DC Medical Malpractice & Patient Safety Blog

The fourth-leading cause of death in the U.S. is stroke—approximately 800,000 people have a stroke each year, and about 130,000 of them die from it. About 9 in 10 strokes result from a clot blocking an artery in the brain. If blood flow isn’t restored quickly, brain tissue is damaged or destroyed, and functions like movement, speech and cognition are crippled.

You would think that taking out these clots with a device would be far superior to the drip-drip-drip of clot-busting drugs administered through an intravenous line. But alas, the studies are not showing that the aggressive methods work any better than the old IV treatment.

In recent years, an increasingly popular stroke treatment has been used to clear the artery blockage mechanically by inserting a catheter or tube into the brain artery to pull it out. The previous standard treatment was to administer clot-busting drugs (called “thrombolytics”) through an IV -- as long as patients were seen within a few hours of when their symptoms began. (See our blog about how long you can wait to get clot-busting drugs.) Timing is key because giving the drugs too late can cause uncontrolled bleeding, and the damage from the blocked artery to sensitive brain tissue may already be done..

But, as reported earlier this month by the Washington Post, three long-awaited studies show that the more invasive mechanical removal of a brain blood clot does not have a better outcome than the older drug treatment. And it’s significantly more expensive.

When the study results were presented at a medical conference, the paper reported, the attendees were shocked—many of them had been using the newer, more aggressive procedure since the FDA approved it for use in the brain in 2004. Early trials of the “endovascular treatment,” or clearing the clot by using a catheter to snag or and pull it out, had shown good results for clots elsewhere in the body. But the three studies reported earlier this month in the New England Journal of Medicine (here and here ) show something different for the brain procedure.

Doctors expected that endovascular treatment would do for stroke patients what it has done for heart attack patients. Treating their blockages with angioplasty (inflating a tiny balloon inside a blocked artery to open it up) and stents (inserting a tiny piece of tube to ensure the artery remains open) are demonstrably more effective than giving clot-dissolving drugs through a vein in the arm.

But when it comes to clots, it appears that a brain is not a heart.

The National Institute of Neurological Disorders and Stroke (NINDS) sponsored two of the trials. One took eight years to complete, according to The Post, because it was so difficult to enroll patients willing to take the chance that they would be randomly assigned to get the older treatment. One study had permission from 30 hospitals but found only 22 willing to participate. More than 10 other hospitals were invited to join the trial but declined because their neurologists were convinced the catheter treatment was better.

Endovascular treatment, according to The Post, costs about $23,000; the intravenous thrombolytics cost about $11,000. So it’s good that an expensive, invasive procedure has been shown to have no benefit over a less expensive approach, right?

Yes, but … Many doctors believe that the newer clot-retrieving devices work better than the ones used in the three trials, and because the procedure was shown to be no more dangerous than IV thrombolytics, they might continue using it, assuming that outcomes can only get better.

Maybe they will, and for now, insurance companies and Medicare cover the endovascular procedure. But as Walter Koroshetz, deputy director of NINDS, told The Post, “The payers may look at this and wonder if they should continue paying for these procedures. If it gets to that point, then clearly things will change.”

In the largest of the three trials, all patients got the IV clot-dissolving drug tPA within three hours of the start of stroke symptoms. Half got an imaging study that examined brain arteries to see whether a blockage remained. If it did, the doctors employed an endovascular procedure. The other half of the patients got the standard drugs, but no endovascular procedure. Forty-one in 100 of the endovascular group recovered completely in the endovascular group; among those who got only the drugs, 39 in 100 recovered completely. Statistically, that’s a tie.

The number of patients who died within three months also was essentially the same—19 versus 22 for the respective groups.

Another study involved 362 stroke patients. After three months, 35 in 100 from the tPA group were alive without any disabilities; 30 in 100 from the endovascular group had that status. Again, that is not a significant statistical difference.

The third study was more complicated. It randomly assigned 118 patients within eight hours of the start of their strokes to receive only the drug treatment or clot removal with a catheter device. They also got CAT or MRI scans to see whether they had a large or small amount of brain tissue still alive and salvageable. Removing the clot with a device was no better than standard care in either group, whether patients had a lot or a little viable brain tissue.

