH: Abciximab Dependent on operator´s decission Bolus 60 U/kg (maximum 4000 U) Infusion for aPTT x 1,5-2 (maximum 1000 U/h) Clopidogrel LD dose 300 mg + MD 75 mg/day Clopidogrel (since Dec 06)  75 mg/day x 28 days Rescue PCI if no reperfusion criteria ↓>50% ST segment at 90´ + clínical data  Urgent PCI (GPI discouraged) Coronary revascularisation only if evidence of recurrent myocardial ischemia (spontaneous/provoked) www.clinicaltrials.gov
  8. 8. Study Design Patients ≥75 years No contraindications for TT STEMI / LBBB < 6 hours • No shock on admission “optimal” candidates for TT • No single BP measured + >180/110 mmHg • Never stroke / TIA TNK + UFH Primary Weight adjusted Angioplasty Primary EndPoint Death / MI / Disabling stroke at 30 days Death / MI / Disabling stroke at 12 months www.clinicaltrials.gov
  9. 9. Analysis Sample size: 570 patients needed to detect with 80% power a 40% RRR (8.9% absolute risk difference) Randomisation: 24 hour central randomisation Analysis: Intention to treat Follow-up: Local - 100% End Point Adjudication: Blinded, by independent committee
  10. 10. Endpoints Primary Incidence of the composite all-cause death, re-infartion or disabling stroke at 30 days Secondary • Recurrent ischemia requiring emergency cath at 30 days • All-cause mortality at 30 days • Cause of death at 30 days (pump failure/mechanical comp/other) • Death, disabling stroke or new HF at 30 days • Major bleeding during hospital admission • All-cause mortality at 12 months • Time to death, reinfarction or disabling stroke during FU • Time to death, reinfarction, disabling stroke or non-elective hospital readmission for cardiac causes during FU
  11. 11. Inclusion Criteria 1. Subjects ≥ 75 years of age or older 2. Diagnosis of STEMI: chest pain or any symptom of myocardial ischemia of, at least, 20 minutes of duration, not responding to nitrate therapy, within first 6 hours from symptom onset and, at least, one of the following: • ST-elevation  2 mm in 2 or more precordial leads • ST-elevation  1 mm in 2 or more anterior leads • De novo (or probably de novo) LBBB 3. Informed consent
  12. 12. Exclusion Criteria 1. Documented contraindication to the use of thrombolytics • Internal active bleeding or known history of hemorrhagic diathesis • History of previous stroke of any kind or at any time • Intracranial tumor, arteriovenous malformation, aneurysm or cerebral aneurysm repair • Major surgery, parenchymal biopsy, ocular surgery or severe trauma within 6 weeks prior to randomisation • Unexplained puncture in a non-compressible vascular location in the last 24 hours prior to randomisation • Confirmed arterial hypertension during the acute phase, previous to randomisation, with one reliable measurement of systolic BP >180 mmHg or diastolic BP >110 mmHg • Known thrombocytopenia < 100.000 platelets/L • Prolonged (>20 minutes) or traumatic cardiopulmonar resuscitation in the 2 weeks prior to randomisation • Symptoms or signs suggesting aortic dissection
