Sidney Goldstein

As the smoke settles over the firestorm created by the recent rosiglitazone revelations, many questions remain and much can be learned from the public discourse in both the medical and lay press. So what can be said about how the story evolved and ultimately reached a nonconclusion?

Rosiglitazone (Avandia, GlaxoSmithKline), a thiazolidinedione (TZD) was approved by the Food and Drug Administration for use in 1999 as an effective agent for lowering blood sugar. A modest amount of clinical data indicates that lowering blood sugar can have a beneficial effect on the microvascular changes associated with diabetes mellitus. Lowering blood sugar became a surrogate end point in the judgment of the FDA for a presumed clinical benefit in diabetes.

Some information existed to suggest that although rosiglitazone did indeed lower blood sugar, it might have some adverse effects on coronary heart disease. In fact, in September 2006, the European Medicines Agency had placed a warning label on rosiglitazone about the risk of cardiac ischemic events. In the United States, the FDA was in the process of reevaluating its judgment on this issue when along came the recent meta-analysis published by Dr. Steven Nissen and Kathy Walski (N. Engl. J. Med. 2007;356:2457-71).

One had to be impressed with the speed at which the authors, editorial writers, and the New England Journal of Medicine achieved major national and international headline exposure from a meta-analysis based on the meager and disparate data created from widely variable event classification.

The fact that a trial aimed at elucidating the potential mortality/morbidity effects of the drug was already underway in Europe and Australia was particularly unfortunate. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial was about halfway through its 6-year follow-up when the uproar occurred. RECORD randomized 4,447 patients to rosiglitazone or placebo in addition to standard oral diabetic agents. Even though its design was flawed by its unblinded nature, it surely might have provided some information relative to the risks of rosiglitazone. With the release of its interim 3-year follow-up data (N. Engl. J. Med. 2007, 357[doi: 10.1056/NEJMoa073394

All of this played out in an atmosphere in which the FDA has been recently taking its hits. The direction the FDA was taking regarding rosiglitazone is not entirely clear. Records suggest that it was under consideration and that one FDA reviewer was chastised for proposing restriction of its use. The slow and possibly flawed response by the FDA can hardly be countenanced. More importantly, the practice of the FDA to accept surrogate data in cardiovascular disease evaluation is a continuing problem. The FDA's approval of a drug based solely on its ability to lower blood sugar, without consideration of major cardiovascular safety and efficacy, is unacceptable.

Whether all of this could have been achieved without all the brouhaha is not certain. It is clear that the authors of the New England Journal paper were in discussion with members of Congress long before its publication. Whether there were discussions with the FDA is not clear. It does suggest that there was an attempt to “get to” the FDA or at least influence its policies. The possible contamination of science by politics is disturbing. Politics needs to be confined to the editorial pages, not in the meat of a scientific manuscript and its publication.

The ultimate decision forced by Congress on GSK and Takeda, the maker of the similar drug pioglitazone, could well have been achieved if cooler heads had been in charge. In addition we might still hold our scientific journals in high regard.

As the smoke settles over the firestorm created by the recent rosiglitazone revelations, many questions remain and much can be learned from the public discourse in both the medical and lay press. So what can be said about how the story evolved and ultimately reached a nonconclusion?

Rosiglitazone (Avandia, GlaxoSmithKline), a thiazolidinedione (TZD) was approved by the Food and Drug Administration for use in 1999 as an effective agent for lowering blood sugar. A modest amount of clinical data indicates that lowering blood sugar can have a beneficial effect on the microvascular changes associated with diabetes mellitus. Lowering blood sugar became a surrogate end point in the judgment of the FDA for a presumed clinical benefit in diabetes.

Some information existed to suggest that although rosiglitazone did indeed lower blood sugar, it might have some adverse effects on coronary heart disease. In fact, in September 2006, the European Medicines Agency had placed a warning label on rosiglitazone about the risk of cardiac ischemic events. In the United States, the FDA was in the process of reevaluating its judgment on this issue when along came the recent meta-analysis published by Dr. Steven Nissen and Kathy Walski (N. Engl. J. Med. 2007;356:2457-71).

One had to be impressed with the speed at which the authors, editorial writers, and the New England Journal of Medicine achieved major national and international headline exposure from a meta-analysis based on the meager and disparate data created from widely variable event classification.

The fact that a trial aimed at elucidating the potential mortality/morbidity effects of the drug was already underway in Europe and Australia was particularly unfortunate. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial was about halfway through its 6-year follow-up when the uproar occurred. RECORD randomized 4,447 patients to rosiglitazone or placebo in addition to standard oral diabetic agents. Even though its design was flawed by its unblinded nature, it surely might have provided some information relative to the risks of rosiglitazone. With the release of its interim 3-year follow-up data (N. Engl. J. Med. 2007, 357[doi: 10.1056/NEJMoa073394

All of this played out in an atmosphere in which the FDA has been recently taking its hits. The direction the FDA was taking regarding rosiglitazone is not entirely clear. Records suggest that it was under consideration and that one FDA reviewer was chastised for proposing restriction of its use. The slow and possibly flawed response by the FDA can hardly be countenanced. More importantly, the practice of the FDA to accept surrogate data in cardiovascular disease evaluation is a continuing problem. The FDA's approval of a drug based solely on its ability to lower blood sugar, without consideration of major cardiovascular safety and efficacy, is unacceptable.

Whether all of this could have been achieved without all the brouhaha is not certain. It is clear that the authors of the New England Journal paper were in discussion with members of Congress long before its publication. Whether there were discussions with the FDA is not clear. It does suggest that there was an attempt to “get to” the FDA or at least influence its policies. The possible contamination of science by politics is disturbing. Politics needs to be confined to the editorial pages, not in the meat of a scientific manuscript and its publication.

The ultimate decision forced by Congress on GSK and Takeda, the maker of the similar drug pioglitazone, could well have been achieved if cooler heads had been in charge. In addition we might still hold our scientific journals in high regard.

As the smoke settles over the firestorm created by the recent rosiglitazone revelations, many questions remain and much can be learned from the public discourse in both the medical and lay press. So what can be said about how the story evolved and ultimately reached a nonconclusion?

Rosiglitazone (Avandia, GlaxoSmithKline), a thiazolidinedione (TZD) was approved by the Food and Drug Administration for use in 1999 as an effective agent for lowering blood sugar. A modest amount of clinical data indicates that lowering blood sugar can have a beneficial effect on the microvascular changes associated with diabetes mellitus. Lowering blood sugar became a surrogate end point in the judgment of the FDA for a presumed clinical benefit in diabetes.

Some information existed to suggest that although rosiglitazone did indeed lower blood sugar, it might have some adverse effects on coronary heart disease. In fact, in September 2006, the European Medicines Agency had placed a warning label on rosiglitazone about the risk of cardiac ischemic events. In the United States, the FDA was in the process of reevaluating its judgment on this issue when along came the recent meta-analysis published by Dr. Steven Nissen and Kathy Walski (N. Engl. J. Med. 2007;356:2457-71).

One had to be impressed with the speed at which the authors, editorial writers, and the New England Journal of Medicine achieved major national and international headline exposure from a meta-analysis based on the meager and disparate data created from widely variable event classification.

The fact that a trial aimed at elucidating the potential mortality/morbidity effects of the drug was already underway in Europe and Australia was particularly unfortunate. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial was about halfway through its 6-year follow-up when the uproar occurred. RECORD randomized 4,447 patients to rosiglitazone or placebo in addition to standard oral diabetic agents. Even though its design was flawed by its unblinded nature, it surely might have provided some information relative to the risks of rosiglitazone. With the release of its interim 3-year follow-up data (N. Engl. J. Med. 2007, 357[doi: 10.1056/NEJMoa073394

All of this played out in an atmosphere in which the FDA has been recently taking its hits. The direction the FDA was taking regarding rosiglitazone is not entirely clear. Records suggest that it was under consideration and that one FDA reviewer was chastised for proposing restriction of its use. The slow and possibly flawed response by the FDA can hardly be countenanced. More importantly, the practice of the FDA to accept surrogate data in cardiovascular disease evaluation is a continuing problem. The FDA's approval of a drug based solely on its ability to lower blood sugar, without consideration of major cardiovascular safety and efficacy, is unacceptable.

Whether all of this could have been achieved without all the brouhaha is not certain. It is clear that the authors of the New England Journal paper were in discussion with members of Congress long before its publication. Whether there were discussions with the FDA is not clear. It does suggest that there was an attempt to “get to” the FDA or at least influence its policies. The possible contamination of science by politics is disturbing. Politics needs to be confined to the editorial pages, not in the meat of a scientific manuscript and its publication.

The ultimate decision forced by Congress on GSK and Takeda, the maker of the similar drug pioglitazone, could well have been achieved if cooler heads had been in charge. In addition we might still hold our scientific journals in high regard.

The translation of clinical trial results to the bedside has always been a complex and often uncertain exercise. The specific patient who precisely fits the evidence-based data is usually the exception to the rule.

Randomized clinical trials by their nature are focused on specific disease states with the exclusion of other concurrent medical problems. They include populations that often have little resemblance to the patients that you and I see in the clinic or hospital free of any comorbidity. The entry restrictions are crafted to identify patients who are most likely to benefit from the drug or device under study and to ensure their safety during its progress. Although not exclusive to the younger patient, the trials tend to recruit younger patients with little comorbidity.

The demographic restrictions on the design and management of clinical trials make it even more difficult to apply their results to guidelines and quality standards. Unfortunately, we have few data which reflect on either the safety or efficacy when “proven” therapy is applied to the general and particularly the Medicare patient.

The Medicare population is considerably older than patients entered into randomized clinical trials, with a greater mortality and morbidity burden of comorbid disease. However, they now represent the majority of patients admitted to the hospital with acute myocardial infarction. A recent publication using data collected over 9 years from 1992–1993 to 2000–2001 from the Medicare database sheds light on important trends that occurred in that population from that period (Circulation 2006;114:2806–14).

