Anne Mounsey, MD

EVIDENCE SUMMARY

Across 3 systematic reviews of yoga for depression, anxiety, and stress, yoga produced overall reductions of symptoms between 12% and 76%, with an average of 39% net reduction in symptom scores across measures (TABLE).^1-3 The RCTs included in the systematic reviews were too heterogeneous to allow quantitative analyses of effect sizes.

Yoga found to significantly reduce depression symptoms
Two 2012 systematic reviews of yoga for depression evaluated 13 RCTs with a total of 782 participants, ages 18 to 80 years with mild to moderate depression. In the 12 RCTs that reported gender, 82% of participants were female; in 6 RCTs a total of 313 patients had cancer.^1,2

The RCTs compared yoga to wait-list controls, counseling, education, exercise, or usual care. They evaluated yoga both as a stand-alone intervention and an adjunct to usual care. Yoga sessions varied from 1 hour weekly to 90 minutes daily over 2 to 24 weeks and included physical postures, relaxation, and breathing techniques.

Eight moderate- to high-quality RCTs with a total of 483 participants reported statistically significant reductions in depression symptoms in the yoga groups compared with control groups. In 3 RCTs, yoga was equivalent to wait-list controls; 2 RCTs showed results equivalent to exercise and superior to wait-list controls.

Yoga alleviates anxiety and stress without adverse effects
A 2012 systematic review of yoga for stress and anxiety evaluated 10 RCTs with a total of 813 heterogeneous participants, ages 18 to 76 years, including pregnant women, breast cancer patients, flood survivors, healthy volunteers, patients with chronic illnesses, perimenopausal women, adults with metabolic syndrome, and people working in finance, all with a range of anxiety and stress symptoms.³ The RCTs compared yoga, as an adjunctive or stand-alone treatment, with wait-list controls, relaxation, therapy, anxiety education, rest, or exercise. Yoga regimens varied from a single 20-minute session to 16 weeks of daily 1-hour sessions, with most regimens lasting 6 to 10 weeks.

Of the 10 RCTs reviewed, 7 moderate- to high-quality studies with a total of 627 participants found statistically significant reductions in anxiety and stress in yoga groups compared with control groups. Of the remaining 3 studies, 1 found yoga equivalent to cognitive therapy; 1 found a nonsignificant benefit for yoga compared with wait-list controls; and 1 found no improvement with either yoga or relaxation.

Study limitations included a range of symptom severity, variable type and length of yoga, lack of participant blinding, wait-list rather than active-treatment controls, and a lack of consistent long-term follow-up data. The RCTs didn’t report any adverse effects of yoga, and yoga is considered safe when taught by a competent instructor.^3,4

Continue for recommendations >>

recommendations

The Institute for Clinical Systems Improvement and the Canadian Network for Mood and Anxiety Treatments recommend yoga as an effective adjunctive treatment to decrease the severity of depression symptoms.^5,6

The Veterans Health Administration and the US Department of Defense recommend yoga as a potential adjunctive treatment to manage the hyperarousal symptoms of post-traumatic stress disorder (PTSD).⁷

The Work Loss Data Institute recommends yoga as an intervention for workers compensation conditions including occupational stress, major depressive disorder, PTSD, and other mental disorders.⁸

EVIDENCE SUMMARY

Across 3 systematic reviews of yoga for depression, anxiety, and stress, yoga produced overall reductions of symptoms between 12% and 76%, with an average of 39% net reduction in symptom scores across measures (TABLE).^1-3 The RCTs included in the systematic reviews were too heterogeneous to allow quantitative analyses of effect sizes.

Yoga found to significantly reduce depression symptoms
Two 2012 systematic reviews of yoga for depression evaluated 13 RCTs with a total of 782 participants, ages 18 to 80 years with mild to moderate depression. In the 12 RCTs that reported gender, 82% of participants were female; in 6 RCTs a total of 313 patients had cancer.^1,2

The RCTs compared yoga to wait-list controls, counseling, education, exercise, or usual care. They evaluated yoga both as a stand-alone intervention and an adjunct to usual care. Yoga sessions varied from 1 hour weekly to 90 minutes daily over 2 to 24 weeks and included physical postures, relaxation, and breathing techniques.

Eight moderate- to high-quality RCTs with a total of 483 participants reported statistically significant reductions in depression symptoms in the yoga groups compared with control groups. In 3 RCTs, yoga was equivalent to wait-list controls; 2 RCTs showed results equivalent to exercise and superior to wait-list controls.

Yoga alleviates anxiety and stress without adverse effects
A 2012 systematic review of yoga for stress and anxiety evaluated 10 RCTs with a total of 813 heterogeneous participants, ages 18 to 76 years, including pregnant women, breast cancer patients, flood survivors, healthy volunteers, patients with chronic illnesses, perimenopausal women, adults with metabolic syndrome, and people working in finance, all with a range of anxiety and stress symptoms.³ The RCTs compared yoga, as an adjunctive or stand-alone treatment, with wait-list controls, relaxation, therapy, anxiety education, rest, or exercise. Yoga regimens varied from a single 20-minute session to 16 weeks of daily 1-hour sessions, with most regimens lasting 6 to 10 weeks.

Of the 10 RCTs reviewed, 7 moderate- to high-quality studies with a total of 627 participants found statistically significant reductions in anxiety and stress in yoga groups compared with control groups. Of the remaining 3 studies, 1 found yoga equivalent to cognitive therapy; 1 found a nonsignificant benefit for yoga compared with wait-list controls; and 1 found no improvement with either yoga or relaxation.

