Immediate, rather than delayed, angiography reduced by 62% the chance of both recurrent heart attack and death in patients with non–ST-segment myocardial infarction.

The significant advantage of early treatment was apparent at both 30 days and 1 year after myocardial infarction, Dr. Aleksandra Milosevic and colleagues wrote (JACC Cardiovasc Interv. 2016;10.1016/j.jcin.2015.11.018).

RIDDLE-NSTEMI (Randomized Study of Immediate vs. Delayed Invasive Intervention in Patients with Non–ST-Segment Elevation MI) is not the first to examine immediate vs. delayed outcomes in coronary angiography. But it is the first to look at a pure cohort of NSTEMI patients, and the first to use purely clinical, rather than biochemical, outcomes, said Dr. Milosevic of the Clinical Center of Serbia, Belgrade.

The study group comprised 323 patients with a confirmed NSTEMI MI to either immediate or delayed angiography. Those in the immediate treatment group went to catheterization as soon as possible (median, 1.4 hours); those in the delayed-treatment group underwent the procedure within 72 hours of randomization (median, 61 hours).

All patients received a loading dose of dual-antiplatelet therapy. For immediate-treatment patients, this consisted of 300 mg aspirin and 600 mg clopidogrel. Those in the delayed-treatment group received 300 mg aspirin and 300 mg clopidogrel. Everyone then received daily treatment of aspirin 100 mg and clopidogrel 75 mg.

Patients who had already been taking dual-antiplatelet therapy continued their maintenance dose. Low-molecular-weight heparin, nitrates, beta-blockers, and ACE inhibitors were given according to clinical guidelines; glycoprotein IIb/IIIa inhibitors were allowed at the treating physician’s discretion.

The time from symptom onset to randomization was 5 hours in the immediate- and 6.5 hours in the delayed-treatment groups. Manual thrombectomy was more common in the immediate-treatment group (3.9% vs. 1%), as was percutaneous coronary intervention (78% vs. 65%). Coronary artery bypass grafting was more common in the delayed-treatment group (23.8% vs. 12%).

At 30 days, the composite primary endpoint of mortality and new MI was significantly less common in the immediate-treatment group (4.3% vs. 13.0%; hazard ratio, 0.32). Mortality was the same in both groups (5 patients; 3%). The difference was driven by the significantly larger number of nonfatal MIs in the delayed-treatment group (16 vs. 2).

The advantage of early treatment held at 1 year, with significantly lower rates of death and new MI in the immediate-treatment group (16.8% vs. 18.8%). This was entirely driven by early events; there was no significant difference after the first 30 days.

A composite secondary endpoint of death, new MI or recurrent ischemia, was also significantly lower in the immediate-intervention group at 30 days (6.8% vs. 26.7%) and 1 year (15.4% vs. 33%).

A multivariate regression analysis controlled for demographics, past medical history, prior coronary procedures, and electrocardiogram changes. After considering these variables, immediate treatment was associated with a 62% reduction in the chance of a new MI within 30 days (HR, 0.42; P = .052).

There was no between-group difference in major bleeding, which was low both at 30 days and 1 year. One patient in the immediate-treatment group and two in the delayed-treatment group needed a transfusion. One intracranial bleed occurred in an immediately treated patient. Four patients in the delayed treatment group were treated for gastrointestinal bleeding.

The authors had no financial declarations.

[email protected]

Immediate, rather than delayed, angiography reduced by 62% the chance of both recurrent heart attack and death in patients with non–ST-segment myocardial infarction.

The significant advantage of early treatment was apparent at both 30 days and 1 year after myocardial infarction, Dr. Aleksandra Milosevic and colleagues wrote (JACC Cardiovasc Interv. 2016;10.1016/j.jcin.2015.11.018).

RIDDLE-NSTEMI (Randomized Study of Immediate vs. Delayed Invasive Intervention in Patients with Non–ST-Segment Elevation MI) is not the first to examine immediate vs. delayed outcomes in coronary angiography. But it is the first to look at a pure cohort of NSTEMI patients, and the first to use purely clinical, rather than biochemical, outcomes, said Dr. Milosevic of the Clinical Center of Serbia, Belgrade.

The study group comprised 323 patients with a confirmed NSTEMI MI to either immediate or delayed angiography. Those in the immediate treatment group went to catheterization as soon as possible (median, 1.4 hours); those in the delayed-treatment group underwent the procedure within 72 hours of randomization (median, 61 hours).

All patients received a loading dose of dual-antiplatelet therapy. For immediate-treatment patients, this consisted of 300 mg aspirin and 600 mg clopidogrel. Those in the delayed-treatment group received 300 mg aspirin and 300 mg clopidogrel. Everyone then received daily treatment of aspirin 100 mg and clopidogrel 75 mg.

Patients who had already been taking dual-antiplatelet therapy continued their maintenance dose. Low-molecular-weight heparin, nitrates, beta-blockers, and ACE inhibitors were given according to clinical guidelines; glycoprotein IIb/IIIa inhibitors were allowed at the treating physician’s discretion.

The time from symptom onset to randomization was 5 hours in the immediate- and 6.5 hours in the delayed-treatment groups. Manual thrombectomy was more common in the immediate-treatment group (3.9% vs. 1%), as was percutaneous coronary intervention (78% vs. 65%). Coronary artery bypass grafting was more common in the delayed-treatment group (23.8% vs. 12%).

At 30 days, the composite primary endpoint of mortality and new MI was significantly less common in the immediate-treatment group (4.3% vs. 13.0%; hazard ratio, 0.32). Mortality was the same in both groups (5 patients; 3%). The difference was driven by the significantly larger number of nonfatal MIs in the delayed-treatment group (16 vs. 2).

The advantage of early treatment held at 1 year, with significantly lower rates of death and new MI in the immediate-treatment group (16.8% vs. 18.8%). This was entirely driven by early events; there was no significant difference after the first 30 days.

A composite secondary endpoint of death, new MI or recurrent ischemia, was also significantly lower in the immediate-intervention group at 30 days (6.8% vs. 26.7%) and 1 year (15.4% vs. 33%).

