Reversing Acute Ischemic Stroke

More than 2,000 Americans suffer a stroke on an average day.¹ Some will recover with minor outward effects, while others who survive endure paralysis and lifelong nursing home confinement.

Most strokes happen when a blood clot blocks an artery that feeds a portion of the brain.² As neurons die from oxygen starvation, the result too often is paralysis, blindness, and cognitive dysfunction.³

Stroke is a leading cause of long-term disability in the United States. It’s also the fifth-leading cause of death.^4,5

The tragedy is that many strokes can be reversed if competent arterial intervention is timely delivered.⁶

Emergency response personnel are dropping the ball when it comes to implementing common-sense procedures to remove blood clots before permanent brain damage occurs.

This article reveals how hundreds of thousands of stroke-induced catastrophes can be prevented each year and what you should do if a stroke symptom ever manifests.

Horrific consequences occur when scientific advances are delayed from entering everyday medical practice.

The term “ischemia” means insufficient blood flow to a body part. This article addresses acute ischemia to the brain, which is commonly referred to as a stroke.⁷

In the treatment of acute ischemic stroke, significant advances are being made in the re-opening of blocked cerebral arteries. These lifesaving procedures enable blood flow to be restored before permanent brain damage is inflicted.^8,9

The problem is that not enough emergency response personnel are trained to properly utilize these brain-saving techniques. The result is nursing homes that are filled with permanently paralyzed stroke victims whose conditions were reversible after they entered the hospital emergency room—if only appropriate procedures were administered.

The economic cost of not prioritizing implementation of even basic cerebral recanalization (re-opening) techniques is staggering. The human toll of needless paralysis, dementia, and death is beyond civil description in the English nomenclature.

Despite a preponderance of favorable data, there is still debate amongst clinicians as to when to employ advanced techniques in attempting to reverse acute ischemic stroke.

How Larry King Saved Millions Of Lives

Talk show host Larry King is a nonstop workaholic. For most of his life, he smoked three packs of cigarettes a day, ate anything and everything fried, and piled on the desserts. All of this was combined with no exercise and a high level of job-related stress.

In February 1987, as pain ripped through his shoulder and stomach, Larry King headed to the hospital emergency room. It was clear to the staff at George Washington University Hospital that Larry was in the midst of a severe heart attack.¹⁰

In order to save his life, the doctors decided to try the then-experimental clot-busting drug called tPA (tissue plasminogen activator).

In early 1987, tPA had not yet been approved by the FDA.¹¹ Before administering tPA to open Larry’s blocked coronary arteries, the doctors placed a clipboard with a release form in front of Larry so he could sign away any liability. Fortunately, he was at one of the few hospitals at the time who were “allowed” to provide this clot-dissolving drug to consenting patients.

Larry King was so impressed by how quickly his crushing pain was alleviated by tPA that he spearheaded a campaign attacking the FDA for not approving widespread use of this drug. The FDA was delaying approval of tPA because the agency wanted proof that tPA benefited heart attack victims in addition to acutely saving lives.¹²

Back in the mid-1980s, The Wall Street Journal and Life Extension Foundation were challenging the FDA’s delay of tPA. The agency’s reason for not approving tPA is that they did not know if it would prolong the life span of acute heart attack patients who otherwise had only minutes to live.

Larry King tilted the public against the FDA and the merciful result was that tPA gained official approval to treat acute heart attack in November 1987—nine months after it saved Larry King’s life.¹³

Two years later, the FDA conceded that tPA indeed improved survival in heart attack victims, which had been the agency’s basis for delaying initial approval of the drug.¹⁴ It was not until 1996 that tPA was approved to treat acute ischemic stroke.¹¹

Here we are in year 2015, and controversy continues regarding the best protocols to treat acute stroke with clot-dissolving drugs like tPA and/or mechanical recanalization techniques like cerebral artery stenting.

What I find remarkable, however, was the impact that one celebrity activist such as Larry King had in breaking down bureaucratic barriers that had cost so many human lives.

Why Stroke Treatment Is Challenging

Acute myocardial infarction (heart attack) is relatively easy to diagnose. The heart muscle can also withstand oxygen deprivation far longer than the brain, where neurons die within minutes of blood flow cessation.⁷ These and other factors make using clot-dissolving drugs like tPA in heart attack patients easier than in those stricken by stroke.

A stroke can be either ischemic (blockage) or hemorrhagic (bleeding). A CT scan or MRI of the brain must be done quickly at a hospital’s emergency department to diagnose what kind of stroke is occurring (about 85% of strokes are ischemic).^15,16

Based on brain imaging results, a quick decision must be made whether to implement a clot dissolving drug and/or utilize intracerebral arterial stenting to reverse the blockage causing an ischemic stroke.