Apart from raising questions about the best stroke treatment and the best use of medical resources in stroke care, The Post noted that the studies demonstrated how difficult is to test treatments once they’re in widespread use: “History is replete with treatments … and devices … used routinely before being shown to be harmful or of little value.”

And now we’re left to wonder if this accepted but now questionable treatment will continue to be used because of momentum, insurance compensation or because the newer generation of devices might be measurably better. Is any of those a compelling reason?

Not in our estimation. Sometimes you just have to accept that what looked good turned out to be the same—only more expensive and invasive.

To learn more about stroke and brain surgery, see our backgrounders here and here.

The blood-thinning drug Pradaxa has starred in a long-running drama with hundreds of adverse event reports, scores of lawsuits and more than 500 deaths. Introduced in 2010 as an option to Coumadin (warfarin), Pradaxa is under fire for dire side effects including hemorrhage and internal bleeding, as we wrote earlier this year. Unlike older anti-clotting drugs, Pradaxa has no antidote for uncontrolled bleeding.

The latest chapter in this tale was told earlier this month by the New York Times, when the FDA released a report concluding that Pradaxa did not show a higher risk of bleeding than warfarin. As The Times noted, the report did not mention the lack of an antidote.

Medical professionals and patients alike have complained about Pradaxa, expressing concern that the approval process was insufficient, and that such a potentially dangerous drug should not be on the market without a way to reverse its unwanted effects. Pradaxa has made $1 billion for its manufacturer, Boehringer Ingelheim, but critics say it’s exemplary, as The Times puts it, “of what can happen when a drug that performs well in tightly controlled trials is released into the messy world of real-life medicine.”

The FDA report says that bleeding rates associated with Pradaxa don’t appear to be higher than those associated with warfarin. At the American Heart Association Scientific Session a week after the FDA report, Boehringer Ingelheim presented findings that, according to its news release, an antidote in development shows promise, and clinical trials are being initiated.

We have to ask: Didn’t they put the cart so far in front that you can’t even see the horse?

When reports began to surface of bleeding problems, Boehringer Ingelheim recommended dialysis to flush the drug out. Dialysis involves bypassing the kidneys to purify the blood through a machine. But the company, according to The Times, acknowledges that “the amount of data supporting this approach is limited.”

The boneheaded dialysis advice was described perfectly by one doctor in The Times’ story: “People that are bleeding to death aren’t going to tolerate being put on dialysis.”

The problem is compounded, according to The Times, if doctors prescribe the drug to the wrong patients. Older people and people with kidney problems are not good candidates for Pradaxa—their bleeding risks are higher than for other people. Boehringer Ingelheim advises testing a patient’s kidney function before prescribing Pradaxa, and notes that the risk of bleeding increases with age.

“The problem is that the people that prescribe this, as a general rule, are cardiologists and family practitioners,” Dr. Mark L. Mosley, director of the emergency room at Wesley Medical Center in Wichita, Kan., told The Times. “The people that see the harm are your E.R. docs and your trauma docs.”

When Pradaxa was approved, its lower maintenance seemed superior to the nearly 60-year-old warfarin (Coumadin) for preventing prevent strokes in people with atrial fibrillation (a heart-rhythm disorder commonly called A-fib). Warfarin patients must be carefully monitored for diet and drugs, and must have frequent blood tests. Not so for Pradaxa patients.

In little more than a year, The Times reports, 17 in 100 a-fib patients got Pradaxa; 44 in 100 got warfarin. The FDA estimates that in the U.S., about 725,000 patients have taken Pradaxa.

But in 2011, according to The Times, Pradaxa “was linked to more reports of injury or death than any of the more than 800 drugs regularly monitored by the Institute for Safe Medication Practices.”

Other new drugs intended as an option to warfarin (Xarelto, which has been approved to treat blot clots, and Eliquis, for which FDA approval is pending) also lack antidotes, but they haven’t shown the same bleeding-death risk as Pradaxa.

