Archive for March, 2010
To Cath or Not to Cath
On September 9, 2009, I blogged about the increase of radiation exposure in our population that results from medical imaging. As someone who is partially responsible for this, I am very interested in the topic and I follow it closely. (Disclosure: I am an Interventional Cardiologist.) Now data that surprises even me has been published in the New England Journal of Medicine. I knew the problem was bad, but not even I realized it was this bad. First some background information.
Cardiac catheterization started as a measuring test. The test was used to measure the pressures inside various heart chambers and then to take large volume dye injections to document congenital birth defects. This is because all the doctors were pediatric cardiologists and all the surgeons were pediatric surgeons. That’s because there wasn’t much adult cardiac surgery until the development of artificial heart valves in the 1950’s and coronary bypass surgery that started in 1968. When coronary bypass started all the cardiac surgeons were pediatric cardiac surgeons or thoracic surgeons like Dr. DeBakey, who recently passed away on July 11, 2008 at almost 100 years old. Cardiac catheterization has morphed over the years to become almost exclusively a test of the angiographic evaluation of coronary arteries.
The first human cardiac catheterization occurred in the 1929 when Werner Forssmann, a young physician tied up his assistant and then placed a urinary catheter into his own arm vein and used fluoroscopy to advance it into his lungs. Forssmann then went upstairs to take a chest x-ray to document it. This was the first use of radiation in diagnostic cardiology. His superior at the clinic Eberswalde urged him to write and publish a paper and he won a spot at the Berliner Charite Hospital under Ferdinand Sauerbruch. Dr. Sauerbruch saw the paper and promptly fired him. Dr Forssmann went on to become an Urologist. But, wait there’s more.
During the 1940’s, Dr. Andre Frederic Cournand and Dickinson Richards at Columbia University and Bellevue Hospital read his paper and went on to formally develop right and left heart catheterization, including catheters that were named after them. In 1956, Forssmann, Cournand and Dickinson were awarded the Nobel Prize in Physiology and Medicine for their work so the Urologist had the last laugh.
Next… how angiography changed what we do.
One Down, Two to Go
Let’s start with a surprising and disturbing fact. As published in the New England Journal of Medicine 1988:339:229-234 and titled Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction, was the conclusion that and I quote “Patients with type 2 diabetes mellitus without a history of myocardial infarction have the same risk of a coronary event as patients without diabetes who do have a history of myocardial infarction.” In other words, just having diabetes is the equivalent of having coronary disease.
This well done study became the impetus to attempt to alter this risk. Surely, a well placed endeavor. We have seen that very strict control of hemoglobin A1C was harmful. What about blood pressure control?
The investigators wanted to determine if a blood pressure target of systolic 120 was better than a target of systolic 140. Presently, the target is systolic 130. After 4.7 years, there was no significant difference in a composite outcome of nonfatal myocardial infarction, nonfatal stroke or death from cardiovascular causes. There were more frequent serious adverse events in the intensive therapy group.
So, better glucose control and lower blood pressure causes more harm and no benefit. Doesn’t look good for the third arm that of lipid control?
In this part of the study, subjects were randomly assigned to simvastatin (Zocor) or simvastatin plus fenofibrate. Additions of fenofibrate to simvastatin were supposed to lower triglycerides and increase the level of HDL and provide benefit but it did not result in a significant improvement in the composite endpoint. In fact there was a signal of harm in women subjects.
Well, three for three. This is how we learn. This is how we move medicine along. We will not stop trying to improve the quality of life for patients with diabetes. It should be pointed out that one of the best ways to prevent the problem is to control your weight and get regular exercise, easily written but hard to do. As we can see from these studies it is probably still the best advice.
Good is Not Better Than Excellent
The ACCORD trial started in September of 1999. One of the reasons that medical progress is so slow is that it takes so long to do the trials. Mice are easier but they don’t have the illnesses that we do and humans are not as easy to control. 10,000 patients were enrolled in the National Institutes of Health study. This might be a good time to explain this point.