Study limitations included a range of symptom severity, variable type and length of yoga, lack of participant blinding, wait-list rather than active-treatment controls, and a lack of consistent long-term follow-up data. The RCTs didn’t report any adverse effects of yoga, and yoga is considered safe when taught by a competent instructor.^3,4

Continue for recommendations >>

recommendations

The Institute for Clinical Systems Improvement and the Canadian Network for Mood and Anxiety Treatments recommend yoga as an effective adjunctive treatment to decrease the severity of depression symptoms.^5,6

The Veterans Health Administration and the US Department of Defense recommend yoga as a potential adjunctive treatment to manage the hyperarousal symptoms of post-traumatic stress disorder (PTSD).⁷

The Work Loss Data Institute recommends yoga as an intervention for workers compensation conditions including occupational stress, major depressive disorder, PTSD, and other mental disorders.⁸

EVIDENCE SUMMARY

Across 3 systematic reviews of yoga for depression, anxiety, and stress, yoga produced overall reductions of symptoms between 12% and 76%, with an average of 39% net reduction in symptom scores across measures (TABLE).^1-3 The RCTs included in the systematic reviews were too heterogeneous to allow quantitative analyses of effect sizes.

Yoga found to significantly reduce depression symptoms
Two 2012 systematic reviews of yoga for depression evaluated 13 RCTs with a total of 782 participants, ages 18 to 80 years with mild to moderate depression. In the 12 RCTs that reported gender, 82% of participants were female; in 6 RCTs a total of 313 patients had cancer.^1,2

The RCTs compared yoga to wait-list controls, counseling, education, exercise, or usual care. They evaluated yoga both as a stand-alone intervention and an adjunct to usual care. Yoga sessions varied from 1 hour weekly to 90 minutes daily over 2 to 24 weeks and included physical postures, relaxation, and breathing techniques.

Eight moderate- to high-quality RCTs with a total of 483 participants reported statistically significant reductions in depression symptoms in the yoga groups compared with control groups. In 3 RCTs, yoga was equivalent to wait-list controls; 2 RCTs showed results equivalent to exercise and superior to wait-list controls.

Yoga alleviates anxiety and stress without adverse effects
A 2012 systematic review of yoga for stress and anxiety evaluated 10 RCTs with a total of 813 heterogeneous participants, ages 18 to 76 years, including pregnant women, breast cancer patients, flood survivors, healthy volunteers, patients with chronic illnesses, perimenopausal women, adults with metabolic syndrome, and people working in finance, all with a range of anxiety and stress symptoms.³ The RCTs compared yoga, as an adjunctive or stand-alone treatment, with wait-list controls, relaxation, therapy, anxiety education, rest, or exercise. Yoga regimens varied from a single 20-minute session to 16 weeks of daily 1-hour sessions, with most regimens lasting 6 to 10 weeks.

Of the 10 RCTs reviewed, 7 moderate- to high-quality studies with a total of 627 participants found statistically significant reductions in anxiety and stress in yoga groups compared with control groups. Of the remaining 3 studies, 1 found yoga equivalent to cognitive therapy; 1 found a nonsignificant benefit for yoga compared with wait-list controls; and 1 found no improvement with either yoga or relaxation.

Study limitations included a range of symptom severity, variable type and length of yoga, lack of participant blinding, wait-list rather than active-treatment controls, and a lack of consistent long-term follow-up data. The RCTs didn’t report any adverse effects of yoga, and yoga is considered safe when taught by a competent instructor.^3,4

Continue for recommendations >>

recommendations

The Institute for Clinical Systems Improvement and the Canadian Network for Mood and Anxiety Treatments recommend yoga as an effective adjunctive treatment to decrease the severity of depression symptoms.^5,6

The Veterans Health Administration and the US Department of Defense recommend yoga as a potential adjunctive treatment to manage the hyperarousal symptoms of post-traumatic stress disorder (PTSD).⁷

The Work Loss Data Institute recommends yoga as an intervention for workers compensation conditions including occupational stress, major depressive disorder, PTSD, and other mental disorders.⁸

Illustrative case

A 67-year-old woman with diabetes, hypertension, and hyperlipidemia comes to your office for an evaluation before undergoing a total hip arthroplasty. She is not taking a beta-blocker. Should you prescribe one?

Current guidelines from the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) recommend starting beta-blockers to prevent cardiac events in patients about to undergo intermediate- or high-risk surgery or vascular surgery who have a history of inducible ischemia, coronary artery disease (CAD), or at least one risk factor for CAD.² However, the majority of the evidence for these guidelines, which were published in 2009 and are in the process of being updated, came from the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography) trials, which have been discredited due to serious methodological flaws, including falsified descriptions of how outcomes were determined and fictitious databases.³ A new meta-analysis by Bouri et al¹ that excluded the DECREASE trials found that although preoperative beta-blockers reduce the rate of certain nonfatal outcomes, they increase the risk of death and stroke.

STUDY SUMMARY: Multiple RCTs find preop beta-blockers do more harm, than good

Bouri et al¹ conducted a meta-analysis of published RCTs evaluating preoperative beta-blockers vs placebo for patients undergoing noncardiac surgery. Of the 11 studies that met eligibility criteria, 2 were the discredited DECREASE trials. Thus, Bouri et al¹ analyzed 9 high-quality RCTs that included 10,529 patients.

Most studies included patients undergoing vascular surgery. Some studies also included intra-abdominal, intrathoracic, neurosurgical, orthopedic, urologic, and gynecologic surgeries. Beta-blockers were started no more than a day before surgery and were discontinued at hospital discharge or up to 30 days postop. Metoprolol was used in 5 trials, bisoprolol in one trial, atenolol in 2 trials, and propranolol in one trial. The primary endpoint was all-cause mortality within 30 days.

A total of 5264 patients were randomized to beta-blockers and 5265 to placebo. There were 162 deaths in the beta-blocker group and 129 deaths in the placebo group. Patients who received beta-blockers had a 27% increased risk of all-cause mortality (risk ratio [RR]=1.27; 95% confidence interval [CI], 1.01-1.60; P=.04). The number needed to harm was 160.

Six of the studies also evaluated rates of nonfatal myocardial infarction (MI), nonfatal stroke, and hypotension. Beta-blockers lowered the risk of nonfatal MI (RR=.73; 95% CI, .61-.88; P=.001), but increased the risk of nonfatal stroke (RR=1.73; 95% CI, 1.00-2.99; P=.05) and hypotension (RR=1.51; 95% CI, 1.37-1.67; P=.00001).

