Clinical question: To what extent does diagnostic phlebotomy contribute to hospital-acquired anemia (HAA) during acute myocardial infarction (AMI)?

Background: During AMI, hospital-acquired HAA is associated with higher mortality and poorer health status. Moderate to severe HAA (nadir hemoglobin level <11 g/dL) has been shown to be prognostically important. The contribution of diagnostic phlebotomy blood loss on HAA is unknown and is a potentially modifiable factor.

Study design: Retrospective observational cohort study.

Setting: Fifty-seven U.S. hospitals.

Synopsis: Using Cerner Corp.'s Health Facts database, information was collected on 17,676 patients with AMI. Moderate to severe HAA developed in 3,551 (20%) patients who were not anemic upon admission. The diagnostic blood loss was estimated by assuming minimal blood volume per adult tube required to perform the lab work obtained. The mean phlebotomy volume was higher in patients with HAA compared with patients without HAA (173.8 mL vs. 83.5 mL; P<0.001). There was significant variation of diagnostic blood loss between hospitals. The risk of HAA increased by 18% (RR 1.18; 95% CI, 1.13-1.22) for every 50 mL of diagnostic blood loss.

Patients with HAA were noted to have greater disease severity and comorbidities. No causal inference can be made given the observational nature of the study. Randomized trials are needed to evaluate if strategies to reduce diagnostic blood loss can reduce HAA and improve clinical outcomes for patients with AMI.

Bottom line: Diagnostic blood loss is associated with development of hospital-acquired anemia in patients with acute myocardial infarction.

Citation: Salisbury AC, Reid KJ, Alexander KP, et al. Diagnostic blood loss from phlebotomy and hospital-acquired anemia during acute myocardial infarction. Arch Intern Med. 2011;171:1646-1653.

For more physician reviews of HM-relevant research, visit our website.

Clinical question: To what extent does diagnostic phlebotomy contribute to hospital-acquired anemia (HAA) during acute myocardial infarction (AMI)?

Background: During AMI, hospital-acquired HAA is associated with higher mortality and poorer health status. Moderate to severe HAA (nadir hemoglobin level <11 g/dL) has been shown to be prognostically important. The contribution of diagnostic phlebotomy blood loss on HAA is unknown and is a potentially modifiable factor.

Study design: Retrospective observational cohort study.

Setting: Fifty-seven U.S. hospitals.

Synopsis: Using Cerner Corp.'s Health Facts database, information was collected on 17,676 patients with AMI. Moderate to severe HAA developed in 3,551 (20%) patients who were not anemic upon admission. The diagnostic blood loss was estimated by assuming minimal blood volume per adult tube required to perform the lab work obtained. The mean phlebotomy volume was higher in patients with HAA compared with patients without HAA (173.8 mL vs. 83.5 mL; P<0.001). There was significant variation of diagnostic blood loss between hospitals. The risk of HAA increased by 18% (RR 1.18; 95% CI, 1.13-1.22) for every 50 mL of diagnostic blood loss.

Patients with HAA were noted to have greater disease severity and comorbidities. No causal inference can be made given the observational nature of the study. Randomized trials are needed to evaluate if strategies to reduce diagnostic blood loss can reduce HAA and improve clinical outcomes for patients with AMI.

Bottom line: Diagnostic blood loss is associated with development of hospital-acquired anemia in patients with acute myocardial infarction.

Citation: Salisbury AC, Reid KJ, Alexander KP, et al. Diagnostic blood loss from phlebotomy and hospital-acquired anemia during acute myocardial infarction. Arch Intern Med. 2011;171:1646-1653.

For more physician reviews of HM-relevant research, visit our website.

Clinical question: To what extent does diagnostic phlebotomy contribute to hospital-acquired anemia (HAA) during acute myocardial infarction (AMI)?

Background: During AMI, hospital-acquired HAA is associated with higher mortality and poorer health status. Moderate to severe HAA (nadir hemoglobin level <11 g/dL) has been shown to be prognostically important. The contribution of diagnostic phlebotomy blood loss on HAA is unknown and is a potentially modifiable factor.

Study design: Retrospective observational cohort study.

Setting: Fifty-seven U.S. hospitals.

Synopsis: Using Cerner Corp.'s Health Facts database, information was collected on 17,676 patients with AMI. Moderate to severe HAA developed in 3,551 (20%) patients who were not anemic upon admission. The diagnostic blood loss was estimated by assuming minimal blood volume per adult tube required to perform the lab work obtained. The mean phlebotomy volume was higher in patients with HAA compared with patients without HAA (173.8 mL vs. 83.5 mL; P<0.001). There was significant variation of diagnostic blood loss between hospitals. The risk of HAA increased by 18% (RR 1.18; 95% CI, 1.13-1.22) for every 50 mL of diagnostic blood loss.

Patients with HAA were noted to have greater disease severity and comorbidities. No causal inference can be made given the observational nature of the study. Randomized trials are needed to evaluate if strategies to reduce diagnostic blood loss can reduce HAA and improve clinical outcomes for patients with AMI.

Bottom line: Diagnostic blood loss is associated with development of hospital-acquired anemia in patients with acute myocardial infarction.

Citation: Salisbury AC, Reid KJ, Alexander KP, et al. Diagnostic blood loss from phlebotomy and hospital-acquired anemia during acute myocardial infarction. Arch Intern Med. 2011;171:1646-1653.

For more physician reviews of HM-relevant research, visit our website.

These are hard times for the United States. Our economy is floundering. Unemployment is high. Bankers and financiers seem to be getting away with immoral and even illegal actions. People are disgruntled and dissatisfied. Our government seems to be unable or unwilling to right the obvious wrongs or to get us out of the morass. There is general malaise.

I believe there is a common thread that underlies our present situation. It is the overarching attitude that behavior in our society is primarily determined by the WIIFM principle or ‘What’s in it for me’.

Let us look at some specific examples. Elected politicians in the executive and legislative branches of our federal government should make decisions on the basis of what is best for society and our country. Unfortunately this consideration is a minor motivation.

Uniformly our President and Congress do what is most likely to get themselves re-elected, i.e., what is best for them personally, not what is best for our country. They are constantly campaigning rather than governing. As a result, actions to support entrepreneurship and private job creation are not taken, and class warfare is encouraged because more votes will be gained than lost.

Attorneys who block tort reform are another example of the WIIFM principle. They must know that the present system is imperfect and costing our society billions of dollars, at least some of which are unjustified. Yet they spend millions supporting the re-election campaigns of legislators to block even a wisp of reform. Both the attorneys and the legislators who are influenced by this legal form of bribery are clearly guided by WIIFM. Society pays and suffers.

Similarly, bankers and others in the financial community, known collectively as Wall Street, guided by the WIIFM principle expend great efforts to preserve a system riddled with opaque derivative securities and other practices which benefit a few clever manipulators and harm our financial system and our society. Financial donations to politicians, again legalized bribery, and unfair executive compensation help to sustain a system in which rewards are far in excess of the value contributed to society.

Labor unions and their leaders are also substantially motivated by WIIFM. Otherwise they might compromise on demands to preserve unsustainable pension and benefit systems that are bankrupting our state and federal governments. The promise of votes and again contribution-associated influence over elected leaders are part of the toxic mix. Once again WIIFM triumphs over what is good for our overall economy and our country. The effort to close the job-creating Boeing plant in South Carolina and the pension preserving battles in Wisconsin and Ohio are glaring examples of the evils of WIIFM.

So also are the efforts of some to block any tax increase. If government waste, spending excesses, and unfair tax loopholes can be sharply diminished, reasonable tax increases can be considered part of a shared sacrifice for the common good of deficit reduction. All must acknowledge that our economic problems can only be solved by the compromise of such shared sacrifice. We will be better off in the long run and so will our progeny.

Physicians can also be motivated by the WIIFM principle. There is the temptation to maintain diminishing incomes at all costs – even by performing procedures that may not be fully indicated or justified, or by spending less than adequate time with individual patients. Our health care system is imperfect in many ways, but physicians too must resist the urge to be guided predominantly by WIIFM.

Finally there is the public at large. Are we guided in our voting by short-term WIIFM? Should we vote for the candidate who will lower our personal taxes the most in the next few years? Or should we vote for the individual who we believe will act in the best interests of our country at-large and its future long-term well-being?