Drug companies are responsible for much of the research that goes on in medicine, but they are generally not the sponsor of trials to determine the “best practices” to take care of chronic illnesses. This is simply because there is no money in it. Therefore, much of the work is done by the government in the form of grants to the National Institutes of Health and often money, drugs, equipment or support is given by drug companies to help the work get done. Sometimes this is voluntary and sometimes it is mandated by the FDA. The work we are doing on the DAPT (Dual Antiplatelet Therapy) Study is an example. It is being run by Harvard with money from various sources heavily supported by Industry because the FDA demanded it. Sometimes this support is very large but not as large as the hundreds of millions of dollars that it takes to approve a new drug.
The ACCORD trial had three parts as described in my last blog. Perhaps the most important part was the first, which asked a simple question. If you normalize a patient Hemoglobin A1C, does that benefit the patient? Diabetes is usually described in many ways but one is a hemoglobin A1C of >6.0%. Hemoglobin A1C is a measure of glucose control over the preceding two to three months. In non-diabetic patients, it is less than 6.0%.
Honestly if you asked any doctor, we would have said of course that is a benefit. Well it’s not the case. In fact it is harmful. Of the 5,123 participants in the standard arm, one half had reached the goal of Hemoglobin A1C of less than 7.5%. Of the 5,128 participants in the intensive arm, half reached the goal of less than 6.0%. This part of the study was to last five years but was stopped after 3.5 years because there was an excess of 54 deaths in the intensive arm. That’s a 22% increased death rate in the intensive group.
The causes of death were similar in both groups and the mechanism for the increased rate of death has not been determined in spite of extensive analysis. The recommendation of the American Diabetes Association clinical guidelines is that Hemoglobin A1C less than 7.0% be maintained.
So much for glucose control, what about blood pressure?
Why We Need to be in ACCORD
My favorite reason for doing research is that I have been fascinated in the past twenty years by what we as doctors think is the correct way to treat patients only to find that when we study the condition, we just have it all wrong. I know that that doesn’t fit with the perception that we “know it all” and can always make “the right call,” but it keeps us real. We can only use the data that is driven by the studies in our attempt to treat patients to the best of our ability. We want the best outcomes for patients.
Diabetes is a terrible chronic illness and it goes hand-in-hand with atherosclerotic disease in all of its forms, stroke, myocardial infarctions, and amputations. It is a terrible scourge, and I deal with it on a daily basis.
In an attempt to determine optimal diabetic treatment, a study was devised and named ACCORD or Action to Control Cardiovascular Risk in Diabetes. This study used the same group of patients to answer three questions that seemed simple at the time.
1. Is intensive gylcemic (sugar) control better?
2. Is lower blood pressure better?
3. Is better lipid control better?
To answer the first question patients were divided into two groups and one was treated in the standard way and one was forced to lower hemoglobin A1C levels than previously recommended. Hemoglobin A1C is a long-term measure of gylcemic control.
To answer the second question, the groups were targeted to a systolic blood pressure of 140 or forced to a systolic of 120. This was unblinded i.e. the investigators knew what they were supposed to do.
To answer the third question the groups received either a statin or a statin and a fenofibrate.
See if you can guess the results. The answer next time…
And Now The Bad…
Over the past several blogs, I wrote about how more and more patients should take statins. Now we have the news that taking statins may increase your risk of diabetes. Published online on February 17th in the journal Lancet was a Meta analysis that was performed on multiple trials of statin use, which included 91,140 patients. As I have mentioned before, statins are the most studied drug known to medical science.
The findings were surprising and widely discussed in the lay press. The authors found that one patient in 255 treated for 4 years will develop diabetes. An individual has a 9% chance of developing diabetes but is given a benefit of the reduction of 5.4 deaths or MI’s per 255 patients. There was no correlation with body mass or with the level of reduction of LDL. Further it doesn’t appear to be related to type of statin or dose.
In individual trials, this risk was greater. In the PROSPER trial with pravastatin, the risk was 32% of developing diabetes and in two trials with rosuvastatin the risk was 18%. Niacin therapy has also been associated with this effect.