A multivariate regression analysis controlled for demographics, past medical history, prior coronary procedures, and electrocardiogram changes. After considering these variables, immediate treatment was associated with a 62% reduction in the chance of a new MI within 30 days (HR, 0.42; P = .052).

There was no between-group difference in major bleeding, which was low both at 30 days and 1 year. One patient in the immediate-treatment group and two in the delayed-treatment group needed a transfusion. One intracranial bleed occurred in an immediately treated patient. Four patients in the delayed treatment group were treated for gastrointestinal bleeding.

The authors had no financial declarations.

[email protected]

Immediate, rather than delayed, angiography reduced by 62% the chance of both recurrent heart attack and death in patients with non–ST-segment myocardial infarction.

The significant advantage of early treatment was apparent at both 30 days and 1 year after myocardial infarction, Dr. Aleksandra Milosevic and colleagues wrote (JACC Cardiovasc Interv. 2016;10.1016/j.jcin.2015.11.018).

RIDDLE-NSTEMI (Randomized Study of Immediate vs. Delayed Invasive Intervention in Patients with Non–ST-Segment Elevation MI) is not the first to examine immediate vs. delayed outcomes in coronary angiography. But it is the first to look at a pure cohort of NSTEMI patients, and the first to use purely clinical, rather than biochemical, outcomes, said Dr. Milosevic of the Clinical Center of Serbia, Belgrade.

The study group comprised 323 patients with a confirmed NSTEMI MI to either immediate or delayed angiography. Those in the immediate treatment group went to catheterization as soon as possible (median, 1.4 hours); those in the delayed-treatment group underwent the procedure within 72 hours of randomization (median, 61 hours).

All patients received a loading dose of dual-antiplatelet therapy. For immediate-treatment patients, this consisted of 300 mg aspirin and 600 mg clopidogrel. Those in the delayed-treatment group received 300 mg aspirin and 300 mg clopidogrel. Everyone then received daily treatment of aspirin 100 mg and clopidogrel 75 mg.

Patients who had already been taking dual-antiplatelet therapy continued their maintenance dose. Low-molecular-weight heparin, nitrates, beta-blockers, and ACE inhibitors were given according to clinical guidelines; glycoprotein IIb/IIIa inhibitors were allowed at the treating physician’s discretion.

The time from symptom onset to randomization was 5 hours in the immediate- and 6.5 hours in the delayed-treatment groups. Manual thrombectomy was more common in the immediate-treatment group (3.9% vs. 1%), as was percutaneous coronary intervention (78% vs. 65%). Coronary artery bypass grafting was more common in the delayed-treatment group (23.8% vs. 12%).

At 30 days, the composite primary endpoint of mortality and new MI was significantly less common in the immediate-treatment group (4.3% vs. 13.0%; hazard ratio, 0.32). Mortality was the same in both groups (5 patients; 3%). The difference was driven by the significantly larger number of nonfatal MIs in the delayed-treatment group (16 vs. 2).

The advantage of early treatment held at 1 year, with significantly lower rates of death and new MI in the immediate-treatment group (16.8% vs. 18.8%). This was entirely driven by early events; there was no significant difference after the first 30 days.

A composite secondary endpoint of death, new MI or recurrent ischemia, was also significantly lower in the immediate-intervention group at 30 days (6.8% vs. 26.7%) and 1 year (15.4% vs. 33%).

A multivariate regression analysis controlled for demographics, past medical history, prior coronary procedures, and electrocardiogram changes. After considering these variables, immediate treatment was associated with a 62% reduction in the chance of a new MI within 30 days (HR, 0.42; P = .052).

There was no between-group difference in major bleeding, which was low both at 30 days and 1 year. One patient in the immediate-treatment group and two in the delayed-treatment group needed a transfusion. One intracranial bleed occurred in an immediately treated patient. Four patients in the delayed treatment group were treated for gastrointestinal bleeding.

The authors had no financial declarations.

[email protected]

Nick Fitterman, MD, SFHM, vice chair of hospital medicine for the Hofstra North Shore-LIJ School of Medicine in Hempstead, N.Y., and North Shore-Long Island Jewish Health System in New Hyde Park, N.Y., discusses how hospital medicine factors into population health—where is the intersection and what is the hospitalist’s role?

Nick Fitterman, MD, SFHM, vice chair of hospital medicine for the Hofstra North Shore-LIJ School of Medicine in Hempstead, N.Y., and North Shore-Long Island Jewish Health System in New Hyde Park, N.Y., discusses how hospital medicine factors into population health—where is the intersection and what is the hospitalist’s role?

Nick Fitterman, MD, SFHM, vice chair of hospital medicine for the Hofstra North Shore-LIJ School of Medicine in Hempstead, N.Y., and North Shore-Long Island Jewish Health System in New Hyde Park, N.Y., discusses how hospital medicine factors into population health—where is the intersection and what is the hospitalist’s role?

Movement is key to hospitalist Jaime Upegui, MD,  who says riding a motorcycle is a lot like yoga, "you have to focus on the moment, the task at hand." Listen to more of our interview:

Movement is key to hospitalist Jaime Upegui, MD,  who says riding a motorcycle is a lot like yoga, "you have to focus on the moment, the task at hand." Listen to more of our interview:

Movement is key to hospitalist Jaime Upegui, MD,  who says riding a motorcycle is a lot like yoga, "you have to focus on the moment, the task at hand." Listen to more of our interview:

Listen to more of our interview on the GOP candidates with Robert Blendon, ScD, professor of health policy and political analysis at the Harvard School of Public Health and Harvard Kennedy School of Government in Cambridge, Mass.

Listen to more of our interview on the GOP candidates with Robert Blendon, ScD, professor of health policy and political analysis at the Harvard School of Public Health and Harvard Kennedy School of Government in Cambridge, Mass.

Listen to more of our interview on the GOP candidates with Robert Blendon, ScD, professor of health policy and political analysis at the Harvard School of Public Health and Harvard Kennedy School of Government in Cambridge, Mass.

[WpProQuiz 3]

[WpProQuiz_toplist 3]

Read more about provider risks from needlesticks.

[WpProQuiz 3]

[WpProQuiz_toplist 3]

Read more about provider risks from needlesticks.