During that time, the Medicare MI patients increased in age from 75.7 years to 78.3 years and a quarter of those patients were over 85. The incidence of ST-segment elevation MI decreased from 37.4% to 23.5%. Because of the increased incidence of concomitant morbidity such as diabetes, chronic renal disease, and pulmonary disease, only about a third of patients surviving their MIs were “ideal patients” to whom guidelines or quality standards could be applied. During the study period the days in the hospital decreased from 10.1 days to 6.9 days. Although mortality adjusted for comorbidity had decreased during that period, the 1-year crude mortality increased from 27.6% to 31.0%.

It is clear from these observations that much of the clinical trial research that influences “evidence-based” medicine does not fully describe the reality of the world we function in. The science of clinical trials, highly refined in the last 50 years, has provided an immense amount of information about medical therapeutics. Yet it provides only a snapshot in time in a clinical environment that is changing rapidly around us. This is particularly true when studying degenerative diseases such as cardiovascular disease, which is influenced by a rapidly aging population. This study emphasizes the striking difficulty associated with the application of MI guidelines and standards to the Medicare population that has to a large degree been essentially excluded from contemporary clinical research studies. It is clear that a more dynamic access to the Medicare database could provide important insight into the risks and benefits of cardiac therapy. The sooner we have that information, the sooner we can be more effective at applying appropriate therapy to the real world and our aging patients.

The translation of clinical trial results to the bedside has always been a complex and often uncertain exercise. The specific patient who precisely fits the evidence-based data is usually the exception to the rule.

Randomized clinical trials by their nature are focused on specific disease states with the exclusion of other concurrent medical problems. They include populations that often have little resemblance to the patients that you and I see in the clinic or hospital free of any comorbidity. The entry restrictions are crafted to identify patients who are most likely to benefit from the drug or device under study and to ensure their safety during its progress. Although not exclusive to the younger patient, the trials tend to recruit younger patients with little comorbidity.

The demographic restrictions on the design and management of clinical trials make it even more difficult to apply their results to guidelines and quality standards. Unfortunately, we have few data which reflect on either the safety or efficacy when “proven” therapy is applied to the general and particularly the Medicare patient.

The Medicare population is considerably older than patients entered into randomized clinical trials, with a greater mortality and morbidity burden of comorbid disease. However, they now represent the majority of patients admitted to the hospital with acute myocardial infarction. A recent publication using data collected over 9 years from 1992–1993 to 2000–2001 from the Medicare database sheds light on important trends that occurred in that population from that period (Circulation 2006;114:2806–14).

During that time, the Medicare MI patients increased in age from 75.7 years to 78.3 years and a quarter of those patients were over 85. The incidence of ST-segment elevation MI decreased from 37.4% to 23.5%. Because of the increased incidence of concomitant morbidity such as diabetes, chronic renal disease, and pulmonary disease, only about a third of patients surviving their MIs were “ideal patients” to whom guidelines or quality standards could be applied. During the study period the days in the hospital decreased from 10.1 days to 6.9 days. Although mortality adjusted for comorbidity had decreased during that period, the 1-year crude mortality increased from 27.6% to 31.0%.

It is clear from these observations that much of the clinical trial research that influences “evidence-based” medicine does not fully describe the reality of the world we function in. The science of clinical trials, highly refined in the last 50 years, has provided an immense amount of information about medical therapeutics. Yet it provides only a snapshot in time in a clinical environment that is changing rapidly around us. This is particularly true when studying degenerative diseases such as cardiovascular disease, which is influenced by a rapidly aging population. This study emphasizes the striking difficulty associated with the application of MI guidelines and standards to the Medicare population that has to a large degree been essentially excluded from contemporary clinical research studies. It is clear that a more dynamic access to the Medicare database could provide important insight into the risks and benefits of cardiac therapy. The sooner we have that information, the sooner we can be more effective at applying appropriate therapy to the real world and our aging patients.

The translation of clinical trial results to the bedside has always been a complex and often uncertain exercise. The specific patient who precisely fits the evidence-based data is usually the exception to the rule.

Randomized clinical trials by their nature are focused on specific disease states with the exclusion of other concurrent medical problems. They include populations that often have little resemblance to the patients that you and I see in the clinic or hospital free of any comorbidity. The entry restrictions are crafted to identify patients who are most likely to benefit from the drug or device under study and to ensure their safety during its progress. Although not exclusive to the younger patient, the trials tend to recruit younger patients with little comorbidity.

The demographic restrictions on the design and management of clinical trials make it even more difficult to apply their results to guidelines and quality standards. Unfortunately, we have few data which reflect on either the safety or efficacy when “proven” therapy is applied to the general and particularly the Medicare patient.

The Medicare population is considerably older than patients entered into randomized clinical trials, with a greater mortality and morbidity burden of comorbid disease. However, they now represent the majority of patients admitted to the hospital with acute myocardial infarction. A recent publication using data collected over 9 years from 1992–1993 to 2000–2001 from the Medicare database sheds light on important trends that occurred in that population from that period (Circulation 2006;114:2806–14).

During that time, the Medicare MI patients increased in age from 75.7 years to 78.3 years and a quarter of those patients were over 85. The incidence of ST-segment elevation MI decreased from 37.4% to 23.5%. Because of the increased incidence of concomitant morbidity such as diabetes, chronic renal disease, and pulmonary disease, only about a third of patients surviving their MIs were “ideal patients” to whom guidelines or quality standards could be applied. During the study period the days in the hospital decreased from 10.1 days to 6.9 days. Although mortality adjusted for comorbidity had decreased during that period, the 1-year crude mortality increased from 27.6% to 31.0%.

It is clear from these observations that much of the clinical trial research that influences “evidence-based” medicine does not fully describe the reality of the world we function in. The science of clinical trials, highly refined in the last 50 years, has provided an immense amount of information about medical therapeutics. Yet it provides only a snapshot in time in a clinical environment that is changing rapidly around us. This is particularly true when studying degenerative diseases such as cardiovascular disease, which is influenced by a rapidly aging population. This study emphasizes the striking difficulty associated with the application of MI guidelines and standards to the Medicare population that has to a large degree been essentially excluded from contemporary clinical research studies. It is clear that a more dynamic access to the Medicare database could provide important insight into the risks and benefits of cardiac therapy. The sooner we have that information, the sooner we can be more effective at applying appropriate therapy to the real world and our aging patients.

Mr. Salvatore Armani is on my schedule today. I saw him about 4 weeks ago when he was referred because he was experiencing chest pressure climbing up a flight of stairs.

I had seen him almost 3 years ago when he was 65 and was referred to me for the treatment of his hypertension. In the interval, he had been followed by his internist until the development of his recent symptoms. His blood pressure was fairly well controlled on thiazide diuretics and a calcium entry blocker. His internist had started him on statin therapy.

Although it was clear that his symptoms represented angina, I ordered an exercise echocardiogram to define the ischemic region of his ventricle and to get a feeling about the severity of his symptoms. Last week, his stress echocardiogram came back indicating that he had significant ECG and echocardiographic evidence of ischemia in the posterolateral region of the ventricle occurring in the second phase of his stress test when his heart rate reached 120 and his blood pressure was 170/80. He had experienced some chest pressure at that time.

Before the report of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial (CARDIOLOGY NEWS, April 2007, p. 1) I would have automatically referred him to my interventional colleagues for angiography and almost certain angioplasty. Today, I paused and reflected on the message of the trial.

It was information that was not new to me. I knew for some time that angioplasty and, for that matter, coronary artery bypass graft, had little or no impact on mortality or morbidity of coronary artery disease. The Coronary Artery Surgery Study (Circulation 1983;68:939–50) more than 20 years ago had clearly shown that, with the exception of those patients with left ventricular dysfunction, there was no mortality benefit achieved by bypass surgery. Even in those patients with left ventricular dysfunction, the benefits were uncertain.

More recently, a meta-analysis of percutaneous coronary intervention over the past 10 years (Circulation 2005;111:2906–12) showed that there was no mortality benefit, but a marginal benefit in angina could be achieved with angioplasty in an era devoid of statin therapy and when ?-blockade was less than optimal. This was information that was easily accessible to anyone reading the cardiology literature, and it was reinforced by American College of Cardiology/American Heart Association guidelines.

On numerous occasions, I had sat down with patients in an attempt to outline these facts, but my lecture routinely fell on deaf ears and my reluctance to arrange an angiogram was perceived by my patients. They thanked me for my advice and went “up the street” to get their angioplasty. I had even given the same lecture to my close friends. They figured that I had not kept up with what was going on in cardiology and drove off to have there angioplasties performed by more “forward looking” cardiologists. Frankly, I had been beaten down and I found it easier to go along with the crowd.

The results of COURAGE may bring in a new era in our understanding of the benefits and risks of percutaneous coronary intervention and how we should apply it in the treatment of coronary artery disease. Today, I have not only medical science behind me, but the Wall Street Journal, the New York Times, and even the Detroit Free Press. All of these papers and many more prided themselves in hyping up the miracles that could be achieved by stents and extolling the wonders performed by the cardiologists “up the street.” Now they were suddenly on my side. They printed in bold headlines that pills were as good as a stent.

I guess I'll try it out again on Sal.

Mr. Salvatore Armani is on my schedule today. I saw him about 4 weeks ago when he was referred because he was experiencing chest pressure climbing up a flight of stairs.

I had seen him almost 3 years ago when he was 65 and was referred to me for the treatment of his hypertension. In the interval, he had been followed by his internist until the development of his recent symptoms. His blood pressure was fairly well controlled on thiazide diuretics and a calcium entry blocker. His internist had started him on statin therapy.

Although it was clear that his symptoms represented angina, I ordered an exercise echocardiogram to define the ischemic region of his ventricle and to get a feeling about the severity of his symptoms. Last week, his stress echocardiogram came back indicating that he had significant ECG and echocardiographic evidence of ischemia in the posterolateral region of the ventricle occurring in the second phase of his stress test when his heart rate reached 120 and his blood pressure was 170/80. He had experienced some chest pressure at that time.

