In previous blog posts (08/10/09, 08/16/09) I have reviewed the concept of antiplatelet drugs and their primary role in the protection of patients with coronary atherosclerotic heart disease from heart attack and death. They also serve to help prevent stent closure by clotting. In my next several blogs I will show how, although these concepts seem simple, they continue to engender controversy. The first controversy again concerns aspirin. I find aspirin's history compelling. This compound has been in use since ancient times. The active compound acetylsalicylic acid was first prepared by the French chemist Charles Gerhardt in 1853. The name was patented in 1899 after scientists at Bayer decided it was less irritating than salicylate alone. Aspirin soon became quite a hit and now an estimated 40,000 metric tons are used a year. Two fun facts about aspirin: why is the dose of aspirin 325 mg? It's because that was the amount of medicine in the tablet that withstood the manufacturing process including the stamping of the Bayer "cross" on the pill. Second, Germany was forced to give up the patent on aspirin in France, Russia, England and the United States after WW I as part of the war reparations. You would think that since this substance has been around since Hippocrates that we would know how it worked. That piece of science waited until1971 when John Robert Vane showed that aspirin suppressed prostaglandin and thromboxane production. In 1982, he won the Nobel Prize in Medicine for this discovery and was knighted. Aspirin has been further characterized as a COX-1 (cyclooxygenase enzyme) inhibitor which irreversibly blocks the formation of thromboxane A2 in platelets leading them to lose their ability to form clots. It is this action that we as cardiologists depend upon. The amount of aspirin to accomplish this is small -- roughly 40mg a day, which is where the use of 81mg of aspirin gets its recommendation. This is a source of controversy among physicians and in many cases, more aspirin is needed to accomplish the clinical goal of preventing heart attacks, death from cardiovascular causes or stent closure. The more aspirin you take, the higher the likelihood of GI bleed; so that balance is what comes into play. Next...the beginning of the trials.
The recent European Society of Cardiology meeting in Barcelona, Spain, was the opportunity for the release of several groundbreaking trials. I will report on many of them in detail in the coming weeks. The first is on a class of drugs that I have worked on for many years and we at the JMHVRI are still working on. They are oral thrombin inhibitors and Dr. Charles Russo is leading the Aristotle study here at the Institute. These drugs are for the anticoagulation therapy of Atrial Fibrillation for which the current standard is warfarin. The first of these drugs known as ximelagatran failed in testing due to liver toxicity. As I have discussed, research is an additive experience and now we have a compound in the same class that is very successful and non-toxic. The drug being tested in Aristotle (apixaban) is in the same class as the drug which I will discuss below and our study remains open for recruitment. Atrial fibrillation has a prevalence of 0.4%-1% of the general population. The risk increases with age, so that by the time you are 80 you have an 8% chance of having it. Atrial fibrillation is common in patients who have congestive heart failure and it worsens the prognosis of both these illnesses.
There are different types, chronic or persistent, intermittent and secondary. Secondary such as from open heart surgery where roughly >70% of recovering patients will have at least an episode or at times related to another illness such as hyperthyroidism. At times it is chronic and persistent or at times intermittent. All types suffer from the major adverse effect of atrial fibrillation, which is stroke. One in every 6 strokes occurs in patients with atrial fibrillation. When transient ischemic attacks and "silent strokes" are figured in, the rate of stroke exceeds 7% a year. The risk of stroke increases with age and is 23.5% in those over age 80. It is the most common arrhythmia that cardiologists see and accounts for one-third of the hospitalizations for cardiac rhythm disturbances. It is estimated that more than 2.2 million people in the United States has it and it is increasing. In the past 20 years there has been an increase of more than 60% in the hospitalizations for this condition. The annual cost per patient is said to be around $3,600 or close to a billion dollars. Anticoagulation with warfarin (Coumadin) is the current treatment for atrial fibrillation with either rate control or conversion back to normal sinus rhythm. Warfarin reduces the rate of stroke significantly but it is associated with increased rates of major bleeding. It is very tedious to regulate and time-consuming for the patients and health care personnel involved. Even a more expensive drug would save tremendous amounts of money. Up next...the RE-LY study and its groundbreaking conclusions.
Recently, a review article was published in the Journal of the American College of Cardiology. This article reviewed the studies concerning omega-3 polyunsaturated fatty acids, better known as fish oil.