It is not clear why this is so. It is confusing because the use of statins in patients with diabetes reduces their risk of death and MI. It would seem prudent to be on the watch for the development of this problem with further testing of glucose levels during treatment. A study is soon to start to determine whether high dose or low dose statins put individuals at more risk.
Although this risk seems clear the benefit here far outweighs the risk. It is important to exercise and to eat as healthy as possible. It is important to be as lean as possible. The cholesterol in your body is 90% manufactured and that is from your particular genetic inheritance. Some thin patients get heart disease, some overweight patients don’t. As I have said before we don’t have a very good understanding of much of this because we lack a basic model to study. No animal gets coronary disease except humans and we don’t study easily. If you are at risk for cardiovascular events, do your heart and brain a favor and take your statins.
FDA Gives Crestor New Indication
On this blog on June 15th 2009, I wrote about the JUPITER Study and its meaning to patients who are at risk for cardiovascular events. Crestor or rosuvastatin is the most potent statin in the family of statin drugs. Its potency is derived from the drug’s half life. The longer the drug is in your system, the lower your LDL goes.
All companies strive to have drugs approved and then to enlarge the group of patients that the drug can possibly benefit. Even though I can give any drug I want to for any reason to any patient, the FDA does not allow the process of “detailing” for other than “approved” indications. Detailing is the process where a representative of the company will come into my office and give me very specific information regarding the drug. This material is highly vetted by the government and the company and serves as a major source of drug information for busy doctors, who have difficulty in keeping up with the latest in fields that might not be their expertise.
So when a drug gets a new indication, it’s a big deal. The FDA was stricter in their new indication than the inclusion criteria for the study, but none the less, this indication lowers the bar to whom this drug should be offered. I personally believe that as the readers of my blogs know; I am a big fan of widespread use of the statin drugs to possibly prevent cardiovascular events.
Specifically the FDA has approved the use of Crestor in men greater than or equal to 50 years old and women greater than or equal to 60 years old, who have fasting LDL levels <130 mg/dl, hs-CRP > 2.0 mg/dl, triglycerides <500 mg/dl and one additional cardiac risk factor. The study required no additional risk factors but in an analysis of the study, all the benefit was in those patients who had additional risk factors. Further analysis showed that the greatest benefit was in those patients with a 10-yr Framingham risk of 5% to 20% and who would not have been treated under the guidelines.
It is estimated that close to 17 million more patients are now eligible for treatment and the reduction of cardiovascular events in this many patients can decrease the overall healthcare costs substantially.
I congratulate the authors of the JUPITER study on a job well done and I predict that we will have a further lowering of the bar as time goes on. There is even a movement to not test for cholesterol levels at all but just give the drug in moderate levels to everyone who has hypertension. This concept is know as the “polypill” and gets more interest in Europe than the United States. I predict, however, that I will be writing more blogs in the future about how more and more people will possibly derive benefit from these wonderful drugs.
New Reports On Statins
In the past few days much has been written about statins, and I would like to bring you up to date on these reports. Some show deficiencies and some show the promise and benefits of these amazing drugs.
Let’s start out by the report which admonishes us as doctors and you as possible patients. This report concerns the well known fact that many patients do not take their drugs in the prescribed way or not at all. This is particularly true when it comes to drugs that have a “potential” future benefit such as blood pressure meds and statins.
It is recommended that people who have a >20% risk of cardiovascular disease be placed on statins. As mentioned before, you can go to the risk calculator that I have referred to in previous blogs to calculate your own risk. I usually calculate the number when patients come to see me. By five years, the number of patients started on medication who still take it is approximately 50%.
Health organizations often consider lowering the threshold for treatment to treat more patients and lower the incident rates of disease. However, if you could increase the compliance to 75% of those that “need it,” more lives can be saved than if you just treat more patients.
How do you get better adherence to taking medication? No method has been tried in a randomized fashion. In today’s healthcare morass, it is becoming increasingly common for patients to see different practitioners each time they visit. I have found that a good understanding of why you are taking the medication helps but once the heart attack occurs you usually have patient’s attention. It’s the primary prevention patients that you want to capture and have them understand just how important it is to take this medication.
Having written the above, I will now tell you about a whole new group of patients that have been added to the “need statin” list.