[WpProQuiz 3]

[WpProQuiz_toplist 3]

Read more about provider risks from needlesticks.

The longer a woman’s reproductive years last, the less she may be prone to postmenopausal depression, a large meta-analysis has determined.

The risk of depression declined by 2% for every 2 premenopausal years after age 40. Women who entered menopause after age 40 experienced a 50% decrease in the risk of depression, compared with women who experienced premature menopause, Dr. Marios K. Georgakis and colleagues reported Jan. 6 in JAMA Psychiatry (2016. doi:10.1001/jamapsychiatry.2015.2653).

Thinkstock/Thinkstock.com

The findings suggest that longer exposure to endogenous estrogens mediates the pathophysiology of late-life depression, wrote Dr. Georgakis of the National and Kapodistrian University of Athens and coauthors.

“If confirmed in prospective and culturally diverse studies … these findings could have a significant clinical effect by allowing for the identification of a group of women at higher risk for depression who may benefit from psychiatric monitoring or estrogen-based therapies.”

The meta-analysis comprised 14 studies that included 67,714 women. They controlled for numerous factors, including age, body mass index, obesity, smoking, and hormone therapy. However, only two controlled for past depression – one of the biggest risk factors for recurring depression.

In addition to the 2% decline per 2 premenopausal years after 40, a subanalysis of three studies examining severe depression found a 5% decreased risk for the same time measure. Another analysis of women with premature menopause found a doubling in the risk of depression for those who experienced menopause before age 40.

Estrogen is known to have neuroprotective and antidepressive properties, and the brain is richly endowed with estrogen receptors, the authors said. The exact pathway of protection against depression, however, remains unknown. Potentiation of neurotransmitters and moderation of atherosclerosis might play protective roles.

“Given the results of our study, it remains to be investigated whether women with menopause at younger ages could benefit by preventive use of hormone therapy against late-life depression, provided that adverse effects associated with long-term use are considered,” the authors said. “In this context, the development of estrogen receptor subtype–specific ligands could decrease the proportion of estrogen therapy adverse effects.”

Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.

[email protected]

The longer a woman’s reproductive years last, the less she may be prone to postmenopausal depression, a large meta-analysis has determined.

The risk of depression declined by 2% for every 2 premenopausal years after age 40. Women who entered menopause after age 40 experienced a 50% decrease in the risk of depression, compared with women who experienced premature menopause, Dr. Marios K. Georgakis and colleagues reported Jan. 6 in JAMA Psychiatry (2016. doi:10.1001/jamapsychiatry.2015.2653).

Thinkstock/Thinkstock.com

The findings suggest that longer exposure to endogenous estrogens mediates the pathophysiology of late-life depression, wrote Dr. Georgakis of the National and Kapodistrian University of Athens and coauthors.

“If confirmed in prospective and culturally diverse studies … these findings could have a significant clinical effect by allowing for the identification of a group of women at higher risk for depression who may benefit from psychiatric monitoring or estrogen-based therapies.”

The meta-analysis comprised 14 studies that included 67,714 women. They controlled for numerous factors, including age, body mass index, obesity, smoking, and hormone therapy. However, only two controlled for past depression – one of the biggest risk factors for recurring depression.

In addition to the 2% decline per 2 premenopausal years after 40, a subanalysis of three studies examining severe depression found a 5% decreased risk for the same time measure. Another analysis of women with premature menopause found a doubling in the risk of depression for those who experienced menopause before age 40.

Estrogen is known to have neuroprotective and antidepressive properties, and the brain is richly endowed with estrogen receptors, the authors said. The exact pathway of protection against depression, however, remains unknown. Potentiation of neurotransmitters and moderation of atherosclerosis might play protective roles.

“Given the results of our study, it remains to be investigated whether women with menopause at younger ages could benefit by preventive use of hormone therapy against late-life depression, provided that adverse effects associated with long-term use are considered,” the authors said. “In this context, the development of estrogen receptor subtype–specific ligands could decrease the proportion of estrogen therapy adverse effects.”

Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.

[email protected]

The longer a woman’s reproductive years last, the less she may be prone to postmenopausal depression, a large meta-analysis has determined.

The risk of depression declined by 2% for every 2 premenopausal years after age 40. Women who entered menopause after age 40 experienced a 50% decrease in the risk of depression, compared with women who experienced premature menopause, Dr. Marios K. Georgakis and colleagues reported Jan. 6 in JAMA Psychiatry (2016. doi:10.1001/jamapsychiatry.2015.2653).

Thinkstock/Thinkstock.com

The findings suggest that longer exposure to endogenous estrogens mediates the pathophysiology of late-life depression, wrote Dr. Georgakis of the National and Kapodistrian University of Athens and coauthors.

“If confirmed in prospective and culturally diverse studies … these findings could have a significant clinical effect by allowing for the identification of a group of women at higher risk for depression who may benefit from psychiatric monitoring or estrogen-based therapies.”

The meta-analysis comprised 14 studies that included 67,714 women. They controlled for numerous factors, including age, body mass index, obesity, smoking, and hormone therapy. However, only two controlled for past depression – one of the biggest risk factors for recurring depression.

In addition to the 2% decline per 2 premenopausal years after 40, a subanalysis of three studies examining severe depression found a 5% decreased risk for the same time measure. Another analysis of women with premature menopause found a doubling in the risk of depression for those who experienced menopause before age 40.

Estrogen is known to have neuroprotective and antidepressive properties, and the brain is richly endowed with estrogen receptors, the authors said. The exact pathway of protection against depression, however, remains unknown. Potentiation of neurotransmitters and moderation of atherosclerosis might play protective roles.

“Given the results of our study, it remains to be investigated whether women with menopause at younger ages could benefit by preventive use of hormone therapy against late-life depression, provided that adverse effects associated with long-term use are considered,” the authors said. “In this context, the development of estrogen receptor subtype–specific ligands could decrease the proportion of estrogen therapy adverse effects.”

Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.

[email protected]

It’s 2016. Where am I?

2015 was a mixed year for neurologists and doctors in general. The Sustainable Growth Rate was repealed in a rare moment of bipartisan cooperation. Whether this will stem the tide of doctors leaving Medicare remains to be seen. In my area, it seems like another internist changes to concierge practice every week.