While beta-blockers protect against nonfatal MIs, they increase the risk of nonfatal strokes and death.This meta-analysis was dominated by the 2008 Peri-Operative ISchemic Evaluation (POISE) trial, an RCT that compared placebo to extended-release metoprolol, 100 mg 2 to 4 hours before surgery followed by 200 mg/d for 30 days, in 8351 patients with, or at risk for, atherosclerotic disease.⁴ While beta-blockers reduced the risk of MI and atrial fibrillation, they increased the risk of mortality and stroke, likely due to drug-induced hypotension. The slightly larger-than-typical doses of beta-blockers used in the POISE study may have contributed to the excess mortality.

WHAT'S NEW: Avoiding beta-blockers in surgery patients will prevent deaths

Bouri et al¹ found that while beta-blockers protect against nonfatal MIs, they increase the risk for nonfatal strokes and death. This new meta-analysis challenges the ACCF/AHA recommendations by suggesting that abandoning the use of beta-blockers for preoperative patients who aren’t already taking them will prevent a substantial number of perioperative deaths. Bouri et al¹ estimate that in the United Kingdom, where 47,286 deaths occur annually within 30 days of intermediate or high-risk procedures, the number of iatrogenic deaths would drop by approximately 10,000 if beta-blockers were not used.¹

CAVEATS: Don't stop beta-blockers in patients who already take them

This meta-analysis did not evaluate outcomes in patients who were already taking beta-blockers. Patients who are already on beta-blockers should continue to take them in the perioperative period, which is in line with current ACCF/AHA guidelines.

CHALLENGES TO IMPLEMENTATION: Some physician may be reluctant to disregard published guidelines 

Some physicians may not be comfortable ignoring the current ACCF/AHA guidelines that make a Class IIa recommendation (it is reasonable to administer this treatment) for the use of preoperative beta-blockade for patients at risk of cardiovascular events who were not previously taking a beta-blocker. This updated meta-analysis excludes the discredited DECREASE trials and challenges us to act against these current guidelines while we wait for updated recommendations.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

A 67-year-old woman with diabetes, hypertension, and hyperlipidemia comes to your office for an evaluation before undergoing a total hip arthroplasty. She is not taking a beta-blocker. Should you prescribe one?

Current guidelines from the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) recommend starting beta-blockers to prevent cardiac events in patients about to undergo intermediate- or high-risk surgery or vascular surgery who have a history of inducible ischemia, coronary artery disease (CAD), or at least one risk factor for CAD.² However, the majority of the evidence for these guidelines, which were published in 2009 and are in the process of being updated, came from the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography) trials, which have been discredited due to serious methodological flaws, including falsified descriptions of how outcomes were determined and fictitious databases.³ A new meta-analysis by Bouri et al¹ that excluded the DECREASE trials found that although preoperative beta-blockers reduce the rate of certain nonfatal outcomes, they increase the risk of death and stroke.

STUDY SUMMARY: Multiple RCTs find preop beta-blockers do more harm, than good

Bouri et al¹ conducted a meta-analysis of published RCTs evaluating preoperative beta-blockers vs placebo for patients undergoing noncardiac surgery. Of the 11 studies that met eligibility criteria, 2 were the discredited DECREASE trials. Thus, Bouri et al¹ analyzed 9 high-quality RCTs that included 10,529 patients.

Most studies included patients undergoing vascular surgery. Some studies also included intra-abdominal, intrathoracic, neurosurgical, orthopedic, urologic, and gynecologic surgeries. Beta-blockers were started no more than a day before surgery and were discontinued at hospital discharge or up to 30 days postop. Metoprolol was used in 5 trials, bisoprolol in one trial, atenolol in 2 trials, and propranolol in one trial. The primary endpoint was all-cause mortality within 30 days.

A total of 5264 patients were randomized to beta-blockers and 5265 to placebo. There were 162 deaths in the beta-blocker group and 129 deaths in the placebo group. Patients who received beta-blockers had a 27% increased risk of all-cause mortality (risk ratio [RR]=1.27; 95% confidence interval [CI], 1.01-1.60; P=.04). The number needed to harm was 160.

Six of the studies also evaluated rates of nonfatal myocardial infarction (MI), nonfatal stroke, and hypotension. Beta-blockers lowered the risk of nonfatal MI (RR=.73; 95% CI, .61-.88; P=.001), but increased the risk of nonfatal stroke (RR=1.73; 95% CI, 1.00-2.99; P=.05) and hypotension (RR=1.51; 95% CI, 1.37-1.67; P=.00001).

While beta-blockers protect against nonfatal MIs, they increase the risk of nonfatal strokes and death.This meta-analysis was dominated by the 2008 Peri-Operative ISchemic Evaluation (POISE) trial, an RCT that compared placebo to extended-release metoprolol, 100 mg 2 to 4 hours before surgery followed by 200 mg/d for 30 days, in 8351 patients with, or at risk for, atherosclerotic disease.⁴ While beta-blockers reduced the risk of MI and atrial fibrillation, they increased the risk of mortality and stroke, likely due to drug-induced hypotension. The slightly larger-than-typical doses of beta-blockers used in the POISE study may have contributed to the excess mortality.

WHAT'S NEW: Avoiding beta-blockers in surgery patients will prevent deaths

Bouri et al¹ found that while beta-blockers protect against nonfatal MIs, they increase the risk for nonfatal strokes and death. This new meta-analysis challenges the ACCF/AHA recommendations by suggesting that abandoning the use of beta-blockers for preoperative patients who aren’t already taking them will prevent a substantial number of perioperative deaths. Bouri et al¹ estimate that in the United Kingdom, where 47,286 deaths occur annually within 30 days of intermediate or high-risk procedures, the number of iatrogenic deaths would drop by approximately 10,000 if beta-blockers were not used.¹

CAVEATS: Don't stop beta-blockers in patients who already take them

This meta-analysis did not evaluate outcomes in patients who were already taking beta-blockers. Patients who are already on beta-blockers should continue to take them in the perioperative period, which is in line with current ACCF/AHA guidelines.

