Sidney Goldstein

In this issue of CARDIOLOGY NEWS, observations reported at the meeting of the European Society of Cardiology in Stockholm provide insights into the real-world use of drug-eluting stents.

Much of our knowledge of DESs has come from carefully controlled clinical trials using highly selected patients and conducted in academic institutions. What happens after the device is approved and introduced for use in everyday medical practice is often very different.

Human nature drives interventional cardiologists to use the latest new toy, regardless of price, while patients are educated by the media to demand state-of-the-art stents.

At the same time, cardiologists tend to expand the indications for use of the device or drug beyond the patient inclusion criteria used to established efficacy and safety. In addition, information about the application of new therapies after the FDA has approved them is scarce. In some cases, drugs have been used in patients who differed from those in the seminal clinical trial, resulting in increased major adverse clinical events (MACE).

Gregory J. Mishkel, M.D., described how he and his associates observed that in more than 3,000 patients in a general cardiology practice, most of those who received DESs did not fit the criteria used in the trials that established the benefits of the stents. (See page 23.) As the patients' characteristics were expanded beyond the initial inclusion criteria, the incidence of MACE increased. The more risk factors the patients had, the more likely was the occurrence of MACE. In the context of patients demanding the latest procedure to get the best results, the investigators found that the patients were, in fact, being shortchanged.

The investigators suggest that enthusiasm for DESs also led to stenting when coronary bypass surgery might have been a better choice, but they did not provide data to support that possibility.

Another result of the overuse of DESs has been the impact on health care costs. The actual cost of stents varies from institution to institution. Current estimates suggest that a bare-metal stent (BMS) costs about $1,000, whereas a DES costs about three times that. If one considers that it usually takes at least two stents to completely treat stenosis, then the cost of DES implantation, compared with that of BMS implantation, begins to mount up.

In the Basel Stent Cost Effectiveness Trial (BASKET, page 1), researchers compared the costs and efficacy of the implantation of the paclitaxel-eluting Taxus and sirolimus-eluting Cypher stents with the Vision stent, a cobalt-chromium-based BMS. Although the DESs resulted in an improved target vessel revascularization, they also tacked on almost $90,000 per year of quality-adjusted life-year gained by the DES.

These reports provide an unusual glimpse into how new devices are actually being used in clinical medicine, as well as how drugs and devices are applied to the general populations based on data from narrowly defined patient samples in clinical trials. Patients in enrolled in clinical trials are recruited to answer specific questions, which results in the exclusion of many in the general population with complicating illnesses. Unfortunately, those complicating illnesses that exclude patients from clinical trials are the problems that the physician deals with every day.

In this issue of CARDIOLOGY NEWS, observations reported at the meeting of the European Society of Cardiology in Stockholm provide insights into the real-world use of drug-eluting stents.

Much of our knowledge of DESs has come from carefully controlled clinical trials using highly selected patients and conducted in academic institutions. What happens after the device is approved and introduced for use in everyday medical practice is often very different.

Human nature drives interventional cardiologists to use the latest new toy, regardless of price, while patients are educated by the media to demand state-of-the-art stents.

At the same time, cardiologists tend to expand the indications for use of the device or drug beyond the patient inclusion criteria used to established efficacy and safety. In addition, information about the application of new therapies after the FDA has approved them is scarce. In some cases, drugs have been used in patients who differed from those in the seminal clinical trial, resulting in increased major adverse clinical events (MACE).

Gregory J. Mishkel, M.D., described how he and his associates observed that in more than 3,000 patients in a general cardiology practice, most of those who received DESs did not fit the criteria used in the trials that established the benefits of the stents. (See page 23.) As the patients' characteristics were expanded beyond the initial inclusion criteria, the incidence of MACE increased. The more risk factors the patients had, the more likely was the occurrence of MACE. In the context of patients demanding the latest procedure to get the best results, the investigators found that the patients were, in fact, being shortchanged.

The investigators suggest that enthusiasm for DESs also led to stenting when coronary bypass surgery might have been a better choice, but they did not provide data to support that possibility.

Another result of the overuse of DESs has been the impact on health care costs. The actual cost of stents varies from institution to institution. Current estimates suggest that a bare-metal stent (BMS) costs about $1,000, whereas a DES costs about three times that. If one considers that it usually takes at least two stents to completely treat stenosis, then the cost of DES implantation, compared with that of BMS implantation, begins to mount up.

In the Basel Stent Cost Effectiveness Trial (BASKET, page 1), researchers compared the costs and efficacy of the implantation of the paclitaxel-eluting Taxus and sirolimus-eluting Cypher stents with the Vision stent, a cobalt-chromium-based BMS. Although the DESs resulted in an improved target vessel revascularization, they also tacked on almost $90,000 per year of quality-adjusted life-year gained by the DES.

These reports provide an unusual glimpse into how new devices are actually being used in clinical medicine, as well as how drugs and devices are applied to the general populations based on data from narrowly defined patient samples in clinical trials. Patients in enrolled in clinical trials are recruited to answer specific questions, which results in the exclusion of many in the general population with complicating illnesses. Unfortunately, those complicating illnesses that exclude patients from clinical trials are the problems that the physician deals with every day.

In this issue of CARDIOLOGY NEWS, observations reported at the meeting of the European Society of Cardiology in Stockholm provide insights into the real-world use of drug-eluting stents.

Much of our knowledge of DESs has come from carefully controlled clinical trials using highly selected patients and conducted in academic institutions. What happens after the device is approved and introduced for use in everyday medical practice is often very different.

Human nature drives interventional cardiologists to use the latest new toy, regardless of price, while patients are educated by the media to demand state-of-the-art stents.

At the same time, cardiologists tend to expand the indications for use of the device or drug beyond the patient inclusion criteria used to established efficacy and safety. In addition, information about the application of new therapies after the FDA has approved them is scarce. In some cases, drugs have been used in patients who differed from those in the seminal clinical trial, resulting in increased major adverse clinical events (MACE).

Gregory J. Mishkel, M.D., described how he and his associates observed that in more than 3,000 patients in a general cardiology practice, most of those who received DESs did not fit the criteria used in the trials that established the benefits of the stents. (See page 23.) As the patients' characteristics were expanded beyond the initial inclusion criteria, the incidence of MACE increased. The more risk factors the patients had, the more likely was the occurrence of MACE. In the context of patients demanding the latest procedure to get the best results, the investigators found that the patients were, in fact, being shortchanged.

The investigators suggest that enthusiasm for DESs also led to stenting when coronary bypass surgery might have been a better choice, but they did not provide data to support that possibility.

Another result of the overuse of DESs has been the impact on health care costs. The actual cost of stents varies from institution to institution. Current estimates suggest that a bare-metal stent (BMS) costs about $1,000, whereas a DES costs about three times that. If one considers that it usually takes at least two stents to completely treat stenosis, then the cost of DES implantation, compared with that of BMS implantation, begins to mount up.

In the Basel Stent Cost Effectiveness Trial (BASKET, page 1), researchers compared the costs and efficacy of the implantation of the paclitaxel-eluting Taxus and sirolimus-eluting Cypher stents with the Vision stent, a cobalt-chromium-based BMS. Although the DESs resulted in an improved target vessel revascularization, they also tacked on almost $90,000 per year of quality-adjusted life-year gained by the DES.

These reports provide an unusual glimpse into how new devices are actually being used in clinical medicine, as well as how drugs and devices are applied to the general populations based on data from narrowly defined patient samples in clinical trials. Patients in enrolled in clinical trials are recruited to answer specific questions, which results in the exclusion of many in the general population with complicating illnesses. Unfortunately, those complicating illnesses that exclude patients from clinical trials are the problems that the physician deals with every day.

A significant shift in recent years to treating heart failure with device implantation and surgery has made its way into clinical guidelines, published last month by the American College of Cardiology and the American Heart Association. The value of these therapies is most apparent in young patients with little concomitant disease and in whom the long-term risks and benefits can be measured in many symptom-free years.

The decision to implant a cardioverter-defibrillator in a young patient with an ejection fraction of 20% and with active ventricular ectopia is easy, as is the choice of mitral valve surgery in a similar patient with symptomatic heart failure. However, physicians using the heart failure-guideline update should appreciate that many of our heart failure patients to whom these guidelines will be applied are elderly. The summary article recommends and deems it “reasonable” to consider a wide range of therapies, including surgery and devices. But the full text, which includes the background discussions of the decision-making process, makes it clear that the authors struggled with the universality of their application to all ages and all persons. (Both articles are available at www.acc.org/clinical/statements.htm

There is concern that some elderly patients will be persuaded to accept these therapies as essential to survival, as they well may be. But at what cost to quality of survival?

It is important to understand that these are indeed guidelines and not requirements. However, there are concerns that they will become imperatives for the measurement of quality, like β-blockers, aspirin, and ACE inhibitors, and thus fall into the gun sights of aggressive medical administrators who will penalize hospitals and doctors who do not comply. In the realm of quality improvement, variation is not appreciated.