All medicine carries a risk of side effects; some can be life-threatening. Sometimes, the risk is worth it, which is the position adopted by medical professionals who believe in Pradaxa. The Times referred to a recent study showing that about 4 in 10 people with atrial fibrillation don’t take any drugs, leaving them at risk for strokes. Many cardiologists say the risk of stroke is more dangerous than the risk of bleeding complications.

Maybe. But if you’re an A-fib patient whose doctor recommends Pradaxa, find out why he or she prefers it to warfarin, which also can cause a host of side effects, some of them serious. If you’re older or have a history of kidney problems, beware, and seek a second opinion.

Warfarin, the generic name for the most widely prescribed oral anticoagulant (blood thinner) in America, is used to prevent thrombosis (blood clots) and thromboembolism (blood clots that migrate throughout the body). People diagnosed with atrial fibrillation (rapid or irregular heartbeat), narrowed coronary arteries, who have had valve or stent replacement surgery or have a history of blood clots in the legs or lungs, often are prescribed warfarin, or its most common brand name, Coumadin.

The blood thinner can be a lifesaver for people at risk of stroke or heart attack caused by blood clots. (To learn more about maintaining heart health, see our newsletter, “A Healthy Heart: Unlocking the Key to Long Life.”)

But according to the Harvard Medical School heart health newsletter, these patients must ensure that they’re not posing additional risks by taking warfarin with certain antibiotics and antifungal drugs, which enhance warfarin’s blood-thinning effect, and possibly prompt internal bleeding.

The amount of warfarin in the bloodstream is measured by clotting time, and is expressed by the international normalized ratio, or INR. The higher the INR, the longer it takes blood to clot. In warfarin patients, medical practitioners look for a ratio of 2 to 3, although individual numbers might vary. Antibiotics affect these levels. Somebody who’s stable at 2.5 and takes an antibiotic can measure 5. If that level is sustained, it can cause gastrointestinal bleeding; a bump on the head, as the newsletter notes, can prompt bleeding in the brain.

Because antibiotics affect people differently, warfarin patients must be evaluated carefully and monitored regularly as soon as they begin a long-term antibiotic regimen. (With a short-term prescription, such as that used for two or three days in advance of dental work, an increase in INR isn’t necessarily worrisome, as the antibiotic clears the system quickly.)

Potential problems must be monitored particularly with broad-spectrum antibiotics, including erythromycin, penicillin and ciprofloxacin. Sometimes their doses must be lowered to accommodate warfarin patients.

In addition to pills, topical antibiotics—those delivered via ointment, cream or suppository—also are absorbed into the bloodstream and interfere with warfarin. Antifungal cream is a prime example. It’s often prescribed to women with vaginal yeast infections.

Like all drugs, warfarin taken alone carries potential side effects and risks. A recent story in Forbes noted that last year, warfarin was the second most prevalent drug in FDA safety reports “and has been high on the FDA list for many years.” It was the subject of 1,106 serious adverse events, including 72 deaths.

Although doctors generally discuss the risks of antibiotics with their warfarin patients, there’s plenty of opportunity for an adverse event if:

• a patient doesn’t understand the potential significance of the drug-drug interaction;


• a patient forgets the drug information;


• a doctor prescribing the antibiotic is different from the doctor prescribing the warfarin, and communication between the two falters;


• a patient doesn’t comply with INR testing;


• the drug-interaction alert function in the doctor’s computerized medical records is inoperative and/or the medications it lists is out of date;


• a patient uses different pharmacies for filling the warfarin and antibiotic prescriptions, so the pharmacists aren’t aware that a warning should be issued;


• a patient gets an antibiotic sample or handwritten prescription, bypassing a computer system alert.

So both prescribing doctors and their warfarin patients both must take responsibility for managing drug use.

Common sense says that putting stents into blocked arteries in the brain should help prevent strokes, just like propping open heart arteries cuts heart attacks.

But Medicare asked for a scientific study before it started paying for widespread use of the brain stents. So doctors tested stents versus medical therapy in high-risk patients. After one month, a dramatic answer: in one group, 6 in 100 patients got a stroke, but in the other group, 15 in 100 had strokes.

