Just what we didn’t need – More Avandia Fallout
It’s bad enough that the Senate report on Avandia has resurrected the issue of adverse cardiovascular events and diabetes medications, once again giving patients one more reason not to be compliant with their therapy regimen. Today the American Heart Association (AHA) decided to provide their perspective on this controversy. Unfortunately as well intentioned as their effort may be its likely the AHA has only added more questions.
According to an article published in Circulation, the Journal of the AHA, entitled “Thiazolidinedione Drugs and Cardiovascular Risks. A Science Advisory From the American Heart Association and American College of Cardiology Foundation” the authors write: “Minimization of the risk of microvascular and macrovascular disease is a critical clinical goal in the management of patients with diabetes. Control of hyperglycemia is recommended to reduce microvascular complications; achievement of hemoglobin A1c less than 7% without causing hypoglycemia may be particularly important, if accomplished early in the disease and maintained successfully. Attainment of this glycemic goal when lifestyle modification is not enough will require a choice of 1 or more glucose-lowering agents.
Conventional risk-reduction measures, such as lifestyle modification, the use of aspirin (especially in patients with preexisting CVD), and appropriate blood pressure– and lipid-lowering drugs, are of proven benefit in reducing macrovascular disease and saving lives; however, the evidence concerning the effects of specific glucose-lowering agents on macrovascular disease is limited and inconclusive. There is evidence that suggests a macrovascular benefit with metformin, especially for obese diabetic patients, and some inconclusive evidence of potential harm from rosiglitazone but not pioglitazone. For most of the other glucose lowering agents, there are few or no data to support either harm or benefit with regard to macrovascular disease.
More data are urgently needed to clarify the effects of all existing and future glucose-lowering agents, including thiazolidinediones, on IHD events. In the meantime, patients and clinicians will need to weigh the accepted benefits of improved glycemic control on risk for microvascular disease from glucose lowering agents against the worrisome, inconclusive, or completely absent information about the effects of these agents on macrovascular disease.”
In a corresponding perspective published in the same issue the author states; “In the meantime, with the limited evidence available, the advisory states that there is inconclusive evidence that rosiglitazone, but not pioglitazone, increases cardiovascular risk. The constant challenge is determining how best to communicate this information to the public. Given the uncertainty, there is no compelling reason to alarm patients. They should, however, be informed that there may be differences in the risk profiles of the thiazolidinedione drugs. The information is laden with nuance and concise messages are difficult. Nevertheless, the message that emerges from this advisory is that given the choice of various thiazolidinedione drugs, it is hard to make a case for rosiglitazone. Thus, the simplest message might suggest the avoidance of rosiglitazone until more reassuring evidence for the drug becomes available.”
These two articles are about as much help to patients and the physicians that treat them as adding gasoline to a ragging wild fire. While both articles seem to support the belief there is enough evidence for patients not to use Avandia, neither provides much in the way of clear guidance on the use of Actos and other medications used to treat type 2 diabetes. The statement made in the first article; “In the meantime, patients and clinicians will need to weigh the accepted benefits of improved glycemic control on risk for microvascular disease from glucose lowering agents against the worrisome, inconclusive, or completely absent information about the effects of these agents on macrovascular disease.” (Highlighting added by Diabetic Investor) Is hardly reassuring, the authors are basically reinforcing the belief that patients are basically rolling the dice when it comes to taking their medications.
The authors also state; “Conventional risk-reduction measures, such as lifestyle modification, the use of aspirin (especially in patients with preexisting CVD), and appropriate blood pressure– and lipid-lowering drugs, are of proven benefit in reducing macrovascular disease and saving lives; however, the evidence concerning the effects of specific glucose-lowering agents on macrovascular disease is limited and inconclusive.” (Highlighting, bold and underlining added by Diabetic Investor) This statement seems to fly in the face of two recent studies, one calling into question the use of aspirin and the other that indicated there is a link between statins and developing diabetes. Drugs which these authors note have “PROVEN BENEFIT IN REDUCING MACROVASCULAR DISEASE AND SAVING LIVES”!