Before the report of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial (CARDIOLOGY NEWS, April 2007, p. 1) I would have automatically referred him to my interventional colleagues for angiography and almost certain angioplasty. Today, I paused and reflected on the message of the trial.

It was information that was not new to me. I knew for some time that angioplasty and, for that matter, coronary artery bypass graft, had little or no impact on mortality or morbidity of coronary artery disease. The Coronary Artery Surgery Study (Circulation 1983;68:939–50) more than 20 years ago had clearly shown that, with the exception of those patients with left ventricular dysfunction, there was no mortality benefit achieved by bypass surgery. Even in those patients with left ventricular dysfunction, the benefits were uncertain.

More recently, a meta-analysis of percutaneous coronary intervention over the past 10 years (Circulation 2005;111:2906–12) showed that there was no mortality benefit, but a marginal benefit in angina could be achieved with angioplasty in an era devoid of statin therapy and when ?-blockade was less than optimal. This was information that was easily accessible to anyone reading the cardiology literature, and it was reinforced by American College of Cardiology/American Heart Association guidelines.

On numerous occasions, I had sat down with patients in an attempt to outline these facts, but my lecture routinely fell on deaf ears and my reluctance to arrange an angiogram was perceived by my patients. They thanked me for my advice and went “up the street” to get their angioplasty. I had even given the same lecture to my close friends. They figured that I had not kept up with what was going on in cardiology and drove off to have there angioplasties performed by more “forward looking” cardiologists. Frankly, I had been beaten down and I found it easier to go along with the crowd.

The results of COURAGE may bring in a new era in our understanding of the benefits and risks of percutaneous coronary intervention and how we should apply it in the treatment of coronary artery disease. Today, I have not only medical science behind me, but the Wall Street Journal, the New York Times, and even the Detroit Free Press. All of these papers and many more prided themselves in hyping up the miracles that could be achieved by stents and extolling the wonders performed by the cardiologists “up the street.” Now they were suddenly on my side. They printed in bold headlines that pills were as good as a stent.

I guess I'll try it out again on Sal.

Mr. Salvatore Armani is on my schedule today. I saw him about 4 weeks ago when he was referred because he was experiencing chest pressure climbing up a flight of stairs.

I had seen him almost 3 years ago when he was 65 and was referred to me for the treatment of his hypertension. In the interval, he had been followed by his internist until the development of his recent symptoms. His blood pressure was fairly well controlled on thiazide diuretics and a calcium entry blocker. His internist had started him on statin therapy.

Although it was clear that his symptoms represented angina, I ordered an exercise echocardiogram to define the ischemic region of his ventricle and to get a feeling about the severity of his symptoms. Last week, his stress echocardiogram came back indicating that he had significant ECG and echocardiographic evidence of ischemia in the posterolateral region of the ventricle occurring in the second phase of his stress test when his heart rate reached 120 and his blood pressure was 170/80. He had experienced some chest pressure at that time.

Before the report of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial (CARDIOLOGY NEWS, April 2007, p. 1) I would have automatically referred him to my interventional colleagues for angiography and almost certain angioplasty. Today, I paused and reflected on the message of the trial.

It was information that was not new to me. I knew for some time that angioplasty and, for that matter, coronary artery bypass graft, had little or no impact on mortality or morbidity of coronary artery disease. The Coronary Artery Surgery Study (Circulation 1983;68:939–50) more than 20 years ago had clearly shown that, with the exception of those patients with left ventricular dysfunction, there was no mortality benefit achieved by bypass surgery. Even in those patients with left ventricular dysfunction, the benefits were uncertain.

More recently, a meta-analysis of percutaneous coronary intervention over the past 10 years (Circulation 2005;111:2906–12) showed that there was no mortality benefit, but a marginal benefit in angina could be achieved with angioplasty in an era devoid of statin therapy and when ?-blockade was less than optimal. This was information that was easily accessible to anyone reading the cardiology literature, and it was reinforced by American College of Cardiology/American Heart Association guidelines.

On numerous occasions, I had sat down with patients in an attempt to outline these facts, but my lecture routinely fell on deaf ears and my reluctance to arrange an angiogram was perceived by my patients. They thanked me for my advice and went “up the street” to get their angioplasty. I had even given the same lecture to my close friends. They figured that I had not kept up with what was going on in cardiology and drove off to have there angioplasties performed by more “forward looking” cardiologists. Frankly, I had been beaten down and I found it easier to go along with the crowd.

The results of COURAGE may bring in a new era in our understanding of the benefits and risks of percutaneous coronary intervention and how we should apply it in the treatment of coronary artery disease. Today, I have not only medical science behind me, but the Wall Street Journal, the New York Times, and even the Detroit Free Press. All of these papers and many more prided themselves in hyping up the miracles that could be achieved by stents and extolling the wonders performed by the cardiologists “up the street.” Now they were suddenly on my side. They printed in bold headlines that pills were as good as a stent.

I guess I'll try it out again on Sal.

Achieving selection at a national or international program for the late-breaking clinical trials session is the “brass ring” for both the clinical trialist and sponsor, whether they are the pharmaceutical industry or the National Institutes of Health. A double brass ring is achieved if you can get simultaneous publication of your results in JAMA or, even better, in the New England Journal of Medicine.

This year at the American College of Cardiology meeting there were three separate late-breaking clinical trial (LBCT) sessions with 13 presentations and three sessions devoted to “smaller” LBCTs with 18 presentations. The mini-LBCT is a new addition to the program, as if the 13 LBCTs were not enough. In addition, the Innovations in Intervention Summit (I2) held five LBCT sessions with a total of 24 presentations. This seems to be a high water mark and may be a manifestation of either the plethora of clinical trials coming to fruition at this time or a lowering of scientific standards.

These are high-visibility sessions presented in auditoriums with audiences of up to 5,000, made up of doctors, nurses, a smattering of members of the press and, most importantly, representatives of the investment community. Measured against the more than 30 simultaneous sessions held at the mammoth Morial Convention Center in New Orleans with audiences averaging 100 or less, the magnetism of the LBCTs is obvious. At least 20% of the attendees at the annual meeting are breathlessly awaiting the next LBCT presentation.

The selection process for the program and its presentation, and, if you are lucky, a simultaneous publication, is tied up in a litany of embargo agreements meant to prevent any release of information prior to that magic moment of presentation. The precise penalty for breaking the embargo and the prerelease of data is not spelled out. Unlike other scientific presentations, no abstracts are printed in the program, so the audience is in the dark about both the design and the outcome of the trial. The reason for all this secrecy is not entirely clear, but more than likely it can be ascribed to marketing on the part of both the College and the journals.

Why good science should be cloaked in such mystery is not obvious. This year, the veil of secrecy was lifted from two presentations—on ranolazine and the investigational antioxidant succinobucol—that were preceded by reports by the drug makers of their failure to achieve the primary end points because of a potential impact on the stock price of the drug. Of course, not all of the trials present have positive outcomes. In fact, a positive outcome is somewhat of a rarity even though the science may be very important.

All of this hocus-pocus has absolutely nothing to do with science or with the dissemination of information other than restricting it. If anything, it suppresses and delays the process. It does result in inflating the impact of the LBCTs, no matter what their scientific and clinical importance, and it diminishes the value of the science of other presentations.

One way to deflate the hype is to publish in advance the abstracts of the LBCT, either in the program or as a supplement handed out at registration. This would provide the audience with some background to evaluate and understand the importance of the data when the magic moment of presentation occurs. Of course, the best way to deal with it is to remove all the restrictions associated with the presentation and publication of LBCTs, but, as one cardiology wonk put it, “It's all theater.”

Achieving selection at a national or international program for the late-breaking clinical trials session is the “brass ring” for both the clinical trialist and sponsor, whether they are the pharmaceutical industry or the National Institutes of Health. A double brass ring is achieved if you can get simultaneous publication of your results in JAMA or, even better, in the New England Journal of Medicine.

This year at the American College of Cardiology meeting there were three separate late-breaking clinical trial (LBCT) sessions with 13 presentations and three sessions devoted to “smaller” LBCTs with 18 presentations. The mini-LBCT is a new addition to the program, as if the 13 LBCTs were not enough. In addition, the Innovations in Intervention Summit (I2) held five LBCT sessions with a total of 24 presentations. This seems to be a high water mark and may be a manifestation of either the plethora of clinical trials coming to fruition at this time or a lowering of scientific standards.

These are high-visibility sessions presented in auditoriums with audiences of up to 5,000, made up of doctors, nurses, a smattering of members of the press and, most importantly, representatives of the investment community. Measured against the more than 30 simultaneous sessions held at the mammoth Morial Convention Center in New Orleans with audiences averaging 100 or less, the magnetism of the LBCTs is obvious. At least 20% of the attendees at the annual meeting are breathlessly awaiting the next LBCT presentation.

The selection process for the program and its presentation, and, if you are lucky, a simultaneous publication, is tied up in a litany of embargo agreements meant to prevent any release of information prior to that magic moment of presentation. The precise penalty for breaking the embargo and the prerelease of data is not spelled out. Unlike other scientific presentations, no abstracts are printed in the program, so the audience is in the dark about both the design and the outcome of the trial. The reason for all this secrecy is not entirely clear, but more than likely it can be ascribed to marketing on the part of both the College and the journals.

Why good science should be cloaked in such mystery is not obvious. This year, the veil of secrecy was lifted from two presentations—on ranolazine and the investigational antioxidant succinobucol—that were preceded by reports by the drug makers of their failure to achieve the primary end points because of a potential impact on the stock price of the drug. Of course, not all of the trials present have positive outcomes. In fact, a positive outcome is somewhat of a rarity even though the science may be very important.

All of this hocus-pocus has absolutely nothing to do with science or with the dissemination of information other than restricting it. If anything, it suppresses and delays the process. It does result in inflating the impact of the LBCTs, no matter what their scientific and clinical importance, and it diminishes the value of the science of other presentations.