Next…a new indication for Crestor.
Checking Up On the Doctor
I have often blogged about our guidelines. Guidelines are recommendations promulgated by my society, the American College of Cardiology, which are written by a committee made up of some of the most distinguished cardiologists today. The recommendations come from the research that is done and are powered into various groups with multiple large randomized trials, receiving the most weight and the strongest recommendation.
Over time these guidelines are adjusted as new information is developed and are not “secret” they can be viewed by anyone at the college’s web site at www.acc.org. They are not intended to replace patient-centered decision making by experienced clinicians. That being said it is interesting to see whether or not guidelines are being followed in certain areas.
The review chosen was my area of expertise cardiac catheterization and the choices made after cath; i.e. the recommendations for medical therapy, angioplasty or coronary bypass surgery based on the coronary anatomy identified. The study used the New York State Cardiac Diagnostic Catheterization database and was published in Circ 2009; 121: 267-275.
The findings were that 94% of those indicated for angioplasty received it. That 93% of the patients who needed bypass surgery or angioplasty, received angioplasty. However, in those patients that the guidelines indicated surgery, 53% had surgery and 34% received angioplasty. Of the patients that neither surgery nor angioplasty were indicated; 6% received surgery and 21% received angioplasty.
It seems that those of us with the “hammer,” the doctor, doing the cath often find the “nail,” the patient. These data don’t take into account the multiple other factors that come into play such as patient preference to not have surgery, status of the patients medical therapy and other co morbid issues, which may limit surgical options.
The group that received therapy when not indicated is the most troubling but a very small proportion of the total 10,333 patients in the study. What the study does show is that Interventional Cardiologists may be “growing the business” by pushing the limits of angioplasty. Many hospitals like Holy Cross have committees to review cases to help critique and improve the work done at the facility. I am proud of my profession in our ability to look at ourselves and present findings that may not reflect well on us. This is how we learn and continue to improve so we can perform in the best interests of our patients.
Just Stop… Smoking!
Let me start by saying that I have never smoked. I preface this blog with that statement because unlike many people and many of my patients, I have never had to quit smoking. I appreciate the struggle to deal with what used to be a socially accepted action and now, as we realize just how harmful it is smoking itself becomes less and less accepted. Even our President has been vocal in his attempt to quit and still struggles with it. His recent physical over the weekend again highlighted that he is still smoking intermittently.
Smoking is by far one of the most destructive things that human beings do to themselves. It truly is an act of self mutilation and it causes multiple problems. The risk of myocardial infarction increases with the number of cigarettes smoked. Cigarettes are the ultimate drug delivery device. The drug is nicotine and the smoke issue is a by product as are most of the carcinogens. They are now formally under the jurisdiction of the FDA but it remains to be seen exactly what that means.
Some facts:
In 2007 19.8% (43.4) adults smoked
Attempts to quit smoking decreased from 47% in 1993 to 48.8% in 2007
Only 4%to 7% of smokers trying to quit will eventually succeed
There is a 36% reduction in the crude relative risk of mortality in those smokers that stop
This benefit starts within one year and continues to become more powerful over time
The best way to stop is not to start. It is imperative that we focus education in young people so that they never start smoking. Cessation activities include psychosocial and pharmacological or both combined. The pharmacological approach entails bupropion SR, which is Wellbutrin, an antidepressant, nicotine replacement therapy and varenicline which is Chantix.
Recently, another study with varenicline was published Circ 2010; 121:221-229. This study used a group of patients with cardiac disease who were still smoking. Those taking the drug did better than those that stopped and the drug group did better than placebo. At the end of a year 27.9% were not smoking in the drug group and in the control group 15.9% were not smoking. Wow, even in a study with considerable counseling and support people can not stop. By the way, people were not asked if they stopped they were tested, to all those out there who smoke we have blood tests that now prove it. 10% of the drug group stopped because of side effects but the number of psychiatric side effects were not greater in the drug group.
Clearly we need better ways to help these people. My patients tell me that “cold turkey” is the only way to go. Whatever means you take you must stop, for you and everyone you know who cares about you.
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