We must all recognize the intrinsic dangers of being motivated excessively by WIIFM. Our country cannot survive and prosper if everyone pursues that motivation. We do not have the resources to do so. We must all display some of the courage, restraint, and spirit of compromise of our forefathers who took huge political and physical risks to found our country. They were motivated by a desire to do what was best for the country at large, to work for the greater good, to do what was right for the whole society. It often required self-denial, shared sacrifice, compromise, altruism, and the responsibility to act for the common good. The WIIFM principle had to be suppressed. The result was a United States of unparalleled greatness.

Today we are drifting away from that greatness. Aside from our military and a few other rare exceptions, the WIIFM principle seems to underlie that drift. Although some self-interest is acceptable and part of the human nature, we must all resist the temptation to make that our predominant motivation. Otherwise our country will decline, and we are doomed to failure.

Clearly, this recognition and movement away from WIIFM, this ‘me-first attitude’, this idea of ‘let someone else sacrifice’ should begin with our key political leaders. They must find the courage to do what is right for our country, and give up their WIIFM motivation of acting solely to get re-elected. If they can start the ball rolling in the right direction, surely other segments of society and indeed all of us should be able to follow.

Dr. Veith is Professor of Surgery at New York University Medical Center and the Cleveland Clinic. He is also an associate medical editor for Vascular Specialist.

The ideas and opinions expresssed in Vascular Specialist do not necessarily reflect those of the Society or the Publisher.

These are hard times for the United States. Our economy is floundering. Unemployment is high. Bankers and financiers seem to be getting away with immoral and even illegal actions. People are disgruntled and dissatisfied. Our government seems to be unable or unwilling to right the obvious wrongs or to get us out of the morass. There is general malaise.

I believe there is a common thread that underlies our present situation. It is the overarching attitude that behavior in our society is primarily determined by the WIIFM principle or ‘What’s in it for me’.

Let us look at some specific examples. Elected politicians in the executive and legislative branches of our federal government should make decisions on the basis of what is best for society and our country. Unfortunately this consideration is a minor motivation.

Uniformly our President and Congress do what is most likely to get themselves re-elected, i.e., what is best for them personally, not what is best for our country. They are constantly campaigning rather than governing. As a result, actions to support entrepreneurship and private job creation are not taken, and class warfare is encouraged because more votes will be gained than lost.

Attorneys who block tort reform are another example of the WIIFM principle. They must know that the present system is imperfect and costing our society billions of dollars, at least some of which are unjustified. Yet they spend millions supporting the re-election campaigns of legislators to block even a wisp of reform. Both the attorneys and the legislators who are influenced by this legal form of bribery are clearly guided by WIIFM. Society pays and suffers.

Similarly, bankers and others in the financial community, known collectively as Wall Street, guided by the WIIFM principle expend great efforts to preserve a system riddled with opaque derivative securities and other practices which benefit a few clever manipulators and harm our financial system and our society. Financial donations to politicians, again legalized bribery, and unfair executive compensation help to sustain a system in which rewards are far in excess of the value contributed to society.

Labor unions and their leaders are also substantially motivated by WIIFM. Otherwise they might compromise on demands to preserve unsustainable pension and benefit systems that are bankrupting our state and federal governments. The promise of votes and again contribution-associated influence over elected leaders are part of the toxic mix. Once again WIIFM triumphs over what is good for our overall economy and our country. The effort to close the job-creating Boeing plant in South Carolina and the pension preserving battles in Wisconsin and Ohio are glaring examples of the evils of WIIFM.

So also are the efforts of some to block any tax increase. If government waste, spending excesses, and unfair tax loopholes can be sharply diminished, reasonable tax increases can be considered part of a shared sacrifice for the common good of deficit reduction. All must acknowledge that our economic problems can only be solved by the compromise of such shared sacrifice. We will be better off in the long run and so will our progeny.

Physicians can also be motivated by the WIIFM principle. There is the temptation to maintain diminishing incomes at all costs – even by performing procedures that may not be fully indicated or justified, or by spending less than adequate time with individual patients. Our health care system is imperfect in many ways, but physicians too must resist the urge to be guided predominantly by WIIFM.

Finally there is the public at large. Are we guided in our voting by short-term WIIFM? Should we vote for the candidate who will lower our personal taxes the most in the next few years? Or should we vote for the individual who we believe will act in the best interests of our country at-large and its future long-term well-being?

We must all recognize the intrinsic dangers of being motivated excessively by WIIFM. Our country cannot survive and prosper if everyone pursues that motivation. We do not have the resources to do so. We must all display some of the courage, restraint, and spirit of compromise of our forefathers who took huge political and physical risks to found our country. They were motivated by a desire to do what was best for the country at large, to work for the greater good, to do what was right for the whole society. It often required self-denial, shared sacrifice, compromise, altruism, and the responsibility to act for the common good. The WIIFM principle had to be suppressed. The result was a United States of unparalleled greatness.

Today we are drifting away from that greatness. Aside from our military and a few other rare exceptions, the WIIFM principle seems to underlie that drift. Although some self-interest is acceptable and part of the human nature, we must all resist the temptation to make that our predominant motivation. Otherwise our country will decline, and we are doomed to failure.

Clearly, this recognition and movement away from WIIFM, this ‘me-first attitude’, this idea of ‘let someone else sacrifice’ should begin with our key political leaders. They must find the courage to do what is right for our country, and give up their WIIFM motivation of acting solely to get re-elected. If they can start the ball rolling in the right direction, surely other segments of society and indeed all of us should be able to follow.

Dr. Veith is Professor of Surgery at New York University Medical Center and the Cleveland Clinic. He is also an associate medical editor for Vascular Specialist.

The ideas and opinions expresssed in Vascular Specialist do not necessarily reflect those of the Society or the Publisher.

These are hard times for the United States. Our economy is floundering. Unemployment is high. Bankers and financiers seem to be getting away with immoral and even illegal actions. People are disgruntled and dissatisfied. Our government seems to be unable or unwilling to right the obvious wrongs or to get us out of the morass. There is general malaise.

I believe there is a common thread that underlies our present situation. It is the overarching attitude that behavior in our society is primarily determined by the WIIFM principle or ‘What’s in it for me’.

Let us look at some specific examples. Elected politicians in the executive and legislative branches of our federal government should make decisions on the basis of what is best for society and our country. Unfortunately this consideration is a minor motivation.

Uniformly our President and Congress do what is most likely to get themselves re-elected, i.e., what is best for them personally, not what is best for our country. They are constantly campaigning rather than governing. As a result, actions to support entrepreneurship and private job creation are not taken, and class warfare is encouraged because more votes will be gained than lost.

Attorneys who block tort reform are another example of the WIIFM principle. They must know that the present system is imperfect and costing our society billions of dollars, at least some of which are unjustified. Yet they spend millions supporting the re-election campaigns of legislators to block even a wisp of reform. Both the attorneys and the legislators who are influenced by this legal form of bribery are clearly guided by WIIFM. Society pays and suffers.

Similarly, bankers and others in the financial community, known collectively as Wall Street, guided by the WIIFM principle expend great efforts to preserve a system riddled with opaque derivative securities and other practices which benefit a few clever manipulators and harm our financial system and our society. Financial donations to politicians, again legalized bribery, and unfair executive compensation help to sustain a system in which rewards are far in excess of the value contributed to society.

Labor unions and their leaders are also substantially motivated by WIIFM. Otherwise they might compromise on demands to preserve unsustainable pension and benefit systems that are bankrupting our state and federal governments. The promise of votes and again contribution-associated influence over elected leaders are part of the toxic mix. Once again WIIFM triumphs over what is good for our overall economy and our country. The effort to close the job-creating Boeing plant in South Carolina and the pension preserving battles in Wisconsin and Ohio are glaring examples of the evils of WIIFM.

So also are the efforts of some to block any tax increase. If government waste, spending excesses, and unfair tax loopholes can be sharply diminished, reasonable tax increases can be considered part of a shared sacrifice for the common good of deficit reduction. All must acknowledge that our economic problems can only be solved by the compromise of such shared sacrifice. We will be better off in the long run and so will our progeny.

Physicians can also be motivated by the WIIFM principle. There is the temptation to maintain diminishing incomes at all costs – even by performing procedures that may not be fully indicated or justified, or by spending less than adequate time with individual patients. Our health care system is imperfect in many ways, but physicians too must resist the urge to be guided predominantly by WIIFM.