In the United States, physicians generally prescribe statin drugs for the treatment and the prevention of atherosclerotic disease. In Europe it is very common for the treatment protocols to use fish oil pills first and then statins.
The review discussed the varying conditions that were studied. Over 40,000 patients were enrolled in the various trials. These studies involved primary prevention, secondary prevention after sustaining a myocardial infarction heart failure and heart rhythms, such as atrial fibrillation.
Three large trials were done regarding the primary and secondary effects of this compound vs. placebo. Two decades ago the DART (Diet and Reinfarction) showed a 29% reduction in all cause mortality mostly driven by the reduction of cardiovascular mortality. More recently, the GISSI study group randomized over 11,000 patients and found a 15% reduction in the primary endpoint including 21% and 30% reductions in total and CV mortality. This was driven by a 45% reduction in sudden cardiac death.
Additionally, heart rhythms were found to be suppressed by these compounds. These include atrial fibrillation and rhythms which cause sudden cardiac death. Up to a 30% reduction over 12 years was found for atrial fibrillation. We were to participate in a new large trial regarding these compounds which the sponsor cancelled just before inception.
Heart failure is also improved. In a study of patients vigorously treated for heart failure those that took these compounds had an 8-9% reduction in death.
In my next blog I will discuss the various factors you need to know to take these compounds.
Statins have been found to have many attributes that are not always readily explainable. Recently, an article was published in JACC concerning the ARMYDA-RECAPTURE trial. Done in Italy, this study was designed to investigate whether receiving an acute reload of Lipitor before an angioplasty protects patients, who are chronically on Lipitor after periprocedural heart attacks.
383 patients were studied, who were on chronic statin therapy and needed angioplasty. These patients were either stable or unstable. They were randomized 1:1. Half received 80mg Lipitor 12 hours before and 40 mg Lipitor right before the angioplasty. The other half got none. All the patients took 40mg Lipitor after the procedure.
The end points were cardiac death, myocardial infarction, or unplanned repeat angioplasty. These events occurred in 3.7% of treated patients and 9.4% of untreated patients. The difference was primarily driven by the finding of more myocardial infarctions in the untreated group.
One further finding was that most of the benefit was in the unstable patient group. 9 unstable patients need to be treated for one patient to have a benefit. In the stable group, 111 patients need to be treated for one to have a benefit.
Reloading of high dose Lipitor may become a “standard of care” if this study is borne out by other work. If you are asked to take pills right before an angioplasty it’s because we are trying to provide you with “evidence based medicine,” which is derived from clinical research trials. These benefits are what we work for on a daily basis. It is our commitment to our community here at the Jim Moran Heart and Vascular Research Institute.
Is there something you'd like to know about cardiovascular health that has not been addressed in the blog? To submit your question to Dr. Niederman, post it in the comments section below. For more information on cardiovascular health, click here to subscribe to our e-newsletter. Posts are published by Holy Cross Hospital to provide general health information. They are not intended to provide personal medical advice, which should be obtained directly from your physician.
Heart failure has reached epidemic proportions in the United States owing to our aging population and the advances in treating myocardial infarctions. Over 5 million people carry the diagnosis and 550,000 new cases a year occur. In 2001, there were nearly 1 million hospital discharges.
We have multiple therapeutic options which include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, cardiac resynchronization, diuretics and since the 1700s, digitalis. Now the latest innovation, stem cell injections.
Bioheart is a biotech company located in Sunrise, Florida. They have developed a process to find and grow skeletal muscle stem cells. We do not yet have a process to biopsy and grow cardiac stem cells. There are several very early stage studies in Europe with progenitor cardiac stem cells but they are still in pilot stage. Bioheart's Marvel study is the third and final step to FDA approval of these cells for the treatment of congestive heart failure. A pilot study and a safety study showed that this treatment was safe with a robust trend to effective. In fact, the first 20 patients of the third study - of which three are from our site - have been studied and also found to have a robust effect.
The process involves taking a biopsy from the leg muscle of patients. This is then sent to Bioheart and processed to find the 6-8 fibroblast stem cells in the biopsy specimen. These cells are then grown out and in 14-21 days become billions of cells. These cells are then given to me to inject in the heart after NOGA mapping shows me the appropriate place. See the blogs of June 22 and / or 29 for details of the NOGA procedure.
We are proud to be the only team in South Florida doing this important work. The study will open for enrollment again in the Fall and we look forward to helping our patients with this technique. Please feel free to contact us for more information at 954-229-8400.