CHALLENGES TO IMPLEMENTATION: Some physician may be reluctant to disregard published guidelines 

Some physicians may not be comfortable ignoring the current ACCF/AHA guidelines that make a Class IIa recommendation (it is reasonable to administer this treatment) for the use of preoperative beta-blockade for patients at risk of cardiovascular events who were not previously taking a beta-blocker. This updated meta-analysis excludes the discredited DECREASE trials and challenges us to act against these current guidelines while we wait for updated recommendations.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

A 67-year-old woman with diabetes, hypertension, and hyperlipidemia comes to your office for an evaluation before undergoing a total hip arthroplasty. She is not taking a beta-blocker. Should you prescribe one?

Current guidelines from the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) recommend starting beta-blockers to prevent cardiac events in patients about to undergo intermediate- or high-risk surgery or vascular surgery who have a history of inducible ischemia, coronary artery disease (CAD), or at least one risk factor for CAD.² However, the majority of the evidence for these guidelines, which were published in 2009 and are in the process of being updated, came from the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography) trials, which have been discredited due to serious methodological flaws, including falsified descriptions of how outcomes were determined and fictitious databases.³ A new meta-analysis by Bouri et al¹ that excluded the DECREASE trials found that although preoperative beta-blockers reduce the rate of certain nonfatal outcomes, they increase the risk of death and stroke.

STUDY SUMMARY: Multiple RCTs find preop beta-blockers do more harm, than good

Bouri et al¹ conducted a meta-analysis of published RCTs evaluating preoperative beta-blockers vs placebo for patients undergoing noncardiac surgery. Of the 11 studies that met eligibility criteria, 2 were the discredited DECREASE trials. Thus, Bouri et al¹ analyzed 9 high-quality RCTs that included 10,529 patients.

Most studies included patients undergoing vascular surgery. Some studies also included intra-abdominal, intrathoracic, neurosurgical, orthopedic, urologic, and gynecologic surgeries. Beta-blockers were started no more than a day before surgery and were discontinued at hospital discharge or up to 30 days postop. Metoprolol was used in 5 trials, bisoprolol in one trial, atenolol in 2 trials, and propranolol in one trial. The primary endpoint was all-cause mortality within 30 days.

A total of 5264 patients were randomized to beta-blockers and 5265 to placebo. There were 162 deaths in the beta-blocker group and 129 deaths in the placebo group. Patients who received beta-blockers had a 27% increased risk of all-cause mortality (risk ratio [RR]=1.27; 95% confidence interval [CI], 1.01-1.60; P=.04). The number needed to harm was 160.

Six of the studies also evaluated rates of nonfatal myocardial infarction (MI), nonfatal stroke, and hypotension. Beta-blockers lowered the risk of nonfatal MI (RR=.73; 95% CI, .61-.88; P=.001), but increased the risk of nonfatal stroke (RR=1.73; 95% CI, 1.00-2.99; P=.05) and hypotension (RR=1.51; 95% CI, 1.37-1.67; P=.00001).

While beta-blockers protect against nonfatal MIs, they increase the risk of nonfatal strokes and death.This meta-analysis was dominated by the 2008 Peri-Operative ISchemic Evaluation (POISE) trial, an RCT that compared placebo to extended-release metoprolol, 100 mg 2 to 4 hours before surgery followed by 200 mg/d for 30 days, in 8351 patients with, or at risk for, atherosclerotic disease.⁴ While beta-blockers reduced the risk of MI and atrial fibrillation, they increased the risk of mortality and stroke, likely due to drug-induced hypotension. The slightly larger-than-typical doses of beta-blockers used in the POISE study may have contributed to the excess mortality.

WHAT'S NEW: Avoiding beta-blockers in surgery patients will prevent deaths

Bouri et al¹ found that while beta-blockers protect against nonfatal MIs, they increase the risk for nonfatal strokes and death. This new meta-analysis challenges the ACCF/AHA recommendations by suggesting that abandoning the use of beta-blockers for preoperative patients who aren’t already taking them will prevent a substantial number of perioperative deaths. Bouri et al¹ estimate that in the United Kingdom, where 47,286 deaths occur annually within 30 days of intermediate or high-risk procedures, the number of iatrogenic deaths would drop by approximately 10,000 if beta-blockers were not used.¹

CAVEATS: Don't stop beta-blockers in patients who already take them

This meta-analysis did not evaluate outcomes in patients who were already taking beta-blockers. Patients who are already on beta-blockers should continue to take them in the perioperative period, which is in line with current ACCF/AHA guidelines.

CHALLENGES TO IMPLEMENTATION: Some physician may be reluctant to disregard published guidelines 

Some physicians may not be comfortable ignoring the current ACCF/AHA guidelines that make a Class IIa recommendation (it is reasonable to administer this treatment) for the use of preoperative beta-blockade for patients at risk of cardiovascular events who were not previously taking a beta-blocker. This updated meta-analysis excludes the discredited DECREASE trials and challenges us to act against these current guidelines while we wait for updated recommendations.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

PRACTICE CHANGER

Recommend American ginseng (1,000 mg bid) for four weeks to improve cancer-related fatigue in patients who are undergoing radiation or chemotherapy; no other treatment has been shown to be effective.¹

STRENGTH OF RECOMMENDATION

B: Based on a single well-done randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE

A 54-year-old woman is receiving chemotherapy for adenocarcinoma of the right breast (T2N1M0) and has persistent, disabling fatigue. She has been unable to work or care for her family since starting chemotherapy. She says she gets enough sleep and denies being depressed or in pain. Lab testing for anemia and thyroid dysfunction is negative. Is there a safe and effective intervention?