Finally there is the public at large. Are we guided in our voting by short-term WIIFM? Should we vote for the candidate who will lower our personal taxes the most in the next few years? Or should we vote for the individual who we believe will act in the best interests of our country at-large and its future long-term well-being?

We must all recognize the intrinsic dangers of being motivated excessively by WIIFM. Our country cannot survive and prosper if everyone pursues that motivation. We do not have the resources to do so. We must all display some of the courage, restraint, and spirit of compromise of our forefathers who took huge political and physical risks to found our country. They were motivated by a desire to do what was best for the country at large, to work for the greater good, to do what was right for the whole society. It often required self-denial, shared sacrifice, compromise, altruism, and the responsibility to act for the common good. The WIIFM principle had to be suppressed. The result was a United States of unparalleled greatness.

Today we are drifting away from that greatness. Aside from our military and a few other rare exceptions, the WIIFM principle seems to underlie that drift. Although some self-interest is acceptable and part of the human nature, we must all resist the temptation to make that our predominant motivation. Otherwise our country will decline, and we are doomed to failure.

Clearly, this recognition and movement away from WIIFM, this ‘me-first attitude’, this idea of ‘let someone else sacrifice’ should begin with our key political leaders. They must find the courage to do what is right for our country, and give up their WIIFM motivation of acting solely to get re-elected. If they can start the ball rolling in the right direction, surely other segments of society and indeed all of us should be able to follow.

Dr. Veith is Professor of Surgery at New York University Medical Center and the Cleveland Clinic. He is also an associate medical editor for Vascular Specialist.

The ideas and opinions expresssed in Vascular Specialist do not necessarily reflect those of the Society or the Publisher.

ORLANDO – The ACE inhibitor ramipril boosted both walking ability and quality of life in patients with peripheral arterial disease in a double-blind, randomized trial.

"The magnitude of these effects is greater than that reported for conventional medical therapies," Dr. Anna A. Ahimastos observed when presenting the study findings at the annual meeting of the American Heart Association.

She reported on 343 patients with peripheral arterial disease (PAD) who were randomized to 24 weeks of ramipril at 10 mg once daily or placebo. They averaged 65 years of age, 80% were men, the baseline ankle-brachial index was 0.56, and 36% had diabetes.

At 24 weeks, the average pain-free walking time (PFWT) in the ramipril group had increased by 87%, compared with a baseline of 131 seconds. The maximum walk time (MWT) improved by 139% from a baseline of 229 seconds. This corresponded to a clinically meaningful 172-meter increase in walking distance on a standardized treadmill test conducted at a speed of 3.2 km/hr and a 12% gradient, according to Dr. Ahimastos of the Baker IDI Heart and Diabetes Institute at Alfred Hospital in Melbourne. In contrast, both PFWT and MWT decreased modestly over the course of 24 weeks in the control group.

A finding of particular importance in this impaired population was the documented improvement in quality of life that accompanied 24 weeks of ramipril, she continued. Daily functional capacity as measured by the WIQ (Walking Impairment Questionnaire) score domains of walking distance, speed, and stair climbing improved by 184%-213%. Scores on the SF-36 (36-Item Short Form) physical function component showed a significant 7% improvement from a baseline average of 38.5.

Results of this study are consistent with those of an earlier randomized, double-blind pilot study that Dr. Ahimastos and coworkers conducted in 40 patients (Ann. Intern. Med. 2006;144:660-4).

The pilot study showed average gains of 164% in PFWT and 243% in MWT with 24 weeks of ramipril, a magnitude of benefit roughly twice that seen in the new, much larger trial. This is probably because the pilot study employed quite restrictive inclusion criteria, whereas the new study included a broader spectrum of PAD patients, including those with diabetes and with aortoiliac or infrainguinal disease.

Outcomes in the two randomized trials of ramipril for PAD – gains of 87%-164% in PFWT and 139%-243% in MWT – compare favorably with the results of placebo-controlled studies of conventional therapies. The phosphodiesterase-3 inhibitor cilostazol has shown 32%-82% improvements in PFWT and MWT. Pentoxifylline, another phosphodiesterase inhibitor, produced a 12% gain in MWT. And exercise training has shown a 150% improvement in both MWT and PFWT. However, the compliance rate with exercise is quite low in the PAD population, she noted.

Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition. And they were curious as to Dr. Ahimastos’s thoughts on the mechanism of benefit.

She replied that at this point she can only speculate, since clinical trials don’t provide answers regarding mechanisms and the data from the new study were unblinded only the week prior to her presentation. She noted that ACE inhibitors have antiangiogenic and vasodilatory effects. The enhanced nitric oxide release and the drugs’ effects on bradykinin might also be relevant.

The improvement in walking doesn’t appear to stem from ramipril’s blood pressure–lowering effect, however, as the blood pressure reductions were minimal – less than 3 mm Hg in both systolic and diastolic blood pressure – and the degree of blood pressure reduction in individual patients didn’t correlate with their magnitude of walking improvement.

She and her colleagues don’t know whether angiotensin-receptor blockers would have similar clinical benefits on walking in PAD patients. That will prove difficult to study. For ethical reasons, future clinical trials are unlikely, as there is now evidence-based agreement among experts that patients with PAD should be on an ACE inhibitor or ARB anyway for cardiovascular protection.

The study was funded by Australia’s National Heart Foundation. Dr. Ahimastos declared having no financial conflicts.

ORLANDO – The ACE inhibitor ramipril boosted both walking ability and quality of life in patients with peripheral arterial disease in a double-blind, randomized trial.

"The magnitude of these effects is greater than that reported for conventional medical therapies," Dr. Anna A. Ahimastos observed when presenting the study findings at the annual meeting of the American Heart Association.

She reported on 343 patients with peripheral arterial disease (PAD) who were randomized to 24 weeks of ramipril at 10 mg once daily or placebo. They averaged 65 years of age, 80% were men, the baseline ankle-brachial index was 0.56, and 36% had diabetes.

At 24 weeks, the average pain-free walking time (PFWT) in the ramipril group had increased by 87%, compared with a baseline of 131 seconds. The maximum walk time (MWT) improved by 139% from a baseline of 229 seconds. This corresponded to a clinically meaningful 172-meter increase in walking distance on a standardized treadmill test conducted at a speed of 3.2 km/hr and a 12% gradient, according to Dr. Ahimastos of the Baker IDI Heart and Diabetes Institute at Alfred Hospital in Melbourne. In contrast, both PFWT and MWT decreased modestly over the course of 24 weeks in the control group.

A finding of particular importance in this impaired population was the documented improvement in quality of life that accompanied 24 weeks of ramipril, she continued. Daily functional capacity as measured by the WIQ (Walking Impairment Questionnaire) score domains of walking distance, speed, and stair climbing improved by 184%-213%. Scores on the SF-36 (36-Item Short Form) physical function component showed a significant 7% improvement from a baseline average of 38.5.

Results of this study are consistent with those of an earlier randomized, double-blind pilot study that Dr. Ahimastos and coworkers conducted in 40 patients (Ann. Intern. Med. 2006;144:660-4).

The pilot study showed average gains of 164% in PFWT and 243% in MWT with 24 weeks of ramipril, a magnitude of benefit roughly twice that seen in the new, much larger trial. This is probably because the pilot study employed quite restrictive inclusion criteria, whereas the new study included a broader spectrum of PAD patients, including those with diabetes and with aortoiliac or infrainguinal disease.

Outcomes in the two randomized trials of ramipril for PAD – gains of 87%-164% in PFWT and 139%-243% in MWT – compare favorably with the results of placebo-controlled studies of conventional therapies. The phosphodiesterase-3 inhibitor cilostazol has shown 32%-82% improvements in PFWT and MWT. Pentoxifylline, another phosphodiesterase inhibitor, produced a 12% gain in MWT. And exercise training has shown a 150% improvement in both MWT and PFWT. However, the compliance rate with exercise is quite low in the PAD population, she noted.

Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition. And they were curious as to Dr. Ahimastos’s thoughts on the mechanism of benefit.

She replied that at this point she can only speculate, since clinical trials don’t provide answers regarding mechanisms and the data from the new study were unblinded only the week prior to her presentation. She noted that ACE inhibitors have antiangiogenic and vasodilatory effects. The enhanced nitric oxide release and the drugs’ effects on bradykinin might also be relevant.