Even with these changes, I can’t say the reimbursement rates have returned to previous levels. Neurologists, in a primarily thinking field, often take the brunt of cuts on the few procedures we have. Like other fields, we try to cram more things into limited time and hope it all somehow works out.

2016 brings an election year, and again doctors will be in the unenviable position of ping-pong balls whacked between both sides to score political points. It would be nice to have political parties willing to work out what’s best for the health of Americans as a whole rather than trying to fire up the extreme ends of the political spectrum.

2015 was the year a new International Classification of Diseases system was foisted on us for reasons I still don’t understand. With it came a whole new wave of codes and modifiers to learn. This in turn takes a lot of time, for which we aren’t paid. Time is something I, and most docs, don’t have a lot of. I’d like to focus on caring for patients, and nothing more, but the powers that be appear to have a dim view of such silliness. This brings me back to watching internists gradually shift to cash-pay models and wondering how big the demand would be for a general neurologist in that world. The only one I know who actually did it shut down in a few months.

What’s on my wish list in 2016? Obviously, the health and welfare of myself and those around me comes first. For my patients, it’s some breakthroughs for the terrible diseases we still have no real treatments for. For my practice, it’s staying strong enough to remain independent. Some better reimbursement and non–snake oil sources of revenue are always nice. I’m hoping that in 1 year I’ll be able to write something more optimistic.

Wishing you all a great 2016!

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

It’s 2016. Where am I?

2015 was a mixed year for neurologists and doctors in general. The Sustainable Growth Rate was repealed in a rare moment of bipartisan cooperation. Whether this will stem the tide of doctors leaving Medicare remains to be seen. In my area, it seems like another internist changes to concierge practice every week.

Even with these changes, I can’t say the reimbursement rates have returned to previous levels. Neurologists, in a primarily thinking field, often take the brunt of cuts on the few procedures we have. Like other fields, we try to cram more things into limited time and hope it all somehow works out.

2016 brings an election year, and again doctors will be in the unenviable position of ping-pong balls whacked between both sides to score political points. It would be nice to have political parties willing to work out what’s best for the health of Americans as a whole rather than trying to fire up the extreme ends of the political spectrum.

2015 was the year a new International Classification of Diseases system was foisted on us for reasons I still don’t understand. With it came a whole new wave of codes and modifiers to learn. This in turn takes a lot of time, for which we aren’t paid. Time is something I, and most docs, don’t have a lot of. I’d like to focus on caring for patients, and nothing more, but the powers that be appear to have a dim view of such silliness. This brings me back to watching internists gradually shift to cash-pay models and wondering how big the demand would be for a general neurologist in that world. The only one I know who actually did it shut down in a few months.

What’s on my wish list in 2016? Obviously, the health and welfare of myself and those around me comes first. For my patients, it’s some breakthroughs for the terrible diseases we still have no real treatments for. For my practice, it’s staying strong enough to remain independent. Some better reimbursement and non–snake oil sources of revenue are always nice. I’m hoping that in 1 year I’ll be able to write something more optimistic.

Wishing you all a great 2016!

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

It’s 2016. Where am I?

2015 was a mixed year for neurologists and doctors in general. The Sustainable Growth Rate was repealed in a rare moment of bipartisan cooperation. Whether this will stem the tide of doctors leaving Medicare remains to be seen. In my area, it seems like another internist changes to concierge practice every week.

Even with these changes, I can’t say the reimbursement rates have returned to previous levels. Neurologists, in a primarily thinking field, often take the brunt of cuts on the few procedures we have. Like other fields, we try to cram more things into limited time and hope it all somehow works out.

2016 brings an election year, and again doctors will be in the unenviable position of ping-pong balls whacked between both sides to score political points. It would be nice to have political parties willing to work out what’s best for the health of Americans as a whole rather than trying to fire up the extreme ends of the political spectrum.

2015 was the year a new International Classification of Diseases system was foisted on us for reasons I still don’t understand. With it came a whole new wave of codes and modifiers to learn. This in turn takes a lot of time, for which we aren’t paid. Time is something I, and most docs, don’t have a lot of. I’d like to focus on caring for patients, and nothing more, but the powers that be appear to have a dim view of such silliness. This brings me back to watching internists gradually shift to cash-pay models and wondering how big the demand would be for a general neurologist in that world. The only one I know who actually did it shut down in a few months.

What’s on my wish list in 2016? Obviously, the health and welfare of myself and those around me comes first. For my patients, it’s some breakthroughs for the terrible diseases we still have no real treatments for. For my practice, it’s staying strong enough to remain independent. Some better reimbursement and non–snake oil sources of revenue are always nice. I’m hoping that in 1 year I’ll be able to write something more optimistic.

Wishing you all a great 2016!

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Highlights from the January 2016 issue of The Hospitalist feature Dr. Nick Fitterman on population health, Dr. Robert Blendon on how healthcare reform might impact the Republican primary race, and Dr. Jaime Upegui on living life to the fullest.

Highlights from the January 2016 issue of The Hospitalist feature Dr. Nick Fitterman on population health, Dr. Robert Blendon on how healthcare reform might impact the Republican primary race, and Dr. Jaime Upegui on living life to the fullest.

Highlights from the January 2016 issue of The Hospitalist feature Dr. Nick Fitterman on population health, Dr. Robert Blendon on how healthcare reform might impact the Republican primary race, and Dr. Jaime Upegui on living life to the fullest.

A 59-year-old man is admitted to the ICU with a myocardial infarction. He is discharged after 5 days on enalapril, metoprolol, simvastatin, and aspirin. At a 3-month follow-up, he is noted to have marked anhedonia, complaints of insomnia, feelings of worthlessness, and psychomotor retardation.

What would you do?

A) Stop the enalapril.

B) Stop the metoprolol.

C) Stop the simvastatin.

D) Begin a tricyclic antidepressant.

E) Begin an SSRI.