On the next page: Study summary >>

Cancer-related fatigue is a common, distressing symptom that occurs in more than half of all patients undergoing chemotherapy and more than two-thirds of those receiving radiation therapy.² For many cancer survivors, fatigue can persist for five to 10 years after treatment.³

Because no treatments have proven effective, many clinicians and patients accept fatigue as inevitable. In RCTs, psychostimulants (eg, methylphenidate) and antidepressants (eg, donepezil and paroxetine) have not been found effective.^4-6 Dietary supplements, such as coenzyme Q10 and l-carnitine, also have not been found effective in placebo-controlled trials.^7,8

The double-blind RCT reported on here looked at whether American ginseng might be effective in relieving cancer-related fatigue.

STUDY SUMMARY

Ginseng reduced fatigue after eight weeks

There are two major species of ginseng—Asian and American—and they have varying amounts, strengths, and varieties of ginsenosides, which are the active ingredients. In this eight-week, double-blind RCT, Barton et al¹ randomly assigned more than 300 patients from 40 US cancer facilities to receive either 1,000 mg of American ginseng twice daily (in the morning and at noon) or matched placebo capsules.

Patients were either currently receiving treatment for cancer or were posttreatment but within two years of receiving a cancer diagnosis. All participants had experienced fatigue of at least a month’s duration that they rated as 4 or higher on a scale of 0 to 10. Patients with other causes of fatigue were excluded, as were those who had pain or insomnia rated 4 or higher, those with brain cancer or central nervous system (CNS) lymphoma, those taking systemic steroids or opioids, and those who were using, or had used, ginseng or other agents for fatigue.

Of the 364 randomized participants, 300 (147 ginseng patients, 153 placebo patients) remained in the study through the primary endpoint at four weeks, and 261 completed the entire eight-week study. There were no baseline differences between groups in demographic characteristics, time since cancer diagnosis, cancer type, current or prior treatment, and fatigue at baseline.

The primary outcome was a change in score on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI–SF) at four weeks. Secondary outcomes included a change in MFSI–SF score at eight weeks. The authors also conducted a subset analysis comparing ginseng and placebo in only those patients currently undergoing cancer treatment versus those who had completed treatment. To make it easier to compare results, all scores were converted to a 100-point scale; higher scores indicated less fatigue. Adverse events were documented by patient self-report questionnaires and also by researchers who called or visited patients every other week.

While ginseng did not appear to significantly impact fatigue scores versus placebo at four weeks (14.4 vs 8.2), fatigue scores at eight weeks were significantly improved (20 vs 10.3). Interestingly, though, there was a significant improvement in fatigue scores with ginseng at both four weeks and eight weeks when researchers looked at only those patients who were currently receiving cancer treatment. On the other hand, those patients who were not currently undergoing treatment did not show a significant improvement at either time cutoff.

There was no statistically significant difference in adverse events between the ginseng and placebo groups over the eight-week study.

On the next page: What's new >>

WHAT’S NEW

First evidence-based therapy

We now have good evidence that American ginseng (1,000 mg bid) is safe and effective for ameliorating cancer-related fatigue. Before this study, no other effective treatment had been identified.

CAVEATS

Ginseng may not help posttreatment

In this study, ginseng did not improve fatigue at four weeks, which was the primary outcome, although benefits were noted after eight weeks of treatment. Interestingly, though, participants who were receiving radiation and/or chemotherapy during the study experienced significant improvements at four and eight weeks, while those with previous (but not current) treatment did not significantly improve at either time point.

It may be that ginseng works best to ameliorate cancer-related fatigue in patients simultaneously receiving cancer treatment but not in those who have completed treatment. The findings also suggest that patients who have completed treatment may wish to try ginseng for longer than eight weeks to see if it offers any benefit.

Because this study excluded patients with brain cancer, CNS lymphoma, moderate to severe pain, or insomnia and those taking steroids, it is not known if ginseng would help them.

In one study, a low-dose methanolic extract of American ginseng caused a breast cancer cell line to proliferate; however, it was later discovered that this extract had been contaminated with Fusarium fungi containing zearalenone, which has strong estrogenic activity.^9,10 However, higher doses of a similar methanolic extract, as well as other water-based extracts, have reduced proliferation of breast cancer cells.¹¹

Proceed carefully if a patient is taking warfarin. Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient’s international normalized ratio (INR).¹² Therefore, carefully monitor INR in patients concurrently taking ginseng and warfarin. Furthermore, ginseng may lower blood glucose in patients with diabetes, so carefully monitor blood glucose in these patients when initiating or discontinuing ginseng.¹³

CHALLENGES TO IMPLEMENTATION

It’s hard to know exactly what you’re getting

Regulating dietary supplements, especially verifying ingredients and potency, has been a challenge for the FDA. Although ginseng commonly is adulterated, this is more common with the Asian species (Panax ginseng) than with the American species (Panax quinquefolius) used in this study.¹⁰ Clinicians who want to recommend ginseng for cancer-related fatigue should advise patients to use American ginseng root products produced in the US. Additionally, the products should contain at least 3% ginsenosides to match the dose used in this study.          

REFERENCES

1. Barton DL, Liu H, Dakhil SR, et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013;105(16):1230-1238.

2. Hofman M, Ryan JL, Figueroa-Moseley CD, et al. Cancer-related fatigue: the scale of the problem. Oncologist. 2007;12 (suppl 1):4-10.

3. Bower JE, Ganz PA, Desmond KA, et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer. 2006;106(4):751-758.

4. Moraska AR, Sood A, Dakhil SR, et al. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Oncol. 2010;28(23):3673-3679.

5. Bruera E, El Osta B, Valero V, et al. Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol. 2007;25(23):3475-3481.

6. Morrow GR, Hickok JT, Roscoe JA, et al; University of Rochester Cancer Center Community Clinical Oncology Program. Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. J Clin Oncol. 2003;21(24):4635-4641.

7. Lesser GJ, Case D, Stark N, et al; Wake Forest University Community Clinical Oncology ­Program Research Base. A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer. J Support Oncol. 2013;11(1):31-42.

8. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012;30(31):3864-3869.

9. Duda RB, Zhong Y, Navas V, et al. American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7
breast cancer cell growth. J Surg Oncol. 1999;72(4):230-239.

