Penumbra [NYSE: PEN]

James F. Benenati

Interventional Radiology Builder

Acute pulmonary embolism (PE) is common, affecting more than  300,000 people in the U.S. each year. The severity of these blood clots in the lungs cannot be understated.  They are complicated to diagnose – there are many variable clinical presentations—  and, if not treated quickly, can at times be life-threatening. 

When I first became a practicing interventional radiologist 30+ years ago, treatment for PE was limited to anticoagulation therapy. This is still considered standard-of-care today. More recently,  thrombolytic therapy has become common place for life threatening pulmonary emboli but this therapy comes with a host of potential complications. Patients may experience excessive bleeding and use of these thrombolytic agents also require stays in monitored care units or the intensive care unit (ICU). 

Over the past decade, advancements in technologies have allowed for the development of potentially more efficient clot removal methods for patients with pulmonary emboli that are causing severe symptoms such as shortness of breath, tachycardia (fast heart rate), low blood pressure, and other life-threatening symptoms. 

The following is a brief overview of how the treatment of  PE has evolved beyond drug treatment to include advanced technology. 

Mainstay PE Treatment:  Anticoagulation and  Thrombolysis 

Anticoagulation has been the mainstay of  PE treatment. These medications decrease the blood’s ability to clot, and patients with  PE typically take them for 3 to 6 months and sometimes for life. While anticoagulants can be lifesaving because it helps stabilize the patient’s symptoms, these agents do not remove or dissolve the clot. Anticoagulants work by preventing clot from continuing to form and then it is up the body’s own inherent thrombolytic system to try to dissolve the clot. While this works well with less symptomatic clot, patients with larger clots can experience lasting debilitating symptoms and these symptoms can affect the patient’s well-being for the remainder of their life. 

“When I first became a practicing interventional radiologist 30+ years ago, treatment for PE was limited to anticoagulation therapy”

Another treatment option for PE has been thrombolytic therapy, or thrombolysis, which uses medications to dissolve the blood clots and prevent new clots from forming. The most commonly used drug for thrombolytic therapy is tissue plasminogen activator (tPA). Thrombolysis is performed in the hospital setting to dissolve the clots and improve cardiorespiratory hemodynamics. However, careful patient selection for this therapy is critical as it is associated with several potential complications, including bleeding that can be catastrophic. As a result, not everyone can be treated with thrombolytics and patients need to be closely monitored in either a monitored bed or an ICU post-procedure. 

New Approach— Removing Clots With  Mechanical Thrombectomy 

Given the limitations of anticoagulation and thrombolytic therapy, physicians have been searching for years for a safer and more efficient way to manage pulmonary emboli as well as blood clots in arteries and veins. Penumbra Inc. was instrumental in pioneering the mechanical thrombectomy to remove blood clots in the brain for stroke using a continuous aspiration pump and specially designed atraumatic catheters. This technique of removing clot in the brain worked well and revolutionized the way clot was managed in strokes. 

With this as a background, a number of physicians began to adapt similar techniques to clear blood clots from arteries in the legs. As one of the early pioneers to look at this new form of therapy, I helped the Penumbra team develop catheters for use outside the brain. In a short period of time, it became obvious to many that this therapy would work in different parts of the body. Soon after this  we began to develop catheters and aspiration systems for larger vessels such as veins and pulmonary arteries. 

This early work led to what would become Penumbra’s  Indigo Aspiration System, which uses continuous aspiration thrombectomy to remove blood clots throughout the body.  The Indigo System has continued to evolve since it was first introduced and now uses a unique computer-aided clot detection technology that can differentiate for the user between clot and flowing blood by indicating to the physician whether the catheter is engaged in thrombus with audiovisual cues. This advanced technology is called Lightning  Aspiration. It is designed to reduce blood loss and the need for clot dissolving drugs, which may lower the risk of  bleeding complications. 

During a  continuous aspiration thrombectomy procedure, we guide a catheter through the patient’s arteries or veins using X-ray guidance to the vessel where the clot is located. The catheter is placed in the clot and the pump is then turned on to begin the process of clot extraction. Advances in design provide catheters that are more torque able and trackable, enabling us to reach target vessels efficiently. These advancements have shortened the time to treat patients with conditions like PE, as well as venous thrombosis and acute limb ischemia in the arteries.  These procedures which are done without surgery can potentially allow patients to leave the hospital more quickly vs. traditional treatments.

Recent Data Demonstrates Safety  And Performance Of Mechanical  Thrombectomy

Initial data of the STRIKE-PE study suggest that Penumbra’s  Indigo Aspiration System with Lightning is safe and effective for treating sub-massive and massive pulmonary emboli in a  real-world population.

The prospective, multi-center study showed that both right ventricle/left ventricle ratio and pulmonary artery pressure significantly decreased by 24 percent and nearly 20 percent,  respectively. The interim data also showed improved patient  reported quality-of-life outcomes, including improved mobility and ability to provide self-care and a decrease in pain/discomfort from discharge to 90-day follow-up. 

The data is encouraging as it highlights the positive impact these advancements can have on patients.  To obtain additional data, we also plan on launching a  randomized controlled trial for PE to assess how mechanical thrombectomy compares to anticoagulation, the standard of care. With the growing body of evidence that supports the effectiveness of mechanical thrombectomy in the management of PE, we may potentially see a shift in PE care to include mechanical thrombectomy as a frontline treatment option in the future.