The improvement in walking doesn’t appear to stem from ramipril’s blood pressure–lowering effect, however, as the blood pressure reductions were minimal – less than 3 mm Hg in both systolic and diastolic blood pressure – and the degree of blood pressure reduction in individual patients didn’t correlate with their magnitude of walking improvement.

She and her colleagues don’t know whether angiotensin-receptor blockers would have similar clinical benefits on walking in PAD patients. That will prove difficult to study. For ethical reasons, future clinical trials are unlikely, as there is now evidence-based agreement among experts that patients with PAD should be on an ACE inhibitor or ARB anyway for cardiovascular protection.

The study was funded by Australia’s National Heart Foundation. Dr. Ahimastos declared having no financial conflicts.

ORLANDO – The ACE inhibitor ramipril boosted both walking ability and quality of life in patients with peripheral arterial disease in a double-blind, randomized trial.

"The magnitude of these effects is greater than that reported for conventional medical therapies," Dr. Anna A. Ahimastos observed when presenting the study findings at the annual meeting of the American Heart Association.

She reported on 343 patients with peripheral arterial disease (PAD) who were randomized to 24 weeks of ramipril at 10 mg once daily or placebo. They averaged 65 years of age, 80% were men, the baseline ankle-brachial index was 0.56, and 36% had diabetes.

At 24 weeks, the average pain-free walking time (PFWT) in the ramipril group had increased by 87%, compared with a baseline of 131 seconds. The maximum walk time (MWT) improved by 139% from a baseline of 229 seconds. This corresponded to a clinically meaningful 172-meter increase in walking distance on a standardized treadmill test conducted at a speed of 3.2 km/hr and a 12% gradient, according to Dr. Ahimastos of the Baker IDI Heart and Diabetes Institute at Alfred Hospital in Melbourne. In contrast, both PFWT and MWT decreased modestly over the course of 24 weeks in the control group.

A finding of particular importance in this impaired population was the documented improvement in quality of life that accompanied 24 weeks of ramipril, she continued. Daily functional capacity as measured by the WIQ (Walking Impairment Questionnaire) score domains of walking distance, speed, and stair climbing improved by 184%-213%. Scores on the SF-36 (36-Item Short Form) physical function component showed a significant 7% improvement from a baseline average of 38.5.

Results of this study are consistent with those of an earlier randomized, double-blind pilot study that Dr. Ahimastos and coworkers conducted in 40 patients (Ann. Intern. Med. 2006;144:660-4).

The pilot study showed average gains of 164% in PFWT and 243% in MWT with 24 weeks of ramipril, a magnitude of benefit roughly twice that seen in the new, much larger trial. This is probably because the pilot study employed quite restrictive inclusion criteria, whereas the new study included a broader spectrum of PAD patients, including those with diabetes and with aortoiliac or infrainguinal disease.

Outcomes in the two randomized trials of ramipril for PAD – gains of 87%-164% in PFWT and 139%-243% in MWT – compare favorably with the results of placebo-controlled studies of conventional therapies. The phosphodiesterase-3 inhibitor cilostazol has shown 32%-82% improvements in PFWT and MWT. Pentoxifylline, another phosphodiesterase inhibitor, produced a 12% gain in MWT. And exercise training has shown a 150% improvement in both MWT and PFWT. However, the compliance rate with exercise is quite low in the PAD population, she noted.

Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition. And they were curious as to Dr. Ahimastos’s thoughts on the mechanism of benefit.

She replied that at this point she can only speculate, since clinical trials don’t provide answers regarding mechanisms and the data from the new study were unblinded only the week prior to her presentation. She noted that ACE inhibitors have antiangiogenic and vasodilatory effects. The enhanced nitric oxide release and the drugs’ effects on bradykinin might also be relevant.

The improvement in walking doesn’t appear to stem from ramipril’s blood pressure–lowering effect, however, as the blood pressure reductions were minimal – less than 3 mm Hg in both systolic and diastolic blood pressure – and the degree of blood pressure reduction in individual patients didn’t correlate with their magnitude of walking improvement.

She and her colleagues don’t know whether angiotensin-receptor blockers would have similar clinical benefits on walking in PAD patients. That will prove difficult to study. For ethical reasons, future clinical trials are unlikely, as there is now evidence-based agreement among experts that patients with PAD should be on an ACE inhibitor or ARB anyway for cardiovascular protection.

The study was funded by Australia’s National Heart Foundation. Dr. Ahimastos declared having no financial conflicts.

Welcome to the debut of the EHR Report Podcast!

Starting this month, the authors of the EHR Report column, Dr. Neil Skolnik and Dr. Chris Notte, will deliver even more of their EHR know-how via their new podcast. Tune in regularly for candid analyses of EHR strategies, advanced tips on best practices, and one-on-one interviews with innovators in the field of EHRs.

In this, the first of a two-part series, Dr. Skolnik and Dr. Notte offer listeners an in-depth discussion of exactly what it takes for physicians to achieve meaningful use of their electronic health records software and earn federal incentives.

To download the podcast, click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Welcome to the debut of the EHR Report Podcast!

Starting this month, the authors of the EHR Report column, Dr. Neil Skolnik and Dr. Chris Notte, will deliver even more of their EHR know-how via their new podcast. Tune in regularly for candid analyses of EHR strategies, advanced tips on best practices, and one-on-one interviews with innovators in the field of EHRs.

In this, the first of a two-part series, Dr. Skolnik and Dr. Notte offer listeners an in-depth discussion of exactly what it takes for physicians to achieve meaningful use of their electronic health records software and earn federal incentives.

To download the podcast, click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Welcome to the debut of the EHR Report Podcast!

Starting this month, the authors of the EHR Report column, Dr. Neil Skolnik and Dr. Chris Notte, will deliver even more of their EHR know-how via their new podcast. Tune in regularly for candid analyses of EHR strategies, advanced tips on best practices, and one-on-one interviews with innovators in the field of EHRs.

In this, the first of a two-part series, Dr. Skolnik and Dr. Notte offer listeners an in-depth discussion of exactly what it takes for physicians to achieve meaningful use of their electronic health records software and earn federal incentives.

To download the podcast, click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Welcome to the debut of the EHR Report Podcast!

Starting this month, the authors of the EHR Report column, Dr. Neil Skolnik and Dr. Chris Notte, will deliver even more of their EHR know-how via their new podcast. Tune in regularly for candid analyses of EHR strategies, advanced tips on best practices, and one-on-one interviews with innovators in the field of EHRs.

In this, the first of a two-part series, Dr. Skolnik and Dr. Notte offer listeners an in-depth discussion of exactly what it takes for physicians to achieve meaningful use of their electronic health records software and earn federal incentives.

To download the podcast, click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Welcome to the debut of the EHR Report Podcast!

Starting this month, the authors of the EHR Report column, Dr. Neil Skolnik and Dr. Chris Notte, will deliver even more of their EHR know-how via their new podcast. Tune in regularly for candid analyses of EHR strategies, advanced tips on best practices, and one-on-one interviews with innovators in the field of EHRs.

In this, the first of a two-part series, Dr. Skolnik and Dr. Notte offer listeners an in-depth discussion of exactly what it takes for physicians to achieve meaningful use of their electronic health records software and earn federal incentives.

To download the podcast, click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Welcome to the debut of the EHR Report Podcast!

Starting this month, the authors of the EHR Report column, Dr. Neil Skolnik and Dr. Chris Notte, will deliver even more of their EHR know-how via their new podcast. Tune in regularly for candid analyses of EHR strategies, advanced tips on best practices, and one-on-one interviews with innovators in the field of EHRs.

In this, the first of a two-part series, Dr. Skolnik and Dr. Notte offer listeners an in-depth discussion of exactly what it takes for physicians to achieve meaningful use of their electronic health records software and earn federal incentives.

To download the podcast, click here.

To read the related column, click here.

To listen via this Web page, click on the player below:

Julie Totten was 24 years old when her brother Mark took his life. Shortly after, she helped her father, who had been suffering from undiagnosed depression all his life, get treated for the illness. In dealing with the depression that afflicted her father and brother, she felt alone, lost, and responsible. She thought there must be a lot of other families like hers.

So, 10 years after Mark’s death, Julie founded Families for Depression Awareness, a nonprofit organization to help families, including family caregivers like her, recognize and cope with depressive disorders to get people well and prevent suicides. The organization’s website, helps families recognize and cope with depression, and focuses on getting people into treatment to prevent suicide.