The FDA and most medical authorities claim that clot-dissolving therapy must be initiated within 3.0 to 4.5 hours from initial onset of symptoms for the benefits to outweigh the side-effect risks (such as cerebral bleeding).¹⁷ New studies indicate that advanced clot-removing therapies are efficacious for a longer period after initial stroke symptoms present.¹⁸

For example, technologies have now progressed to a level where a catheter can be inserted into a major artery and threaded directly into the brain’s vasculature. This enables the mechanical removal of a blood clot blocking an artery. The procedure is called a thrombectomy.¹⁹

Thrombectomy techniques have advanced to the point where a trained physician utilizing a retrievable stent can re-open a blocked cerebral artery mechanically when a clot-dissolving therapy using a tPA drug is not working.²⁰

The challenge in treating ischemic stroke is that there are many factors that dictate the risk-to-reward ratio of tPA administration and/or thrombectomy for individual stroke patients. This has caused clot-removing therapies to be under-
utilized by emergency physicians, with the tragic result being needless paralysis and death.

Narrow Window Of Therapeutic Opportunity

Brain cells quickly become impaired and die when oxygen-rich blood flow is interrupted. Even a 15-minute delay in initiating clot-removing therapy reduces the chances that a patient will avoid a stroke-induced disability.²¹

A consensus today is that in most cases, clot-removing therapy in ischemic stroke patients should commence within one hour of arrival in a hospital’s emergency room.²²

With properly trained staff, initiation of tPA within one hour is feasible, yet a 2009 study found that “door-to-needle” for tPA treatment within one hour was occurring in only 29% of cases. This was an improvement compared to 19% in year 2003.²³

As you might expect, hospitals treating patients in greater volume are better at meeting the one-hour treatment initiation objective with tPA compared to hospitals treating fewer stroke patients. Patients also have a higher probability of receiving timely tPA treatment if they are younger, male, of white race, had no prior stroke, or if they arrive by ambulance.²³

When stroke symptoms initially develop, the patient or a family member is sometimes able to drive to a hospital emergency room. The downside to this is less priority given by the ER staff and the risk that tPA therapy will be delayed.

To clarify this critical point, the therapeutic window of opportunity with tPA drug therapy and/or surgical stenting is time sensitive. The initial protocol was that tPA had to be initiated within three hours of the onset of the first stroke symptom. This was later expanded to 4.5 hours after onset of first indication of ischemic stroke. More recent studies suggest that more advanced clot-removing therapies may be used up to 12 hours after first onset of stroke symptoms.²⁴

The reason it is so critical for emergency physicians to initiate clot-removing therapy within one hour is that there is often a significant delay between the patient realizing they are having a stroke and making it into the hospital.

The sidebar on page 12 lists the most common symptoms of stroke. If any of these symptoms develop in you, don’t hesitate to call an ambulance to be transported to a hospital for immediate evaluation. It could mean the difference in you quickly returning to a normal life or permanent confinement to a nursing home or cemetery.

I suspect most Life Extension^® members detest going to a hospital, but when it comes to symptoms of a stroke (or heart attack), any delay can mean permanent institutional confinement.

Why Clot-Removing Therapies Are Underutilized

Despite stroke being the fifth-leading cause of death and a leading cause of disability in the United States, less than 7% of stroke survivors (as of year 2010) receive tissue plasminogen activator (tPA) as initial treatment.²⁷

A review of two studies, one that examined 45 published articles and one that examined 54 published articles, revealed common barriers to greater tPA use in both pre-hospital and in-hospital settings.^29,30

Pre-hospital delays were related to trying to contact primary care physicians instead of immediately rushing to the emergency room, the mode of arrival to the hospital, and patient’s lack of knowledge regarding stroke symptoms.^29,30

The causes of in-hospital delays included non-stroke center status, lack of training of emergency department, delays in CT (computed tomography) scans, and poor understanding regarding priority of stroke treatment.^29,30

The major issues behind the underutilization of tPA for acute stroke is lack of hospital readiness/preparation, inadequate staff training, and failure to rapidly administer tPA. Patients’ lack of awareness of stroke symptoms is another critical factor that precludes more stroke victims from benefiting from clot-removal therapies.

As a result of these and other factors, some clinicians question the efficacy of tPA and other brain clot-removing procedures. Interpreting sometimes flawed and contradictory clinical studies contributes to confusion and delay in administering tPA in the emergency room setting.

A 2011 study found only 1 to 3% of ischemic stroke patients in community settings receive clot-dissolving therapy.³¹ While some of these stroke victims were ineligible, others were tPA candidates that were denied for reasons that should not be permitted to continue.

A Growing Consensus In Favor Of tPA

A study published in 2012 on the use of tPA in the treatment of acute stroke found that:³²

“tPA is an effective treatment for stroke when given in prepared stroke centers; emergency physicians and hospitals treating stroke patients with tPA need to have the necessary resources in place and a specific plan for timely care of patients with acute stroke.”