One way to deflate the hype is to publish in advance the abstracts of the LBCT, either in the program or as a supplement handed out at registration. This would provide the audience with some background to evaluate and understand the importance of the data when the magic moment of presentation occurs. Of course, the best way to deal with it is to remove all the restrictions associated with the presentation and publication of LBCTs, but, as one cardiology wonk put it, “It's all theater.”

Achieving selection at a national or international program for the late-breaking clinical trials session is the “brass ring” for both the clinical trialist and sponsor, whether they are the pharmaceutical industry or the National Institutes of Health. A double brass ring is achieved if you can get simultaneous publication of your results in JAMA or, even better, in the New England Journal of Medicine.

This year at the American College of Cardiology meeting there were three separate late-breaking clinical trial (LBCT) sessions with 13 presentations and three sessions devoted to “smaller” LBCTs with 18 presentations. The mini-LBCT is a new addition to the program, as if the 13 LBCTs were not enough. In addition, the Innovations in Intervention Summit (I2) held five LBCT sessions with a total of 24 presentations. This seems to be a high water mark and may be a manifestation of either the plethora of clinical trials coming to fruition at this time or a lowering of scientific standards.

These are high-visibility sessions presented in auditoriums with audiences of up to 5,000, made up of doctors, nurses, a smattering of members of the press and, most importantly, representatives of the investment community. Measured against the more than 30 simultaneous sessions held at the mammoth Morial Convention Center in New Orleans with audiences averaging 100 or less, the magnetism of the LBCTs is obvious. At least 20% of the attendees at the annual meeting are breathlessly awaiting the next LBCT presentation.

The selection process for the program and its presentation, and, if you are lucky, a simultaneous publication, is tied up in a litany of embargo agreements meant to prevent any release of information prior to that magic moment of presentation. The precise penalty for breaking the embargo and the prerelease of data is not spelled out. Unlike other scientific presentations, no abstracts are printed in the program, so the audience is in the dark about both the design and the outcome of the trial. The reason for all this secrecy is not entirely clear, but more than likely it can be ascribed to marketing on the part of both the College and the journals.

Why good science should be cloaked in such mystery is not obvious. This year, the veil of secrecy was lifted from two presentations—on ranolazine and the investigational antioxidant succinobucol—that were preceded by reports by the drug makers of their failure to achieve the primary end points because of a potential impact on the stock price of the drug. Of course, not all of the trials present have positive outcomes. In fact, a positive outcome is somewhat of a rarity even though the science may be very important.

All of this hocus-pocus has absolutely nothing to do with science or with the dissemination of information other than restricting it. If anything, it suppresses and delays the process. It does result in inflating the impact of the LBCTs, no matter what their scientific and clinical importance, and it diminishes the value of the science of other presentations.

One way to deflate the hype is to publish in advance the abstracts of the LBCT, either in the program or as a supplement handed out at registration. This would provide the audience with some background to evaluate and understand the importance of the data when the magic moment of presentation occurs. Of course, the best way to deal with it is to remove all the restrictions associated with the presentation and publication of LBCTs, but, as one cardiology wonk put it, “It's all theater.”

The schism that has opened between the Society for Cardiovascular Angiography and Interventions and the guideline committee of the American Heart Association and American College of Cardiology in regard to stand-alone percutaneous coronary intervention is reminiscent of the advice given to teenagers about alcohol. It is clear that they shouldn't drink, but if they do, we should tell them how to do it safely. On the other hand, some would suggest that they should just say “No.”

The SCAI indicates that it is not “promoting” elective PCI without on-site surgical support. It is just providing “how-to” guidelines in case you are thinking about setting up a system to perform elective PCI in that setting. After all, PCI can be addicting. The fact that stand-alone PCI is being carried out in many communities in North America, not to mention most of the rest of the world, makes little difference to the AHA and ACC guideline committees. They are sticking to their previous statements that were supported by the SCAI, and just saying “No.”

Where is all of this coming from? It is hard to believe that with almost a million elective PCIs performed in the United States, there are patients going untreated because of a shortage of facilities or trained cardiologists. One could make a case that patients in remote areas of this country are not being well served if they need a PCI for the treatment of an acute MI, but thrombolysis is still a reasonable alternative with proven benefits.

There is a sense that although there is a concern about the patients in remote settings, much of the pressure for these changes is coming from urban areas. Many hospitals that are performing emergency primary PCI for acute MI in urban areas without on-site surgical backup use interventionalists who have elective PCI experience in other surgically supported laboratories. Expansion of elective PCI to these hospitals will not expand the availability of PCI to new populations, but will decrease the number of procedures performed at the established laboratories. If quality can be measured by quantity, these efforts will certainly not improve it. In addition, many of these established laboratories require a large volume of patients to train interventionalists.

Although it is quite possible that surgically supported interventional laboratories are in short supply in some places, such is not the case in the United States. In fact, there is an expansion of cardiosurgical programs, in part to support access to elective PCI. This is, of course, occurring largely as hospital marketing ventures in the paradoxical setting of a nationwide decrease in volume of coronary artery bypass surgeries. Cardiac surgery remains a profit center and often adds to the eminence of community hospitals.

It is clear that the SCAI statement represents a push to wider acceptance of stand-alone PCI throughout the country. The fact that complications and need for surgical intervention are rare in the centers now performing PCI has been used as an argument for its broader availability. Whether the same safety profile can be achieved when performed at smaller institutions with lower volumes remains to be seen.

The experience of transferring therapeutic interventions to the real world has not always been successful. In weighing the benefits of the expansion of PCI to this wider community, it may be that the appropriate response is just to say “No.”

The schism that has opened between the Society for Cardiovascular Angiography and Interventions and the guideline committee of the American Heart Association and American College of Cardiology in regard to stand-alone percutaneous coronary intervention is reminiscent of the advice given to teenagers about alcohol. It is clear that they shouldn't drink, but if they do, we should tell them how to do it safely. On the other hand, some would suggest that they should just say “No.”

The SCAI indicates that it is not “promoting” elective PCI without on-site surgical support. It is just providing “how-to” guidelines in case you are thinking about setting up a system to perform elective PCI in that setting. After all, PCI can be addicting. The fact that stand-alone PCI is being carried out in many communities in North America, not to mention most of the rest of the world, makes little difference to the AHA and ACC guideline committees. They are sticking to their previous statements that were supported by the SCAI, and just saying “No.”

Where is all of this coming from? It is hard to believe that with almost a million elective PCIs performed in the United States, there are patients going untreated because of a shortage of facilities or trained cardiologists. One could make a case that patients in remote areas of this country are not being well served if they need a PCI for the treatment of an acute MI, but thrombolysis is still a reasonable alternative with proven benefits.

There is a sense that although there is a concern about the patients in remote settings, much of the pressure for these changes is coming from urban areas. Many hospitals that are performing emergency primary PCI for acute MI in urban areas without on-site surgical backup use interventionalists who have elective PCI experience in other surgically supported laboratories. Expansion of elective PCI to these hospitals will not expand the availability of PCI to new populations, but will decrease the number of procedures performed at the established laboratories. If quality can be measured by quantity, these efforts will certainly not improve it. In addition, many of these established laboratories require a large volume of patients to train interventionalists.

Although it is quite possible that surgically supported interventional laboratories are in short supply in some places, such is not the case in the United States. In fact, there is an expansion of cardiosurgical programs, in part to support access to elective PCI. This is, of course, occurring largely as hospital marketing ventures in the paradoxical setting of a nationwide decrease in volume of coronary artery bypass surgeries. Cardiac surgery remains a profit center and often adds to the eminence of community hospitals.

It is clear that the SCAI statement represents a push to wider acceptance of stand-alone PCI throughout the country. The fact that complications and need for surgical intervention are rare in the centers now performing PCI has been used as an argument for its broader availability. Whether the same safety profile can be achieved when performed at smaller institutions with lower volumes remains to be seen.

The experience of transferring therapeutic interventions to the real world has not always been successful. In weighing the benefits of the expansion of PCI to this wider community, it may be that the appropriate response is just to say “No.”

The schism that has opened between the Society for Cardiovascular Angiography and Interventions and the guideline committee of the American Heart Association and American College of Cardiology in regard to stand-alone percutaneous coronary intervention is reminiscent of the advice given to teenagers about alcohol. It is clear that they shouldn't drink, but if they do, we should tell them how to do it safely. On the other hand, some would suggest that they should just say “No.”

The SCAI indicates that it is not “promoting” elective PCI without on-site surgical support. It is just providing “how-to” guidelines in case you are thinking about setting up a system to perform elective PCI in that setting. After all, PCI can be addicting. The fact that stand-alone PCI is being carried out in many communities in North America, not to mention most of the rest of the world, makes little difference to the AHA and ACC guideline committees. They are sticking to their previous statements that were supported by the SCAI, and just saying “No.”

Where is all of this coming from? It is hard to believe that with almost a million elective PCIs performed in the United States, there are patients going untreated because of a shortage of facilities or trained cardiologists. One could make a case that patients in remote areas of this country are not being well served if they need a PCI for the treatment of an acute MI, but thrombolysis is still a reasonable alternative with proven benefits.

There is a sense that although there is a concern about the patients in remote settings, much of the pressure for these changes is coming from urban areas. Many hospitals that are performing emergency primary PCI for acute MI in urban areas without on-site surgical backup use interventionalists who have elective PCI experience in other surgically supported laboratories. Expansion of elective PCI to these hospitals will not expand the availability of PCI to new populations, but will decrease the number of procedures performed at the established laboratories. If quality can be measured by quantity, these efforts will certainly not improve it. In addition, many of these established laboratories require a large volume of patients to train interventionalists.

Although it is quite possible that surgically supported interventional laboratories are in short supply in some places, such is not the case in the United States. In fact, there is an expansion of cardiosurgical programs, in part to support access to elective PCI. This is, of course, occurring largely as hospital marketing ventures in the paradoxical setting of a nationwide decrease in volume of coronary artery bypass surgeries. Cardiac surgery remains a profit center and often adds to the eminence of community hospitals.

It is clear that the SCAI statement represents a push to wider acceptance of stand-alone PCI throughout the country. The fact that complications and need for surgical intervention are rare in the centers now performing PCI has been used as an argument for its broader availability. Whether the same safety profile can be achieved when performed at smaller institutions with lower volumes remains to be seen.