Some questions can be raised about the class I recommendation for the use of biventricular pacing with patients with prolonged QRS intervals at a time when we are still learning about the physiology of the device, where the electrodes should be implanted, and which patients will benefit most. The results of those studies will determine who will receive the most benefit. This information will be essential for cardiologists as they make their recommendations to individual patients. Similarly, the advisory class I for mitral valve replacement in “severe” mitral insufficiency in patients with asymptomatic left ventricular dysfunction is puzzling without a definition of severity and without any randomized clinical trial to support the procedure.

The application of these technical advances to elderly patients, who make up a large part of heart failure population, should be a concern of physicians. Some writing to this newspaper are worried that any deviation from the published guidelines will make them vulnerable to litigation. To those who have those concerns—and they are indeed real—I would suggest they read beyond the guideline summary and appreciate the gray zones that surround many of the recommendations. And the writing committee should try to bring its recommendations into a somewhat “grayer” reality of care and perhaps reemphasize the need for the physician's judgment in applying them.

A significant shift in recent years to treating heart failure with device implantation and surgery has made its way into clinical guidelines, published last month by the American College of Cardiology and the American Heart Association. The value of these therapies is most apparent in young patients with little concomitant disease and in whom the long-term risks and benefits can be measured in many symptom-free years.

The decision to implant a cardioverter-defibrillator in a young patient with an ejection fraction of 20% and with active ventricular ectopia is easy, as is the choice of mitral valve surgery in a similar patient with symptomatic heart failure. However, physicians using the heart failure-guideline update should appreciate that many of our heart failure patients to whom these guidelines will be applied are elderly. The summary article recommends and deems it “reasonable” to consider a wide range of therapies, including surgery and devices. But the full text, which includes the background discussions of the decision-making process, makes it clear that the authors struggled with the universality of their application to all ages and all persons. (Both articles are available at www.acc.org/clinical/statements.htm

There is concern that some elderly patients will be persuaded to accept these therapies as essential to survival, as they well may be. But at what cost to quality of survival?

It is important to understand that these are indeed guidelines and not requirements. However, there are concerns that they will become imperatives for the measurement of quality, like β-blockers, aspirin, and ACE inhibitors, and thus fall into the gun sights of aggressive medical administrators who will penalize hospitals and doctors who do not comply. In the realm of quality improvement, variation is not appreciated.

Some questions can be raised about the class I recommendation for the use of biventricular pacing with patients with prolonged QRS intervals at a time when we are still learning about the physiology of the device, where the electrodes should be implanted, and which patients will benefit most. The results of those studies will determine who will receive the most benefit. This information will be essential for cardiologists as they make their recommendations to individual patients. Similarly, the advisory class I for mitral valve replacement in “severe” mitral insufficiency in patients with asymptomatic left ventricular dysfunction is puzzling without a definition of severity and without any randomized clinical trial to support the procedure.

The application of these technical advances to elderly patients, who make up a large part of heart failure population, should be a concern of physicians. Some writing to this newspaper are worried that any deviation from the published guidelines will make them vulnerable to litigation. To those who have those concerns—and they are indeed real—I would suggest they read beyond the guideline summary and appreciate the gray zones that surround many of the recommendations. And the writing committee should try to bring its recommendations into a somewhat “grayer” reality of care and perhaps reemphasize the need for the physician's judgment in applying them.

A significant shift in recent years to treating heart failure with device implantation and surgery has made its way into clinical guidelines, published last month by the American College of Cardiology and the American Heart Association. The value of these therapies is most apparent in young patients with little concomitant disease and in whom the long-term risks and benefits can be measured in many symptom-free years.

The decision to implant a cardioverter-defibrillator in a young patient with an ejection fraction of 20% and with active ventricular ectopia is easy, as is the choice of mitral valve surgery in a similar patient with symptomatic heart failure. However, physicians using the heart failure-guideline update should appreciate that many of our heart failure patients to whom these guidelines will be applied are elderly. The summary article recommends and deems it “reasonable” to consider a wide range of therapies, including surgery and devices. But the full text, which includes the background discussions of the decision-making process, makes it clear that the authors struggled with the universality of their application to all ages and all persons. (Both articles are available at www.acc.org/clinical/statements.htm

There is concern that some elderly patients will be persuaded to accept these therapies as essential to survival, as they well may be. But at what cost to quality of survival?

It is important to understand that these are indeed guidelines and not requirements. However, there are concerns that they will become imperatives for the measurement of quality, like β-blockers, aspirin, and ACE inhibitors, and thus fall into the gun sights of aggressive medical administrators who will penalize hospitals and doctors who do not comply. In the realm of quality improvement, variation is not appreciated.

Some questions can be raised about the class I recommendation for the use of biventricular pacing with patients with prolonged QRS intervals at a time when we are still learning about the physiology of the device, where the electrodes should be implanted, and which patients will benefit most. The results of those studies will determine who will receive the most benefit. This information will be essential for cardiologists as they make their recommendations to individual patients. Similarly, the advisory class I for mitral valve replacement in “severe” mitral insufficiency in patients with asymptomatic left ventricular dysfunction is puzzling without a definition of severity and without any randomized clinical trial to support the procedure.

The application of these technical advances to elderly patients, who make up a large part of heart failure population, should be a concern of physicians. Some writing to this newspaper are worried that any deviation from the published guidelines will make them vulnerable to litigation. To those who have those concerns—and they are indeed real—I would suggest they read beyond the guideline summary and appreciate the gray zones that surround many of the recommendations. And the writing committee should try to bring its recommendations into a somewhat “grayer” reality of care and perhaps reemphasize the need for the physician's judgment in applying them.

In the beginning, randomized clinical trials were designed to move the observations made at the bench and from small clinical studies to the community at large.

One example of this transition was the Beta-Blocker Heart Attack Trial, which evolved from positive observations in small clinical studies of 100 patients or less. Because of intense skepticism, recruitment was difficult since many felt that β-blockers were dangerous. The positive benefit reported in 1982 was a surprise to everyone, including the investigators. Even though the results were replicated by at least two other RCTs, the incorporation of β-blocker therapy in post-MI patients took more than a decade to gain traction in contemporary therapy. It was difficult to get the ear of the practicing physician, but no one ever thought that one day physicians would be forced, much less given a bonus, to prescribe β-blockers after an MI.

Concern about the inconsistency of the application of beneficial therapy and in the desire to insure that every American was appropriately treated, guidelines based on RCTs were created to help physicians make the best therapeutic choices. Largely as a result of ACC/AHA guideline, β-blockers became accepted therapy following an acute myocardial infarction. From an average use of 30% in the 1990s, utilization rates began to climb 65% by the beginning of this century. Physician education was the mechanism by which this advance occurred. β-Blocker utilization became an important quality measure advanced by a variety of private and federal insurers. Now utilization rates approach 80%–85% of patients discharged after an MI, and the percent of patients receiving β-blocker therapy became part of the well-publicized quality standards that measure the performance of hospitals and clinics nationwide.

RCTs became the foundation of what is now called evidence-based medicine. We are bombarded by RCTs supporting the use of a plethora of drugs and devices that improve the lives of cardiac patients. It no longer takes a decade to incorporate these therapies into clinical practice; they are now certified within months. Guidelines committees that at one time met every 2–3 years are now in almost continuous session.

Now in the interest of uniformity, education is no longer regarded as sufficient to influence physicians, but economic incentives are proposed to prevent variation, the enemy of the “quality gurus,” in order to ensure uniformity. Physicians and their representatives are now considering accepting payment incentives in order to achieve uniformity and expedite adherence to evidence-based medicine. Variation in the application of these guidelines will lead to financial penalties.

Much of this is motivated by the idea that by achieving uniformity of care, health care costs will decrease at a time when almost 45 million Americans do not have health insurance to pay for it. In an era in which postgraduate medical education is funded largely by the pharmaceutical industry, education is no longer important. Financial incentives are the only answer to compliance. Something just doesn't sound right. Is it really no longer possible to educate physicians about how to treat their patients?

In the beginning, randomized clinical trials were designed to move the observations made at the bench and from small clinical studies to the community at large.

One example of this transition was the Beta-Blocker Heart Attack Trial, which evolved from positive observations in small clinical studies of 100 patients or less. Because of intense skepticism, recruitment was difficult since many felt that β-blockers were dangerous. The positive benefit reported in 1982 was a surprise to everyone, including the investigators. Even though the results were replicated by at least two other RCTs, the incorporation of β-blocker therapy in post-MI patients took more than a decade to gain traction in contemporary therapy. It was difficult to get the ear of the practicing physician, but no one ever thought that one day physicians would be forced, much less given a bonus, to prescribe β-blockers after an MI.

Concern about the inconsistency of the application of beneficial therapy and in the desire to insure that every American was appropriately treated, guidelines based on RCTs were created to help physicians make the best therapeutic choices. Largely as a result of ACC/AHA guideline, β-blockers became accepted therapy following an acute myocardial infarction. From an average use of 30% in the 1990s, utilization rates began to climb 65% by the beginning of this century. Physician education was the mechanism by which this advance occurred. β-Blocker utilization became an important quality measure advanced by a variety of private and federal insurers. Now utilization rates approach 80%–85% of patients discharged after an MI, and the percent of patients receiving β-blocker therapy became part of the well-publicized quality standards that measure the performance of hospitals and clinics nationwide.