Harlan Krumholz, MD, SM the author of the perspective states; “With millions of patients treated, how is it possible to miss an important risk? Even with the trials, should such risks be evident? It is problematic that cardiovascular risk in these patients is difficult to detect because cardiovascular disease is common. If the drugs caused an uncommon adverse effect such as pulmonary fibrosis, detection would be easy. If they caused people to turn blue, we would immediately recognize the risk. However, an increase in the risk of a commonly occurring outcome actually obscures the problem. No physician is surprised to see a patient with diabetes suffer from a cardiovascular event. Even a doubling of that risk would be difficult to detect in clinical practice. Clinical trials that carefully collect adverse outcomes data are the best way to detect risk. High-quality observational data can be helpful. In any case, the risk will not be apparent to the casual observer.” (Highlighting added by Diabetic Investor) If this is the case how could anyone reasonably draw a straight line between Avandia usage and an increased risk of adverse cardiovascular events?
Reading both the article and perspective one begins to gain a better understanding of why things are so screwed up. Just where is a physician supposed to turn, when once again we have studies that offer contradictory conclusions? When with each passing day another study or perspective comes out that provides more questions and no clear guidance? Have we reached a point where physicians will have nothing but their kind words to help patients? This may seem ludicrous but given the way things are going where no drug is safe and drugs that everyone thought saved lives really are no better than a mother’s chicken soup as a treatment option. And it wouldn’t surprise Diabetic Investor at all if there isn’t someone out there studying the risk/reward profile of mom’s chicken soup and will likely conclude that chicken soup also is linked to diabetes.
When will these people learn that diabetes is a very complex disease and there is no one single drug or therapy regimen that works 100% of the time in every patient and comes with no possible adverse events. It’s about time these people realized that diabetes is not a one size fits all disease and that there is no such thing as a completely safe drug. The fact is in the real world, somewhere were these people do not live, patients need information to make informed decisions about the drugs they take. Patients, unlike these people, understand that every drug no matter how well tested, carries with it some risk. They just want to know what these risks are so they can make an informed decision.
Diabetes is not like a broken arm where the arm can be set in a cast to heel. Unlike a broken arm, which a physician can see through an x-ray whether it’s heeled or not, controlling diabetes is a 24x7x365 battle. A battle which is truly never won, as just getting a patient to control is only half the battle, it’s just as important to keep them under control. In one way controlling diabetes is like weight loss, while it’s great when a patient loses weight, all that hard work goes down the tubes should the patient regain the weight they have lost.
The facts are that diabetes even when well controlled carries with it numerous risks. It is equally true that the majorities of patients with diabetes don’t just have diabetes and must also deal with other issues such as obesity, high cholesterol and hypertension- Issues, that when combined with their diabetes, unfortunately increases the likelihood that the patient will experience adverse events.
Before we leave this issue it’s just as important to note the role the patient plays in this controversy. While patient education is beginning to improve, how many times have we seen patients ignore their physician’s recommendations? As Diabetic Investor has reported a leading reason as to why nearly two thirds of patients with diabetes are not adequately controlling their diabetes is because patients are not compliant with their therapy regimen. Are we to blame the drug companies and the FDA when the patient doesn’t do their part? The fact is patient responsibility or lack thereof does play a role and should not be ignored.
The time has come for some serious reforms in the way drugs are approved, the use of meta-analysis and how information is disseminated to the public. We need to acknowledge that diabetes is not a one size fits all disease and there is no such thing as a silver bullet to treat it. It needs to be made clear that no drug no matter how well studied is completely free from adverse events. Finally and most importantly, it needs to acknowledged that no matter how hard we try things will go wrong and there is nothing that can be done to stop that.
Diabetic Investor doesn’t know who said it, but someone once said when it comes to war rule number one is fine young men will die and rule number two is that no one can change rule number one. What’s happening today is that the fallout from the Avandia controversy is making matters worse. Each entity is staking out their turf while leaving patients and the physicians who treat them with little clear guidance as to what to do. It’s time for the Senate, FDA, drug companies, researchers and these entities to stop the blame game and come up with some answers that will actually help and not confuse patients. They must acknowledge that diabetes is the enemy and with their actions they are taking away, and not adding, new weapons that would help patients fight this disease.
Diabetes is now the 8th leading killer in this country and moving up fast. Diabetes continues to grow at epidemic rates and a cure remains a pipedream. Diabetes is not just a healthcare crisis but an economic crisis as well. These are the facts and all the finger pointing, chest thumping and pontificating won’t change the facts. What’s needed is some leadership, true leadership when everyone puts the public’s interest ahead of their own. The bottom line here is that everyone would be wise to remember the words of David Cooper who said: “Perhaps the most central characteristic of authentic leadership is the relinquishing of the impulse to dominate others.”