Dr. Bill Beardslee, chairman of psychiatry at Children’s Hospital Boston, lost an older sister to suicide when he was in medical school. "The depression took her over and after a valiant struggle against it, she took her own life some years later.

"It has taken me many years to deal with that and many conversations with my father, my mother and my wife, my friends, and, more recently, my children. Above all, it has given me a sense of how awful this illness can be for families," he wrote on the Hachette Book Group website. In his book, Out of the Darkened Room (New York: Little, Brown & Co., 2002), he describes the experiences of families with depression and strategies that families find helpful. It is highly recommended to psychiatrists to share with their patients and families.

Parents with depression worry that their children are suffering. Dr. Beardslee, who also is the Gardner-Monks Professor of Child Psychiatry at Harvard Medical School, Boston, has developed interventions with his colleagues aimed at helping these families. A major goal is "breaking the silence and helping the family talk together about depression." He conceptualizes depression as a chronic medical illness but also a family calamity and has developed an intervention to help families talk together and make meaning together.

His website, Families Preventing and Overcoming Depression provides details on the Family Talk Preventive Intervention. This is a public health, strength-based, and family-centered intervention designed to support families in which one or both parents have depression. This evidence-based practice partners with families to improve relationships and functioning by educating families on depression risk factors and understanding the benefits of applying protective factors to promote resilience.

Dr. Beardslee has many international collaborators in many different countries: Australia, Finland, the Netherlands, Norway, Sweden, Columbia, Costa Rica, and Iceland. Family interventions in these countries are supported by government, and in the public health, and medical and mental health systems. Interventions in these countries are more widespread and systematically available than they are in the United States.

A symposium on this topic will be held at the American Psychiatric Association’s annual meeting in Philadelphia, moderated by Dr. Ellen Berman. It is called "When Your Patient Is a Parent: Supporting the Family and Addressing the Needs of Children." As part of that symposium, Dr. Beardslee will present "Clinical Implications of Evidence-Based Preventive Interventions for Families With Parental Depression." Finally, Ms. Totten will present "A Family Perspective," and I will present "Overview of Needs of the Children of Parents With Mental Illness." See you there!

Dr. Heru is an associate professor of psychiatry at the University of Colorado at Denver, Aurora. She has been a member of the Association of Family Psychiatrists since 2002 and currently serves as the organization’s treasurer. In addition, she is the coauthor of two books on working with families and is the author of numerous articles on this topic

Julie Totten was 24 years old when her brother Mark took his life. Shortly after, she helped her father, who had been suffering from undiagnosed depression all his life, get treated for the illness. In dealing with the depression that afflicted her father and brother, she felt alone, lost, and responsible. She thought there must be a lot of other families like hers.

So, 10 years after Mark’s death, Julie founded Families for Depression Awareness, a nonprofit organization to help families, including family caregivers like her, recognize and cope with depressive disorders to get people well and prevent suicides. The organization’s website, helps families recognize and cope with depression, and focuses on getting people into treatment to prevent suicide.

Dr. Bill Beardslee, chairman of psychiatry at Children’s Hospital Boston, lost an older sister to suicide when he was in medical school. "The depression took her over and after a valiant struggle against it, she took her own life some years later.

"It has taken me many years to deal with that and many conversations with my father, my mother and my wife, my friends, and, more recently, my children. Above all, it has given me a sense of how awful this illness can be for families," he wrote on the Hachette Book Group website. In his book, Out of the Darkened Room (New York: Little, Brown & Co., 2002), he describes the experiences of families with depression and strategies that families find helpful. It is highly recommended to psychiatrists to share with their patients and families.

Parents with depression worry that their children are suffering. Dr. Beardslee, who also is the Gardner-Monks Professor of Child Psychiatry at Harvard Medical School, Boston, has developed interventions with his colleagues aimed at helping these families. A major goal is "breaking the silence and helping the family talk together about depression." He conceptualizes depression as a chronic medical illness but also a family calamity and has developed an intervention to help families talk together and make meaning together.

His website, Families Preventing and Overcoming Depression provides details on the Family Talk Preventive Intervention. This is a public health, strength-based, and family-centered intervention designed to support families in which one or both parents have depression. This evidence-based practice partners with families to improve relationships and functioning by educating families on depression risk factors and understanding the benefits of applying protective factors to promote resilience.

Dr. Beardslee has many international collaborators in many different countries: Australia, Finland, the Netherlands, Norway, Sweden, Columbia, Costa Rica, and Iceland. Family interventions in these countries are supported by government, and in the public health, and medical and mental health systems. Interventions in these countries are more widespread and systematically available than they are in the United States.

A symposium on this topic will be held at the American Psychiatric Association’s annual meeting in Philadelphia, moderated by Dr. Ellen Berman. It is called "When Your Patient Is a Parent: Supporting the Family and Addressing the Needs of Children." As part of that symposium, Dr. Beardslee will present "Clinical Implications of Evidence-Based Preventive Interventions for Families With Parental Depression." Finally, Ms. Totten will present "A Family Perspective," and I will present "Overview of Needs of the Children of Parents With Mental Illness." See you there!

Dr. Heru is an associate professor of psychiatry at the University of Colorado at Denver, Aurora. She has been a member of the Association of Family Psychiatrists since 2002 and currently serves as the organization’s treasurer. In addition, she is the coauthor of two books on working with families and is the author of numerous articles on this topic

Julie Totten was 24 years old when her brother Mark took his life. Shortly after, she helped her father, who had been suffering from undiagnosed depression all his life, get treated for the illness. In dealing with the depression that afflicted her father and brother, she felt alone, lost, and responsible. She thought there must be a lot of other families like hers.

So, 10 years after Mark’s death, Julie founded Families for Depression Awareness, a nonprofit organization to help families, including family caregivers like her, recognize and cope with depressive disorders to get people well and prevent suicides. The organization’s website, helps families recognize and cope with depression, and focuses on getting people into treatment to prevent suicide.

Dr. Bill Beardslee, chairman of psychiatry at Children’s Hospital Boston, lost an older sister to suicide when he was in medical school. "The depression took her over and after a valiant struggle against it, she took her own life some years later.

"It has taken me many years to deal with that and many conversations with my father, my mother and my wife, my friends, and, more recently, my children. Above all, it has given me a sense of how awful this illness can be for families," he wrote on the Hachette Book Group website. In his book, Out of the Darkened Room (New York: Little, Brown & Co., 2002), he describes the experiences of families with depression and strategies that families find helpful. It is highly recommended to psychiatrists to share with their patients and families.

Parents with depression worry that their children are suffering. Dr. Beardslee, who also is the Gardner-Monks Professor of Child Psychiatry at Harvard Medical School, Boston, has developed interventions with his colleagues aimed at helping these families. A major goal is "breaking the silence and helping the family talk together about depression." He conceptualizes depression as a chronic medical illness but also a family calamity and has developed an intervention to help families talk together and make meaning together.

His website, Families Preventing and Overcoming Depression provides details on the Family Talk Preventive Intervention. This is a public health, strength-based, and family-centered intervention designed to support families in which one or both parents have depression. This evidence-based practice partners with families to improve relationships and functioning by educating families on depression risk factors and understanding the benefits of applying protective factors to promote resilience.

Dr. Beardslee has many international collaborators in many different countries: Australia, Finland, the Netherlands, Norway, Sweden, Columbia, Costa Rica, and Iceland. Family interventions in these countries are supported by government, and in the public health, and medical and mental health systems. Interventions in these countries are more widespread and systematically available than they are in the United States.

A symposium on this topic will be held at the American Psychiatric Association’s annual meeting in Philadelphia, moderated by Dr. Ellen Berman. It is called "When Your Patient Is a Parent: Supporting the Family and Addressing the Needs of Children." As part of that symposium, Dr. Beardslee will present "Clinical Implications of Evidence-Based Preventive Interventions for Families With Parental Depression." Finally, Ms. Totten will present "A Family Perspective," and I will present "Overview of Needs of the Children of Parents With Mental Illness." See you there!

Dr. Heru is an associate professor of psychiatry at the University of Colorado at Denver, Aurora. She has been a member of the Association of Family Psychiatrists since 2002 and currently serves as the organization’s treasurer. In addition, she is the coauthor of two books on working with families and is the author of numerous articles on this topic

A little more than a year after the new anticoagulant dabigatran (Pradaxa) was approved for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients, the FDA is evaluating post-marketing reports of serious bleeds in patients taking the drug.