RCTs became the foundation of what is now called evidence-based medicine. We are bombarded by RCTs supporting the use of a plethora of drugs and devices that improve the lives of cardiac patients. It no longer takes a decade to incorporate these therapies into clinical practice; they are now certified within months. Guidelines committees that at one time met every 2–3 years are now in almost continuous session.

Now in the interest of uniformity, education is no longer regarded as sufficient to influence physicians, but economic incentives are proposed to prevent variation, the enemy of the “quality gurus,” in order to ensure uniformity. Physicians and their representatives are now considering accepting payment incentives in order to achieve uniformity and expedite adherence to evidence-based medicine. Variation in the application of these guidelines will lead to financial penalties.

Much of this is motivated by the idea that by achieving uniformity of care, health care costs will decrease at a time when almost 45 million Americans do not have health insurance to pay for it. In an era in which postgraduate medical education is funded largely by the pharmaceutical industry, education is no longer important. Financial incentives are the only answer to compliance. Something just doesn't sound right. Is it really no longer possible to educate physicians about how to treat their patients?

In the beginning, randomized clinical trials were designed to move the observations made at the bench and from small clinical studies to the community at large.

One example of this transition was the Beta-Blocker Heart Attack Trial, which evolved from positive observations in small clinical studies of 100 patients or less. Because of intense skepticism, recruitment was difficult since many felt that β-blockers were dangerous. The positive benefit reported in 1982 was a surprise to everyone, including the investigators. Even though the results were replicated by at least two other RCTs, the incorporation of β-blocker therapy in post-MI patients took more than a decade to gain traction in contemporary therapy. It was difficult to get the ear of the practicing physician, but no one ever thought that one day physicians would be forced, much less given a bonus, to prescribe β-blockers after an MI.

Concern about the inconsistency of the application of beneficial therapy and in the desire to insure that every American was appropriately treated, guidelines based on RCTs were created to help physicians make the best therapeutic choices. Largely as a result of ACC/AHA guideline, β-blockers became accepted therapy following an acute myocardial infarction. From an average use of 30% in the 1990s, utilization rates began to climb 65% by the beginning of this century. Physician education was the mechanism by which this advance occurred. β-Blocker utilization became an important quality measure advanced by a variety of private and federal insurers. Now utilization rates approach 80%–85% of patients discharged after an MI, and the percent of patients receiving β-blocker therapy became part of the well-publicized quality standards that measure the performance of hospitals and clinics nationwide.

RCTs became the foundation of what is now called evidence-based medicine. We are bombarded by RCTs supporting the use of a plethora of drugs and devices that improve the lives of cardiac patients. It no longer takes a decade to incorporate these therapies into clinical practice; they are now certified within months. Guidelines committees that at one time met every 2–3 years are now in almost continuous session.

Now in the interest of uniformity, education is no longer regarded as sufficient to influence physicians, but economic incentives are proposed to prevent variation, the enemy of the “quality gurus,” in order to ensure uniformity. Physicians and their representatives are now considering accepting payment incentives in order to achieve uniformity and expedite adherence to evidence-based medicine. Variation in the application of these guidelines will lead to financial penalties.

Much of this is motivated by the idea that by achieving uniformity of care, health care costs will decrease at a time when almost 45 million Americans do not have health insurance to pay for it. In an era in which postgraduate medical education is funded largely by the pharmaceutical industry, education is no longer important. Financial incentives are the only answer to compliance. Something just doesn't sound right. Is it really no longer possible to educate physicians about how to treat their patients?

The recalls of Vioxx and implantable cardioverter defibrillators have beset the cardiology community with a cloud of uncertainty on how to advise our patients in a variety of areas.

Any patient who is the least bit aware of current events and has an ICD or has been taking Vioxx (rofecoxib) knows of the dangers they face. Some are grateful that they “dodged the bullet” before they stopped taking the pill. Others will have to make more complex decisions about the removal of an ICD.

Drug and device recalls are not new to cardiology. In the 1980s and 1990s, several “magic” antiarrhythmic drugs were recalled after they were shown to be proarrhythmic. Even now, there are patients with Björk-Shiley aortic valves in place who remain under radiologic surveillance to ensure the integrity of the faulty devices.

What has changed is the magnitude of the problem, as well as public awareness of the issues. Drugs advertised on television as a panacea for pain have now been shown to cause heart attacks, and devices presumed to prevent sudden cardiac death can fail.

People have been led to believe that there is no downside to therapy. Even though we have no data on the long-term benefits and safety of many devices or drugs, patients and doctors have ignored long-term risks. Those who raised caution flags were dismissed as “nattering nabobs” of nonconformity. The Food and Drug Administration has relied on the pharmaceutical manufacturers and device makers to disclose negative information about their products. Such naiveté hardly befits a governmental agency charged with such an important safety role.

What should we expect from regulatory agencies and the pharmaceutical and device industry to assure us that products are safe? Transparency, at the least. We should be able to see within the industrial databases in order to understand what is going on. We also need to have simpler surveillance procedures, so that we understand the issues. It is clear that, as reported widely in the press, Guidant erred greatly when it continued to sell a product it knew was defective and that Merck was less than forthcoming about Vioxx. It is also disingenuous of both physicians and industry to recommend that patients make their own decisions. It is equally mindless to suggest that physicians decide which of their patients—whom they have already defined as being at high risk of sudden death and in need of an ICD—are at the highest risk when advising device replacement.

It is just possible that patients and physicians will learn that there is no free lunch and that all devices and drugs carry some degree of risk. Beyond the immediate risks of implantation in high-risk patients, adverse effects may take years to emerge.

In the meantime, it is imperative that the FDA and the Centers for Medicare and Medicaid Services establish surveillance procedures and registries that will ensure the safety of the products being implanted and ingested. Clinical trials, on which we rely for safety and efficacy data, often are too short and frequently are conducted in populations too small and specific to determine safety in a larger and more heterogeneous population over a lifetime of therapy.

The recalls of Vioxx and implantable cardioverter defibrillators have beset the cardiology community with a cloud of uncertainty on how to advise our patients in a variety of areas.

Any patient who is the least bit aware of current events and has an ICD or has been taking Vioxx (rofecoxib) knows of the dangers they face. Some are grateful that they “dodged the bullet” before they stopped taking the pill. Others will have to make more complex decisions about the removal of an ICD.

Drug and device recalls are not new to cardiology. In the 1980s and 1990s, several “magic” antiarrhythmic drugs were recalled after they were shown to be proarrhythmic. Even now, there are patients with Björk-Shiley aortic valves in place who remain under radiologic surveillance to ensure the integrity of the faulty devices.

What has changed is the magnitude of the problem, as well as public awareness of the issues. Drugs advertised on television as a panacea for pain have now been shown to cause heart attacks, and devices presumed to prevent sudden cardiac death can fail.

People have been led to believe that there is no downside to therapy. Even though we have no data on the long-term benefits and safety of many devices or drugs, patients and doctors have ignored long-term risks. Those who raised caution flags were dismissed as “nattering nabobs” of nonconformity. The Food and Drug Administration has relied on the pharmaceutical manufacturers and device makers to disclose negative information about their products. Such naiveté hardly befits a governmental agency charged with such an important safety role.

What should we expect from regulatory agencies and the pharmaceutical and device industry to assure us that products are safe? Transparency, at the least. We should be able to see within the industrial databases in order to understand what is going on. We also need to have simpler surveillance procedures, so that we understand the issues. It is clear that, as reported widely in the press, Guidant erred greatly when it continued to sell a product it knew was defective and that Merck was less than forthcoming about Vioxx. It is also disingenuous of both physicians and industry to recommend that patients make their own decisions. It is equally mindless to suggest that physicians decide which of their patients—whom they have already defined as being at high risk of sudden death and in need of an ICD—are at the highest risk when advising device replacement.

It is just possible that patients and physicians will learn that there is no free lunch and that all devices and drugs carry some degree of risk. Beyond the immediate risks of implantation in high-risk patients, adverse effects may take years to emerge.

In the meantime, it is imperative that the FDA and the Centers for Medicare and Medicaid Services establish surveillance procedures and registries that will ensure the safety of the products being implanted and ingested. Clinical trials, on which we rely for safety and efficacy data, often are too short and frequently are conducted in populations too small and specific to determine safety in a larger and more heterogeneous population over a lifetime of therapy.

The recalls of Vioxx and implantable cardioverter defibrillators have beset the cardiology community with a cloud of uncertainty on how to advise our patients in a variety of areas.

Any patient who is the least bit aware of current events and has an ICD or has been taking Vioxx (rofecoxib) knows of the dangers they face. Some are grateful that they “dodged the bullet” before they stopped taking the pill. Others will have to make more complex decisions about the removal of an ICD.

Drug and device recalls are not new to cardiology. In the 1980s and 1990s, several “magic” antiarrhythmic drugs were recalled after they were shown to be proarrhythmic. Even now, there are patients with Björk-Shiley aortic valves in place who remain under radiologic surveillance to ensure the integrity of the faulty devices.