The experience of transferring therapeutic interventions to the real world has not always been successful. In weighing the benefits of the expansion of PCI to this wider community, it may be that the appropriate response is just to say “No.”

The American College of Cardiology and the American College of Physicians have signed on to “pay for performance” whether we like it or not.

To prevent the scheduled 5% cut in physicians' fees under Medicare, our representatives agreed to a program that will pay physicians who volunteer to participate, an opportunity to win quality points to receive an additional 1.5% annually.

It is worth noting that the ACC and the ACP were 2 of only 4 out of 21 medical groups that supported the legislation. Notably, the American Medical Association chose to decline, having resisted this deal in part because of its reluctance to accept the concept of pay for performance.

Pay for performance will reward those physicians who adhere to quality standards, whatever they may be, and penalize those who do not. Most observers feel that this has nothing to do with quality and everything to do with the cost of care. Many are skeptical that it will achieve either objective.

The idea that doctors must be financially rewarded to provide quality medical care should be abhorrent to any practitioner. It suggests that doctors know what is best for the patient but will not provide that care unless they get a few more dollars in their pockets.

The Centers for Medicare and Medicaid Services and the Institute of Medicine have been the main enthusiasts for pay for performance. If they were serious about the quality of medical care, they might at least provide casual support for postgraduate education. Instead, postgraduate education remains the province of the pharmaceutical and device industries, which pay for at least 60% of these programs.

Long gone is the federal and academic support of postgraduate education. Instead, industry gets to set the educational agenda.

That agenda speaks to the increased use of new and expensive drugs and devices, which has a profound effect on increasing health care costs with marginal benefit to quality of care in a public health context.

Quality improvement has been the hallmark of the programs developed by the cardiology community and the ACC. In fact, improvements in the treatment and prevention of heart disease have comprised the major quality achievements of the past decade. They have been driven not by money, but by peer pressure and education. The quality standards that have been developed have gone a long way in decreasing hospital mortality.

The New York State coronary bypass surgery report-card system, instituted in 1989, has been the poster child of quality programs. The measurement and publication of mortality rates led to the establishment of benchmarks for performance and a significant decrease in bypass surgical mortality.

The establishment of quality standards for the treatment of myocardial infarction and heart failure has resulted in the incorporation of optimal standard therapy for discharge medication. At the same time, the establishment of optimal door-to-balloon time to angioplasty for ST-elevation myocardial infarctions remains under study but has already led to methodologies to achieve optimal time and improve infarct survival.

All of these initiatives have been led by the cardiology community and the ACC and were achieved by the profession without the onerous method of paying a doctor for better performance. The cardiology community has been at the forefront of quality initiatives, yet it was all scrapped when the ACC agreed to the Faustian deal of accepting pay for performance to prevent the 5% cut in physician pay. To do that, our representatives agreed to pay for quality rather than making it a professional duty.

So much for peer pressure and education to effect change. Now it's all in your paycheck.

The American College of Cardiology and the American College of Physicians have signed on to “pay for performance” whether we like it or not.

To prevent the scheduled 5% cut in physicians' fees under Medicare, our representatives agreed to a program that will pay physicians who volunteer to participate, an opportunity to win quality points to receive an additional 1.5% annually.

It is worth noting that the ACC and the ACP were 2 of only 4 out of 21 medical groups that supported the legislation. Notably, the American Medical Association chose to decline, having resisted this deal in part because of its reluctance to accept the concept of pay for performance.

Pay for performance will reward those physicians who adhere to quality standards, whatever they may be, and penalize those who do not. Most observers feel that this has nothing to do with quality and everything to do with the cost of care. Many are skeptical that it will achieve either objective.

The idea that doctors must be financially rewarded to provide quality medical care should be abhorrent to any practitioner. It suggests that doctors know what is best for the patient but will not provide that care unless they get a few more dollars in their pockets.

The Centers for Medicare and Medicaid Services and the Institute of Medicine have been the main enthusiasts for pay for performance. If they were serious about the quality of medical care, they might at least provide casual support for postgraduate education. Instead, postgraduate education remains the province of the pharmaceutical and device industries, which pay for at least 60% of these programs.

Long gone is the federal and academic support of postgraduate education. Instead, industry gets to set the educational agenda.

That agenda speaks to the increased use of new and expensive drugs and devices, which has a profound effect on increasing health care costs with marginal benefit to quality of care in a public health context.

Quality improvement has been the hallmark of the programs developed by the cardiology community and the ACC. In fact, improvements in the treatment and prevention of heart disease have comprised the major quality achievements of the past decade. They have been driven not by money, but by peer pressure and education. The quality standards that have been developed have gone a long way in decreasing hospital mortality.

The New York State coronary bypass surgery report-card system, instituted in 1989, has been the poster child of quality programs. The measurement and publication of mortality rates led to the establishment of benchmarks for performance and a significant decrease in bypass surgical mortality.

The establishment of quality standards for the treatment of myocardial infarction and heart failure has resulted in the incorporation of optimal standard therapy for discharge medication. At the same time, the establishment of optimal door-to-balloon time to angioplasty for ST-elevation myocardial infarctions remains under study but has already led to methodologies to achieve optimal time and improve infarct survival.

All of these initiatives have been led by the cardiology community and the ACC and were achieved by the profession without the onerous method of paying a doctor for better performance. The cardiology community has been at the forefront of quality initiatives, yet it was all scrapped when the ACC agreed to the Faustian deal of accepting pay for performance to prevent the 5% cut in physician pay. To do that, our representatives agreed to pay for quality rather than making it a professional duty.

So much for peer pressure and education to effect change. Now it's all in your paycheck.

The American College of Cardiology and the American College of Physicians have signed on to “pay for performance” whether we like it or not.

To prevent the scheduled 5% cut in physicians' fees under Medicare, our representatives agreed to a program that will pay physicians who volunteer to participate, an opportunity to win quality points to receive an additional 1.5% annually.

It is worth noting that the ACC and the ACP were 2 of only 4 out of 21 medical groups that supported the legislation. Notably, the American Medical Association chose to decline, having resisted this deal in part because of its reluctance to accept the concept of pay for performance.

Pay for performance will reward those physicians who adhere to quality standards, whatever they may be, and penalize those who do not. Most observers feel that this has nothing to do with quality and everything to do with the cost of care. Many are skeptical that it will achieve either objective.

The idea that doctors must be financially rewarded to provide quality medical care should be abhorrent to any practitioner. It suggests that doctors know what is best for the patient but will not provide that care unless they get a few more dollars in their pockets.

The Centers for Medicare and Medicaid Services and the Institute of Medicine have been the main enthusiasts for pay for performance. If they were serious about the quality of medical care, they might at least provide casual support for postgraduate education. Instead, postgraduate education remains the province of the pharmaceutical and device industries, which pay for at least 60% of these programs.

Long gone is the federal and academic support of postgraduate education. Instead, industry gets to set the educational agenda.

That agenda speaks to the increased use of new and expensive drugs and devices, which has a profound effect on increasing health care costs with marginal benefit to quality of care in a public health context.

Quality improvement has been the hallmark of the programs developed by the cardiology community and the ACC. In fact, improvements in the treatment and prevention of heart disease have comprised the major quality achievements of the past decade. They have been driven not by money, but by peer pressure and education. The quality standards that have been developed have gone a long way in decreasing hospital mortality.

The New York State coronary bypass surgery report-card system, instituted in 1989, has been the poster child of quality programs. The measurement and publication of mortality rates led to the establishment of benchmarks for performance and a significant decrease in bypass surgical mortality.

The establishment of quality standards for the treatment of myocardial infarction and heart failure has resulted in the incorporation of optimal standard therapy for discharge medication. At the same time, the establishment of optimal door-to-balloon time to angioplasty for ST-elevation myocardial infarctions remains under study but has already led to methodologies to achieve optimal time and improve infarct survival.

All of these initiatives have been led by the cardiology community and the ACC and were achieved by the profession without the onerous method of paying a doctor for better performance. The cardiology community has been at the forefront of quality initiatives, yet it was all scrapped when the ACC agreed to the Faustian deal of accepting pay for performance to prevent the 5% cut in physician pay. To do that, our representatives agreed to pay for quality rather than making it a professional duty.

So much for peer pressure and education to effect change. Now it's all in your paycheck.

Randomized clinical trials are built on the premise that if you know the answer you should not ask the question. With that framework, they are risky business.

The stock market has recently learned all about the downside of those risks. Nevertheless, the scientific community and industry have invested large amounts of time and energy in randomized clinical trials (RCTs) in an attempt to translate bench research to the patient's bedside. They also have required the patient's commitment to participate in these studies. RCTs have exposed the fallacies of many concepts but also have elucidated the benefits of a host of cardiovascular drugs. The success of clinical trials has resulted in the profound decrease in cardiovascular mortality that we have experienced in the last half-century.

It was not too long ago that RCTs provided the proof of the concept that lowering LDL cholesterol could result in improved survival in patients with coronary artery disease. As a result, statins have become established as one of the foundations of contemporary therapy for the treatment of atherosclerotic disease. Prior to statins, there was a variety of drugs that were studied in RCTs in an attempt to prevent coronary disease. The clinical success associated with the lowering of LDL was followed by the tantalizing potential of even greater benefit that might be attained by raising HDL. Supported with both epidemiologic and laboratory data, the pharmaceutical industry responded to the challenge by designing drugs that could specifically raise HDL.

Unfortunately, we still do not have data to support the concept that raising HDL is beneficial to humans. In the last few weeks we have learned, as a result of the ILLUMINATE trial, that our first, and probably not last, foray into the realm of raising HDL was associated with increased mortality in the patients receiving the active drug. We know little else about the trial to explain these findings, with the exception that the drug torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, results in increases not only in HDL but also in systemic blood pressure. Whether the blood pressure response observed in the recent Pfizer trial is inherent in all molecules of this class or unique to torcetrapib remains for further investigation. There also is a suspicion that CETP inhibitors actually may increase cholesterol deposition in the atherosclerotic plaque. Niacin and exercise have been known to increase HDL, but there is little information to suggest that this is beneficial. The results from ILLUMINATE may cause some reflection on the purported benefit of raising HDL.