10. Upton R, ed. American ginseng root Panax quinquefolius, standards of analysis, quality control, and therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2012.

11. King ML, Adler SR, Murphy LL. Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast ­cancer cell proliferation and estrogen receptor activation. Integr Cancer Ther. 2006;5(3): 236-243.

12. Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled trial. Ann Intern Med. 2004;141(1):23-27.

13. Vuksan V, Stavro MP, Sievenpiper JL, et al. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care. 2000;23(9):1221-1226.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):270-272.

PRACTICE CHANGER

Recommend American ginseng (1,000 mg bid) for four weeks to improve cancer-related fatigue in patients who are undergoing radiation or chemotherapy; no other treatment has been shown to be effective.¹

STRENGTH OF RECOMMENDATION

B: Based on a single well-done randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE

A 54-year-old woman is receiving chemotherapy for adenocarcinoma of the right breast (T2N1M0) and has persistent, disabling fatigue. She has been unable to work or care for her family since starting chemotherapy. She says she gets enough sleep and denies being depressed or in pain. Lab testing for anemia and thyroid dysfunction is negative. Is there a safe and effective intervention?

On the next page: Study summary >>

Cancer-related fatigue is a common, distressing symptom that occurs in more than half of all patients undergoing chemotherapy and more than two-thirds of those receiving radiation therapy.² For many cancer survivors, fatigue can persist for five to 10 years after treatment.³

Because no treatments have proven effective, many clinicians and patients accept fatigue as inevitable. In RCTs, psychostimulants (eg, methylphenidate) and antidepressants (eg, donepezil and paroxetine) have not been found effective.^4-6 Dietary supplements, such as coenzyme Q10 and l-carnitine, also have not been found effective in placebo-controlled trials.^7,8

The double-blind RCT reported on here looked at whether American ginseng might be effective in relieving cancer-related fatigue.

STUDY SUMMARY

Ginseng reduced fatigue after eight weeks

There are two major species of ginseng—Asian and American—and they have varying amounts, strengths, and varieties of ginsenosides, which are the active ingredients. In this eight-week, double-blind RCT, Barton et al¹ randomly assigned more than 300 patients from 40 US cancer facilities to receive either 1,000 mg of American ginseng twice daily (in the morning and at noon) or matched placebo capsules.

Patients were either currently receiving treatment for cancer or were posttreatment but within two years of receiving a cancer diagnosis. All participants had experienced fatigue of at least a month’s duration that they rated as 4 or higher on a scale of 0 to 10. Patients with other causes of fatigue were excluded, as were those who had pain or insomnia rated 4 or higher, those with brain cancer or central nervous system (CNS) lymphoma, those taking systemic steroids or opioids, and those who were using, or had used, ginseng or other agents for fatigue.

Of the 364 randomized participants, 300 (147 ginseng patients, 153 placebo patients) remained in the study through the primary endpoint at four weeks, and 261 completed the entire eight-week study. There were no baseline differences between groups in demographic characteristics, time since cancer diagnosis, cancer type, current or prior treatment, and fatigue at baseline.

The primary outcome was a change in score on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI–SF) at four weeks. Secondary outcomes included a change in MFSI–SF score at eight weeks. The authors also conducted a subset analysis comparing ginseng and placebo in only those patients currently undergoing cancer treatment versus those who had completed treatment. To make it easier to compare results, all scores were converted to a 100-point scale; higher scores indicated less fatigue. Adverse events were documented by patient self-report questionnaires and also by researchers who called or visited patients every other week.

While ginseng did not appear to significantly impact fatigue scores versus placebo at four weeks (14.4 vs 8.2), fatigue scores at eight weeks were significantly improved (20 vs 10.3). Interestingly, though, there was a significant improvement in fatigue scores with ginseng at both four weeks and eight weeks when researchers looked at only those patients who were currently receiving cancer treatment. On the other hand, those patients who were not currently undergoing treatment did not show a significant improvement at either time cutoff.

There was no statistically significant difference in adverse events between the ginseng and placebo groups over the eight-week study.

On the next page: What's new >>

WHAT’S NEW

First evidence-based therapy

We now have good evidence that American ginseng (1,000 mg bid) is safe and effective for ameliorating cancer-related fatigue. Before this study, no other effective treatment had been identified.

CAVEATS

Ginseng may not help posttreatment

In this study, ginseng did not improve fatigue at four weeks, which was the primary outcome, although benefits were noted after eight weeks of treatment. Interestingly, though, participants who were receiving radiation and/or chemotherapy during the study experienced significant improvements at four and eight weeks, while those with previous (but not current) treatment did not significantly improve at either time point.

It may be that ginseng works best to ameliorate cancer-related fatigue in patients simultaneously receiving cancer treatment but not in those who have completed treatment. The findings also suggest that patients who have completed treatment may wish to try ginseng for longer than eight weeks to see if it offers any benefit.

Because this study excluded patients with brain cancer, CNS lymphoma, moderate to severe pain, or insomnia and those taking steroids, it is not known if ginseng would help them.

In one study, a low-dose methanolic extract of American ginseng caused a breast cancer cell line to proliferate; however, it was later discovered that this extract had been contaminated with Fusarium fungi containing zearalenone, which has strong estrogenic activity.^9,10 However, higher doses of a similar methanolic extract, as well as other water-based extracts, have reduced proliferation of breast cancer cells.¹¹

Proceed carefully if a patient is taking warfarin. Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient’s international normalized ratio (INR).¹² Therefore, carefully monitor INR in patients concurrently taking ginseng and warfarin. Furthermore, ginseng may lower blood glucose in patients with diabetes, so carefully monitor blood glucose in these patients when initiating or discontinuing ginseng.¹³

CHALLENGES TO IMPLEMENTATION

It’s hard to know exactly what you’re getting

Regulating dietary supplements, especially verifying ingredients and potency, has been a challenge for the FDA. Although ginseng commonly is adulterated, this is more common with the Asian species (Panax ginseng) than with the American species (Panax quinquefolius) used in this study.¹⁰ Clinicians who want to recommend ginseng for cancer-related fatigue should advise patients to use American ginseng root products produced in the US. Additionally, the products should contain at least 3% ginsenosides to match the dose used in this study.          