What has changed is the magnitude of the problem, as well as public awareness of the issues. Drugs advertised on television as a panacea for pain have now been shown to cause heart attacks, and devices presumed to prevent sudden cardiac death can fail.

People have been led to believe that there is no downside to therapy. Even though we have no data on the long-term benefits and safety of many devices or drugs, patients and doctors have ignored long-term risks. Those who raised caution flags were dismissed as “nattering nabobs” of nonconformity. The Food and Drug Administration has relied on the pharmaceutical manufacturers and device makers to disclose negative information about their products. Such naiveté hardly befits a governmental agency charged with such an important safety role.

What should we expect from regulatory agencies and the pharmaceutical and device industry to assure us that products are safe? Transparency, at the least. We should be able to see within the industrial databases in order to understand what is going on. We also need to have simpler surveillance procedures, so that we understand the issues. It is clear that, as reported widely in the press, Guidant erred greatly when it continued to sell a product it knew was defective and that Merck was less than forthcoming about Vioxx. It is also disingenuous of both physicians and industry to recommend that patients make their own decisions. It is equally mindless to suggest that physicians decide which of their patients—whom they have already defined as being at high risk of sudden death and in need of an ICD—are at the highest risk when advising device replacement.

It is just possible that patients and physicians will learn that there is no free lunch and that all devices and drugs carry some degree of risk. Beyond the immediate risks of implantation in high-risk patients, adverse effects may take years to emerge.

In the meantime, it is imperative that the FDA and the Centers for Medicare and Medicaid Services establish surveillance procedures and registries that will ensure the safety of the products being implanted and ingested. Clinical trials, on which we rely for safety and efficacy data, often are too short and frequently are conducted in populations too small and specific to determine safety in a larger and more heterogeneous population over a lifetime of therapy.

With the approval of BiDil for the treatment of heart failure in African Americans, the Food and Drug Administration has essentially excluded the use of this combination of isosorbide dinitrate and hydralazine in non-African Americans.

In the African-American Heart Failure Trial (A-HeFT), BiDil decreased mortality in 1,050 exclusively African American patients with New York Heart Association class III and IV heart failure randomized to the drug or a placebo. Most impressively, this benefit occurred in the presence of concomitant therapy with ACE inhibitors and β-blockers within 10 months (N. Engl. J. Med. 2004;351:2049–57).

A major question remains whether this approval should indicate that its use be limited to African American patients only or extended also to all patients. Now that it is approved, it will almost certainly be used in heart failure patients regardless of race. The two drugs are readily available as generic preparations in any pharmacy.

Much has been made of the observation that the antihypertensive effects of ACE inhibitors are less in African Americans than in whites. In addition, the mortality benefit observed in African Americans, compared with whites, in the Vasodilator Heart Failure Trial (V-HeFT I) provides additional foundation for A-HeFT. If a differential blood pressure response was the cause of improved response in A-HeFT, there is little evidence for that. Very minimal decreases of systolic (0.7 mm Hg) and diastolic (1.6 mm Hg) pressure in diastole were seen in the BiDil-treated patients.

It has been suggested that the benefit of BiDil may be related to the antioxidant effect of hydralazine. This theory is supported in part by observation that African Americans may be deficient in nitric oxide, a major source of oxidant metabolism. A lack of nitric oxide at the cellular level as a result of a decrease in endothelial nitric oxide synthase (eNOS) is thought to be a potential putative process of heart failure. If African Americans with heart failure were more deficient in eNOS, they could be more likely to benefit from chronic therapy with BiDil. However, if not, one would expect the effect to be the same, regardless of race.

Some aspects of the therapy are puzzling. The drug was rather poorly tolerated, with only 68% of the BiDil patients staying on the drug, compared with 89% in the placebo group during the 10 months of follow-up. Much of this was presumably due to headache and dizziness, which occurred in 48% and 29% of the patients, respectively. In addition, long-term hydralazine use has been reported to result in a lupus-like syndrome with arthritis at doses greater than 200 mg/day, particularly in patients with renal dysfunction. The dose used in A-HeFT was 225 mg/day. Unfortunately, the duration A-HeFT was short, owing to its observed benefit.

The A-HeFT findings provide a new approach to treating heart failure, regardless of race. If the antioxidant hypothesis is correct, its application should not be limited to African Americans. Given that previous clinical trials in heart failure—which, unfortunately, have been dominated by whites—have been applied to all heart failure patients, regardless of race, it is reasonable that the results in A-HeFT should also be applied to all heart failure patients.

With the approval of BiDil for the treatment of heart failure in African Americans, the Food and Drug Administration has essentially excluded the use of this combination of isosorbide dinitrate and hydralazine in non-African Americans.

In the African-American Heart Failure Trial (A-HeFT), BiDil decreased mortality in 1,050 exclusively African American patients with New York Heart Association class III and IV heart failure randomized to the drug or a placebo. Most impressively, this benefit occurred in the presence of concomitant therapy with ACE inhibitors and β-blockers within 10 months (N. Engl. J. Med. 2004;351:2049–57).

A major question remains whether this approval should indicate that its use be limited to African American patients only or extended also to all patients. Now that it is approved, it will almost certainly be used in heart failure patients regardless of race. The two drugs are readily available as generic preparations in any pharmacy.

Much has been made of the observation that the antihypertensive effects of ACE inhibitors are less in African Americans than in whites. In addition, the mortality benefit observed in African Americans, compared with whites, in the Vasodilator Heart Failure Trial (V-HeFT I) provides additional foundation for A-HeFT. If a differential blood pressure response was the cause of improved response in A-HeFT, there is little evidence for that. Very minimal decreases of systolic (0.7 mm Hg) and diastolic (1.6 mm Hg) pressure in diastole were seen in the BiDil-treated patients.

It has been suggested that the benefit of BiDil may be related to the antioxidant effect of hydralazine. This theory is supported in part by observation that African Americans may be deficient in nitric oxide, a major source of oxidant metabolism. A lack of nitric oxide at the cellular level as a result of a decrease in endothelial nitric oxide synthase (eNOS) is thought to be a potential putative process of heart failure. If African Americans with heart failure were more deficient in eNOS, they could be more likely to benefit from chronic therapy with BiDil. However, if not, one would expect the effect to be the same, regardless of race.

Some aspects of the therapy are puzzling. The drug was rather poorly tolerated, with only 68% of the BiDil patients staying on the drug, compared with 89% in the placebo group during the 10 months of follow-up. Much of this was presumably due to headache and dizziness, which occurred in 48% and 29% of the patients, respectively. In addition, long-term hydralazine use has been reported to result in a lupus-like syndrome with arthritis at doses greater than 200 mg/day, particularly in patients with renal dysfunction. The dose used in A-HeFT was 225 mg/day. Unfortunately, the duration A-HeFT was short, owing to its observed benefit.

The A-HeFT findings provide a new approach to treating heart failure, regardless of race. If the antioxidant hypothesis is correct, its application should not be limited to African Americans. Given that previous clinical trials in heart failure—which, unfortunately, have been dominated by whites—have been applied to all heart failure patients, regardless of race, it is reasonable that the results in A-HeFT should also be applied to all heart failure patients.

With the approval of BiDil for the treatment of heart failure in African Americans, the Food and Drug Administration has essentially excluded the use of this combination of isosorbide dinitrate and hydralazine in non-African Americans.

In the African-American Heart Failure Trial (A-HeFT), BiDil decreased mortality in 1,050 exclusively African American patients with New York Heart Association class III and IV heart failure randomized to the drug or a placebo. Most impressively, this benefit occurred in the presence of concomitant therapy with ACE inhibitors and β-blockers within 10 months (N. Engl. J. Med. 2004;351:2049–57).

A major question remains whether this approval should indicate that its use be limited to African American patients only or extended also to all patients. Now that it is approved, it will almost certainly be used in heart failure patients regardless of race. The two drugs are readily available as generic preparations in any pharmacy.

Much has been made of the observation that the antihypertensive effects of ACE inhibitors are less in African Americans than in whites. In addition, the mortality benefit observed in African Americans, compared with whites, in the Vasodilator Heart Failure Trial (V-HeFT I) provides additional foundation for A-HeFT. If a differential blood pressure response was the cause of improved response in A-HeFT, there is little evidence for that. Very minimal decreases of systolic (0.7 mm Hg) and diastolic (1.6 mm Hg) pressure in diastole were seen in the BiDil-treated patients.

It has been suggested that the benefit of BiDil may be related to the antioxidant effect of hydralazine. This theory is supported in part by observation that African Americans may be deficient in nitric oxide, a major source of oxidant metabolism. A lack of nitric oxide at the cellular level as a result of a decrease in endothelial nitric oxide synthase (eNOS) is thought to be a potential putative process of heart failure. If African Americans with heart failure were more deficient in eNOS, they could be more likely to benefit from chronic therapy with BiDil. However, if not, one would expect the effect to be the same, regardless of race.