Other drugs are under investigation in regard to their possible beneficial effects on the progression of plaque formation. Antisense drugs directed at modifying apolipoprotein B and 5-lipoxygenase-activating proteins directed at down-regulation of leukotrienes are in the preliminary phase of clinical studies. In addition, preliminary data suggest that the administration of recombinant apo-A₁ Milano may have a significant effect on decreasing plaque size using intravascular ultrasound imaging.

It is clear that the universality of atherosclerosis speaks to the need for further investigation. The experience with torcetrapib is just one phase in our search for better therapy. It does send a message to the investment community that the buyer should beware: Science is a tricky business.

Randomized clinical trials are built on the premise that if you know the answer you should not ask the question. With that framework, they are risky business.

The stock market has recently learned all about the downside of those risks. Nevertheless, the scientific community and industry have invested large amounts of time and energy in randomized clinical trials (RCTs) in an attempt to translate bench research to the patient's bedside. They also have required the patient's commitment to participate in these studies. RCTs have exposed the fallacies of many concepts but also have elucidated the benefits of a host of cardiovascular drugs. The success of clinical trials has resulted in the profound decrease in cardiovascular mortality that we have experienced in the last half-century.

It was not too long ago that RCTs provided the proof of the concept that lowering LDL cholesterol could result in improved survival in patients with coronary artery disease. As a result, statins have become established as one of the foundations of contemporary therapy for the treatment of atherosclerotic disease. Prior to statins, there was a variety of drugs that were studied in RCTs in an attempt to prevent coronary disease. The clinical success associated with the lowering of LDL was followed by the tantalizing potential of even greater benefit that might be attained by raising HDL. Supported with both epidemiologic and laboratory data, the pharmaceutical industry responded to the challenge by designing drugs that could specifically raise HDL.

Unfortunately, we still do not have data to support the concept that raising HDL is beneficial to humans. In the last few weeks we have learned, as a result of the ILLUMINATE trial, that our first, and probably not last, foray into the realm of raising HDL was associated with increased mortality in the patients receiving the active drug. We know little else about the trial to explain these findings, with the exception that the drug torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, results in increases not only in HDL but also in systemic blood pressure. Whether the blood pressure response observed in the recent Pfizer trial is inherent in all molecules of this class or unique to torcetrapib remains for further investigation. There also is a suspicion that CETP inhibitors actually may increase cholesterol deposition in the atherosclerotic plaque. Niacin and exercise have been known to increase HDL, but there is little information to suggest that this is beneficial. The results from ILLUMINATE may cause some reflection on the purported benefit of raising HDL.

Other drugs are under investigation in regard to their possible beneficial effects on the progression of plaque formation. Antisense drugs directed at modifying apolipoprotein B and 5-lipoxygenase-activating proteins directed at down-regulation of leukotrienes are in the preliminary phase of clinical studies. In addition, preliminary data suggest that the administration of recombinant apo-A₁ Milano may have a significant effect on decreasing plaque size using intravascular ultrasound imaging.

It is clear that the universality of atherosclerosis speaks to the need for further investigation. The experience with torcetrapib is just one phase in our search for better therapy. It does send a message to the investment community that the buyer should beware: Science is a tricky business.

Randomized clinical trials are built on the premise that if you know the answer you should not ask the question. With that framework, they are risky business.

The stock market has recently learned all about the downside of those risks. Nevertheless, the scientific community and industry have invested large amounts of time and energy in randomized clinical trials (RCTs) in an attempt to translate bench research to the patient's bedside. They also have required the patient's commitment to participate in these studies. RCTs have exposed the fallacies of many concepts but also have elucidated the benefits of a host of cardiovascular drugs. The success of clinical trials has resulted in the profound decrease in cardiovascular mortality that we have experienced in the last half-century.

It was not too long ago that RCTs provided the proof of the concept that lowering LDL cholesterol could result in improved survival in patients with coronary artery disease. As a result, statins have become established as one of the foundations of contemporary therapy for the treatment of atherosclerotic disease. Prior to statins, there was a variety of drugs that were studied in RCTs in an attempt to prevent coronary disease. The clinical success associated with the lowering of LDL was followed by the tantalizing potential of even greater benefit that might be attained by raising HDL. Supported with both epidemiologic and laboratory data, the pharmaceutical industry responded to the challenge by designing drugs that could specifically raise HDL.

Unfortunately, we still do not have data to support the concept that raising HDL is beneficial to humans. In the last few weeks we have learned, as a result of the ILLUMINATE trial, that our first, and probably not last, foray into the realm of raising HDL was associated with increased mortality in the patients receiving the active drug. We know little else about the trial to explain these findings, with the exception that the drug torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, results in increases not only in HDL but also in systemic blood pressure. Whether the blood pressure response observed in the recent Pfizer trial is inherent in all molecules of this class or unique to torcetrapib remains for further investigation. There also is a suspicion that CETP inhibitors actually may increase cholesterol deposition in the atherosclerotic plaque. Niacin and exercise have been known to increase HDL, but there is little information to suggest that this is beneficial. The results from ILLUMINATE may cause some reflection on the purported benefit of raising HDL.

Other drugs are under investigation in regard to their possible beneficial effects on the progression of plaque formation. Antisense drugs directed at modifying apolipoprotein B and 5-lipoxygenase-activating proteins directed at down-regulation of leukotrienes are in the preliminary phase of clinical studies. In addition, preliminary data suggest that the administration of recombinant apo-A₁ Milano may have a significant effect on decreasing plaque size using intravascular ultrasound imaging.

It is clear that the universality of atherosclerosis speaks to the need for further investigation. The experience with torcetrapib is just one phase in our search for better therapy. It does send a message to the investment community that the buyer should beware: Science is a tricky business.

After a few days in Chicago at the meeting of the American Heart Association one cannot help but be impressed by the dimension of research and the youth and vigor of the attendees. Hardly a gray hair was seen, and coming from a “gray head” like this, it was inspirational.

This year's president, Dr. Raymond J. Gibbons of the Mayo Clinic, Rochester, Minn., called attention to the fact that in spite of our success, there are many barriers to overcome in translating our success to patients worldwide. In this country, we face the fact that almost 46 million Americans have no health insurance and are essentially excluded from preventive cardiac care and the fruits of our research. Many of our patients, both urban and rural, might just as well be in Africa as to live around the corner from a major medical center like mine.

It became apparent during the meeting that our success has made it increasingly difficult to prove new, potentially beneficial treatments. A number of randomized clinical trials were presented, testing therapy in acute myocardial infarction where the reported annual placebo mortality was 4% over a 1-year period. Although mortality has gone down, the incidence of coronary artery disease has not.

The success of our combined reperfusion and remodeling therapy for acute myocardial infarction has reduced the event rates to levels that require huge populations or therapies with efficacy that exceeds anything that we have studied to date. The problem of recruiting large populations was reemphasized by Dr. Robert Califf, newly appointed head of the Duke Translational Medicine Institute in Durham, N.C., who noted that because of the poor participation of American cardiologists, most current randomized clinical trials are being carried out in Europe and Asia. Although the diseases of the heart are ubiquitous, therapeutic interventions tested in diverse social and clinical settings may not be applicable to Americans. We are, in fact, “outsourcing” our research.

The issues relating to drug eluting stents (DES) and bare metal stents were extensively discussed. It is clear that the decrease in in-stent restenosis attributed to DES has some significant disadvantages. But the failure of the DES to endothelialize appears to lead to inflammation and thrombus formation in and around the stent and confers in those patients a lifetime risk of in-stent thrombosis and dependency on a very expensive antiplatelet therapy. What emerged from these sessions was the imperative for new types of stents.

An additional cautionary note injected into the world of percutaneous coronary intervention was provided by the report of the Occluded Artery Trial, which shocked many angiographers. The investigators examined the benefit of PCI in persistent total occlusion from 3 to 28 days after an MI and were surprised to learn that there was no benefit associated with late PCI (see p. 1).

One additional study, the Alternans Before Cardioverter Defibrillator trial, may give some hope that we can begin to define patients who will gain the most benefit from implantable cardioverter defibrillators. Using microwave T-wave alternans and electrophysiologic studies in heart failure patients with ejection fractions of less than 40%, the investigators were able to identify patients who are at low risk and may not need an ICD (see p. 8). These diagnostic techniques provide the possibility that we may be able to make better choices for ICD therapy.

As always, awards were given to distinguished scientists involved in cardiovascular research. None was more deserving than Dr. William Kannel, the creator and driving force of the Framingham Heart Study, who is professor of medicine and public health at Boston University School of Medicine. Initiated almost half a century ago, the massive study created the scientific foundation upon which we have built much of today's clinical science. It is hard to imagine where cardiovascular research would be without that center and his leadership. It was a long overdue award to a true pioneer to whom the cardiology community and the world owe a great debt. Congratulations, Bill!

After a few days in Chicago at the meeting of the American Heart Association one cannot help but be impressed by the dimension of research and the youth and vigor of the attendees. Hardly a gray hair was seen, and coming from a “gray head” like this, it was inspirational.

This year's president, Dr. Raymond J. Gibbons of the Mayo Clinic, Rochester, Minn., called attention to the fact that in spite of our success, there are many barriers to overcome in translating our success to patients worldwide. In this country, we face the fact that almost 46 million Americans have no health insurance and are essentially excluded from preventive cardiac care and the fruits of our research. Many of our patients, both urban and rural, might just as well be in Africa as to live around the corner from a major medical center like mine.

It became apparent during the meeting that our success has made it increasingly difficult to prove new, potentially beneficial treatments. A number of randomized clinical trials were presented, testing therapy in acute myocardial infarction where the reported annual placebo mortality was 4% over a 1-year period. Although mortality has gone down, the incidence of coronary artery disease has not.