REFERENCES

1. Barton DL, Liu H, Dakhil SR, et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013;105(16):1230-1238.

2. Hofman M, Ryan JL, Figueroa-Moseley CD, et al. Cancer-related fatigue: the scale of the problem. Oncologist. 2007;12 (suppl 1):4-10.

3. Bower JE, Ganz PA, Desmond KA, et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer. 2006;106(4):751-758.

4. Moraska AR, Sood A, Dakhil SR, et al. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Oncol. 2010;28(23):3673-3679.

5. Bruera E, El Osta B, Valero V, et al. Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol. 2007;25(23):3475-3481.

6. Morrow GR, Hickok JT, Roscoe JA, et al; University of Rochester Cancer Center Community Clinical Oncology Program. Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. J Clin Oncol. 2003;21(24):4635-4641.

7. Lesser GJ, Case D, Stark N, et al; Wake Forest University Community Clinical Oncology ­Program Research Base. A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer. J Support Oncol. 2013;11(1):31-42.

8. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012;30(31):3864-3869.

9. Duda RB, Zhong Y, Navas V, et al. American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7
breast cancer cell growth. J Surg Oncol. 1999;72(4):230-239.

10. Upton R, ed. American ginseng root Panax quinquefolius, standards of analysis, quality control, and therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2012.

11. King ML, Adler SR, Murphy LL. Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast ­cancer cell proliferation and estrogen receptor activation. Integr Cancer Ther. 2006;5(3): 236-243.

12. Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled trial. Ann Intern Med. 2004;141(1):23-27.

13. Vuksan V, Stavro MP, Sievenpiper JL, et al. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care. 2000;23(9):1221-1226.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):270-272.

PRACTICE CHANGER

Recommend American ginseng (1,000 mg bid) for four weeks to improve cancer-related fatigue in patients who are undergoing radiation or chemotherapy; no other treatment has been shown to be effective.¹

STRENGTH OF RECOMMENDATION

B: Based on a single well-done randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE

A 54-year-old woman is receiving chemotherapy for adenocarcinoma of the right breast (T2N1M0) and has persistent, disabling fatigue. She has been unable to work or care for her family since starting chemotherapy. She says she gets enough sleep and denies being depressed or in pain. Lab testing for anemia and thyroid dysfunction is negative. Is there a safe and effective intervention?

On the next page: Study summary >>

Cancer-related fatigue is a common, distressing symptom that occurs in more than half of all patients undergoing chemotherapy and more than two-thirds of those receiving radiation therapy.² For many cancer survivors, fatigue can persist for five to 10 years after treatment.³

Because no treatments have proven effective, many clinicians and patients accept fatigue as inevitable. In RCTs, psychostimulants (eg, methylphenidate) and antidepressants (eg, donepezil and paroxetine) have not been found effective.^4-6 Dietary supplements, such as coenzyme Q10 and l-carnitine, also have not been found effective in placebo-controlled trials.^7,8

The double-blind RCT reported on here looked at whether American ginseng might be effective in relieving cancer-related fatigue.

STUDY SUMMARY

Ginseng reduced fatigue after eight weeks

There are two major species of ginseng—Asian and American—and they have varying amounts, strengths, and varieties of ginsenosides, which are the active ingredients. In this eight-week, double-blind RCT, Barton et al¹ randomly assigned more than 300 patients from 40 US cancer facilities to receive either 1,000 mg of American ginseng twice daily (in the morning and at noon) or matched placebo capsules.

Patients were either currently receiving treatment for cancer or were posttreatment but within two years of receiving a cancer diagnosis. All participants had experienced fatigue of at least a month’s duration that they rated as 4 or higher on a scale of 0 to 10. Patients with other causes of fatigue were excluded, as were those who had pain or insomnia rated 4 or higher, those with brain cancer or central nervous system (CNS) lymphoma, those taking systemic steroids or opioids, and those who were using, or had used, ginseng or other agents for fatigue.

Of the 364 randomized participants, 300 (147 ginseng patients, 153 placebo patients) remained in the study through the primary endpoint at four weeks, and 261 completed the entire eight-week study. There were no baseline differences between groups in demographic characteristics, time since cancer diagnosis, cancer type, current or prior treatment, and fatigue at baseline.

The primary outcome was a change in score on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI–SF) at four weeks. Secondary outcomes included a change in MFSI–SF score at eight weeks. The authors also conducted a subset analysis comparing ginseng and placebo in only those patients currently undergoing cancer treatment versus those who had completed treatment. To make it easier to compare results, all scores were converted to a 100-point scale; higher scores indicated less fatigue. Adverse events were documented by patient self-report questionnaires and also by researchers who called or visited patients every other week.

While ginseng did not appear to significantly impact fatigue scores versus placebo at four weeks (14.4 vs 8.2), fatigue scores at eight weeks were significantly improved (20 vs 10.3). Interestingly, though, there was a significant improvement in fatigue scores with ginseng at both four weeks and eight weeks when researchers looked at only those patients who were currently receiving cancer treatment. On the other hand, those patients who were not currently undergoing treatment did not show a significant improvement at either time cutoff.

There was no statistically significant difference in adverse events between the ginseng and placebo groups over the eight-week study.

On the next page: What's new >>

WHAT’S NEW

First evidence-based therapy

We now have good evidence that American ginseng (1,000 mg bid) is safe and effective for ameliorating cancer-related fatigue. Before this study, no other effective treatment had been identified.

CAVEATS

Ginseng may not help posttreatment

In this study, ginseng did not improve fatigue at four weeks, which was the primary outcome, although benefits were noted after eight weeks of treatment. Interestingly, though, participants who were receiving radiation and/or chemotherapy during the study experienced significant improvements at four and eight weeks, while those with previous (but not current) treatment did not significantly improve at either time point.