Some aspects of the therapy are puzzling. The drug was rather poorly tolerated, with only 68% of the BiDil patients staying on the drug, compared with 89% in the placebo group during the 10 months of follow-up. Much of this was presumably due to headache and dizziness, which occurred in 48% and 29% of the patients, respectively. In addition, long-term hydralazine use has been reported to result in a lupus-like syndrome with arthritis at doses greater than 200 mg/day, particularly in patients with renal dysfunction. The dose used in A-HeFT was 225 mg/day. Unfortunately, the duration A-HeFT was short, owing to its observed benefit.

The A-HeFT findings provide a new approach to treating heart failure, regardless of race. If the antioxidant hypothesis is correct, its application should not be limited to African Americans. Given that previous clinical trials in heart failure—which, unfortunately, have been dominated by whites—have been applied to all heart failure patients, regardless of race, it is reasonable that the results in A-HeFT should also be applied to all heart failure patients.

There was a time when one could almost explain what a cardiologist does. But things are changing. The boundaries of professional performance and competence are expanding and becoming increasingly blurred.

The traditional domain of the interventional cardiologist has been expanded to include the carotid artery and peripheral vessels. If we can dilate and stent a coronary artery, why not do the same to the carotid or femoral artery? The improvement in imaging also has led to the cardiologists invading areas traditionally assigned to radiologists. And in a very short period of time we have challenged the turf of many of our colleagues in vascular, cardiac, and neurologic surgery.

Many of these changes are driven by new technologies that have expanded the clinical parameters of skilled physicians. They also have occurred as a result of the dynamic changes in therapy that have evolved at the same time. The urgency for care and the desire for cardiovascular “one-stop” therapy have made accessibility an important driving force. If you saw a tight iliac lesion as you passed a catheter toward the coronary artery in a patient with claudication, wouldn't you take care of it?

The shifting of therapeutic boundaries also has occurred within cardiology as we see the transfer of clinical responsibility from the electrophysiologists to the general cardiologists for pacemaker and defibrillator implantation to meet the increased demand for these devices. We may even see cardiac surgeons implanting these devices as they did in years past as they find time on their hands.

As the parameters of cardiology expand, it is becoming clear that we are unable to meet the demands for our core clinical services. Emergency and internal medicine physicians, who can now be trained and certified in echocardiography, play a large role in providing echocardiographic services. This has occurred as a result of the availability of inexpensive and portable echocardiograph equipment. The need for heart failure care has led to the training of internal medicine physicians outside of the cardiology fellowship tract in this field.

These unrestrained movements are reflected in cardiology training programs. Young physicians who wish to become cardiologists are limited by the scarcity of training positions. Many trainees find that the programs are inflexible, making it impossible to concentrate in certain areas of interest. Significant changes in training programs must be made to address the needs of trainees who wish to pursue training exclusive of interventional procedures. Every cardiologist does not need to know how to push a catheter. In fact, pushing a catheter may become a lost art as MRI and CT technologies advance.

The direction of patient care will remain with the physician who provides the care. For the most part, the treatment of cardiovascular disease in the broadest sense remains in the hands of the cardiologist. It is the cardiologist who answers the call at 3 in the morning. No one is going to call the neighborhood radiologist for chest pain or the neurosurgeon for syncope. The cardiology community must ensure the availability of a sufficient number of cardiologists for the future. It will also need to provide more flexibility in training to provide the diversity of services for the 21st century.

There was a time when one could almost explain what a cardiologist does. But things are changing. The boundaries of professional performance and competence are expanding and becoming increasingly blurred.

The traditional domain of the interventional cardiologist has been expanded to include the carotid artery and peripheral vessels. If we can dilate and stent a coronary artery, why not do the same to the carotid or femoral artery? The improvement in imaging also has led to the cardiologists invading areas traditionally assigned to radiologists. And in a very short period of time we have challenged the turf of many of our colleagues in vascular, cardiac, and neurologic surgery.

Many of these changes are driven by new technologies that have expanded the clinical parameters of skilled physicians. They also have occurred as a result of the dynamic changes in therapy that have evolved at the same time. The urgency for care and the desire for cardiovascular “one-stop” therapy have made accessibility an important driving force. If you saw a tight iliac lesion as you passed a catheter toward the coronary artery in a patient with claudication, wouldn't you take care of it?

The shifting of therapeutic boundaries also has occurred within cardiology as we see the transfer of clinical responsibility from the electrophysiologists to the general cardiologists for pacemaker and defibrillator implantation to meet the increased demand for these devices. We may even see cardiac surgeons implanting these devices as they did in years past as they find time on their hands.

As the parameters of cardiology expand, it is becoming clear that we are unable to meet the demands for our core clinical services. Emergency and internal medicine physicians, who can now be trained and certified in echocardiography, play a large role in providing echocardiographic services. This has occurred as a result of the availability of inexpensive and portable echocardiograph equipment. The need for heart failure care has led to the training of internal medicine physicians outside of the cardiology fellowship tract in this field.

These unrestrained movements are reflected in cardiology training programs. Young physicians who wish to become cardiologists are limited by the scarcity of training positions. Many trainees find that the programs are inflexible, making it impossible to concentrate in certain areas of interest. Significant changes in training programs must be made to address the needs of trainees who wish to pursue training exclusive of interventional procedures. Every cardiologist does not need to know how to push a catheter. In fact, pushing a catheter may become a lost art as MRI and CT technologies advance.

The direction of patient care will remain with the physician who provides the care. For the most part, the treatment of cardiovascular disease in the broadest sense remains in the hands of the cardiologist. It is the cardiologist who answers the call at 3 in the morning. No one is going to call the neighborhood radiologist for chest pain or the neurosurgeon for syncope. The cardiology community must ensure the availability of a sufficient number of cardiologists for the future. It will also need to provide more flexibility in training to provide the diversity of services for the 21st century.

There was a time when one could almost explain what a cardiologist does. But things are changing. The boundaries of professional performance and competence are expanding and becoming increasingly blurred.

The traditional domain of the interventional cardiologist has been expanded to include the carotid artery and peripheral vessels. If we can dilate and stent a coronary artery, why not do the same to the carotid or femoral artery? The improvement in imaging also has led to the cardiologists invading areas traditionally assigned to radiologists. And in a very short period of time we have challenged the turf of many of our colleagues in vascular, cardiac, and neurologic surgery.

Many of these changes are driven by new technologies that have expanded the clinical parameters of skilled physicians. They also have occurred as a result of the dynamic changes in therapy that have evolved at the same time. The urgency for care and the desire for cardiovascular “one-stop” therapy have made accessibility an important driving force. If you saw a tight iliac lesion as you passed a catheter toward the coronary artery in a patient with claudication, wouldn't you take care of it?

The shifting of therapeutic boundaries also has occurred within cardiology as we see the transfer of clinical responsibility from the electrophysiologists to the general cardiologists for pacemaker and defibrillator implantation to meet the increased demand for these devices. We may even see cardiac surgeons implanting these devices as they did in years past as they find time on their hands.

As the parameters of cardiology expand, it is becoming clear that we are unable to meet the demands for our core clinical services. Emergency and internal medicine physicians, who can now be trained and certified in echocardiography, play a large role in providing echocardiographic services. This has occurred as a result of the availability of inexpensive and portable echocardiograph equipment. The need for heart failure care has led to the training of internal medicine physicians outside of the cardiology fellowship tract in this field.

These unrestrained movements are reflected in cardiology training programs. Young physicians who wish to become cardiologists are limited by the scarcity of training positions. Many trainees find that the programs are inflexible, making it impossible to concentrate in certain areas of interest. Significant changes in training programs must be made to address the needs of trainees who wish to pursue training exclusive of interventional procedures. Every cardiologist does not need to know how to push a catheter. In fact, pushing a catheter may become a lost art as MRI and CT technologies advance.

The direction of patient care will remain with the physician who provides the care. For the most part, the treatment of cardiovascular disease in the broadest sense remains in the hands of the cardiologist. It is the cardiologist who answers the call at 3 in the morning. No one is going to call the neighborhood radiologist for chest pain or the neurosurgeon for syncope. The cardiology community must ensure the availability of a sufficient number of cardiologists for the future. It will also need to provide more flexibility in training to provide the diversity of services for the 21st century.

Randomized clinical trials have had an immense effect on the practice of medicine. However, in order to answer the questions posed in such trials, relevant and sufficient patient populations and treatments must be identified.

Large RCTs, or megatrials, can identify small differences in populations but tend to exaggerate their significance. Several megatrials have questionable relevance to clinical care.

The recent COMMIT/CCS-2 study examined the role of early intravenous metoprolol in nearly 46,000 Chinese patients with Killip class I-III ST-segment-elevation MI (STEMI). But in contrast to U.S. treatment practices, fibrinolysis was common and percutaneous coronary intervention (PCI) was uncommon. In addition, the trial design included intravenous metoprolol for patients with Killip class III with heart failure, a treatment that many U.S. physicians would have been reluctant to give. The data indicated that this reluctance was well founded. Metoprolol caused an increase in death due to shock and heart failure in the Killip class III patients, which counterbalanced the decrease in arrhythmic deaths observed in the Killip I and II patients. Overall, there was no benefit associated with intravenous metoprolol in STEMI patients.

