CAPITAL-AMI: Combined Angioplasty and Pharmacological Intervention Versus Thrombolytics Alone in Acute Myocardial Infarction

Luis Gruberg, MD, FACC

Disclosures

April 16, 2004

Editorial Collaboration

Medscape &

Presenter: Michel R. Le May, MD, University of Ottawa (Ottawa, Ontario, Canada)

DeWood and colleagues demonstrated in 1980 that thrombus in the infarct-related artery was present in 88% of patients undergoing coronary artery angiography within the first 24 hours of acute ST segment elevation myocardial infarction (STEMI).[1] Since then, a series of landmark randomized trials have demonstrated that percutaneous coronary intervention (PCI) can achieve better and more sustained reperfusion when compared with thrombolytic therapy alone, while also improving survival, reducing the rates of recurrent ischemia and reinfarction, and nearly eliminating the risk of intracranial hemorrhage. Previous studies have failed to show a benefit when PCI is performed immediately after initiating thrombolysis, but these studies may be outdated because they preceded significant advances in technology and technique.

Study Design

The Combined Angioplasty and Pharmacological Intervention Versus Thrombolytics Alone in Acute Myocardial Infarction (CAPITAL-AMI) study[2] was designed to assess the use of a combined approach with thrombolytics and primary PCI in high-risk acute myocardial infarction (AMI) patients.

A total of 170 high-risk AMI patients (< 6 hours) were randomized to either thrombolytic therapy alone (TNK-tPA full dose, n = 84) or combined therapy consisting of thrombolytic therapy (TNK-tPA full dose) plus immediate transfer for angiography (n = 88). Thrombolytic therapy consisted of TNK-tPA full dose (weight-adjusted bolus) plus unfractionated heparin 60 U/kg bolus plus 12 U/kg/hr target aPT 50-70 sec.

In order to be classified as high risk, patients had to meet the following criteria:

  • Anterior: ST-elevation ≥ 2 mm in each of at least 2 contiguous precordial leads

  • Extensive nonanterior:

    • ≥ 8 leads with ≥ 1 mm ST elevation or depression or

    • Sum of ST-elevation > 20 mm

  • Killip class 3 and ST elevation > 1 mm in 2 or more contiguous leads or new left bundle branch block (LBBB)

  • Systolic blood pressure < 100 mm Hg and ST elevation > 1 mm in 2 or more contiguous leads or new LBBB

Exclusion Criteria
  • Contraindications to thrombolysis

  • Previous coronary artery bypass graft surgery

  • Percutaneous transcatheter coronary angioplasty performed within past 6 months

  • Glycoprotein IIb/IIIa antagonist therapy within past 7 days

  • Renal impairment

  • Severe contrast allergy

  • Unfractionated heparin (UFH) ≥ 5000 IU or low-molecular-weight heparin within 6 hours after onset of AMI

  • Cardiogenic shock

Primary Endpoint
  • Death, recurrent infarction, recurrent unstable ischemia, or stroke at 30 days

Results

Baseline demographic characteristics were similar between the 2 groups with respect to age, prior MI, and anterior wall MI. Compared with patients in the TNK-only group, there was a higher incidence of diabetes and hyperlipidemia in the combination therapy group (Table).

Table. CAPITAL-AMI: Baseline Characteristics
  TNK (n = 84) TNK and PCI (n = 86)
Age (yrs) 58 57
Male (%) 76 73
Diabetes (%) 12 21
Smoker (%) 62 56
Hyperlipidemia (%) 37 44
Prior MI (%) 8 9
Prior PCI (%) 4 6
Killip class 1 (%) 79 79
Anterior wall MI (%) 49 52
LBBB (%) 0 1
LBBB, left bundle branch block; MI, myocardial infarction; PCI, percutaneous coronary intervention

In patients randomized to the TNK plus PCI group, randomization to first balloon time was 95 minutes. A total of 53% of these patients had normal TIMI 3 blood flow at baseline, and 89% had achieved this goal after the procedure.

Compared with the TNK-only group, patients randomized to combination therapy had a significant reduction in the combined endpoint (death, recurrent infarction, recurrent unstable ischemia, or stroke) during hospitalization (8.1% vs 21.4%, respectively; P = .0173), which was mainly due to a significant reduction in the incidence of reinfarction and recurrent unstable ischemia (Figure 1).

Figure 1. CAPITAL-AMI: In-hospital events.

At 30 days, the primary outcome remained significantly in favor of the combined therapy group (Figure 2) vs TNK-only (9.3% vs 21.4%, respectively; P = .0336). Unscheduled angiograms were performed in 67% of patients in the TNK arm vs 15% in the combined therapy group, mainly due to recurrent ischemia.

Figure 2. CAPITAL-AMI: Clinical events at 30 days.

Major bleeding complication rates were similar in both groups (Figure 3). At 30 days, there was no difference in left ventricular ejection fraction (54.3% vs 51.1%), congestive heart failure, cardiogenic shock, or exercise test duration between either TNK-only or the combination therapy group. Length of hospital stay was 1 day shorter in patients randomized to the combined therapy approach, and the difference was statistically significant (P = .0094).

Figure 3. CAPITAL-AMI: Major bleeding complication rates.
Conclusions

The conclusions reached by the investigators were:

  1. A strategy of TNK plus immediate PCI for patients presenting with high-risk STEMI is superior to TNK alone.

  2. A strategy of TNK plus immediate PCI is relatively safe and is not associated with an increased risk of bleeding complications.

  3. All high-risk patients treated with thrombolytic therapy should be considered for immediate PCI.

References
  1. DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med. 1980;303:897-902.

  2. LeMay MR, Labinaz M, Turek M, et al. Combined Angioplasty and Pharmacological Intervention Versus Thrombolytics Alone in Acute Myocardial Infarction (CAPITAL-AMI). Program and abstracts from the American College of Cardiology 53rd Annual Scientific Session; March 7-10, 2004; New Orleans, Louisiana. Late-Breaking Clinical Trials and Trial Updates: Novel Therapies for Acute Myocardial Infarction.

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