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In a real-world retrospective analysis, symptomatic intracranial hemorrhage (sICH) rates vary by NIHSS score

See data from a retrospective study and review rates from your own institution

The NINDS clinical trial program reported the incidence of sICH in patients treated with Activase. To further analyze the incidence of sICH following Activase treatment, a retrospective study was conducted in 2009-2010 leveraging the Get With The Guidelines (GWTG)–Stroke registry.6,40

Data from parts 1 and 2 of the pivotal NINDS trial6

NINDS was a 2-part randomized trial of Activase® (alteplase) vs placebo for the treatment of acute ischemic stroke. Part 1 (n=291) assessed changes in neurological deficits 24 hours after the onset of stroke. Part 2 (n=333) assessed if treatment with Activase resulted in clinical benefit at 3 months, defined as minimal or no disability using 4 stroke assessment.6

In part 1, median baseline NIHSS score was 14 (min: 1; max: 37) for Activase- and 14 (min: 1; max: 32) for placebo-treated patients. In part 2, median baseline NIHSS score was 14 (min: 2; max: 37) for Activase- and 15 (min: 2; max: 33) for placebo-treated patients.14

Patient identification required positive numerical assessment of NIHSS resulting in exclusion of patients with NIHSS of 0.14

sICH incidence at 36 hours6*

sICH incidence at 36 hour

*sICH within 36 hours was defined as the occurrence of sudden neurological worsening followed by subsequent verification of intracranial hemorrhage through imaging.6
NIHSS=National Institutes of Health Stroke Scale; NINDS=National Institute of Neurological Disorders and Stroke.

Data from a 2012 real-world analysis using the GWTG-Stroke registry40

  • Retrospective analysis of 10,242 patients with acute ischemic stroke (AIS) who received Activase within 3 hours of symptom onset from January 2009 to June 2010. Data were extracted from the GWTG-Stroke registry
  • Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 11 (interquartile range: 7-18). The numbers of patients stratified by NIHSS score were as follows: score of 0-5, 1875 (18.3%); score of 6-10, 2876 (28.1%); score of 11-15, 2146 (21.0%); score of 16-20, 1803 (17.6%); score of >20, 1542 (15.1%)
  • Patient identification utilized varying diagnostic methods resulting in inclusion of patients with NIHSS of 0

Do you know your institution's sICH rates?

Real-world sICH incidence at 36 hours categorized by NIHSS score40†

Real-world sICH incidence at 36 hours categorized by NIHSS score

†A retrospective analysis using real-world evidence is observational in nature. These types of studies are more likely to contain inherent bias and confounding variables than a prospective clinical study, which limits the ability to draw conclusions about the causal effect of any particular factor or intervention. Limitations of this study are patients and hospitals included may not be entirely representative, sICH was determined by a treating physician versus central review, and 11.1% of patients were excluded due to missing information. Study also showed additional variables that contribute to the overall risk for sICH in patients, including blood pressure, age, ethnicity, blood glucose, and gender.40

Data

Download the data from the pivotal clinical trials and real-world analyses.

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IMPORTANT SAFETY INFORMATION & INDICATIONS

Indications

Activase® (alteplase) is indicated for the treatment of acute ischemic stroke. Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment. Initiate treatment as soon as possible but within 3 hours after symptom onset.

Activase is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.

Limitation of Use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose AMI puts them at low risk for death or heart failure.

Activase is indicated for the lysis of acute massive pulmonary embolism (PE), defined as:

  • Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
  • Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.

Important Safety Information

Contraindications

Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit: current intracranial hemorrhage (ICH); subarachnoid hemorrhage; active internal bleeding; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms); bleeding diathesis; and current severe uncontrolled hypertension.

Do not administer Activase to treat acute myocardial infarction or pulmonary embolism in the following situations in which the risk of bleeding is greater than the potential benefit: active internal bleeding; history of recent stroke; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding; bleeding diathesis; and current severe uncontrolled hypertension.

Warnings and Precautions

Bleeding

Activase can cause significant, sometimes fatal internal or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient. Perform venipunctures carefully and only as required. Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported. Aspirin and heparin have been administered concomitantly with and following infusion with Activase in the management of acute myocardial infarction and pulmonary embolism. The concomitant administration of heparin and aspirin with and following infusions of Activase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy. If serious bleeding occurs, terminate the Activase infusion, and treat appropriately.

In the following conditions, the risks of bleeding with Activase are increased and should be weighed against the anticipated benefits: recent major surgery or procedure; cerebrovascular disease; recent intracranial hemorrhage; recent gastrointestinal or genitourinary bleeding; recent trauma; hypertension; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant hepatic dysfunction; pregnancy; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; advanced age; and patients currently receiving oral anticoagulants, or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Hypersensitivity

Hypersensitivity, including urticarial / anaphylactic reactions, have been reported after administration of Activase. Rare fatal outcome for hypersensitivity was reported. Angioedema has been observed during and up to 2 hours after Activase infusion in patients treated for acute ischemic stroke and acute myocardial infarction. In many cases, patients received concomitant angiotensin-converting enzyme inhibitors. Monitor patients treated with Activase during and for several hours after infusion for hypersensitivity. If signs of hypersensitivity occur, e.g. anaphylactoid reaction or angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy (e.g., antihistamines, intravenous corticosteroids, epinephrine).

Thromboembolism

The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation. Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting.

Cholesterol Embolization

Cholesterol embolism, sometimes fatal, has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. It is associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.

Coagulation Tests May be Unreliable during Activase Therapy

Coagulation tests and/or measures of fibrinolytic activity may be unreliable during Activase therapy unless specific precautions are taken to prevent in vitro artifacts. When present in blood at pharmacologic concentrations, Activase remains active under in vitro conditions, which can result in degradation of fibrinogen in blood samples removed for analysis.

Adverse Reactions

The most frequent adverse reaction associated with Activase therapy is bleeding.

Please see the full Prescribing Information for additional Important Safety Information and Instructions for Use.

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