When I was in medical school, the dogma was to never give beta-blockers to patients with systolic heart failure, because it would worsen the heart failure.¹ As we all know, this dogma completely reversed, and beta-blocker therapy is a cornerstone of treatment of patients with systolic heart failure, with improvements in morbidity and mortality.² Underutilization of beta-blockers for indicated conditions is likely due to fear of beta-blocker side effects.²

There has long been concern that beta-blockers can cause, or worsen, depression. As a result, beta-blockers are sometimes withheld from patients with a history of depression who may benefit, or beta-blockers are stopped in patients who develop depression.

Early reports of possible beta-blocker–induced depression surfaced soon after the beta-blocker propranolol became available in the 1960s. A frequently cited reference is a letter to the British Medical Journal in which H.J. Waal reported that 20 of 89 patients on propranolol volunteered or exhibited depressive symptoms.³ Almost half of those patients were diagnosed with grade I depression – symptoms of irritability, insomnia, nightmares, and fatigue. No control group of patients was evaluated to ascertain the prevalence of those symptoms in patients treated with other antihypertensives, or in nonhypertensive patients.

M. H. Pollack and colleagues reported on a series of three patients who developed symptoms of depression after starting propranolol, and the researchers concluded that depression following the administration of propranolol was a real phenomenon.⁴

Many subsequent studies have cast doubt on the association of beta-blockers and depression. Depression is common following myocardial infarction and in patients with coronary artery disease. Several studies have looked closely for association with beta-blocker use in this population.

Dr. Steven J. Schleifer and colleagues evaluated 190 patients who had sustained a myocardial infarction for evidence of depression. The patients were interviewed 8-10 days after the infarct and again at 3 months. No antianginal or antihypertensive medications, including beta-blockers, were associated with an increase in depression.⁵

Dr. Joost P. van Melle and colleagues participated in a multicenter study that looked at patients following myocardial infarction, assessing for depressive symptoms at baseline and at 3, 6, 9, and 12 months using the Beck depression inventory.⁶ A total of 254 patients receiving beta-blockers were matched with 127 control patients post MI not receiving beta-blockers. No significant differences were found between non–beta-blocker users and beta-blocker users on the presence of depressive symptoms.

Robert Carney, Ph.D., and colleagues evaluated 75 patients undergoing elective cardiac catheterization with psychiatric interview and psychological assessments.⁷ Half of the patients in the study were receiving beta-blockers. Thirty-three percent of the patients who were not receiving beta-blockers met DSM-III criteria for depression, and 21% of the beta-blocker–treated patients met criteria for depression.

Dr. Linda Battes and colleagues reported that beta-blocker use actually decreased the risk of depression in patients who had undergone a percutaneous intervention, with a risk reduction of 49% for depression in beta-blocker–treated patients.⁸ In a study of elderly patients, Dr. Hendrika Luijendijk and colleagues followed 5,104 elderly persons for episodes of incident depression. They found that beta-blocker use did not increase the risk of developing depression.⁹

Beta-blockers often have been avoided in patients with obstructive pulmonary disease – both in patients with asthma and those with COPD – because of concern for worsening obstructive pulmonary disease. There is strong evidence now that beta-blocker use is not problematic in patients with COPD.

Dr. Surya Bhatt and colleagues found that beta-blocker use decreased COPD exacerbations.10 Almost 3,500 patients were included. During a median of 2.1 years of follow-up, beta-blocker use was associated with a significantly lower rate of total exacerbations (incidence risk ratio, 0.73; 95% confidence interval, 0.60-0.90; P = .003) and severe exacerbations (IRR, 0.67, 95% CI, 0.48-0.93; P = .016).

Dr. Qingxia Du and colleagues found that beta-blocker use in patients with COPD both reduced exacerbations and reduced mortality.¹¹ In another study, the use of beta-blockers in patients hospitalized for acute exacerbations of COPD reduced mortality.¹² Most of the patients receiving beta-blockers in that study had severe cardiovascular disease.

There are far fewer data on beta-blocker use in patients with asthma. In general, beta-blockers are routinely avoided in patients with asthma. In one small study of asthmatic patients receiving propranolol, there was no effect on methacholine challenge response, histamine responsiveness, or asthma control questionnaire results.¹³ In a murine model of asthma, long-term administration of beta-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect.¹⁴ This topic is an area of interest for further study in asthma control.

So much of what we thought we knew about beta-blockers has turned out to not be so. We keep our eyes open and welcome further enlightenment.

References

1. Circulation. 1983 Jun;67(6 Pt 2):I91.

2. Expert Opin Drug Saf. 2015 Dec;14(12):1855-63.

3. Br Med J. 1967 Apr 1;2(5543):50.

4. J Nerv Ment Dis. 1985 Feb;173(2):118-9.

5. Am Heart J. 1991 May;121(5):1397-402.

6. J Am Coll Cardiol. 2006 Dec 5;48(11):2209-14.

7. Am J Med. 1987 Aug;83(2):223-6.

8. J Affect Disord. 2012 Feb;136(3):751-7.

9. J Clin Psychopharmacol. 2011 Feb;31(1):45-50.

10. Thorax. 2016 Jan;71(1):8-14.

11. PLoS ONE 9(11): e113048.

12. Thorax. 2008 Apr;63(4):301-5.

13. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1308-14.

14. Int J Gen Med. 2013 Jul 8;6:549-55.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

A 59-year-old man is admitted to the ICU with a myocardial infarction. He is discharged after 5 days on enalapril, metoprolol, simvastatin, and aspirin. At a 3-month follow-up, he is noted to have marked anhedonia, complaints of insomnia, feelings of worthlessness, and psychomotor retardation.

What would you do?

A) Stop the enalapril.

B) Stop the metoprolol.

C) Stop the simvastatin.

D) Begin a tricyclic antidepressant.

E) Begin an SSRI.

When I was in medical school, the dogma was to never give beta-blockers to patients with systolic heart failure, because it would worsen the heart failure.¹ As we all know, this dogma completely reversed, and beta-blocker therapy is a cornerstone of treatment of patients with systolic heart failure, with improvements in morbidity and mortality.² Underutilization of beta-blockers for indicated conditions is likely due to fear of beta-blocker side effects.²

There has long been concern that beta-blockers can cause, or worsen, depression. As a result, beta-blockers are sometimes withheld from patients with a history of depression who may benefit, or beta-blockers are stopped in patients who develop depression.