The GUSTO I trial, reported in 1993, randomized 41,021 patients with STEMI to compare the benefit of thrombolysis with streptokinase with accelerated tissue plasminogen activator (TPA), both combined with intravenous heparin. The 30-day mortality was 7.4% in streptokinase-treated patients and 6.3% in TPA patients. Despite this meager absolute difference of 1.1% (P = .001) and in the face of increased hemorrhagic strokes in the TPA-treated patients (P = .03), TPA, at a cost 10 times that of streptokinase, became the U.S. standard of therapy, while streptokinase remains the most common thrombolytic therapy in the rest of the world.

The HOPE trial enrolled 9,297 patients to test the benefit of the ACE inhibitor ramipril in patients at a high risk of CAD on the composite end point of ischemic events including death. In 2000, after 5 years of follow-up, the event rates were 17.8% in the placebo group and 14.0% in the ramipril group (P < .001). These results led to the rapid inclusion of ACE inhibitor therapy in any patients with or at risk of CAD. But meanwhile, another RCT, PEACE, had enrolled 8,290 similar patients to test the benefit of the ACE inhibitor trandolapril in patients who were being treated with β-blockers, statins, and PCI. PEACE reported its findings in 2004 and found no benefit of ACE inhibitors, largely due the more aggressive concomitant therapy, which resulted in a lower placebo event rate. In just a few short years, therapy had changed so rapidly that ACE inhibitors no longer appeared to have an impact on the outcome in patients at risk of ischemic events. In retrospect, HOPE was dated even before it was reported.

RCTs continue to impact on our bedside decisions. These experiences with megatrials, however, give reason to be critical of their importance in the care of our patients. It is best to remember that today's scientific “truths” may be shown to be “false” tomorrow.

Randomized clinical trials have had an immense effect on the practice of medicine. However, in order to answer the questions posed in such trials, relevant and sufficient patient populations and treatments must be identified.

Large RCTs, or megatrials, can identify small differences in populations but tend to exaggerate their significance. Several megatrials have questionable relevance to clinical care.

The recent COMMIT/CCS-2 study examined the role of early intravenous metoprolol in nearly 46,000 Chinese patients with Killip class I-III ST-segment-elevation MI (STEMI). But in contrast to U.S. treatment practices, fibrinolysis was common and percutaneous coronary intervention (PCI) was uncommon. In addition, the trial design included intravenous metoprolol for patients with Killip class III with heart failure, a treatment that many U.S. physicians would have been reluctant to give. The data indicated that this reluctance was well founded. Metoprolol caused an increase in death due to shock and heart failure in the Killip class III patients, which counterbalanced the decrease in arrhythmic deaths observed in the Killip I and II patients. Overall, there was no benefit associated with intravenous metoprolol in STEMI patients.

The GUSTO I trial, reported in 1993, randomized 41,021 patients with STEMI to compare the benefit of thrombolysis with streptokinase with accelerated tissue plasminogen activator (TPA), both combined with intravenous heparin. The 30-day mortality was 7.4% in streptokinase-treated patients and 6.3% in TPA patients. Despite this meager absolute difference of 1.1% (P = .001) and in the face of increased hemorrhagic strokes in the TPA-treated patients (P = .03), TPA, at a cost 10 times that of streptokinase, became the U.S. standard of therapy, while streptokinase remains the most common thrombolytic therapy in the rest of the world.

The HOPE trial enrolled 9,297 patients to test the benefit of the ACE inhibitor ramipril in patients at a high risk of CAD on the composite end point of ischemic events including death. In 2000, after 5 years of follow-up, the event rates were 17.8% in the placebo group and 14.0% in the ramipril group (P < .001). These results led to the rapid inclusion of ACE inhibitor therapy in any patients with or at risk of CAD. But meanwhile, another RCT, PEACE, had enrolled 8,290 similar patients to test the benefit of the ACE inhibitor trandolapril in patients who were being treated with β-blockers, statins, and PCI. PEACE reported its findings in 2004 and found no benefit of ACE inhibitors, largely due the more aggressive concomitant therapy, which resulted in a lower placebo event rate. In just a few short years, therapy had changed so rapidly that ACE inhibitors no longer appeared to have an impact on the outcome in patients at risk of ischemic events. In retrospect, HOPE was dated even before it was reported.

RCTs continue to impact on our bedside decisions. These experiences with megatrials, however, give reason to be critical of their importance in the care of our patients. It is best to remember that today's scientific “truths” may be shown to be “false” tomorrow.

Randomized clinical trials have had an immense effect on the practice of medicine. However, in order to answer the questions posed in such trials, relevant and sufficient patient populations and treatments must be identified.

Large RCTs, or megatrials, can identify small differences in populations but tend to exaggerate their significance. Several megatrials have questionable relevance to clinical care.

The recent COMMIT/CCS-2 study examined the role of early intravenous metoprolol in nearly 46,000 Chinese patients with Killip class I-III ST-segment-elevation MI (STEMI). But in contrast to U.S. treatment practices, fibrinolysis was common and percutaneous coronary intervention (PCI) was uncommon. In addition, the trial design included intravenous metoprolol for patients with Killip class III with heart failure, a treatment that many U.S. physicians would have been reluctant to give. The data indicated that this reluctance was well founded. Metoprolol caused an increase in death due to shock and heart failure in the Killip class III patients, which counterbalanced the decrease in arrhythmic deaths observed in the Killip I and II patients. Overall, there was no benefit associated with intravenous metoprolol in STEMI patients.

The GUSTO I trial, reported in 1993, randomized 41,021 patients with STEMI to compare the benefit of thrombolysis with streptokinase with accelerated tissue plasminogen activator (TPA), both combined with intravenous heparin. The 30-day mortality was 7.4% in streptokinase-treated patients and 6.3% in TPA patients. Despite this meager absolute difference of 1.1% (P = .001) and in the face of increased hemorrhagic strokes in the TPA-treated patients (P = .03), TPA, at a cost 10 times that of streptokinase, became the U.S. standard of therapy, while streptokinase remains the most common thrombolytic therapy in the rest of the world.

The HOPE trial enrolled 9,297 patients to test the benefit of the ACE inhibitor ramipril in patients at a high risk of CAD on the composite end point of ischemic events including death. In 2000, after 5 years of follow-up, the event rates were 17.8% in the placebo group and 14.0% in the ramipril group (P < .001). These results led to the rapid inclusion of ACE inhibitor therapy in any patients with or at risk of CAD. But meanwhile, another RCT, PEACE, had enrolled 8,290 similar patients to test the benefit of the ACE inhibitor trandolapril in patients who were being treated with β-blockers, statins, and PCI. PEACE reported its findings in 2004 and found no benefit of ACE inhibitors, largely due the more aggressive concomitant therapy, which resulted in a lower placebo event rate. In just a few short years, therapy had changed so rapidly that ACE inhibitors no longer appeared to have an impact on the outcome in patients at risk of ischemic events. In retrospect, HOPE was dated even before it was reported.

RCTs continue to impact on our bedside decisions. These experiences with megatrials, however, give reason to be critical of their importance in the care of our patients. It is best to remember that today's scientific “truths” may be shown to be “false” tomorrow.

The competency of older physicians is being questioned as a result of a recent study that concludes “physicians with more experience may paradoxically be at risk for providing lower-quality care.” An accompanying editorial, which challenges the headline of this column, all but reads us oldies out of the profession until we are reeducated into the new method of care.

I admit to some bias on this topic. The authors indicate that older physicians don't adhere to guidelines like the young ones do and therefore adversely affect the quality of care. However, the authors were unable to provide any convincing data to suggest that noncompliance affected outcome, and admitted that the study was limited and not entirely reliable (Ann. Intern. Med. 2005;142:260-73,302-3).

Prior to the meteoric increase in guidelines in the 1990s, doctors were on their own to make medical decisions, based on the knowledge of pathophysiology, physical diagnosis, and the paucity of drugs available to them. Since the development of guidelines, many young physicians think they have little need for these arcane concepts because they can turn to their PalmPilot for the answers. Laboratory data have become the driving force for decision making: Give me the ejection fraction or the percent stenosis, and I will give you the therapy. Never mind that guidelines are meant to guide and are not written in stone. Forget that fewer than 20% of the patients we treat actually fit into any particular guideline, or that guidelines are constructed largely from clinical trials of patients who only vaguely resemble the general population. And don't forget that guidelines are continually changing, as is science itself.

Deviation from guidelines may in fact represent the vanguard of better medicine. Consider that for years, guidelines for the treatment of ST-segment elevation MI said that every patient should receive intravenous β-blockade unless bradycardia or hypotension is present. Many physicians, young and old, deviated from that dictum, assuming that patients in acute heart failure could do very poorly. Guidelines changed, and recent trials, including COMMIT/CCS-2—see page 18—confirm that such treatment actually may increase mortality.

The young physicians I work with are terrific—well motivated and very smart. They have been schooled in the use of guidelines, but they often lose sight of the patient in their attempt to practice evidence-based medicine. They are using guidelines as a haven in the morass of the uncertainties of decision making and in a false sense of protection from malpractice.