This study found a significant reduction in stroke-induced disability was achieved despite inclusion of patients treated with tPA after 4.5 hours. It also found that the improper use of tPA (such as administering it to patients with hemorrhagic stroke) skewed results in a way that could be interpreted as finding no overall benefit to tPA.³¹

The study concluded that tPA has demonstrated benefit in “academic centers and organized stroke centers, but the benefit is not established at other types of hospitals.”³²

This study clears up a lot of misconceptions and criticisms about the use of tPA in the treatment of acute ischemic stroke. As simple as this may sound, more community hospitals need to upgrade their skill levels to those found in organized stroke centers.

Each year, 795,000 strokes occur in the United States.³³ Stroke is not a rare event, yet hospital emergency departments that have skill in treating heart attacks are failing miserably when it comes to reversing acute ischemic stroke, despite there being similarities in the treatment protocols.

A New Year’s Gift

I was pleased to read the January 1, 2015, edition of The New England Journal of Medicine, where the results from a large study on acute stroke were published.³⁴

This study sought to evaluate whether standard intravenous tPA therapy in addition to aggressive use of targeted intra-arterial delivery of tPA and/or advanced intra-arterial surgical procedures was superior to standard intravenous tPA therapy alone in treating a particularly dangerous type of ischemic stroke within six hours of symptom onset.

The effectiveness of intra-venous tPA is limited by several factors compared to what can be achieved by threading a catheter into the blocked cerebral artery and directly administering tPA to the blood clot causing the ischemic stroke. This intra-arterial catheter can further be used to surgically remove the occluding blood clot or install a retrievable stent to prop open the occluded cerebral artery.³⁴

In this study published on New Year’s Day of this year, patients fortunate enough to be treated with aggressive clot-removing techniques were twice as likely to recover independent living capability without major functional restriction compared to the group receiving standard medical therapies.³⁴

What made this study stand out was that it demonstrated convincing efficacy compared to previous studies that produced only neutral results. Some of the differences were that this latest study included an improved intra-arterial “retrievable stenting” device, proper imaging to identify precise location of the occluded artery, and shorter time interval to treatment (under six hours) compared to previous studies.^34,37

Not all findings from this study published on New Year’s Day of this year were positive. Patients requiring mechanical removal of their occluded cerebral artery suffered greater numbers of secondary ischemic events within 90 days, probably due to the physical/mechanical nature of the intervention. Yet in the aggressively treated group there was no significant increase in mortality and no significant increase in serious side effects compared to the control group during the follow-up period.³⁴ The aggressively treated groups showed a consistent trend of benefit that led to a far greater rate of functional recovery.

Said differently, aggressive treatment of this dangerous type of ischemic stroke (proximal arterial occlusion) resulted in significantly more patients avoiding nursing home confinement.

An editorial in this same issue of The New England Journal of Medicine (Jan 1, 2015) posed the question:³⁷

“Is there any doubt left, or should thrombectomy now become the new standard treatment for severe stroke with proximal large-vessel occlusion up to six hours after stroke onset?”

The editor answered his own question by stating he eagerly awaits the results of ongoing trials, but that this latest clinical trial titled MR CLEAN “is the first step in the right direction.”

Turning The Tide

A large volume of published clinical data persuasively demonstrates that far more stroke victims could be leaving the hospital and returning to their homes to resume normal independent activities.

Technologies exist today to reverse huge numbers of ischemic strokes. Yet not enough hospital emergency rooms qualify as competent “stroke centers,” with trained personnel and state-of-the-art protocols.

It probably is not necessary for every hospital emergency room to have advanced “stroke center” capabilities, as there are often several hospitals within reasonable reach for ambulances from places where most people live.

Despite the staggering costs of caring for paralyzed stroke victims, priorities aimed at creating competent “stroke centers” within ambulance range of major population centers is sorely lacking. Life Extension is helping to address this problem by compiling a nationwide listing of comprehensive stroke centers. This listing can be reviewed starting on page 88 of this month’s issue.

Those concerned whether their hospital emergency department is utilizing state-of-the-art stroke treatments should consider making an appointment with the hospital administrator in their neighborhood to encourage them to upgrade to “comprehensive stroke center” status, which includes quick turnaround CT or MRI imaging and timely initiation of intra-arterial tPA and intra-arterial (endovascular) clot removing retrievable stent devices.

If your local hospital refuses, shop around and you may find that a qualified “stroke center” exists not that far away. This will enable you to know where to go in case stroke symptoms ever manifest.

On page 88 of this month’s issue is a listing of comprehensive stroke centers in the United States that Life Extension’s staff has been able to identify so far.

For longer life,

William Faloon

To view a video presentation of how intra-arterial clot removal catheter technology can reverse ischemic stroke, log on to:

LifeExtension.com/strokevideo

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