Primary Angioplasty Versus Fibrinolysis in the Very Elderly - TRIANA

Description:

The goal of the trial was to evaluate the efficacy and safety of primary percutaneous coronary intervention (PCI) compared with fibrinolytic therapy in patients age ≥75 years with ST-elevation myocardial infarction (STEMI).

Hypothesis:

Primary PCI will be superior at reducing adverse events.

Study Design

  • Parallel
  • Randomized

Patients Enrolled: 266
Mean Follow Up: 12 months
Mean Patient Age: 81 years
Female: 44%

Patient Populations:

  • Age ≥75 years and diagnosis of STEMI, defined as chest pain or any symptom of myocardial ischemia ≥20 minutes' duration, not responding to nitrate therapy within first 6 hours, and ≥1 of the following: ST-elevation ≥2 mm in ≥2 precordial leads, ST-elevation ≥1 mm in ≥2 anterior leads, or de novo (or probably de novo) left bundle branch block

Exclusions:

  • Cardiogenic shock
  • Estimated door-to-balloon time >120 minutes
  • Administration of thrombolysis within 14 days prior to randomization, glycoprotein IIb/IIIa inhibitor within 24 hours prior to randomization, or LMWH within 8 hours prior to randomization
  • Current oral anticoagulant treatment
  • Suspected acute MI secondary to occlusion of a coronary lesion treated previously with PCI
  • Known renal failure
  • Reduced expected life expectancy (<12 months)
  • Documented contraindication to the use of thrombolytics, including active internal bleeding or known history of hemorrhagic diathesis
  • History of previous stroke
  • Intracranial tumor, arteriovenous malformation, aneurysm, or cerebral aneurysm repair
  • Major surgery, parenchymal biopsy, ocular surgery, or severe trauma within 6 weeks prior to randomization
  • Unexplained puncture in a noncompressible vascular location within 24 hours of randomization
  • Confirmed arterial hypertension during the acute phase prior to randomization with one reliable measurement of systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg
  • Known thrombocytopenia <100.000 platelets/µL
  • Prolonged (>20 minutes) or traumatic cardiopulmonary resuscitation in the 2 weeks prior to randomization
  • Symptoms or signs suggesting aortic dissection

Primary Endpoints:

Death, reinfarction, or disabling stroke at 30 days

Secondary Endpoints:

  • Recurrent ischemia requiring emergency catheterization at 30 days
  • All-cause mortality at 30 days and 12 months
  • Cause of death at 30 days (pump failure/mechanical comp/other)
  • Death, disabling stroke, or new heart failure at 30 days
  • Major bleeding during hospital admission
  • Time to death, reinfarction, or disabling stroke during follow-up
  • Time to death, reinfarction, disabling stroke, or nonelective hospital readmission for cardiac causes during follow-up

Drug/Procedures Used:

Patients were randomized to fibrinolytic therapy with tenecteplase (TNK) plus unfractionated heparin (UFH) (n = 134) or primary angioplasty (n = 132). In the fibrinolytic group, a single weight-adjusted dose of TNK was administered, along with UFH (60 U/kg bolus plus infusion with an activated partial thromboplastin time 1.5-2). Clopidogrel (75 mg for 28 days) was given from December 2006 onward. Rescue PCI could be performed if reperfusion criteria were not met. In the primary angioplasty group, patients were administered (60 U/kg), clopidogrel (300 mg loading dose and 75 mg/day), and, at the operator's discretion, abciximab. The study was powered based on a sample size of 570 patients to detect a 40% relative risk reduction in the primary endpoint.

Concomitant Medications:

Aspirin (97%), clopidogrel (63% in the thrombolytic group and 92% in the primary PCI group, p < 0.001), UFH (97%), and low molecular weight heparin (LMWH) (37% and 54%, respectively)

Principal Findings:

The trial was discontinued early after approximately one-half of the patients were enrolled due to slow recruitment. Given their older age, patients had high rates of several risk factors, including hypertension (64%), dyslipidemia (35%), and diabetes (30%). MI was located in the anterior region in 49% of the thrombolytic group and 42% of the primary PCI group. Median time from symptom onset to treatment was 195 minutes in the thrombolytic group and 245 minutes in the primary PCI group, while door-to-treatment times were 52 minutes and 99 minutes, respectively. In the thrombolytic group, 16% of patients underwent urgent catheterization and 15% underwent rescue PCI. Mean dose of TNK in the thrombolytic group was 37 mg. In the primary PCI group, 84% of patients received stents and 44% received a glycoprotein IIb/IIIa inhibitor.