NOGA mapping image
One of the primary purposes for the creation of the JMHVRI was to have Holy Cross Hospital involved with cutting-edge research. This has allowed us to participate in the most exciting research development in years.
In my 20 years of research at the clinical level, my team and I have had the privilege of being involved with important breakthroughs in the clinical and drug treatment of cardiac disease. We have participated in the development and approval process of most of the drugs I now use for the treatment of heart disease. Much of our work continues in this mode. Our work with adult stem cells portends an improved future for cardiac patients.
To date, we have been involved with two stem cell projects and one project utilizing a stem cell protein. We are the only site in south Florida and one of three sites in Florida.
Adult stem cells are undifferentiated cells that multiply by cell division to replenish dying cells and regenerate damaged tissue. They are derived from adult tissue samples. Although the process is unique, it is not strong enough to repair all the cells that die naturally or by accident. If you have a heart attack, the few adult cardiac stem cells in your heart are not numerous enough to repair the damage. The reasons are unknown and an active area of research. We have no way of obtaining adult cardiac stem cells because we cannot biopsy the heart adequately to obtain them.
Therefore, the studies utilize other stem cells to obtain the results we are clinically trying to obtain. These cells or protein material are then injected directly into the heart from the leg in a manner similar to angiography and angioplasty using an additional special machine known as NOGA. NOGA technology is similar to the technology used in electrophysiology studies to isolate and identify areas of the heart of interest; in our case, those areas of the heart which are scarred or lacking adequate blood supply. After identification, special catheters are used for the injections.
Next... The Baxter CD34+ stem cell study for the treatment of angina.
Angina is what we call the symptom of chest discomfort that is caused by lack of blood flow to the heart muscle. It has multiple causes but the one that is most common is atheroscelerotic blockages in the heart arteries causing limitation of blood flow. It can be at rest or exercise because the symptom is a result of a combination of a person's heart rate and blood pressure. These same blockages can lead to heart attack in other circumstances. The most common treatment for angina is medication. These drugs fall into various classes of medication. The oldest is nitroglycerine, which has been in use since 1870 when it was first used by Thomas Bruton in England for the treatment of angina and reported in The Lancet in 1879. It is only recently that the mechanism of action of nitroglycerine has been understood as an example of how long it takes for science to catch up with the practice of medicine. Beta-Blockers are a mainstay of treatment. They were invented by a brilliant Scottish doctor and pharmacologist Dr. James Whyte Black in the late 1950s. Interestingly, he also invented Cimetidine, which was a new class of drugs to treat stomach ulcers known to most people as Tagamet. For these and other advances, he was awarded the Nobel Prize for Medicine in 1988. Beta blockers are used to control both the heart rate and the blood pressure in patients with angina. This allows the heart to receive sufficient oxygen carrying blood for energy utilization. Calcium channel blockers are medications that have predominantly heart rate slowing or vasodilatation mechanisms of action. These are commonly used as drugs such as Norvasc, Cardizem, Procardia or Calan. They lower the heart rate and overall blood pressure much as the Beta Blockers. Next week I will discuss what is probably the most important advance, in atherosclerotic heart disease, the statin drugs.
Welcome to the JMHVRI blog. My purpose in hosting this blog is to be personal and educational. I will strive to bring the practice of cardiology and the groundbreaking research that my colleagues and I do to your attention. We are here for our community as Holy Cross and the Sisters of Mercy have been for over 50 years.
Heart disease is the leading cause of death in the United States for both men and women. Much has been learned over the past years but significant issues still remain. Information is now widely available on the Internet but much of it requires interpretation and some is just incorrect. This site will be a place to discuss these issues and concerns.
The JMHVRI is involved in groundbreaking research. We are the only site in South Florida for some of this work. I will highlight these studies so that you can participate or pass the information on to others who might be in need.
Our research institute is currently working on Adult Stem Cell therapy for the treatment of angina which can not be remedied with medication, surgery or angioplasty and as a treatment for heart failure which is still problematic in spite of all known therapies.
We are working on new therapy to replace Coumadin, as well as a new class of drugs known as Thrombin inhibitors for the treatment of clots. On new ways to treat high cholesterol, on new treatments for heart attacks, on novel drugs for the treatment of congestive heart failure to name just a few of our projects. I will inform you in depth about all these projects and more.
It is an exciting journey and I welcome you to join me.