The dissemination of evidence from clinical trials has unquestionably improved the quality of care of cardiac patients worldwide. These trial data have been incorporated into quality standards and care guidelines with great success. Skilled and sensitive physicians, regardless of their age, will take guidelines and apply them to their patients. However, they may appropriately decide to deviate from those guidelines. Adherence to guidelines is an imperfect measure of physician performance. Perhaps older physicians, because of their experience, can function more easily outside the guidelines.

The competency of older physicians is being questioned as a result of a recent study that concludes “physicians with more experience may paradoxically be at risk for providing lower-quality care.” An accompanying editorial, which challenges the headline of this column, all but reads us oldies out of the profession until we are reeducated into the new method of care.

I admit to some bias on this topic. The authors indicate that older physicians don't adhere to guidelines like the young ones do and therefore adversely affect the quality of care. However, the authors were unable to provide any convincing data to suggest that noncompliance affected outcome, and admitted that the study was limited and not entirely reliable (Ann. Intern. Med. 2005;142:260-73,302-3).

Prior to the meteoric increase in guidelines in the 1990s, doctors were on their own to make medical decisions, based on the knowledge of pathophysiology, physical diagnosis, and the paucity of drugs available to them. Since the development of guidelines, many young physicians think they have little need for these arcane concepts because they can turn to their PalmPilot for the answers. Laboratory data have become the driving force for decision making: Give me the ejection fraction or the percent stenosis, and I will give you the therapy. Never mind that guidelines are meant to guide and are not written in stone. Forget that fewer than 20% of the patients we treat actually fit into any particular guideline, or that guidelines are constructed largely from clinical trials of patients who only vaguely resemble the general population. And don't forget that guidelines are continually changing, as is science itself.

Deviation from guidelines may in fact represent the vanguard of better medicine. Consider that for years, guidelines for the treatment of ST-segment elevation MI said that every patient should receive intravenous β-blockade unless bradycardia or hypotension is present. Many physicians, young and old, deviated from that dictum, assuming that patients in acute heart failure could do very poorly. Guidelines changed, and recent trials, including COMMIT/CCS-2—see page 18—confirm that such treatment actually may increase mortality.

The young physicians I work with are terrific—well motivated and very smart. They have been schooled in the use of guidelines, but they often lose sight of the patient in their attempt to practice evidence-based medicine. They are using guidelines as a haven in the morass of the uncertainties of decision making and in a false sense of protection from malpractice.

The dissemination of evidence from clinical trials has unquestionably improved the quality of care of cardiac patients worldwide. These trial data have been incorporated into quality standards and care guidelines with great success. Skilled and sensitive physicians, regardless of their age, will take guidelines and apply them to their patients. However, they may appropriately decide to deviate from those guidelines. Adherence to guidelines is an imperfect measure of physician performance. Perhaps older physicians, because of their experience, can function more easily outside the guidelines.

The competency of older physicians is being questioned as a result of a recent study that concludes “physicians with more experience may paradoxically be at risk for providing lower-quality care.” An accompanying editorial, which challenges the headline of this column, all but reads us oldies out of the profession until we are reeducated into the new method of care.

I admit to some bias on this topic. The authors indicate that older physicians don't adhere to guidelines like the young ones do and therefore adversely affect the quality of care. However, the authors were unable to provide any convincing data to suggest that noncompliance affected outcome, and admitted that the study was limited and not entirely reliable (Ann. Intern. Med. 2005;142:260-73,302-3).

Prior to the meteoric increase in guidelines in the 1990s, doctors were on their own to make medical decisions, based on the knowledge of pathophysiology, physical diagnosis, and the paucity of drugs available to them. Since the development of guidelines, many young physicians think they have little need for these arcane concepts because they can turn to their PalmPilot for the answers. Laboratory data have become the driving force for decision making: Give me the ejection fraction or the percent stenosis, and I will give you the therapy. Never mind that guidelines are meant to guide and are not written in stone. Forget that fewer than 20% of the patients we treat actually fit into any particular guideline, or that guidelines are constructed largely from clinical trials of patients who only vaguely resemble the general population. And don't forget that guidelines are continually changing, as is science itself.

Deviation from guidelines may in fact represent the vanguard of better medicine. Consider that for years, guidelines for the treatment of ST-segment elevation MI said that every patient should receive intravenous β-blockade unless bradycardia or hypotension is present. Many physicians, young and old, deviated from that dictum, assuming that patients in acute heart failure could do very poorly. Guidelines changed, and recent trials, including COMMIT/CCS-2—see page 18—confirm that such treatment actually may increase mortality.

The young physicians I work with are terrific—well motivated and very smart. They have been schooled in the use of guidelines, but they often lose sight of the patient in their attempt to practice evidence-based medicine. They are using guidelines as a haven in the morass of the uncertainties of decision making and in a false sense of protection from malpractice.

The dissemination of evidence from clinical trials has unquestionably improved the quality of care of cardiac patients worldwide. These trial data have been incorporated into quality standards and care guidelines with great success. Skilled and sensitive physicians, regardless of their age, will take guidelines and apply them to their patients. However, they may appropriately decide to deviate from those guidelines. Adherence to guidelines is an imperfect measure of physician performance. Perhaps older physicians, because of their experience, can function more easily outside the guidelines.

The development of the pacemaker in the 1950s led to an entire subspecialty of electrophysiology. The development of ultrasonography and the echocardiogram provided amazing images of the heart, and now it can be viewed in three dimensions. In the not&hyphen;too&hyphen;distant future the incorporation of magnetic resonance imaging and computed tomography hold the promise that they will change our understanding of cardiovascular disease and its treatment.

The accessibility of these current and future technologies to both the investigator and the clinician is key to the expansion of our knowledge and its application to the patient.

In this issue, a radiologist raises serious issues about the appropriateness of the use of current technology by nonradiologists and, particularly, cardiologists. David C. Levin, M.D., suggests that the ready access of diagnostic technologies in the cardiologist's office is self&hyphen;serving and leads to overuse to such an extent that it will “bankrupt the health care system.” These are serious charges that require introspection by cardiologists. He does not speak, however, of the benefit accruing to the patient from the accessibility to diagnostic technology in the physician's office.

We have seen many professional boundaries of diseases become blurred as a result of technological development. The boundaries of cardiac surgery have fallen into the domain of the treating interventional cardiologists with the development of stent technology. Ultrasonography, largely staked out to be the radiologist's domain, lost echocardiography to the cardiologists as they used that technology to understand cardiac physiology.

Now multidetector computed tomography portends to be the next battlefield between the radiologists and the cardiologists. These machines can not only image the degree of cardiac calcification like electron beam CT, which is widely available in a “store front” near you, but also can image with a dye injection the lumen and wall of the coronary artery. Its potential as a screening technique in lieu of angiography has the potential to produce further friction between radiologists and cardiologists. Who owns these new machines and who will interpret the images is of concern to both specialties. Radiologists are already seeking training requirements favorable to their specialty.

Various technologists and scientists can and will add to the development and application of new tools. But the application of these tools to the patients will necessarily reside with the practitioner. This license, however, does not attach to it the right to use it inappropriately. None of us want to put further strains on our health care system, but we do need to have ready access to the diagnostic technologies that we use in the everyday practice of cardiology.

The development of the pacemaker in the 1950s led to an entire subspecialty of electrophysiology. The development of ultrasonography and the echocardiogram provided amazing images of the heart, and now it can be viewed in three dimensions. In the not&hyphen;too&hyphen;distant future the incorporation of magnetic resonance imaging and computed tomography hold the promise that they will change our understanding of cardiovascular disease and its treatment.

The accessibility of these current and future technologies to both the investigator and the clinician is key to the expansion of our knowledge and its application to the patient.

In this issue, a radiologist raises serious issues about the appropriateness of the use of current technology by nonradiologists and, particularly, cardiologists. David C. Levin, M.D., suggests that the ready access of diagnostic technologies in the cardiologist's office is self&hyphen;serving and leads to overuse to such an extent that it will “bankrupt the health care system.” These are serious charges that require introspection by cardiologists. He does not speak, however, of the benefit accruing to the patient from the accessibility to diagnostic technology in the physician's office.

We have seen many professional boundaries of diseases become blurred as a result of technological development. The boundaries of cardiac surgery have fallen into the domain of the treating interventional cardiologists with the development of stent technology. Ultrasonography, largely staked out to be the radiologist's domain, lost echocardiography to the cardiologists as they used that technology to understand cardiac physiology.

Now multidetector computed tomography portends to be the next battlefield between the radiologists and the cardiologists. These machines can not only image the degree of cardiac calcification like electron beam CT, which is widely available in a “store front” near you, but also can image with a dye injection the lumen and wall of the coronary artery. Its potential as a screening technique in lieu of angiography has the potential to produce further friction between radiologists and cardiologists. Who owns these new machines and who will interpret the images is of concern to both specialties. Radiologists are already seeking training requirements favorable to their specialty.

Various technologists and scientists can and will add to the development and application of new tools. But the application of these tools to the patients will necessarily reside with the practitioner. This license, however, does not attach to it the right to use it inappropriately. None of us want to put further strains on our health care system, but we do need to have ready access to the diagnostic technologies that we use in the everyday practice of cardiology.