There was not a significant difference in the primary endpoint of death, reinfarction, or disabling stroke at 30 days between the primary PCI group (18.9%) and the thrombolytic group (25.4%, odds ratio [OR] of thrombolytic therapy vs. primary PCI 1.46, 95% confidence interval [CI] 0.81-2.61, p = 0.21). Likewise, there was no difference in the individual components of the composite endpoints of death (13.6% vs. 17.2%, OR 1.31, 95% CI 0.67-2.56, p = 0.43); reinfarction (5.3% vs. 8.2%, OR 1.60, 95% CI 0.60-4.25, p = 0.35); or stroke (0.8% vs. 3.0%, OR 4.03, 95% CI 0.44-36.5, p = 0.18).

There was a significant reduction in recurrent ischemia (0.8% vs. 9.7%, p < 0.001), but not in the other efficacy outcomes examined including chronic heart failure (10.6% vs. 11.2%, p = 0.90) or shock (9.8% vs. 5.2%, p = 0.15). Safety results were similar between groups, with major bleed in 3.8% of the primary PCI group and 4.5% of the thrombolysis group (p = 0.43), transfusion in 5.3% and 3.0%, respectively (p = 0.35), and renal failure in 6.1% and 7.5%, respectively (p = 0.64).

Twelve-month results for the primary endpoint were similar to 30-day results, with no difference between treatment groups (27.3% vs. 32.1%, p = 0.31). In a pooled analysis of two other trials, death, MI, or stroke was significantly reduced by primary PCI (OR 0.64, p = 0.013).

Interpretation:

Among patients ages ≥75 years with STEMI who were eligible for thrombolytic therapy, treatment with primary PCI was not associated with a significant difference in the composite endpoint of death, reinfarction, or disabling stroke at 30 days compared with treatment with thrombolytic therapy; however, the trial was discontinued early due to slow recruitment and was, thus, underpowered to detect a difference between groups.

Although the present study could not prove a benefit of primary PCI due to small sample size, a trend was evident that favored primary PCI, as well as a significant reduction in the secondary endpoint of recurrent ischemia. There were no apparent safety issues with the two strategies in the present trial, with similar rates of major bleeding, transfusion, and renal failure. The high mortality rate at 30 days in both groups reflects the difficulty in treating these high-risk patients.

Primary PCI in the setting of STEMI is well established in several trials and is guideline-recommended therapy. Despite the recommendations, the efficacy and safety of primary PCI in elderly patients is less certain. The results of the present study are similar to the SENIOR PAMI trial, which also failed to demonstrate a significant difference between primary PCI and thrombolytic therapy in older patients. SENIOR PAMI was also stopped early due to recruitment issues. Although individual trials are limited by lack of power, a pooled analysis of three trials documented reduced adverse cardiac events with primary PCI.

References:

Bueno H, Betriu A, Heras M, et al., on behalf of the TRIANA Investigators. Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies. Eur Heart J 2010;Oct 22:[Epub ahead of print].

Presented by Dr. Héctor Bueno at the European Society of Cardiology Congress, Barcelona, Spain, August 2009.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, EP Basic Science, Lipid Metabolism, Acute Heart Failure, Hypertension

Keywords: Thrombolytic Therapy, Platelet Aggregation Inhibitors, Ticlopidine, Risk Factors, Fibrinolytic Agents, Purinergic P2Y Receptor Antagonists, Dyslipidemias, Partial Thromboplastin Time, Catheterization, Bundle-Branch Block, Confidence Intervals, Tissue Plasminogen Activator, Hypertension, Odds Ratio, Myocardial Infarction, Stroke, Heparin, Immunoglobulin Fab Fragments, Angioplasty, Stents, Percutaneous Coronary Intervention, Renal Insufficiency, Chest Pain, Heart Failure, Diabetes Mellitus


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