Problem is that the stent group was the one that had more than double the strokes of the medical treatment group.

The result was so big that doctors pulled the plug on the study, as they could no longer ethically put patients into the stent group.

This is yet another example of how therapies that seem like they should work, based on our knowledge of the body and medicine, turn out not to work. We have a lot left to learn.

In the case of brain arteries, bypass surgery to put in a new artery to go around blockages, also similar to what's done in the heart, also has failed to prove out in scientific studies.

You can read the new stent study in the New England Journal of Medicine.

A drug prescribed for smoking cessation is linked to an increased risk of heart problems, according to a study published July 4 in CMAJ (Canadian Medical Association Journal). Varenicline, known by the brand name Chantix, was associated with a 72% increased risk of a serious cardiovascular "event."

That sounds huge, but the scientific number-crunching shakes out a bit differently. Although attention must be paid, many critical minds are not ready to dump the drug. Fifty-two (1.06%) of the participants who took Chantix had serious cardiovascular events compared with 27 (0.82%) of those who took a placebo.

One bottom line for smokers who may want to rationalize continuing to puff: It's always better to stop smoking. No excuses.

When varenicline was launched in 2006, the FDA noted that it could raise the risk of cardiac problems, and the federal agency recently updated the label for Chantix to reflect that risk among smokers with heart disease. And we wrote about the drug a couple of years ago. But the new study's authors said, "These increased risks ... are seen in smokers with or without heart disease."

The irony, of course, is that one major risk of smoking is heart disease.

The Chantix-using subjects of this trial were able to abstain from smoking at a significantly higher rate, an achievement that should potentially confer a cardiovascular benefit. Many members of the medical community believe the drug should remained a valuable treatment option, given the devastating effects of smoking. Apart from heart issues, nicotine and the other ingredients of cigarette smoke, of course, compromise lung function and can lead to lung cancer, and also increase the risk of stroke and diabetes.

The results were based on a review of 14 studies of approximately 8,200 smokers or users of smokeless tobacco. Most had no history of heart disease. They were followed for as long as a year, a comparatively short term that gives many researchers pause. It's possible, for example, that the risk diminishes over time.

Dr. Taylor Hays from the Mayo Clinic opined, "Although these results suggest a measure of caution should be taken in prescribing varenicline for tobacco dependence treatment ... [T]he risk for cardiovascular events is low and is far outweighed by the benefits of diminishing the truly 'heartbreaking' effects of cigarette smoking."

If you're taking Chantix, don't stop without consulting your doctor. If you're unable to stop smoking via other methods, discuss the cost-benefit question of treatment with Chantix.

Here's a new research finding that is encouraging but discouraging at the same time for patient safety.

After 16 Michigan hospitals began to share patient safety information, surgical complication rates dropped by nearly 10 percent, according to a recent study.

That's encouraging, of course. The disquieting piece is why it would take a major research study to reach such an intuitively obvious result, and why sharing of data doesn't already happen on a wide and routine scale.

The University of Michigan study followed a program called the Michigan Surgical Quality Collaborative, which involved 300,000 patients who had general or vascular surgery between 2005 and 2007.

The greatest reductions were seen in blood infections, septic shock, prolonged ventilator use and cardiac arrest. Death rates remained the same.

According to the study’s author, Darrell A. Campbell Jr., MD, a professor of surgery and chief medical officer of the University of Michigan Health System, “the collaboration of hospitals in terms of identifying and disseminating information about best practices is actually a much more effective way of improving quality than just relying on each hospital alone to come up with what they think is a way to improve quality. In other words, sharing ideas is important and it's effective." He added that this type of program could help achieve the health care reform goals of improving quality and reducing costs.

“Surgical complications are very expensive,” Campbell says. “Once something bad happens following surgery, it takes a lot of resources for the patient to recover.”

A preventable surgical complication can add weeks to a hospital stay and thousands in added costs. Contracting pneumonia from prolonged ventilator use following a surgical procedure, for example, can add $50,000 to a hospital bill.