Early reports of possible beta-blocker–induced depression surfaced soon after the beta-blocker propranolol became available in the 1960s. A frequently cited reference is a letter to the British Medical Journal in which H.J. Waal reported that 20 of 89 patients on propranolol volunteered or exhibited depressive symptoms.³ Almost half of those patients were diagnosed with grade I depression – symptoms of irritability, insomnia, nightmares, and fatigue. No control group of patients was evaluated to ascertain the prevalence of those symptoms in patients treated with other antihypertensives, or in nonhypertensive patients.

M. H. Pollack and colleagues reported on a series of three patients who developed symptoms of depression after starting propranolol, and the researchers concluded that depression following the administration of propranolol was a real phenomenon.⁴

Many subsequent studies have cast doubt on the association of beta-blockers and depression. Depression is common following myocardial infarction and in patients with coronary artery disease. Several studies have looked closely for association with beta-blocker use in this population.

Dr. Steven J. Schleifer and colleagues evaluated 190 patients who had sustained a myocardial infarction for evidence of depression. The patients were interviewed 8-10 days after the infarct and again at 3 months. No antianginal or antihypertensive medications, including beta-blockers, were associated with an increase in depression.⁵

Dr. Joost P. van Melle and colleagues participated in a multicenter study that looked at patients following myocardial infarction, assessing for depressive symptoms at baseline and at 3, 6, 9, and 12 months using the Beck depression inventory.⁶ A total of 254 patients receiving beta-blockers were matched with 127 control patients post MI not receiving beta-blockers. No significant differences were found between non–beta-blocker users and beta-blocker users on the presence of depressive symptoms.

Robert Carney, Ph.D., and colleagues evaluated 75 patients undergoing elective cardiac catheterization with psychiatric interview and psychological assessments.⁷ Half of the patients in the study were receiving beta-blockers. Thirty-three percent of the patients who were not receiving beta-blockers met DSM-III criteria for depression, and 21% of the beta-blocker–treated patients met criteria for depression.

Dr. Linda Battes and colleagues reported that beta-blocker use actually decreased the risk of depression in patients who had undergone a percutaneous intervention, with a risk reduction of 49% for depression in beta-blocker–treated patients.⁸ In a study of elderly patients, Dr. Hendrika Luijendijk and colleagues followed 5,104 elderly persons for episodes of incident depression. They found that beta-blocker use did not increase the risk of developing depression.⁹

Beta-blockers often have been avoided in patients with obstructive pulmonary disease – both in patients with asthma and those with COPD – because of concern for worsening obstructive pulmonary disease. There is strong evidence now that beta-blocker use is not problematic in patients with COPD.

Dr. Surya Bhatt and colleagues found that beta-blocker use decreased COPD exacerbations.10 Almost 3,500 patients were included. During a median of 2.1 years of follow-up, beta-blocker use was associated with a significantly lower rate of total exacerbations (incidence risk ratio, 0.73; 95% confidence interval, 0.60-0.90; P = .003) and severe exacerbations (IRR, 0.67, 95% CI, 0.48-0.93; P = .016).

Dr. Qingxia Du and colleagues found that beta-blocker use in patients with COPD both reduced exacerbations and reduced mortality.¹¹ In another study, the use of beta-blockers in patients hospitalized for acute exacerbations of COPD reduced mortality.¹² Most of the patients receiving beta-blockers in that study had severe cardiovascular disease.

There are far fewer data on beta-blocker use in patients with asthma. In general, beta-blockers are routinely avoided in patients with asthma. In one small study of asthmatic patients receiving propranolol, there was no effect on methacholine challenge response, histamine responsiveness, or asthma control questionnaire results.¹³ In a murine model of asthma, long-term administration of beta-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect.¹⁴ This topic is an area of interest for further study in asthma control.

So much of what we thought we knew about beta-blockers has turned out to not be so. We keep our eyes open and welcome further enlightenment.

References

1. Circulation. 1983 Jun;67(6 Pt 2):I91.

2. Expert Opin Drug Saf. 2015 Dec;14(12):1855-63.

3. Br Med J. 1967 Apr 1;2(5543):50.

4. J Nerv Ment Dis. 1985 Feb;173(2):118-9.

5. Am Heart J. 1991 May;121(5):1397-402.

6. J Am Coll Cardiol. 2006 Dec 5;48(11):2209-14.

7. Am J Med. 1987 Aug;83(2):223-6.

8. J Affect Disord. 2012 Feb;136(3):751-7.

9. J Clin Psychopharmacol. 2011 Feb;31(1):45-50.

10. Thorax. 2016 Jan;71(1):8-14.

11. PLoS ONE 9(11): e113048.

12. Thorax. 2008 Apr;63(4):301-5.

13. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1308-14.

14. Int J Gen Med. 2013 Jul 8;6:549-55.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

A 59-year-old man is admitted to the ICU with a myocardial infarction. He is discharged after 5 days on enalapril, metoprolol, simvastatin, and aspirin. At a 3-month follow-up, he is noted to have marked anhedonia, complaints of insomnia, feelings of worthlessness, and psychomotor retardation.

What would you do?

A) Stop the enalapril.

B) Stop the metoprolol.

C) Stop the simvastatin.

D) Begin a tricyclic antidepressant.

E) Begin an SSRI.

When I was in medical school, the dogma was to never give beta-blockers to patients with systolic heart failure, because it would worsen the heart failure.¹ As we all know, this dogma completely reversed, and beta-blocker therapy is a cornerstone of treatment of patients with systolic heart failure, with improvements in morbidity and mortality.² Underutilization of beta-blockers for indicated conditions is likely due to fear of beta-blocker side effects.²

There has long been concern that beta-blockers can cause, or worsen, depression. As a result, beta-blockers are sometimes withheld from patients with a history of depression who may benefit, or beta-blockers are stopped in patients who develop depression.

Early reports of possible beta-blocker–induced depression surfaced soon after the beta-blocker propranolol became available in the 1960s. A frequently cited reference is a letter to the British Medical Journal in which H.J. Waal reported that 20 of 89 patients on propranolol volunteered or exhibited depressive symptoms.³ Almost half of those patients were diagnosed with grade I depression – symptoms of irritability, insomnia, nightmares, and fatigue. No control group of patients was evaluated to ascertain the prevalence of those symptoms in patients treated with other antihypertensives, or in nonhypertensive patients.

