CAPTIM / CAPTIM-WEST

The Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial Infarction (CAPTIM) study was a randomised, clinical, multi-centre trial comparing pre-hospital thrombolysis with transfer to an interventional facility (and, if necessary, percutaneous coronary intervention [PCI]) with primary PCI in patients with ST-segment-elevation myocardial infarction (STEMI).

Through the collaboration between the CAPTIM and the WEST trialists more than 300 similarly randomised STEMI patients were added to the initial CAPTIM enrolment. The CAPTIM-WEST study examined the relationship between reperfusion strategy and time from symptom onset on 1-year mortality.

 

In CAPTIM 840 patients who presented within 6 h of onset of symptoms of acute myocardial infarction (characteristic pain lasting for at least 30 min, not responsive to nitrates, with ECG ST-segment elevation of ≥0.2 mV in two or more contiguous leads, or left bundle-branch block) were randomly assigned to either pre-hospital fibrinolysis with accelerated alteplase (n=419) or primary angioplasty (n=421). All patients were then transferred to a centre with access to emergency angioplasty. The trial took part in 27 tertiary hospitals and their affiliated mobile emergency care.

The primary endpoint was a composite of death, non-fatal re-infarction or non-fatal disabling stroke at 30 days.

Secondary endpoints included cardiovascular mortality, refractory recurrent ischaemia, cardiogenic shock, severe bleeding, or emergent revascularisation (angioplasty or CABG).

In CAPTIM-WEST 221 patients from the WEST trial were added to the fibrinolysis arm of CAPTIM and 107 patients were added to the primary PCI arm of CAPTIM. A total of 1168 STEMI patients were examined in the combined analysis.

The primary endpoint was all-cause mortality within 1 year.

CAPTIM/ CAPTIM-WEST: study design

CAPTIM  CAPTIM  WEST  study  design     In CAPTIM patients within 6h of onset of symptoms of acute myocardial infarction were randomised to either pre-hospital fibrinolysis or primary angioplasty. In CAPTIM-WEST, patients from WEST trial were added to both the treatment arm of CAPTIM.

There was no significant difference in the composite primary endpoint between the pre-hospital fibrinolysis group and the primary PCI group at 30 days (8.2% versus 6.2%; risk difference 1.96; 95% confidence interval [CI] -1.53 to 5.46; p=0.29).

There were some differences in benefit between the two groups when the time elapsed from treatment onset was considered.

  • Randomisation within 2 h (n=460) or beyond 2 h (n=374) of symptom onset had no impact on the effect of treatment on the 30-day composite primary endpoint. However, patients randomised within 2 h had a strong trend toward lower 30-day mortality with pre-hospital fibrinolysis compared to those randomised to primary PCI (2.2% versus 5.7%, p=0.058) whereas patients randomised after 2 h had similar mortality (5.9% versus 3.7%, p=0.47).
  • Patients randomised 2 h to receive pre-hospital fibrinolysis had a lower incidence of cardiogenic shock than patients receiving primary PCI (1.3% versus 5.3%, p=0.032) whereas incidences were similar for patients randomised >2 h.
  • The differences in cardiogenic shock were mainly driven by lower incidences of shock developing in <2 h pre-hospital fibrinolysis patients during transport to the hospital.

CAPTIM: 30-day survival, patients treated within and after 2 hours of symptom onset

CAPTIM  30  day  survival  patients  treated  within  and  after  2  hours  of  symptom  onset     Patients randomised within 2h show lower mortality and incidence of cardiogenic shock with pre-hospital fibrinolysis in comparison with primary PCI

 

Overall 1-year mortality in CAPTIM-WEST was not significantly different between thrombolysis and primary PCI (4.6% vs. 6.5%, p=0.263).

CAPTIM-WEST: Kaplan-Meier curve of 1-year survival according to treatment

CAPTIM  WEST  Kaplan  Meier  curve  of  1  year  survival  according  to treatment      No significant difference is observed between thrombolysis and primary PCI in overall mortality.

The interaction between treatment and time from symptom onset to randomisation was statistically significant (p = 0.043).

  • Patients randomised < 2 hours of symptom onset benefited from treatment with thrombolysis compared to those receiving primary PCI (2.8% vs 6.9%, p = 0.021, HR 0.43, 95% CI 0.20- 0.91).
  • Beyond 2 hours, no treatment difference in 1-year mortality was observed (6.9% vs 6.0%, p = 0.529, HR 1.23, 95% CI 0.61-2.46).

CAPTIM-WEST: 1-year mortality, patients treated within and after 2 hours of symptom onset

CAPTIM  WEST  1  year  mortality  patients  treated  within  and  after  2  hours  of  symptom  onset   Thrombolysis treatment had improved outcome in comparison with primary PCI on treatment before 2 hours but no difference is observed after 2 hours.

Data from the CAPTIM 5-year follow-up largely support the findings from the 30-day clinical outcome data.

  • Mortality at 5 years was similar for the pre-hospital fibrinolysis group and the primary PCI group (9.7% versus 12.6%; HR 0.75; 95% CI 0.50 to 1.14; p=0.18).
  • However, for patients randomised within 2 h of symptom onset, mortality was lower in the pre-hospital fibrinolysis group than the primary PCI group (5.8% versus 11.1%; HR 0.50; 95% CI 0.25 to 0.97; p=0.04).
  • For patients randomised after 2 h, mortality was similar.

 

CAPTIM: 5-year follow-up patient treated within 2 hours

CAPTIM  5  year  follow  up  patient  treated  within  2  hours  Mortality was lower in the pre-hospital fibrinolysis group in comparison with primary PCI with patients randomised within 2 hrs.

  • Both, the 1- year follow-up of CAPTIM-WEST and the long-term follow-up of the CAPTIM study confirm that in reference to mortality, a strategy of pre-hospital fibrinolysis with immediate transfer and rescue angioplasty if needed appears to yield similar long-term survival benefits to primary PCI in STEMI patients managed within 6 h of symptom onset.
  • In patients managed within 2 hours, the pre-hospital fibrinolysis strategy reduced long-term mortality
  • The data underline that different reperfusion strategies might bring similar results at the acute phase of a myocardial infarction when an appropriate pre-hospital organisation is operative.
References: 

 

  1. Bonnefoy, E, Lapostolle, F, Leizorovicz, A, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. The Lancet 2002;360:825-829.
  2. Bonnefoy, E, Steg, PG, Boutitie, F, et al. Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up. Eur Heart J 2009;30:1598-1606.
  3. Steg, PG, Bonnefoy, E, Chabaud, S, et al. Impact of Time to Treatment on Mortality After Prehospital Fibrinolysis or Primary Angioplasty. Circulation 2003;108:2851-2856.
  4. Westerhout, CM, Bonnefoy, E, Welsh, RC, et al. The influence of time from symptom onset and reperfusion strategy on 1-year survival in ST-elevation myocardial infarction: A pooled analysis of an early fibrinolytic strategy versus primary percutaneous coronary intervention from CAPTIM and WEST. Am Heart J 2011;161(2):283-290.

 

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