Given the high cost of surgical complications, authors estimate that it would take only a 1.8 percent reduction in complications a year for three years to offset the cost of supporting the pay for participation program.

“If this system was adopted nationally, not just in Michigan, I think you would find a greatly accelerated pace of surgical quality improvement,” Campbell says.

Inspired by the Michigan group, surgeons in Tennessee and upper New York have launched collaboratives. Similar ones are in the works in Pennsylvania, Virginia and Illinois.

Source: University of Michigan press release.

You can view an abstract of the study in Archives of Surgery here.

A diet drug which safety advocates called to be withdrawn from public use eight years ago has finally bit the dust. Under pressure from the Food and Drug Administration, the drug’s manufacturer, Abbott Laboratories, voluntarily pulled the drug from the market due to longstanding concerns that it increased the risk of heart attacks and strokes.

“There was no identifiable population of patients for whom the benefits of Meridia outweighed its risks,” said John Jenkins, MD, director of the office of new drugs at the FDA. “Meridia’s continued availability is not justified when you compare the very modest weight loss that people achieve on this drug to their risk of heart attack or stroke.”

The move was described as “commendable but dangerously too late,” by Sidney Wolfe, MD, a member of the FDA’s Drug Safety and Risk Management Committee and director of the Health Research Group of Public Citizen, a consumer and health advocacy group.

The pressure from the FDA came after results of a clinical trial involving more than 10,000 patients showed that people who took Meridia had a 16% increase in relative risk of heart attacks. The trial also showed that individuals taking Meridia only lost approximately 2.5% more weight than those on placebo and that the weight loss didn't last very long.

Abbott maintained these results weren’t relevant because most of the individuals in the trial had cardiovascular disease and should not have taken the drug in the first place. The company continues to maintaion that for the right patients, the drug is safe.

European regulators took the drug off the market in January 2010. An FDA advisory committee was split on whether to remove the drug, but the ultimately decided to recommend doing so because “there was no identifiable population of patients for whom the benefits of Meridia outweighed its risks,” Jenkins said, adding that he did not believe Meridia users would have any residual increased risk once they stopped taking the drug.

Source: The New York Times

You can view an abstract of the clinical trial that led to the FDA recommendation here.

When is a radiation overdose not an overdose? When the facility giving the CT scans says so. At least that's what the Food and Drug Administration concluded when it dropped a safety investigation of the Huntsville, Alabama Hospital.

Now the FDA, which monitors radiation safety for the medical industry, is considering re-starting its investigation, once a New York Times reporting team found that the doses of radiation given to patients at the Huntsville Hospital were 13 times the normal dose for this type of scan, called a CT brain perfusion scan. The scan is used to test patients for stroke.

Even a properly done CT brain perfusion scan delivers about 200 times more radiation to a patient's head than a skull X-ray.

According to the Times, the hospital claims it used higher doses to get sharper images.

A quotable quote from the article, the latest in a series about medical radiation overdoses:

“It is absolutely shocking and mind-boggling that this facility would say the doses are acceptable,” said Dr. Rebecca Smith-Bindman, a radiology professor who has testified before Congress about the need for more controls over CT scans.

Stroke experts have widened the window for when the clot-busting drug tPA can be given intravenously. The previous U.S. guideline was to give the drug only if treatment could be started within three hours of the onset of symptoms. Many patients did not get the drug because they didn't get to the hospital in time or it took too long to do tests to make sure the drug could be helpful. (Everyone with stroke symptoms has to have a CT scan to make sure the stroke is not caused by bleeding in the brain, because if tPA is given on top of bleeding, it could worsen the hemorrhage or even kill the patient.)

The new guideline widens the effective time window to four and one-half hours after symptoms start. It comes from the American Heart Association/American Stroke Association and is based on European studies.

Stroke experts stress that just because there is more time now to administer this drug does not mean patients or doctors should think they can go slow. The faster treatment is begun, the more likely it is to help break up the clot and restore normal blood flow in the brain. Anyone with stroke symptoms needs to be rushed to a hospital with special expertise in stroke treatment.