  13. 13. Exclusion Criteria 1. . 2. Cardiogenic shock 3. Estimated door-to-balloon time 120 minutes 4. Administration of thrombolysis within 14 days prior to randomisation 5. Administration of any GP IIa/IIIb inhibitor within 24 hours prior to randomisation 6. Administration of any LMWH within 8 hours prior to randomization 7. Current oral anticoagulant treatment 8. Suspected AMI secondary to occlusion of a coronary lesion treated previously with PCI (within previous 30 days for conventional stents and within previous 12 months for DES) 9. Dementia or acute confusional state at the time of randomisation 10. Incapacity/unwillingness to give informed consent 11. Known renal failure (basal creatinine> 2,5 mg/dl) 12. Reduced expected life expectancy (<12 months) 13. Participation in another RCT trial within previous 30 days
  14. 14. Results: Recruitment • Study initiated in March 2005 • 23 hospitals participated • 266 patients were recruited • Study interrupted in December 2007 for slow recruitment
  15. 15. Results: Baseline Characteristics Thrombolysis Primary PCI n=134 n=132 Age (years) 81.2 ± 4.6 81.0 ± 4.3 Gender (% males) 56.1 56.7 Risk Factors (%) HTN 59.1 67.9 Dyslipidemia 27.3 41.8 * Diabetes 34.1 26.1 Current smoker 15.2 11.2 Previous CVD (%) MI 7.6 9 Stable angina 13.6 10.4 PCI 3.8 5.2 CHF 0.8 1.5 PAD 9.1 10.4 *p=0.013
  16. 16. Results: Baseline Characteristics Thrombolysis Primary PCI n=134 n=132 Time to randomisation (min) 180 (135 - 255) 180 (135 - 262) Admission SBP (mmHg) 132 ± 23 136 ± 25 Admission DBP (mmHg) 74 ± 13 75 ± 16 Admission HR (bpm) 73 ± 18 76 ± 18 Killip class (% I / II / III) 82 / 15 / 3 84 / 11 / 3 Anterior location (%) 49 42 Baseline Creatinine (mg/dl) 1.13 ± 0.34 1.09 ± 0.36 Baseline Glucose (mg/dl) 176 ± 75 167 ± 81 Baseline Hemoglobin (g/dl) 13.7 ± 1.9 13.8 ± 1.6
  17. 17. Results: Management Thrombolysis Primary PCI n=134 n=132 Times (min) Door to treatment 52 (32 - 72) 99 (73 - 131) * Randomisation-treatmet 10 (5 - 15) 59 (35 - 75) * Symptom onset-treatment 195 (150 - 270) 245 (191 - 310) * Dose TNK (mg) 37 ± 6.1 - UFH(%) 78 - Dose UFH bolus (U) 3851 ± 729 - Effective reperfusion (%) 74 - Urgent cath (%) 16 - Rescue PCI (%) 15 - *p<0.001
  18. 18. Results: Angiographic results and management Thrombolysis Primary PCI n=134 n=132 IRA: LM/LAD/CX/RCA (%) - 1 / 42 / 14 / 37 Pre-PCI lesion stenosis (%) - 96.4 ± 11.6 TIMI flow pre-PCI 0/1/2/3 (%) - 67 / 13 / 11 / 9 Stent (%) - 84 Dose UFH (U) - 5069 ± 1793 GP Ib/IIIA inhibitors (%) - 44 IABP (%) - 4.5 Post PCI stenosis (%) - 10.6 ± 25 TIMI flow post-PCI (% 0/1/2/3) - 6 / 2 / 10 / 82
  19. 19. Results: In-hospital treatments Thrombolysis Primary PCI n=134 n=132 Aspirin 97 96 Clopidogrel 63 92 <0.001 UFH 98 96 LMWH 37 54 0.006 GP lIb/III inhibitors 8 44 0.003 iv GTN 68 50 0.004 Beta-blockers 76 77 ACEI 86 82 Statins 87 89 Diuretics 45 50 Nitrates 41 37 Inotropic agents 16 20
  20. 20. Results: Primary Endpoint Death, reinfarction or disabling stroke incidence at 30 days % 30 OR 1.46 (0.81-2.61) P = 0.21 25 20 25.4 15 10 18.9 5 0 Primary Angioplasty Thrombolysis
  21. 21. Results: Primary Endpoint components Death, reinfarction or disabling stroke incidence at 30 days Primary Angioplasty % 20 OR 1.31 (0.67-2.56) P = 0.43 Thrombolysis OR 1.60 (0.60-4.25) 15 P = 0.35 17.2 OR 4.03 (0.44-36.5) 10 P = 0.18 13.6 5 8.2 5.3 0.8 3.0 0 Death Reinfarction Disabling stroke
  22. 22. Results: Other outcomes % 20 Primary Angioplasty Thrombolysis OR 1.06 (0.49-2.03) 15 P = 0.90 OR 14.1 (1.8-39) OR 0.50 (0.19-1.31) P < 0.001 P = 0.15 2.58 (0.79-8.45) 10 P = 0.11 10.6 11.2 9.7 9.8 5 7.5 5.2 0.8 3.0 0 Recurrent CHF Shock Mechanical ischemia Comp.