The FDA is trying to determine if patients on Pradaxa are experiencing severe bleeding more than expected based on results of the clinical trial that led to Pradaxa’s approval, according to FDA spokeswoman Sandy Walsh.

“At this time, FDA continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label,” Walsh tells The Hospitalist.

It won’t cause me to take people who I have prescribed Pradaxa and switch them back to warfarin.

—Robert Pendleton, MD, director of the hospitalist program, University of Utah Healthcare; medical director, University Healthcare Thrombosis Service

Patients should not stop taking dabigatran without first talking to their doctors, the FDA announcement cautions. While “serious, even fatal events have been reported,” according to the FDA’s announcement, Walsh says the FDA isn’t prepared to say how many reports of serious bleeding events have been received because they’re still being reviewed.

“We often put out ‘early’ communications when we learn of drug safety issues,” she says. “We want to be transparent and make [the] public [aware of] what we do know, but our analysis is not final. At this point, the FDA is still evaluating this issue.”

Bleeding that leads to serious or fatal outcomes is a well-recognized complication of all anticoagulant therapies.

Dabigatran, a direct thrombin inhibitor, was approved in October 2010, becoming the first new oral anticoagulant approved in 50 years. It was the first approved among several new anti-coagulants that are poised to enter the market and are expected to challenge warfarin (Coumadin), the longtime standard of care.

The new drugs—including rivaroxaban (Xarelto), a Factor Xa-inhibitor that was approved in 2011—have been eagerly anticipated because they don’t require frequent blood draws for monitoring, as warfarin does. Hospitalists are especially interested in the new anticoagulant therapies because they treat numerous patients at an increased risk of clotting.

In the RE-LY trial, the 18,000-patient clinical trial comparing dabigatran and warfarin, major bleeding events occurred at similar rates with the two drugs.

Dabigatran manufacturer Boehringer Ingelheim is working with the FDA to evaluate the major bleeding reports, but spokeswoman Anna Moses says the drug has been performing according to expectations.

“Global data collected to date on major bleeding are consistent with our expectations based on the RE-LY trial and are in alignment with the U.S. Prescribing Information, which clearly state the benefits and risks associated with Pradaxa,” Moses says. “Overall, the positive-benefit-risk ratio of Pradaxa in NVAF remains unchanged.” (Visit the manufacturer website for prescribing information [PDF].)

Robert Pendleton, MD, director of the hospitalist program at the University of Utah Healthcare and Medical Director of the University Healthcare Thrombosis Service, expressed no surprise at the FDA’s statement.

“Although the data with new anticoagulants like Pradaxa is very favorable in a clinical trial setting, there’s great risk of enhanced demonstration of harm in the real-world setting if it’s not used optimally,” Dr. Pendleton says. “There will be more liberal sort of prescribing in a less-pure patient population.

So if people are not particularly cognizant of a patient’s renal function, their body weight, prior history of bleeding, etc., then you’re sort of applying new drugs in patients who are even more prone to bleed.”

Dr. Pendleton notes that in subgroup analyses, the slight benefits of the new drugs have come in patients with poor warfarin control, so if patients with good warfarin control are switched, outcomes could generally be expected not to be better, and could be worse.

“It won’t cause me to take people who I have prescribed Pradaxa and switch them back to warfarin,” he says, “but part of that is [that] here, in our healthcare system, we’re pretty cautious in who gets put on one of the new agents. And so those that do are patients who are most like those in the clinical trial.”

Tom Collins is a freelance writer in Florida.

A little more than a year after the new anticoagulant dabigatran (Pradaxa) was approved for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients, the FDA is evaluating post-marketing reports of serious bleeds in patients taking the drug.

The FDA is trying to determine if patients on Pradaxa are experiencing severe bleeding more than expected based on results of the clinical trial that led to Pradaxa’s approval, according to FDA spokeswoman Sandy Walsh.

“At this time, FDA continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label,” Walsh tells The Hospitalist.

It won’t cause me to take people who I have prescribed Pradaxa and switch them back to warfarin.

—Robert Pendleton, MD, director of the hospitalist program, University of Utah Healthcare; medical director, University Healthcare Thrombosis Service

Patients should not stop taking dabigatran without first talking to their doctors, the FDA announcement cautions. While “serious, even fatal events have been reported,” according to the FDA’s announcement, Walsh says the FDA isn’t prepared to say how many reports of serious bleeding events have been received because they’re still being reviewed.

“We often put out ‘early’ communications when we learn of drug safety issues,” she says. “We want to be transparent and make [the] public [aware of] what we do know, but our analysis is not final. At this point, the FDA is still evaluating this issue.”

Bleeding that leads to serious or fatal outcomes is a well-recognized complication of all anticoagulant therapies.

Dabigatran, a direct thrombin inhibitor, was approved in October 2010, becoming the first new oral anticoagulant approved in 50 years. It was the first approved among several new anti-coagulants that are poised to enter the market and are expected to challenge warfarin (Coumadin), the longtime standard of care.

The new drugs—including rivaroxaban (Xarelto), a Factor Xa-inhibitor that was approved in 2011—have been eagerly anticipated because they don’t require frequent blood draws for monitoring, as warfarin does. Hospitalists are especially interested in the new anticoagulant therapies because they treat numerous patients at an increased risk of clotting.

In the RE-LY trial, the 18,000-patient clinical trial comparing dabigatran and warfarin, major bleeding events occurred at similar rates with the two drugs.

Dabigatran manufacturer Boehringer Ingelheim is working with the FDA to evaluate the major bleeding reports, but spokeswoman Anna Moses says the drug has been performing according to expectations.

“Global data collected to date on major bleeding are consistent with our expectations based on the RE-LY trial and are in alignment with the U.S. Prescribing Information, which clearly state the benefits and risks associated with Pradaxa,” Moses says. “Overall, the positive-benefit-risk ratio of Pradaxa in NVAF remains unchanged.” (Visit the manufacturer website for prescribing information [PDF].)

Robert Pendleton, MD, director of the hospitalist program at the University of Utah Healthcare and Medical Director of the University Healthcare Thrombosis Service, expressed no surprise at the FDA’s statement.

“Although the data with new anticoagulants like Pradaxa is very favorable in a clinical trial setting, there’s great risk of enhanced demonstration of harm in the real-world setting if it’s not used optimally,” Dr. Pendleton says. “There will be more liberal sort of prescribing in a less-pure patient population.

So if people are not particularly cognizant of a patient’s renal function, their body weight, prior history of bleeding, etc., then you’re sort of applying new drugs in patients who are even more prone to bleed.”

Dr. Pendleton notes that in subgroup analyses, the slight benefits of the new drugs have come in patients with poor warfarin control, so if patients with good warfarin control are switched, outcomes could generally be expected not to be better, and could be worse.

“It won’t cause me to take people who I have prescribed Pradaxa and switch them back to warfarin,” he says, “but part of that is [that] here, in our healthcare system, we’re pretty cautious in who gets put on one of the new agents. And so those that do are patients who are most like those in the clinical trial.”

Tom Collins is a freelance writer in Florida.

A little more than a year after the new anticoagulant dabigatran (Pradaxa) was approved for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients, the FDA is evaluating post-marketing reports of serious bleeds in patients taking the drug.

The FDA is trying to determine if patients on Pradaxa are experiencing severe bleeding more than expected based on results of the clinical trial that led to Pradaxa’s approval, according to FDA spokeswoman Sandy Walsh.

“At this time, FDA continues to believe that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label,” Walsh tells The Hospitalist.

It won’t cause me to take people who I have prescribed Pradaxa and switch them back to warfarin.

—Robert Pendleton, MD, director of the hospitalist program, University of Utah Healthcare; medical director, University Healthcare Thrombosis Service

Patients should not stop taking dabigatran without first talking to their doctors, the FDA announcement cautions. While “serious, even fatal events have been reported,” according to the FDA’s announcement, Walsh says the FDA isn’t prepared to say how many reports of serious bleeding events have been received because they’re still being reviewed.

“We often put out ‘early’ communications when we learn of drug safety issues,” she says. “We want to be transparent and make [the] public [aware of] what we do know, but our analysis is not final. At this point, the FDA is still evaluating this issue.”