M. H. Pollack and colleagues reported on a series of three patients who developed symptoms of depression after starting propranolol, and the researchers concluded that depression following the administration of propranolol was a real phenomenon.⁴

Many subsequent studies have cast doubt on the association of beta-blockers and depression. Depression is common following myocardial infarction and in patients with coronary artery disease. Several studies have looked closely for association with beta-blocker use in this population.

Dr. Steven J. Schleifer and colleagues evaluated 190 patients who had sustained a myocardial infarction for evidence of depression. The patients were interviewed 8-10 days after the infarct and again at 3 months. No antianginal or antihypertensive medications, including beta-blockers, were associated with an increase in depression.⁵

Dr. Joost P. van Melle and colleagues participated in a multicenter study that looked at patients following myocardial infarction, assessing for depressive symptoms at baseline and at 3, 6, 9, and 12 months using the Beck depression inventory.⁶ A total of 254 patients receiving beta-blockers were matched with 127 control patients post MI not receiving beta-blockers. No significant differences were found between non–beta-blocker users and beta-blocker users on the presence of depressive symptoms.

Robert Carney, Ph.D., and colleagues evaluated 75 patients undergoing elective cardiac catheterization with psychiatric interview and psychological assessments.⁷ Half of the patients in the study were receiving beta-blockers. Thirty-three percent of the patients who were not receiving beta-blockers met DSM-III criteria for depression, and 21% of the beta-blocker–treated patients met criteria for depression.

Dr. Linda Battes and colleagues reported that beta-blocker use actually decreased the risk of depression in patients who had undergone a percutaneous intervention, with a risk reduction of 49% for depression in beta-blocker–treated patients.⁸ In a study of elderly patients, Dr. Hendrika Luijendijk and colleagues followed 5,104 elderly persons for episodes of incident depression. They found that beta-blocker use did not increase the risk of developing depression.⁹

Beta-blockers often have been avoided in patients with obstructive pulmonary disease – both in patients with asthma and those with COPD – because of concern for worsening obstructive pulmonary disease. There is strong evidence now that beta-blocker use is not problematic in patients with COPD.

Dr. Surya Bhatt and colleagues found that beta-blocker use decreased COPD exacerbations.10 Almost 3,500 patients were included. During a median of 2.1 years of follow-up, beta-blocker use was associated with a significantly lower rate of total exacerbations (incidence risk ratio, 0.73; 95% confidence interval, 0.60-0.90; P = .003) and severe exacerbations (IRR, 0.67, 95% CI, 0.48-0.93; P = .016).

Dr. Qingxia Du and colleagues found that beta-blocker use in patients with COPD both reduced exacerbations and reduced mortality.¹¹ In another study, the use of beta-blockers in patients hospitalized for acute exacerbations of COPD reduced mortality.¹² Most of the patients receiving beta-blockers in that study had severe cardiovascular disease.

There are far fewer data on beta-blocker use in patients with asthma. In general, beta-blockers are routinely avoided in patients with asthma. In one small study of asthmatic patients receiving propranolol, there was no effect on methacholine challenge response, histamine responsiveness, or asthma control questionnaire results.¹³ In a murine model of asthma, long-term administration of beta-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect.¹⁴ This topic is an area of interest for further study in asthma control.

So much of what we thought we knew about beta-blockers has turned out to not be so. We keep our eyes open and welcome further enlightenment.

References

1. Circulation. 1983 Jun;67(6 Pt 2):I91.

2. Expert Opin Drug Saf. 2015 Dec;14(12):1855-63.

3. Br Med J. 1967 Apr 1;2(5543):50.

4. J Nerv Ment Dis. 1985 Feb;173(2):118-9.

5. Am Heart J. 1991 May;121(5):1397-402.

6. J Am Coll Cardiol. 2006 Dec 5;48(11):2209-14.

7. Am J Med. 1987 Aug;83(2):223-6.

8. J Affect Disord. 2012 Feb;136(3):751-7.

9. J Clin Psychopharmacol. 2011 Feb;31(1):45-50.

10. Thorax. 2016 Jan;71(1):8-14.

11. PLoS ONE 9(11): e113048.

12. Thorax. 2008 Apr;63(4):301-5.

13. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1308-14.

14. Int J Gen Med. 2013 Jul 8;6:549-55.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

Cancer patient

Photo by Bill Branson

A new study has provided additional insight into the development of cardiac abnormalities in adult survivors of childhood cancer.

Researchers analyzed more than 1800 cancer survivors who were exposed to cardiotoxic therapies as children.

The team said they found evidence of cardiac abnormalities in a substantial number of these subjects, many of whom were younger and did not exhibit symptoms of abnormalities.

Daniel A. Mulrooney, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these findings in Annals of Internal Medicine.

The team assessed cardiac outcomes among 1853 subjects who were 18 and older and had received cancer-related cardiotoxic therapy at least 10 years earlier.

The subjects were pretty evenly split along gender lines (52.3% male), their median age at cancer diagnosis was 8 (range, 0 to 24), and their median age at evaluation was 31 (range, 18 to 60).

At evaluation, 7.4% of subjects had cardiomyopathy (newly identified in 4.7%), 3.8% had coronary artery disease (newly identified in 2.2%), 28% had valvular regurgitation or stenosis (newly identified in 24.8%), and 4.4% had conduction or rhythm abnormalities (newly identified in 1.4%). All but 5 subjects were asymptomatic.

Multivariable analysis suggested the odds of developing cardiomyopathy were significantly associated with being male (odds ratio [OR]=1.9), receiving anthracycline doses of 250 mg/m² or greater (OR=2.7), having cardiac radiation exposure greater than 1500 cGy (OR=1.9), and having hypertension (OR=3.0).

Being younger at diagnosis was associated with higher odds of valvular disease. The ORs were 1.5 for patients who were 0 to 4 years of age at diagnosis and 1.3 for patients who were 5 to 9 at diagnosis.