The success of our combined reperfusion and remodeling therapy for acute myocardial infarction has reduced the event rates to levels that require huge populations or therapies with efficacy that exceeds anything that we have studied to date. The problem of recruiting large populations was reemphasized by Dr. Robert Califf, newly appointed head of the Duke Translational Medicine Institute in Durham, N.C., who noted that because of the poor participation of American cardiologists, most current randomized clinical trials are being carried out in Europe and Asia. Although the diseases of the heart are ubiquitous, therapeutic interventions tested in diverse social and clinical settings may not be applicable to Americans. We are, in fact, “outsourcing” our research.

The issues relating to drug eluting stents (DES) and bare metal stents were extensively discussed. It is clear that the decrease in in-stent restenosis attributed to DES has some significant disadvantages. But the failure of the DES to endothelialize appears to lead to inflammation and thrombus formation in and around the stent and confers in those patients a lifetime risk of in-stent thrombosis and dependency on a very expensive antiplatelet therapy. What emerged from these sessions was the imperative for new types of stents.

An additional cautionary note injected into the world of percutaneous coronary intervention was provided by the report of the Occluded Artery Trial, which shocked many angiographers. The investigators examined the benefit of PCI in persistent total occlusion from 3 to 28 days after an MI and were surprised to learn that there was no benefit associated with late PCI (see p. 1).

One additional study, the Alternans Before Cardioverter Defibrillator trial, may give some hope that we can begin to define patients who will gain the most benefit from implantable cardioverter defibrillators. Using microwave T-wave alternans and electrophysiologic studies in heart failure patients with ejection fractions of less than 40%, the investigators were able to identify patients who are at low risk and may not need an ICD (see p. 8). These diagnostic techniques provide the possibility that we may be able to make better choices for ICD therapy.

As always, awards were given to distinguished scientists involved in cardiovascular research. None was more deserving than Dr. William Kannel, the creator and driving force of the Framingham Heart Study, who is professor of medicine and public health at Boston University School of Medicine. Initiated almost half a century ago, the massive study created the scientific foundation upon which we have built much of today's clinical science. It is hard to imagine where cardiovascular research would be without that center and his leadership. It was a long overdue award to a true pioneer to whom the cardiology community and the world owe a great debt. Congratulations, Bill!

After a few days in Chicago at the meeting of the American Heart Association one cannot help but be impressed by the dimension of research and the youth and vigor of the attendees. Hardly a gray hair was seen, and coming from a “gray head” like this, it was inspirational.

This year's president, Dr. Raymond J. Gibbons of the Mayo Clinic, Rochester, Minn., called attention to the fact that in spite of our success, there are many barriers to overcome in translating our success to patients worldwide. In this country, we face the fact that almost 46 million Americans have no health insurance and are essentially excluded from preventive cardiac care and the fruits of our research. Many of our patients, both urban and rural, might just as well be in Africa as to live around the corner from a major medical center like mine.

It became apparent during the meeting that our success has made it increasingly difficult to prove new, potentially beneficial treatments. A number of randomized clinical trials were presented, testing therapy in acute myocardial infarction where the reported annual placebo mortality was 4% over a 1-year period. Although mortality has gone down, the incidence of coronary artery disease has not.

The success of our combined reperfusion and remodeling therapy for acute myocardial infarction has reduced the event rates to levels that require huge populations or therapies with efficacy that exceeds anything that we have studied to date. The problem of recruiting large populations was reemphasized by Dr. Robert Califf, newly appointed head of the Duke Translational Medicine Institute in Durham, N.C., who noted that because of the poor participation of American cardiologists, most current randomized clinical trials are being carried out in Europe and Asia. Although the diseases of the heart are ubiquitous, therapeutic interventions tested in diverse social and clinical settings may not be applicable to Americans. We are, in fact, “outsourcing” our research.

The issues relating to drug eluting stents (DES) and bare metal stents were extensively discussed. It is clear that the decrease in in-stent restenosis attributed to DES has some significant disadvantages. But the failure of the DES to endothelialize appears to lead to inflammation and thrombus formation in and around the stent and confers in those patients a lifetime risk of in-stent thrombosis and dependency on a very expensive antiplatelet therapy. What emerged from these sessions was the imperative for new types of stents.

An additional cautionary note injected into the world of percutaneous coronary intervention was provided by the report of the Occluded Artery Trial, which shocked many angiographers. The investigators examined the benefit of PCI in persistent total occlusion from 3 to 28 days after an MI and were surprised to learn that there was no benefit associated with late PCI (see p. 1).

One additional study, the Alternans Before Cardioverter Defibrillator trial, may give some hope that we can begin to define patients who will gain the most benefit from implantable cardioverter defibrillators. Using microwave T-wave alternans and electrophysiologic studies in heart failure patients with ejection fractions of less than 40%, the investigators were able to identify patients who are at low risk and may not need an ICD (see p. 8). These diagnostic techniques provide the possibility that we may be able to make better choices for ICD therapy.

As always, awards were given to distinguished scientists involved in cardiovascular research. None was more deserving than Dr. William Kannel, the creator and driving force of the Framingham Heart Study, who is professor of medicine and public health at Boston University School of Medicine. Initiated almost half a century ago, the massive study created the scientific foundation upon which we have built much of today's clinical science. It is hard to imagine where cardiovascular research would be without that center and his leadership. It was a long overdue award to a true pioneer to whom the cardiology community and the world owe a great debt. Congratulations, Bill!

As part of its new Recommendations From the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines, the society, in conjunction with the device manufacturers, is proposing that device recalls should now be called an “advisory notice” or “safety alert.” HRS suggests that this change is meant to lessen the anxiety of patients and doctors about the implication of a recall.

The American public, and I presume much of the rest of the world, is not exactly unaccustomed to recalls. We have at least one recall a month by auto manufacturers, some by the manufacturers of the reputedly solid Japanese makes. Thanks to the watchful eyes of a variety of federal agencies, we have recalls of everything from baby food to spinach, jet airplanes to baby car seats, and Christmas toys to microwave ovens. We also have had recalls of biologic and medical items including antiarrhythmic drugs, aortic valves, and the painkiller rofecoxib (Vioxx).

Most of these recalls are taken in stride, but the recall of an electronic device implanted in your body does have some unique implications, particularly when many of the devices are there to save your life and when their removal is associated with some risk and discomfort.

The HRS is having difficulty getting this nomenclature change to come about. According to an article in this month's CARDIOLOGY NEWS (see p. 4), the Food and Drug Administration is reluctant to remove “recall” from its lexicon since it is rooted in legislation that mandates its safety responsibilities. In an uncharacteristic Washington response, the FDA is not prepared to “spin” its terminology, even when it is part of the problem.

These proposed changes are taking place in an atmosphere where the number of defibrillator devices implanted is falling short of the expectations of the physicians and manufacturers. Based on the current guidelines of the American College of Cardiology, American Heart Association, and HRS, many more of the devices should have been implanted, suggesting that quality standards are being compromised.

The concern of the HRS is that the media attention given to recalls has made both patients and physicians reluctant to follow the guidelines. It also has called attention to the risks of removing recalled devices, raising questions about which devices should be removed when they are identified as recalled. At the same, time many well-meaning physicians who treat patients at risk of sudden death are concerned about the “one size fits all” approach to the implantation guidelines and are looking for better risk stratification of the benefit that can accrue to their patients. Surely, among the millions of patients included in those guidelines, we should be able to determine in which patient individual implantation is imperative.

As a result of the flawed reporting of device failure in the past, there has been an outcry from physicians for more transparency in the reporting of malfunction of these devices. Unfortunately, increased transparency is certain to raise the level of anxiety of all those involved—patients and physicians—in the implantation of the devices. It is unlikely that the changes in nomenclature will lessen the concerns and increase the understanding of the risks and benefits of implantable devices.

As part of its new Recommendations From the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines, the society, in conjunction with the device manufacturers, is proposing that device recalls should now be called an “advisory notice” or “safety alert.” HRS suggests that this change is meant to lessen the anxiety of patients and doctors about the implication of a recall.

The American public, and I presume much of the rest of the world, is not exactly unaccustomed to recalls. We have at least one recall a month by auto manufacturers, some by the manufacturers of the reputedly solid Japanese makes. Thanks to the watchful eyes of a variety of federal agencies, we have recalls of everything from baby food to spinach, jet airplanes to baby car seats, and Christmas toys to microwave ovens. We also have had recalls of biologic and medical items including antiarrhythmic drugs, aortic valves, and the painkiller rofecoxib (Vioxx).

Most of these recalls are taken in stride, but the recall of an electronic device implanted in your body does have some unique implications, particularly when many of the devices are there to save your life and when their removal is associated with some risk and discomfort.

The HRS is having difficulty getting this nomenclature change to come about. According to an article in this month's CARDIOLOGY NEWS (see p. 4), the Food and Drug Administration is reluctant to remove “recall” from its lexicon since it is rooted in legislation that mandates its safety responsibilities. In an uncharacteristic Washington response, the FDA is not prepared to “spin” its terminology, even when it is part of the problem.

These proposed changes are taking place in an atmosphere where the number of defibrillator devices implanted is falling short of the expectations of the physicians and manufacturers. Based on the current guidelines of the American College of Cardiology, American Heart Association, and HRS, many more of the devices should have been implanted, suggesting that quality standards are being compromised.

The concern of the HRS is that the media attention given to recalls has made both patients and physicians reluctant to follow the guidelines. It also has called attention to the risks of removing recalled devices, raising questions about which devices should be removed when they are identified as recalled. At the same, time many well-meaning physicians who treat patients at risk of sudden death are concerned about the “one size fits all” approach to the implantation guidelines and are looking for better risk stratification of the benefit that can accrue to their patients. Surely, among the millions of patients included in those guidelines, we should be able to determine in which patient individual implantation is imperative.

As a result of the flawed reporting of device failure in the past, there has been an outcry from physicians for more transparency in the reporting of malfunction of these devices. Unfortunately, increased transparency is certain to raise the level of anxiety of all those involved—patients and physicians—in the implantation of the devices. It is unlikely that the changes in nomenclature will lessen the concerns and increase the understanding of the risks and benefits of implantable devices.

