Pradaxa: More Concerns. More Myocardial Infarctions?

Pradaxa is part of a new group of anticoagulants (thrombin X inhibitors) that eventually will allow anticoagulation by the pill route without requiring patients to alter their food and medication intake and avoid foods and medications that interfere with the anticoagulant as patients must do with Warfarin. Pradaxa additionally eliminates the need to take blood tests (INR/ PT) to monitor the dosage as one has to do with Warfarin (Coumadin).

There is a large commercial advertising campaign underway on TV and print media to encourage patients with atrial fibrillation to ask their doctors to switch them from Coumadin to Pradaxa (Dabigatrin).  The campaign bases its claims on the RE-LY trial of 18,000 patients at 80 medical centers throughout the world who took the 150 mg dosage and had significantly fewer strokes than patients taking Warfarin.  The original study was criticized because many of the patients in the Warfarin (Coumadin) group were not on enough Warfarin or at a therapeutic PT/INR to prevent embolic strokes so the comparison with Pradaxa may not be valid. Another criticism involved the fact that Pradaxa can cause major bleeding and there is no antidote to stop the bleeding. Patients on Pradaxa who are bleeding are advised to undergo hemodialysis to remove the drug from their system because there are no medications or treatments available to stop Pradaxa related bleeding.

One wonders how the Food and Drug Administration approved this product for general use under these circumstances without conducting further testing?  The issue becomes even more confusing with the addition of data presented by Ken Uchino, MD, and Adrian Hernandez MD, PhD of the Cleveland Clinic in the online version of the Archives of Internal Medicine. They claim that by reviewing the RE-LY data there is a 38% relative increase in the risk of a myocardial infarction (MI) or heart attack in the Pradaxa group. In an accompanying editorial in the same journal, clinicians at the Hadassah- Hebrew University Medical Center in Jerusalem wrote, “The robust finding that Dabigatran is associated with increased rates of MI (heart attack) is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials.”

In my practice I generally will not switch to a new or controversial medication until it has been on the US market for at least one year. I make exceptions for orphan drugs, products to treat incurable diseases with no other choices available. The 12 months gives the medical and scientific community a chance to see how the medication performs and what unexpected adverse effects may be associated with it.

Thrombin X inhibitors are the wave of the future. With no way to stop the bleeding, and data on their safety and efficacy still accumulating, they are just not ready for prime time yet.

The Turnovers are the Difference- Medical “Handoffs” Are Continually Fumbled

This is a humbling football season for those of us who root for Florida teams at the collegiate or professional level. It seems that each week after another loss we are listening to the head coach standing at the podium during a post-loss press conference talking about how if the handoffs had not been fumbled, and the ball dropped and lost, his team could have prevailed. It is hard enough to deal with the turnovers and fumbles when rooting for your team. It is far more difficult to deal with it when we are talking about human beings hospitalized and cared for by hospital employed physicians and then turned back to the community without communicating adequately, or at all, with the care team responsible for their continued care at the community level.

Take the case of GH, an 82 year old obese diabetic with high blood pressure, high cholesterol and heart irregularities requiring the use of Coumadin to prevent a stroke. He awoke one morning two weeks after a major auto fender bender and found his underwear stained in bright red and dark brown blood. His wife was unsure if it was coming from his rectum or penis so she called 911 and allowed the patient to be taken to the nearest emergency department.  He was seen by the emergency room staff and admitted to their contracted hospitalist service for presumed intestinal bleeding due to Coumadin toxicity.

Eight days later he was discharged home with an indwelling Foley catheter needed because of the “clots” in his bladder. His Coumadin had been stopped on admission and never restarted. GH could not get out of the bed and walk while in the hospital and he stubbornly refused to go to a nursing rehabilitation center as an interim step until he was strong enough to walk independently.  His frail 80 year old wife, battling a lymphoma herself, was given the task of caring for this obstinate man at home and emptying and caring for his indwelling urinary catheter.

On his first day back home, I received a phone call from his wife informing me of this. She didn’t know what she could possibly do to care for him because he weighed 230 lbs and he couldn’t get out of bed and walk. A nursing service and physical therapist had been requested but had not yet called to schedule a visit.  She was particularly disturbed because 12 hours had gone by since he got home with no urine appearing in the bladder drainage catheter. At the same time his lower abdomen was growing in size and he was feeling pain and discomfort at that spot.  Once again, 911 was called and he was taken back to the same emergency department. Paramedics transport sick patients to the geographically closest facility not necessarily the one his physician sees patients at.

GH was readmitted because his catheter was blocked with clots and needed irrigation and there were concerns about a urine infection. I spoke with the wife and children and asked for the name of his doctor but they could not remember it. They did remember the name of his consulting urologist. I called the urologist who was a bit put out to discuss the case with me. He told me that “our“ patient was bleeding from the urinary tract due to a transitional cell cancer of the bladder that he discovered and treated during a cystoscopy. He felt the prognosis was excellent.

The urologist declined to discuss whether the patient was additionally bleeding from his intestinal tract or if the appropriate evaluation had been done. He suggested I find the hospitalist responsible for the patient’s care. When I asked for the name of the hospitalist he told me he had no idea who it was. “They all look the same to me,” was his actual response.