Bleeding that leads to serious or fatal outcomes is a well-recognized complication of all anticoagulant therapies.

Dabigatran, a direct thrombin inhibitor, was approved in October 2010, becoming the first new oral anticoagulant approved in 50 years. It was the first approved among several new anti-coagulants that are poised to enter the market and are expected to challenge warfarin (Coumadin), the longtime standard of care.

The new drugs—including rivaroxaban (Xarelto), a Factor Xa-inhibitor that was approved in 2011—have been eagerly anticipated because they don’t require frequent blood draws for monitoring, as warfarin does. Hospitalists are especially interested in the new anticoagulant therapies because they treat numerous patients at an increased risk of clotting.

In the RE-LY trial, the 18,000-patient clinical trial comparing dabigatran and warfarin, major bleeding events occurred at similar rates with the two drugs.

Dabigatran manufacturer Boehringer Ingelheim is working with the FDA to evaluate the major bleeding reports, but spokeswoman Anna Moses says the drug has been performing according to expectations.

“Global data collected to date on major bleeding are consistent with our expectations based on the RE-LY trial and are in alignment with the U.S. Prescribing Information, which clearly state the benefits and risks associated with Pradaxa,” Moses says. “Overall, the positive-benefit-risk ratio of Pradaxa in NVAF remains unchanged.” (Visit the manufacturer website for prescribing information [PDF].)

Robert Pendleton, MD, director of the hospitalist program at the University of Utah Healthcare and Medical Director of the University Healthcare Thrombosis Service, expressed no surprise at the FDA’s statement.

“Although the data with new anticoagulants like Pradaxa is very favorable in a clinical trial setting, there’s great risk of enhanced demonstration of harm in the real-world setting if it’s not used optimally,” Dr. Pendleton says. “There will be more liberal sort of prescribing in a less-pure patient population.

So if people are not particularly cognizant of a patient’s renal function, their body weight, prior history of bleeding, etc., then you’re sort of applying new drugs in patients who are even more prone to bleed.”

Dr. Pendleton notes that in subgroup analyses, the slight benefits of the new drugs have come in patients with poor warfarin control, so if patients with good warfarin control are switched, outcomes could generally be expected not to be better, and could be worse.

“It won’t cause me to take people who I have prescribed Pradaxa and switch them back to warfarin,” he says, “but part of that is [that] here, in our healthcare system, we’re pretty cautious in who gets put on one of the new agents. And so those that do are patients who are most like those in the clinical trial.”

Tom Collins is a freelance writer in Florida.

In this video, Dr. Beers explains why a rear facing car seat is safer for your child. Safety data show that the use of rear facing seats in the first 2 years of life provides better support for a child's back and neck muscles in addition to providing maximum protection in the event of an auto accident.

In this video, Dr. Beers explains why a rear facing car seat is safer for your child. Safety data show that the use of rear facing seats in the first 2 years of life provides better support for a child's back and neck muscles in addition to providing maximum protection in the event of an auto accident.

In this video, Dr. Beers explains why a rear facing car seat is safer for your child. Safety data show that the use of rear facing seats in the first 2 years of life provides better support for a child's back and neck muscles in addition to providing maximum protection in the event of an auto accident.

SAN DIEGO – The novel antibody blinatumomab induced high complete remission rates in adults with relapsed B-precursor acute lymphoblastic leukemia in early clinical trials, according to Dr. Max S. Topp.

In a phase II study with a dose-finding phase, 9 of 12 patients who received blinatumomab 5 mcg/m² per day for 1 week, followed by a 15-mcg dose on subsequent weeks, had either a complete remission (CR) or a CR with partial hematologic recovery (CRh), Dr. Topp of the University of Würzburg (Germany) said at the annual meeting of the American Society of Hematology.

"We have exceptionally high rates of hematological complete remissions in these patients, and it ought to be noted that every patient has achieved MRD [minimal residual disease] negativity," said Dr. Topp.

At a median follow-up of 9.7 months, the median overall survival had not been reached, he added.

Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. It has shown good activity in a phase I clinical trial in patients with relapsed non-Hodgkin’s lymphoma, and in a study of patients with B-ALL who were positive for MRD (J. Clin. Oncol. 2011;29:2493-8).

The MT 103-206 trial was an open-label, multicenter phase II trial of blinatumomab in patients with relapsed/refractory B-precursor ALL, or Philadelphia chromosome–positive ALL (Ph+ALL) who were ineligible for tyrosine kinase inhibitors or who were in relapse following an allogeneic stem cell transplant.

The trial had a dose-finding run-in phase, with four patient cohorts. Dr. Topp focused on cohorts 2a and 3, in which patients received the selected dose schedule: an initial dose of 5 mcg/m² IV daily for the 1st week of cycle 1, followed by 15 mcg/m² per day for weeks 2-4 of every 4-week cycle, and every subsequent cycle. Patients had 2 weeks off between each cycle.

Patients who had a CR or CRh within the first two treatment cycles underwent consolidation with three additional cycles of blinatumonab and allogeneic stem cell transplant.

At the selected dose, the most common clinical adverse events were fever in 67%, headache in 33%, and tremor in 33%. Most of the events occurred during the first cycle, and no patients had to permanently discontinue therapy because of adverse events.

Among all cohorts (totaling 25 patients), there were 17 who had a CR or CRh: 5 of 7 patients who received a 15-mcg dose throughout treatment (cohort 1); 3 of 6 patients who received escalating doses of 5-, 15-, and 30-mcg doses (cohort 2b); and 9 of 12 patients in cohorts 2a and 3 combined. All patients with a CR or CRh were also MRD negative, defined as an MRD less than 104 measured by polymerase chain reaction evaluation of individual rearrangement of immunoglobulin or T-cell receptor genes by a central laboratory.

Dr. Topp explained that there were high response rates among all patient subgroups, including patients with Ph+ALL, and those with the t(4,11) translocation.

As of early November 2011, 6 of 17 patients with complete responses had relapses. One of four patients who had undergone allogeneic hematopoietic stem cell transplant had a medullary relapse; this patient was CD19 negative. A total of 5 of 13 patients had a relapse prior to transplant – 2 medullary relapses (1 CD19-negative and 1 positive) and 3 extramedullary relapses (1 CD19 negative and 2 positive).

One patient who had a medullary relapse but retained CD19 expression was retreated with blinatumomab and had a CRh of 7 months’ duration; the patient achieved a second, ongoing CRh after more blinatumomab.

The median duration of complete hematologic remission was 7.1 months (218 days) among 18 patients (12 responders) in cohorts 1, 2a, and 2b.

Asked in an interview whether an agent targeted against CD19 might work in combination with an anti-CD20 agent such as rituximab (Rituxan), Dr. Alan S. Wayne, a leukemia specialist and session comoderator who was not involved in the study, said that CD20 is not as attractive a target in ALL as it is in lymphoma or other hematologic malignancies.

"The question of CD20 in ALL is a little challenging, because the expression is less universal and even within individual cases across blasts," said Dr. Wayne, who is also head of the hematologic disease division of the pediatric oncology branch at the National Cancer Institute.

He noted, however, that there is evidence to suggest that pretreatment of patients with steroids may increase CD20 expression.

"This is an exciting new era for combining agents with a variety of different mechanisms of action, and also toxicity profiles. One could imagine, for example, [using] steroid to increase CD20 expression, rituximab, and then another CD19- or CD22-targeting agent," he said.

The MT 103-206 trial was supported by Micromet. Dr. Topp and coauthors Dr. Ralf Bargou and Dr. Nicola Goekbuget disclosed consulting for and/or receiving honoraria from the company. Three other coauthors are employees of the company. Dr. Wayne reported no relevant financial disclosures.

SAN DIEGO – The novel antibody blinatumomab induced high complete remission rates in adults with relapsed B-precursor acute lymphoblastic leukemia in early clinical trials, according to Dr. Max S. Topp.

In a phase II study with a dose-finding phase, 9 of 12 patients who received blinatumomab 5 mcg/m² per day for 1 week, followed by a 15-mcg dose on subsequent weeks, had either a complete remission (CR) or a CR with partial hematologic recovery (CRh), Dr. Topp of the University of Würzburg (Germany) said at the annual meeting of the American Society of Hematology.

"We have exceptionally high rates of hematological complete remissions in these patients, and it ought to be noted that every patient has achieved MRD [minimal residual disease] negativity," said Dr. Topp.