As part of its new Recommendations From the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines, the society, in conjunction with the device manufacturers, is proposing that device recalls should now be called an “advisory notice” or “safety alert.” HRS suggests that this change is meant to lessen the anxiety of patients and doctors about the implication of a recall.

The American public, and I presume much of the rest of the world, is not exactly unaccustomed to recalls. We have at least one recall a month by auto manufacturers, some by the manufacturers of the reputedly solid Japanese makes. Thanks to the watchful eyes of a variety of federal agencies, we have recalls of everything from baby food to spinach, jet airplanes to baby car seats, and Christmas toys to microwave ovens. We also have had recalls of biologic and medical items including antiarrhythmic drugs, aortic valves, and the painkiller rofecoxib (Vioxx).

Most of these recalls are taken in stride, but the recall of an electronic device implanted in your body does have some unique implications, particularly when many of the devices are there to save your life and when their removal is associated with some risk and discomfort.

The HRS is having difficulty getting this nomenclature change to come about. According to an article in this month's CARDIOLOGY NEWS (see p. 4), the Food and Drug Administration is reluctant to remove “recall” from its lexicon since it is rooted in legislation that mandates its safety responsibilities. In an uncharacteristic Washington response, the FDA is not prepared to “spin” its terminology, even when it is part of the problem.

These proposed changes are taking place in an atmosphere where the number of defibrillator devices implanted is falling short of the expectations of the physicians and manufacturers. Based on the current guidelines of the American College of Cardiology, American Heart Association, and HRS, many more of the devices should have been implanted, suggesting that quality standards are being compromised.

The concern of the HRS is that the media attention given to recalls has made both patients and physicians reluctant to follow the guidelines. It also has called attention to the risks of removing recalled devices, raising questions about which devices should be removed when they are identified as recalled. At the same, time many well-meaning physicians who treat patients at risk of sudden death are concerned about the “one size fits all” approach to the implantation guidelines and are looking for better risk stratification of the benefit that can accrue to their patients. Surely, among the millions of patients included in those guidelines, we should be able to determine in which patient individual implantation is imperative.

As a result of the flawed reporting of device failure in the past, there has been an outcry from physicians for more transparency in the reporting of malfunction of these devices. Unfortunately, increased transparency is certain to raise the level of anxiety of all those involved—patients and physicians—in the implantation of the devices. It is unlikely that the changes in nomenclature will lessen the concerns and increase the understanding of the risks and benefits of implantable devices.

There are few if any medical therapies that are without any risks. No matter what the treatment, there have always been some risks associated with therapeutic intervention.

Drug-eluting stents (DES) appeared to be an exception to the rule once they were shown to have excellent short-term patency, compared with the bare-metal stents (BMS). DES are now widely used for the treatment of stenotic coronary arteries even in conditions for which there are few data to support a clinical benefit. In the last few years the indication for implantation of stents, and particularly DES, has slipped to a state where clinical judgment has given way to an unfettered response to the “oculostenotic reflex” of the angiographer.

The fact is that the only proven clinical benefit of percutaneous coronary intervention for chronic coronary artery disease is to improve the symptoms of angina. There is nothing to support a mortality or morbidity benefit for the treatment of angina pectoris with PCI. There is also abundant information to indicate that the next acute coronary event usually involves a site in the coronary artery that has little or no preexisting disease. Despite this, PCI with stenting, particularly with the seemingly safe DES, is applied to many asymptomatic patients with anatomic abnormalities alone, to prevent future acute ischemic events.

It now appears that drug-eluting stents, like many previous therapeutic interventions, are not quite as safe as it may seem. Recent press reports indicate that Boston Scientific recently appraised the Food and Drug Administration of its concerns about the long-term morbidity and mortality of the paclitaxel-eluting (Taxus) stent when compared with BMS in regard to the development of thromboses. This follows the reports at the recent meeting of the European Society of Cardiology that Swiss investigators found a significant increase in myocardial infarctions and death in patients receiving DES compared with the BMS in patients followed out to 3 years (see p. 1). In that study, adverse events occurred to a greater degree in the sirolimus-eluting (Sirius) stent than in the Taxus stent.

A proposed mechanism for this late thrombosis is the lack of endothelialization in the DES and the inconsistent use of chronic antiplatelet agents. It was also noted that there was a unique increase in noncardiac deaths, including cancer and infection, suggesting that the antimitotic drug coating of the stents could lead to adverse systemic effects.

All of these reports are preliminary and require further examination. However, if true it could have far reaching effects on the millions of patients who have received DES. It is an even greater paradox for the many asymptomatic patients who received these stents to prevent the morbidity and mortality of coronary artery disease. They now have developed a new disease, the nature and duration of which is uncertain.

Unfortunately, we do not have adequate monitoring systems to fully understand the magnitude of events following implantation of DES. Nevertheless, these very preliminary observations should infuse into the interventional cardiology world caution before implanting DES into asymptomatic patients and in symptomatic patients only after failure with drug therapy.

There are few if any medical therapies that are without any risks. No matter what the treatment, there have always been some risks associated with therapeutic intervention.

Drug-eluting stents (DES) appeared to be an exception to the rule once they were shown to have excellent short-term patency, compared with the bare-metal stents (BMS). DES are now widely used for the treatment of stenotic coronary arteries even in conditions for which there are few data to support a clinical benefit. In the last few years the indication for implantation of stents, and particularly DES, has slipped to a state where clinical judgment has given way to an unfettered response to the “oculostenotic reflex” of the angiographer.

The fact is that the only proven clinical benefit of percutaneous coronary intervention for chronic coronary artery disease is to improve the symptoms of angina. There is nothing to support a mortality or morbidity benefit for the treatment of angina pectoris with PCI. There is also abundant information to indicate that the next acute coronary event usually involves a site in the coronary artery that has little or no preexisting disease. Despite this, PCI with stenting, particularly with the seemingly safe DES, is applied to many asymptomatic patients with anatomic abnormalities alone, to prevent future acute ischemic events.

It now appears that drug-eluting stents, like many previous therapeutic interventions, are not quite as safe as it may seem. Recent press reports indicate that Boston Scientific recently appraised the Food and Drug Administration of its concerns about the long-term morbidity and mortality of the paclitaxel-eluting (Taxus) stent when compared with BMS in regard to the development of thromboses. This follows the reports at the recent meeting of the European Society of Cardiology that Swiss investigators found a significant increase in myocardial infarctions and death in patients receiving DES compared with the BMS in patients followed out to 3 years (see p. 1). In that study, adverse events occurred to a greater degree in the sirolimus-eluting (Sirius) stent than in the Taxus stent.

A proposed mechanism for this late thrombosis is the lack of endothelialization in the DES and the inconsistent use of chronic antiplatelet agents. It was also noted that there was a unique increase in noncardiac deaths, including cancer and infection, suggesting that the antimitotic drug coating of the stents could lead to adverse systemic effects.

All of these reports are preliminary and require further examination. However, if true it could have far reaching effects on the millions of patients who have received DES. It is an even greater paradox for the many asymptomatic patients who received these stents to prevent the morbidity and mortality of coronary artery disease. They now have developed a new disease, the nature and duration of which is uncertain.

Unfortunately, we do not have adequate monitoring systems to fully understand the magnitude of events following implantation of DES. Nevertheless, these very preliminary observations should infuse into the interventional cardiology world caution before implanting DES into asymptomatic patients and in symptomatic patients only after failure with drug therapy.

There are few if any medical therapies that are without any risks. No matter what the treatment, there have always been some risks associated with therapeutic intervention.

Drug-eluting stents (DES) appeared to be an exception to the rule once they were shown to have excellent short-term patency, compared with the bare-metal stents (BMS). DES are now widely used for the treatment of stenotic coronary arteries even in conditions for which there are few data to support a clinical benefit. In the last few years the indication for implantation of stents, and particularly DES, has slipped to a state where clinical judgment has given way to an unfettered response to the “oculostenotic reflex” of the angiographer.

The fact is that the only proven clinical benefit of percutaneous coronary intervention for chronic coronary artery disease is to improve the symptoms of angina. There is nothing to support a mortality or morbidity benefit for the treatment of angina pectoris with PCI. There is also abundant information to indicate that the next acute coronary event usually involves a site in the coronary artery that has little or no preexisting disease. Despite this, PCI with stenting, particularly with the seemingly safe DES, is applied to many asymptomatic patients with anatomic abnormalities alone, to prevent future acute ischemic events.

It now appears that drug-eluting stents, like many previous therapeutic interventions, are not quite as safe as it may seem. Recent press reports indicate that Boston Scientific recently appraised the Food and Drug Administration of its concerns about the long-term morbidity and mortality of the paclitaxel-eluting (Taxus) stent when compared with BMS in regard to the development of thromboses. This follows the reports at the recent meeting of the European Society of Cardiology that Swiss investigators found a significant increase in myocardial infarctions and death in patients receiving DES compared with the BMS in patients followed out to 3 years (see p. 1). In that study, adverse events occurred to a greater degree in the sirolimus-eluting (Sirius) stent than in the Taxus stent.

A proposed mechanism for this late thrombosis is the lack of endothelialization in the DES and the inconsistent use of chronic antiplatelet agents. It was also noted that there was a unique increase in noncardiac deaths, including cancer and infection, suggesting that the antimitotic drug coating of the stents could lead to adverse systemic effects.

All of these reports are preliminary and require further examination. However, if true it could have far reaching effects on the millions of patients who have received DES. It is an even greater paradox for the many asymptomatic patients who received these stents to prevent the morbidity and mortality of coronary artery disease. They now have developed a new disease, the nature and duration of which is uncertain.

Unfortunately, we do not have adequate monitoring systems to fully understand the magnitude of events following implantation of DES. Nevertheless, these very preliminary observations should infuse into the interventional cardiology world caution before implanting DES into asymptomatic patients and in symptomatic patients only after failure with drug therapy.