Receiving higher radiation doses was associated with higher odds of valvular disease as well. But associations between radiation and valvular disease varied according to a patient’s anthracycline exposure (interaction P<0.001). The highest odds were among survivors with the highest doses of radiation exposure and any anthracycline exposure (OR=4.5).

The researchers also noted a reduction in the OR for valvular disease among obese patients (OR=0.4) and those with dyslipidemia (OR=0.7).

The team said there were not enough cases of coronary artery disease and conduction or rhythm abnormalities to support a fully adjusted multivariable model. However, it seemed these outcomes were more common with older age (≥40 years) and among patients with cardiac radiation doses of 1500 cGy or greater.

The researchers said this study revealed “considerable cardiovascular disease” in a large cohort of adult survivors of childhood cancer, which suggests a substantial future healthcare burden.

The team believes their findings could guide stratification of risk factors, screening practices, health counseling, and potential therapeutic measures aimed at changing the disease trajectory in this young adult population.

Cancer patient

Photo by Bill Branson

A new study has provided additional insight into the development of cardiac abnormalities in adult survivors of childhood cancer.

Researchers analyzed more than 1800 cancer survivors who were exposed to cardiotoxic therapies as children.

The team said they found evidence of cardiac abnormalities in a substantial number of these subjects, many of whom were younger and did not exhibit symptoms of abnormalities.

Daniel A. Mulrooney, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these findings in Annals of Internal Medicine.

The team assessed cardiac outcomes among 1853 subjects who were 18 and older and had received cancer-related cardiotoxic therapy at least 10 years earlier.

The subjects were pretty evenly split along gender lines (52.3% male), their median age at cancer diagnosis was 8 (range, 0 to 24), and their median age at evaluation was 31 (range, 18 to 60).

At evaluation, 7.4% of subjects had cardiomyopathy (newly identified in 4.7%), 3.8% had coronary artery disease (newly identified in 2.2%), 28% had valvular regurgitation or stenosis (newly identified in 24.8%), and 4.4% had conduction or rhythm abnormalities (newly identified in 1.4%). All but 5 subjects were asymptomatic.

Multivariable analysis suggested the odds of developing cardiomyopathy were significantly associated with being male (odds ratio [OR]=1.9), receiving anthracycline doses of 250 mg/m² or greater (OR=2.7), having cardiac radiation exposure greater than 1500 cGy (OR=1.9), and having hypertension (OR=3.0).

Being younger at diagnosis was associated with higher odds of valvular disease. The ORs were 1.5 for patients who were 0 to 4 years of age at diagnosis and 1.3 for patients who were 5 to 9 at diagnosis.

Receiving higher radiation doses was associated with higher odds of valvular disease as well. But associations between radiation and valvular disease varied according to a patient’s anthracycline exposure (interaction P<0.001). The highest odds were among survivors with the highest doses of radiation exposure and any anthracycline exposure (OR=4.5).

The researchers also noted a reduction in the OR for valvular disease among obese patients (OR=0.4) and those with dyslipidemia (OR=0.7).

The team said there were not enough cases of coronary artery disease and conduction or rhythm abnormalities to support a fully adjusted multivariable model. However, it seemed these outcomes were more common with older age (≥40 years) and among patients with cardiac radiation doses of 1500 cGy or greater.

The researchers said this study revealed “considerable cardiovascular disease” in a large cohort of adult survivors of childhood cancer, which suggests a substantial future healthcare burden.

The team believes their findings could guide stratification of risk factors, screening practices, health counseling, and potential therapeutic measures aimed at changing the disease trajectory in this young adult population.

Cancer patient

Photo by Bill Branson

A new study has provided additional insight into the development of cardiac abnormalities in adult survivors of childhood cancer.

Researchers analyzed more than 1800 cancer survivors who were exposed to cardiotoxic therapies as children.

The team said they found evidence of cardiac abnormalities in a substantial number of these subjects, many of whom were younger and did not exhibit symptoms of abnormalities.

Daniel A. Mulrooney, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these findings in Annals of Internal Medicine.

The team assessed cardiac outcomes among 1853 subjects who were 18 and older and had received cancer-related cardiotoxic therapy at least 10 years earlier.

The subjects were pretty evenly split along gender lines (52.3% male), their median age at cancer diagnosis was 8 (range, 0 to 24), and their median age at evaluation was 31 (range, 18 to 60).

At evaluation, 7.4% of subjects had cardiomyopathy (newly identified in 4.7%), 3.8% had coronary artery disease (newly identified in 2.2%), 28% had valvular regurgitation or stenosis (newly identified in 24.8%), and 4.4% had conduction or rhythm abnormalities (newly identified in 1.4%). All but 5 subjects were asymptomatic.

Multivariable analysis suggested the odds of developing cardiomyopathy were significantly associated with being male (odds ratio [OR]=1.9), receiving anthracycline doses of 250 mg/m² or greater (OR=2.7), having cardiac radiation exposure greater than 1500 cGy (OR=1.9), and having hypertension (OR=3.0).

Being younger at diagnosis was associated with higher odds of valvular disease. The ORs were 1.5 for patients who were 0 to 4 years of age at diagnosis and 1.3 for patients who were 5 to 9 at diagnosis.

Receiving higher radiation doses was associated with higher odds of valvular disease as well. But associations between radiation and valvular disease varied according to a patient’s anthracycline exposure (interaction P<0.001). The highest odds were among survivors with the highest doses of radiation exposure and any anthracycline exposure (OR=4.5).

The researchers also noted a reduction in the OR for valvular disease among obese patients (OR=0.4) and those with dyslipidemia (OR=0.7).

The team said there were not enough cases of coronary artery disease and conduction or rhythm abnormalities to support a fully adjusted multivariable model. However, it seemed these outcomes were more common with older age (≥40 years) and among patients with cardiac radiation doses of 1500 cGy or greater.

The researchers said this study revealed “considerable cardiovascular disease” in a large cohort of adult survivors of childhood cancer, which suggests a substantial future healthcare burden.

The team believes their findings could guide stratification of risk factors, screening practices, health counseling, and potential therapeutic measures aimed at changing the disease trajectory in this young adult population.