At a median follow-up of 9.7 months, the median overall survival had not been reached, he added.

Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. It has shown good activity in a phase I clinical trial in patients with relapsed non-Hodgkin’s lymphoma, and in a study of patients with B-ALL who were positive for MRD (J. Clin. Oncol. 2011;29:2493-8).

The MT 103-206 trial was an open-label, multicenter phase II trial of blinatumomab in patients with relapsed/refractory B-precursor ALL, or Philadelphia chromosome–positive ALL (Ph+ALL) who were ineligible for tyrosine kinase inhibitors or who were in relapse following an allogeneic stem cell transplant.

The trial had a dose-finding run-in phase, with four patient cohorts. Dr. Topp focused on cohorts 2a and 3, in which patients received the selected dose schedule: an initial dose of 5 mcg/m² IV daily for the 1st week of cycle 1, followed by 15 mcg/m² per day for weeks 2-4 of every 4-week cycle, and every subsequent cycle. Patients had 2 weeks off between each cycle.

Patients who had a CR or CRh within the first two treatment cycles underwent consolidation with three additional cycles of blinatumonab and allogeneic stem cell transplant.

At the selected dose, the most common clinical adverse events were fever in 67%, headache in 33%, and tremor in 33%. Most of the events occurred during the first cycle, and no patients had to permanently discontinue therapy because of adverse events.

Among all cohorts (totaling 25 patients), there were 17 who had a CR or CRh: 5 of 7 patients who received a 15-mcg dose throughout treatment (cohort 1); 3 of 6 patients who received escalating doses of 5-, 15-, and 30-mcg doses (cohort 2b); and 9 of 12 patients in cohorts 2a and 3 combined. All patients with a CR or CRh were also MRD negative, defined as an MRD less than 104 measured by polymerase chain reaction evaluation of individual rearrangement of immunoglobulin or T-cell receptor genes by a central laboratory.

Dr. Topp explained that there were high response rates among all patient subgroups, including patients with Ph+ALL, and those with the t(4,11) translocation.

As of early November 2011, 6 of 17 patients with complete responses had relapses. One of four patients who had undergone allogeneic hematopoietic stem cell transplant had a medullary relapse; this patient was CD19 negative. A total of 5 of 13 patients had a relapse prior to transplant – 2 medullary relapses (1 CD19-negative and 1 positive) and 3 extramedullary relapses (1 CD19 negative and 2 positive).

One patient who had a medullary relapse but retained CD19 expression was retreated with blinatumomab and had a CRh of 7 months’ duration; the patient achieved a second, ongoing CRh after more blinatumomab.

The median duration of complete hematologic remission was 7.1 months (218 days) among 18 patients (12 responders) in cohorts 1, 2a, and 2b.

Asked in an interview whether an agent targeted against CD19 might work in combination with an anti-CD20 agent such as rituximab (Rituxan), Dr. Alan S. Wayne, a leukemia specialist and session comoderator who was not involved in the study, said that CD20 is not as attractive a target in ALL as it is in lymphoma or other hematologic malignancies.

"The question of CD20 in ALL is a little challenging, because the expression is less universal and even within individual cases across blasts," said Dr. Wayne, who is also head of the hematologic disease division of the pediatric oncology branch at the National Cancer Institute.

He noted, however, that there is evidence to suggest that pretreatment of patients with steroids may increase CD20 expression.

"This is an exciting new era for combining agents with a variety of different mechanisms of action, and also toxicity profiles. One could imagine, for example, [using] steroid to increase CD20 expression, rituximab, and then another CD19- or CD22-targeting agent," he said.

The MT 103-206 trial was supported by Micromet. Dr. Topp and coauthors Dr. Ralf Bargou and Dr. Nicola Goekbuget disclosed consulting for and/or receiving honoraria from the company. Three other coauthors are employees of the company. Dr. Wayne reported no relevant financial disclosures.

SAN DIEGO – The novel antibody blinatumomab induced high complete remission rates in adults with relapsed B-precursor acute lymphoblastic leukemia in early clinical trials, according to Dr. Max S. Topp.

In a phase II study with a dose-finding phase, 9 of 12 patients who received blinatumomab 5 mcg/m² per day for 1 week, followed by a 15-mcg dose on subsequent weeks, had either a complete remission (CR) or a CR with partial hematologic recovery (CRh), Dr. Topp of the University of Würzburg (Germany) said at the annual meeting of the American Society of Hematology.

"We have exceptionally high rates of hematological complete remissions in these patients, and it ought to be noted that every patient has achieved MRD [minimal residual disease] negativity," said Dr. Topp.

At a median follow-up of 9.7 months, the median overall survival had not been reached, he added.

Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. It has shown good activity in a phase I clinical trial in patients with relapsed non-Hodgkin’s lymphoma, and in a study of patients with B-ALL who were positive for MRD (J. Clin. Oncol. 2011;29:2493-8).

The MT 103-206 trial was an open-label, multicenter phase II trial of blinatumomab in patients with relapsed/refractory B-precursor ALL, or Philadelphia chromosome–positive ALL (Ph+ALL) who were ineligible for tyrosine kinase inhibitors or who were in relapse following an allogeneic stem cell transplant.

The trial had a dose-finding run-in phase, with four patient cohorts. Dr. Topp focused on cohorts 2a and 3, in which patients received the selected dose schedule: an initial dose of 5 mcg/m² IV daily for the 1st week of cycle 1, followed by 15 mcg/m² per day for weeks 2-4 of every 4-week cycle, and every subsequent cycle. Patients had 2 weeks off between each cycle.

Patients who had a CR or CRh within the first two treatment cycles underwent consolidation with three additional cycles of blinatumonab and allogeneic stem cell transplant.

At the selected dose, the most common clinical adverse events were fever in 67%, headache in 33%, and tremor in 33%. Most of the events occurred during the first cycle, and no patients had to permanently discontinue therapy because of adverse events.

Among all cohorts (totaling 25 patients), there were 17 who had a CR or CRh: 5 of 7 patients who received a 15-mcg dose throughout treatment (cohort 1); 3 of 6 patients who received escalating doses of 5-, 15-, and 30-mcg doses (cohort 2b); and 9 of 12 patients in cohorts 2a and 3 combined. All patients with a CR or CRh were also MRD negative, defined as an MRD less than 104 measured by polymerase chain reaction evaluation of individual rearrangement of immunoglobulin or T-cell receptor genes by a central laboratory.

Dr. Topp explained that there were high response rates among all patient subgroups, including patients with Ph+ALL, and those with the t(4,11) translocation.

As of early November 2011, 6 of 17 patients with complete responses had relapses. One of four patients who had undergone allogeneic hematopoietic stem cell transplant had a medullary relapse; this patient was CD19 negative. A total of 5 of 13 patients had a relapse prior to transplant – 2 medullary relapses (1 CD19-negative and 1 positive) and 3 extramedullary relapses (1 CD19 negative and 2 positive).

One patient who had a medullary relapse but retained CD19 expression was retreated with blinatumomab and had a CRh of 7 months’ duration; the patient achieved a second, ongoing CRh after more blinatumomab.

The median duration of complete hematologic remission was 7.1 months (218 days) among 18 patients (12 responders) in cohorts 1, 2a, and 2b.

Asked in an interview whether an agent targeted against CD19 might work in combination with an anti-CD20 agent such as rituximab (Rituxan), Dr. Alan S. Wayne, a leukemia specialist and session comoderator who was not involved in the study, said that CD20 is not as attractive a target in ALL as it is in lymphoma or other hematologic malignancies.

"The question of CD20 in ALL is a little challenging, because the expression is less universal and even within individual cases across blasts," said Dr. Wayne, who is also head of the hematologic disease division of the pediatric oncology branch at the National Cancer Institute.

He noted, however, that there is evidence to suggest that pretreatment of patients with steroids may increase CD20 expression.

"This is an exciting new era for combining agents with a variety of different mechanisms of action, and also toxicity profiles. One could imagine, for example, [using] steroid to increase CD20 expression, rituximab, and then another CD19- or CD22-targeting agent," he said.

The MT 103-206 trial was supported by Micromet. Dr. Topp and coauthors Dr. Ralf Bargou and Dr. Nicola Goekbuget disclosed consulting for and/or receiving honoraria from the company. Three other coauthors are employees of the company. Dr. Wayne reported no relevant financial disclosures.