I asked the patient’s wife to have her husband sign an authorization to release medical records and obtain the medical records of his admissions for my review. She did that and presented it to the medical records department who sent me a brief summary of his second admission. It took three phone calls to obtain the records of the first admission and another to get the emergency department records.  I needed this material because it was quite easy to convince the patient to come to a local rehab facility after this hospitalization with me as his attending physician.  The patient and family had no idea why he was bleeding other than “I had clots” in the bladder. They didn’t know the name of his hospitalist either.  When I received the records it identified the physician. I called the hospital to page her but was told she was “off “for the next few days. Her colleagues on duty did not know or remember the patient.

The patient records finally arrived. His admission diagnosis was bleeding due to Coumadin toxicity, but the INR (a measure of how effective the Coumadin is in thinning the blood) was very low indicating that his blood was not anticoagulated much at all.  An INR of 1.4 doesn’t cause bleeding and is not toxic. The medical record said he had hematochezia (blood in his stool) but there was no documentation that anyone had performed a rectal exam or examined a stool specimen for the presence of gross or microscopic blood.

There was a lab order to type and cross-match the patient for a blood transfusion but certainly no mention that a transfusion had actually occurred. There was a thorough procedure note from a gastroenterologist who looked in his stomach and colon several days after admission and found no source of bleeding. I called the gastroenterologist on the day I received the records but he was gone for the Thanksgiving weekend.  The records indicated the patient’s blood count showed hemoglobin of 9.3 on the day prior to discharge and 8.3 on the day of discharge but there was no mention of an investigation of why the blood count dropped and why he was released with a dropping blood count.  A chest x-ray report on his first admission showed a right lower lung infiltrate but there was no follow-up performed or reported.

The patient arrived at the local rehab facility on Thanksgiving morning. I saw him and performed a thorough history, review of his records and an exam.  He was no longer bleeding, with no black stools noted on my rectal exam and no microscopic blood on the stool occult blood slide test I performed at the bedside. His Foley catheter was draining clear non bloody urine and the patient looked pale but well.

It was really very easy to convince this patient to come to rehab to learn to walk again once I became aware of his hospitalization and condition.  After my initial exam I sat down with the charge nurse and we constructed a care plan for the next few weeks at the rehab facility and explained it to the patient. Then I told the patient he had bladder cancer with a good prognosis. He was completely unaware of that diagnosis until we had the conversation.  I called his wife and children separately and reviewed the diagnoses and care plans for follow-up.

GH entered the hospital on an emergency basis as an unknown. He was appropriately taken to the nearest receiving facility by the paramedics when he was found to be on a blood thinner and bleeding actively.  His inpatient hospital employed physicians prevented a catastrophe and did what was necessary to make sure one was not ongoing. They did little or nothing to insure the loose ends of his medical problems resulting in hospital admission were addressed or understood by the patient and family.  Little or no effort was made to insure continuity of care and appropriate follow-up.

Judging by the editorials in our peer reviewed medical journals, this has become the norm not the exception in our insurance company / employer driven health care system. The devil is in the details. Unless the loose ends are planned for , understood and addressed, patients like this will continue to be bounced back to the hospital as an “emergency”, unnecessarily spending money we do not have and do not need to waste.

Coumadin versus Pradaxa

Coumadin (Warfarin) is a blood anticoagulant which prevents clotting by inhibiting Vitamin K dependent clotting factors.  It is taken orally and becomes effective after several days of administration when the Vitamin K dependent clotting factors have been depleted.  It is inexpensive and has been used for years to prevent clots from forming in patients with the irregular heart rhythm known as atrial fibrillation.  These clots can form in the chambers of the heart and break off and travel to the brain causing embolic strokes.

Coumadin is additionally used to prevent recurrent blood clots in patients who have had phlebitis (or inflammation of a blood vessel) and in certain postoperative conditions such as joint replacements. Physicians monitor your ability to clot by drawing blood for a test called “the prothrombin time or INR (International Normalized Ratio).  The blood can be drawn from a vein and sent to a lab or performed by a finger stick method in a doctor’s office.  Based on the blood test result we adjust your medication dose up or down. Coumadin’s effect on blood clotting can be easily affected by certain foods rich in Vitamin K (green leafy vegetables in particular) and by medicines which either enhance or limit Coumadin’s effect on clotting.

The major complication of Coumadin is excessive bleeding. We stop the bleeding by administering Vitamin K and infusing blood products intravenously containing active blood clotting factors.

Pradaxa and the new wave of direct thrombin inhibitors that are now being released are designed to do the same job as Coumadin without requiring monitoring by blood test of your ability to clot. This new class of medications should have many fewer interactions with food and other prescription and over the counter medicines. Its two major drawbacks are bleeding and expense.  The drug was tested extensively in Europe and proved to be safe but it has been on the US market for less than six months. While Coumadin costs pennies per tablet, Pradaxa costs about $300 per month. It requires taking a pill twice per day.

It is clear that thrombin inhibitors like Pradaxa will one day replace Coumadin. For now I prefer to have other physicians’ patients use it and compile a safety record before I try it on my patients. We know the pros and cons of Coumadin.  Let Pradaxa survive the test of use on the US market, and time, and show a clear cut safety advantage before giving it to our patients locally.