The development of the pacemaker in the 1950s led to an entire subspecialty of electrophysiology. The development of ultrasonography and the echocardiogram provided amazing images of the heart, and now it can be viewed in three dimensions. In the not&hyphen;too&hyphen;distant future the incorporation of magnetic resonance imaging and computed tomography hold the promise that they will change our understanding of cardiovascular disease and its treatment.

The accessibility of these current and future technologies to both the investigator and the clinician is key to the expansion of our knowledge and its application to the patient.

In this issue, a radiologist raises serious issues about the appropriateness of the use of current technology by nonradiologists and, particularly, cardiologists. David C. Levin, M.D., suggests that the ready access of diagnostic technologies in the cardiologist's office is self&hyphen;serving and leads to overuse to such an extent that it will “bankrupt the health care system.” These are serious charges that require introspection by cardiologists. He does not speak, however, of the benefit accruing to the patient from the accessibility to diagnostic technology in the physician's office.

We have seen many professional boundaries of diseases become blurred as a result of technological development. The boundaries of cardiac surgery have fallen into the domain of the treating interventional cardiologists with the development of stent technology. Ultrasonography, largely staked out to be the radiologist's domain, lost echocardiography to the cardiologists as they used that technology to understand cardiac physiology.

Now multidetector computed tomography portends to be the next battlefield between the radiologists and the cardiologists. These machines can not only image the degree of cardiac calcification like electron beam CT, which is widely available in a “store front” near you, but also can image with a dye injection the lumen and wall of the coronary artery. Its potential as a screening technique in lieu of angiography has the potential to produce further friction between radiologists and cardiologists. Who owns these new machines and who will interpret the images is of concern to both specialties. Radiologists are already seeking training requirements favorable to their specialty.

Various technologists and scientists can and will add to the development and application of new tools. But the application of these tools to the patients will necessarily reside with the practitioner. This license, however, does not attach to it the right to use it inappropriately. None of us want to put further strains on our health care system, but we do need to have ready access to the diagnostic technologies that we use in the everyday practice of cardiology.

In the wake of the Vioxx scandal, the Food and Drug Administration has become the whipping boy of the press, Congress, and even agency.

This column has not been lacking in criticism of the FDA. We have expressed concern about some of its premature decisions and lack of postapproval surveillance of drugs. Nevertheless, let's place some of the blame where it should be placed. The FDA, created in 1906 as part of the Pure Food and Drug Act, has responded to changes in both the industry that it is intended to control and in the human beings it is expected to protect. In its nearly 100 years of life, drugs have become more complex and Americans have grown older. Advances in technology and pharmacology in the last half century have provided physicians and patients a breathtaking array of medical options to prolong and improve the quality of life. But these products have the potential to harm those individuals who are the treatment targets.

It was but a short 12 years ago that Congress pressured the FDA to get in bed with the pharmaceutical industry in order to expedite drug approval and get new drugs to market faster by collecting user fees from applicants. As a result of this and other initiatives, the approval of new molecular entities increased from 30 in 1991 to 53 in 1996. But in order to maintain that pharmaceutical support, other programs had to be cut over time. Now, Congress charges that the FDA has been too hasty and superficial with their drug approval process.

As medical therapy has changed in the last half century, so to has the role of the FDA. Mid-20th-century medical therapy was focused on the treatment of episodic short-term diseases like pneumonia. Safety and efficacy could be measured in days or weeks. Major advances occurred in the 1970s and 1980s that led to the consideration of drugs for the long-term prevention and treatment of chronic diseases that affect an increasingly aging population. Clinical trials suggested that drugs should be taken for a lifetime, and that can be a very long time when therapy was initiated in the midlife or even earlier. These randomized clinical trials, at best, provided information over 1–2 years of therapy and were tested in very unique populations. We have little knowledge of the effects of taking drugs for longer periods and even less information when the drugs are applied to broader and unselected populations. Numerous misadventures emerged. Vioxx (rofecoxib) can be added to a long list of drugs that were not fully investigated prior to their release.

It is therefore critical that we develop methodologies to understand the efficacy and safety of drugs and devices after initial short-term approval.

Some have suggested that we develop a two-track approval process in which drug efficacy and safety are established for a short term, at the same time establishing a surveillance system to monitor the long-term drug safety. The FDA is the proper environment to carry out this mission, but it needs to have Congressional support to make it happen. The Vioxx experience should provide the motivation necessary to achieve this long delayed effort.

In the wake of the Vioxx scandal, the Food and Drug Administration has become the whipping boy of the press, Congress, and even agency.

This column has not been lacking in criticism of the FDA. We have expressed concern about some of its premature decisions and lack of postapproval surveillance of drugs. Nevertheless, let's place some of the blame where it should be placed. The FDA, created in 1906 as part of the Pure Food and Drug Act, has responded to changes in both the industry that it is intended to control and in the human beings it is expected to protect. In its nearly 100 years of life, drugs have become more complex and Americans have grown older. Advances in technology and pharmacology in the last half century have provided physicians and patients a breathtaking array of medical options to prolong and improve the quality of life. But these products have the potential to harm those individuals who are the treatment targets.

It was but a short 12 years ago that Congress pressured the FDA to get in bed with the pharmaceutical industry in order to expedite drug approval and get new drugs to market faster by collecting user fees from applicants. As a result of this and other initiatives, the approval of new molecular entities increased from 30 in 1991 to 53 in 1996. But in order to maintain that pharmaceutical support, other programs had to be cut over time. Now, Congress charges that the FDA has been too hasty and superficial with their drug approval process.

As medical therapy has changed in the last half century, so to has the role of the FDA. Mid-20th-century medical therapy was focused on the treatment of episodic short-term diseases like pneumonia. Safety and efficacy could be measured in days or weeks. Major advances occurred in the 1970s and 1980s that led to the consideration of drugs for the long-term prevention and treatment of chronic diseases that affect an increasingly aging population. Clinical trials suggested that drugs should be taken for a lifetime, and that can be a very long time when therapy was initiated in the midlife or even earlier. These randomized clinical trials, at best, provided information over 1–2 years of therapy and were tested in very unique populations. We have little knowledge of the effects of taking drugs for longer periods and even less information when the drugs are applied to broader and unselected populations. Numerous misadventures emerged. Vioxx (rofecoxib) can be added to a long list of drugs that were not fully investigated prior to their release.

It is therefore critical that we develop methodologies to understand the efficacy and safety of drugs and devices after initial short-term approval.

Some have suggested that we develop a two-track approval process in which drug efficacy and safety are established for a short term, at the same time establishing a surveillance system to monitor the long-term drug safety. The FDA is the proper environment to carry out this mission, but it needs to have Congressional support to make it happen. The Vioxx experience should provide the motivation necessary to achieve this long delayed effort.

In the wake of the Vioxx scandal, the Food and Drug Administration has become the whipping boy of the press, Congress, and even agency.

This column has not been lacking in criticism of the FDA. We have expressed concern about some of its premature decisions and lack of postapproval surveillance of drugs. Nevertheless, let's place some of the blame where it should be placed. The FDA, created in 1906 as part of the Pure Food and Drug Act, has responded to changes in both the industry that it is intended to control and in the human beings it is expected to protect. In its nearly 100 years of life, drugs have become more complex and Americans have grown older. Advances in technology and pharmacology in the last half century have provided physicians and patients a breathtaking array of medical options to prolong and improve the quality of life. But these products have the potential to harm those individuals who are the treatment targets.

It was but a short 12 years ago that Congress pressured the FDA to get in bed with the pharmaceutical industry in order to expedite drug approval and get new drugs to market faster by collecting user fees from applicants. As a result of this and other initiatives, the approval of new molecular entities increased from 30 in 1991 to 53 in 1996. But in order to maintain that pharmaceutical support, other programs had to be cut over time. Now, Congress charges that the FDA has been too hasty and superficial with their drug approval process.

As medical therapy has changed in the last half century, so to has the role of the FDA. Mid-20th-century medical therapy was focused on the treatment of episodic short-term diseases like pneumonia. Safety and efficacy could be measured in days or weeks. Major advances occurred in the 1970s and 1980s that led to the consideration of drugs for the long-term prevention and treatment of chronic diseases that affect an increasingly aging population. Clinical trials suggested that drugs should be taken for a lifetime, and that can be a very long time when therapy was initiated in the midlife or even earlier. These randomized clinical trials, at best, provided information over 1–2 years of therapy and were tested in very unique populations. We have little knowledge of the effects of taking drugs for longer periods and even less information when the drugs are applied to broader and unselected populations. Numerous misadventures emerged. Vioxx (rofecoxib) can be added to a long list of drugs that were not fully investigated prior to their release.

It is therefore critical that we develop methodologies to understand the efficacy and safety of drugs and devices after initial short-term approval.

Some have suggested that we develop a two-track approval process in which drug efficacy and safety are established for a short term, at the same time establishing a surveillance system to monitor the long-term drug safety. The FDA is the proper environment to carry out this mission, but it needs to have Congressional support to make it happen. The Vioxx experience should provide the motivation necessary to achieve this long delayed effort.