  23. 23. Results: Safety outcomes % 20 Primary Angioplasty Thrombolysis 15 OR 0.72 (0.29-1.77) P = 0.47 OR 1.26 (0.48-3.30) OR 0.55 (0.16-1.92) P = 0.64 10 P = 0.35 OR 1.31 (0.67-2.56) P = 0.43 5 9.1 4.5 5.3 6.7 6.1 7.5 3.8 3.0 0 Major bleed* Transfusion Major Bleed or Renal failure Transfusion * One ischemic stroke in TT arm at day 7, after elective PCI  hemorrhaghic conversion 24 hours later
  24. 24. Results: 12-month outcomes Composite endpoint All-cause mortality 1.0 1.0 death reMI or diasbling stroke Cummulative Survival free of Cummulative Survival 0.8 0.8 P=0.31 P=0.65 0.6 0.6 0 60 120 180 240 300 360 0 60 120 180 240 300 360 Follow-up (days) Follow-up (days)
  25. 25. Results: 12-month outcomes Thrombolysis Primary PCI OR (95%CI) n=134 n=132 Death/ReMI/Disabling stroke 32.1 27.3 1.26 (0.74-2.14) Death 23.1 21.2 1.12 (0.63 - 1.99) ReMI 10.4 8.3 1.28 (0.56 - 2.9) Disabling stroke 3.0 0.8 4.03 (0.44 - 36.5) Urgent rehospitalisation 14.3 13.7 1.05 (0.52 – 2.1) Recurrent ischemia 11.9 0.8 17.8 (2.3 – 136.0) New HF 14.9 14.4 1.04 (0.53 – 2.1) Major bleeding 5.2 6.1 0.85 (0.3 - 2.43)
  26. 26. Conclusions • TRIANA did not prove (due to lack of power), but is consistent with, a superiority of primary angioplasty in reducing death, reinfarction and disabling stroke compared with thrombolysis in very old patients with STEMI. • Primary angioplasty is superior to thrombolysis in reducing reintervention due to recurring ischemia. • Whether the potential early advantage of primary angioplasty is mantained during follow-up needs to be explored • Thrombolysis can be performed with an acceptable risk of intracerebral bleeding in such patients
  27. 27. Participating Investigators and Centers Hospital - City PI Cath Lab PI CCU Hospital Gen. Univ. “Gregorio Marañón” - Madrid Eulogio García-Fernández Rafael Rubio Hospital 12 de Octubre - Madrid Felipe Hernández Juan Carlos Tascón Hospital Virgen de la Salud -Toledo José Moreu José Moreu Hospital Clínic - Barcelona Amadeu Betriu Magda Heras Hospital Clínico San Carlos - Madrid Rosana Hernández-Antolín Antonio Fernández-Ortiz Hospital Central de Asturias - Oviedo César Morís Ignacio Sánchez de Posada Hospital Bellvitge - Barcelona Ángel Cequier Enrique Esplugas Hospital Univ. Virgen de las Nieves - Granada Rafael Melgares Rafael Melgares Hospital Univ. de Canarias - Las Palmas Francisco Bosa Martín Jesús García-Glez Hospital de Navarra - Pamplona Román Lezaún José Ramón Carmona Hospital Juan Canalejo - A Coruña José Manuel Vázquez Alfonso Castro-Beiras Hospital Santa Creu i Sant Pau - Barcelona Joan García Picart José Domínguez de Rozas Hospital Juan Ramón Jiménez - Huelva José Díaz Fernández José Díaz Fernández Complejo Hospitalario - León Felipe Fernández Vázquez Norberto Alonso Hospital Marqués de Valdecilla - Santander José Javier Zueco Chema San José Hospital Clínico Universitario - Valladolid Alberto San Román Carolina Hernández Hospital Virgen de la Victoria - Málaga José Mª Hernández García Ángel García Alcántara Hospital Univ. Son Dureta - Palma de Mallorca Armando Bethencourt Miquel Fiol Hospital Cruces - Bilbao Xabier Mancisidor Xabier Mancisidor Hospital Virgen de la Macarena - Sevilla Rafael Ruiz Rafael Hidalgo Hospital Universitario La Paz - Madrid Nicolás Sobrino Isidoro González Hospital Txagorritxu - Vitoria Alfonso Torres Fernando Arós Hospital Universitario - Santiago de Compostela Antonio Amaro Michel Jaquet
  28. 28. Definitions (1) Reinfarction Within first 24 hours: Recurrent symptoms of ischemia at rest accompanied by new or recurrent ST-elevation > 0.1 mV in, at least, 2 or more adjacent leads for at least 30 minutes. After first 24 hours: Presence of new Q-waves in 2 or more leads or increase of CK, CK-MB or troponine levels higher than the upper limit of normal or greater than anticipated levels. Disabling stroke: Presence of new permanent focal or generalized neurologic symptoms affecting the normal life of a patient, associated to abnormal findings in CT scan or MRI (ischemic or hemorrhagic lesions) Heart failure: Presence of new symptoms/signs after the first 24 hours suggesting heart failure (dyspnea, orthopnea, S3, rales on pulmonary auscultation associated to signs of pulmonary congestion in chest X.-ray) Recurrent ischemia: Cardiac catheterization indicated for angina with ST- segment deviation or T-wave inversion, provided that reinfarction criteria are not fulfilled.
  29. 29. Definitions (2) Shock: presence of hypotension (systolic blood pressure < 90 mmHg without body fluids response accompanied with signs of low cardiac output) Mechanical complication: Clinical evidence of severe mitral regurgitation secondary to total/partial rupture of a papillary muscle, rupture of intraventricular septum or rupture of left ventricular free wall confirmed by any diagnostic technique. Major bleeding: Cerebral hemorrhage or any bleeding associated with a hemoglobin drop ≥ 5 gr/dL, or an absolute hematocrit drop ≥15%
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×