It may be that ginseng works best to ameliorate cancer-related fatigue in patients simultaneously receiving cancer treatment but not in those who have completed treatment. The findings also suggest that patients who have completed treatment may wish to try ginseng for longer than eight weeks to see if it offers any benefit.

Because this study excluded patients with brain cancer, CNS lymphoma, moderate to severe pain, or insomnia and those taking steroids, it is not known if ginseng would help them.

In one study, a low-dose methanolic extract of American ginseng caused a breast cancer cell line to proliferate; however, it was later discovered that this extract had been contaminated with Fusarium fungi containing zearalenone, which has strong estrogenic activity.^9,10 However, higher doses of a similar methanolic extract, as well as other water-based extracts, have reduced proliferation of breast cancer cells.¹¹

Proceed carefully if a patient is taking warfarin. Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient’s international normalized ratio (INR).¹² Therefore, carefully monitor INR in patients concurrently taking ginseng and warfarin. Furthermore, ginseng may lower blood glucose in patients with diabetes, so carefully monitor blood glucose in these patients when initiating or discontinuing ginseng.¹³

CHALLENGES TO IMPLEMENTATION

It’s hard to know exactly what you’re getting

Regulating dietary supplements, especially verifying ingredients and potency, has been a challenge for the FDA. Although ginseng commonly is adulterated, this is more common with the Asian species (Panax ginseng) than with the American species (Panax quinquefolius) used in this study.¹⁰ Clinicians who want to recommend ginseng for cancer-related fatigue should advise patients to use American ginseng root products produced in the US. Additionally, the products should contain at least 3% ginsenosides to match the dose used in this study.          

REFERENCES

1. Barton DL, Liu H, Dakhil SR, et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013;105(16):1230-1238.

2. Hofman M, Ryan JL, Figueroa-Moseley CD, et al. Cancer-related fatigue: the scale of the problem. Oncologist. 2007;12 (suppl 1):4-10.

3. Bower JE, Ganz PA, Desmond KA, et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer. 2006;106(4):751-758.

4. Moraska AR, Sood A, Dakhil SR, et al. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Oncol. 2010;28(23):3673-3679.

5. Bruera E, El Osta B, Valero V, et al. Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol. 2007;25(23):3475-3481.

6. Morrow GR, Hickok JT, Roscoe JA, et al; University of Rochester Cancer Center Community Clinical Oncology Program. Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. J Clin Oncol. 2003;21(24):4635-4641.

7. Lesser GJ, Case D, Stark N, et al; Wake Forest University Community Clinical Oncology ­Program Research Base. A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer. J Support Oncol. 2013;11(1):31-42.

8. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012;30(31):3864-3869.

9. Duda RB, Zhong Y, Navas V, et al. American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7
breast cancer cell growth. J Surg Oncol. 1999;72(4):230-239.

10. Upton R, ed. American ginseng root Panax quinquefolius, standards of analysis, quality control, and therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2012.

11. King ML, Adler SR, Murphy LL. Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast ­cancer cell proliferation and estrogen receptor activation. Integr Cancer Ther. 2006;5(3): 236-243.

12. Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled trial. Ann Intern Med. 2004;141(1):23-27.

13. Vuksan V, Stavro MP, Sievenpiper JL, et al. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care. 2000;23(9):1221-1226.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(5):270-272.

Illustrative case

A 54-year-old woman is receiving chemotherapy for adenocarcinoma of the right breast (T2N1M0) and has persistent, disabling fatigue. She has been unable to work or care for her family since starting chemotherapy. She says she gets enough sleep and denies being depressed or in pain. Lab testing for anemia and thyroid dysfunction is negative.

Is there a safe and effective intervention that can reduce her fatigue?

Cancer-related fatigue is a common, distressing symptom that occurs in more than half of all patients undergoing chemotherapy and over two-thirds of those receiving radiation therapy.² For many cancer survivors, fatigue can persist for 5 to 10 years after treatment._³ Because no treatments have been effective, many clinicians and patients accept it as inevitable. In RCTs, psychostimulants such as methylphenidate and antidepressants such as donepezil and paroxetine have not been found effective.^4-6 Dietary supplements such as coenzyme Q10 and L-Carnitine also have not been found effective in placebo-controlled trials.^7,8 The double-blind RCT reported on here looked at whether American ginseng might be effective in relieving cancer-related fatigue.

STUDY SUMMARY: Ginseng reduced fatigue after 8 weeks of treatment

There are 2 major species of ginseng—Asian and American—and they have varying amounts, strengths, and varieties of ginsenosides, which are the active ingredients. In this 8-week, double-blind RCT, Barton et al¹ randomized more than 300 patients from 40 US cancer facilities to receive either 1000 mg of American ginseng twice daily (in the morning and at noon) or matched placebo capsules. Patients were either currently receiving treatment for cancer or were posttreatment, but within 2 years of receiving a cancer diagnosis. All participants had experienced fatigue for at least a month that they rated as ≥4 or higher on a scale of 0 to 10. Patients with other causes of fatigue were excluded, as were those who had pain or insomnia rated ≥4 on a scale of 0 to 10, those with brain cancer or central nervous system (CNS) lymphoma, those taking systemic steroids or opioids, and those who were using, or had used, ginseng or other agents for fatigue.

Of the 364 randomized participants, 300 (147 ginseng patients, 153 placebo patients) remained in the study through the primary endpoint at 4 weeks, and 261 completed the entire 8-week study. There were no baseline differences between groups in demographic characteristics, time since cancer diagnosis, cancer type, current or prior treatment, and fatigue at baseline.

The primary outcome was a change in score on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) at 4 weeks. Secondary outcomes included a change in MFSI-SF score at 8 weeks. The authors also conducted a subset analysis comparing ginseng vs placebo in just those patients currently undergoing cancer treatment vs those who had completed treatment. To make it easier to compare results, all scores were converted to a 100-point scale; higher scores indicated less fatigue. Adverse events were documented by patient self-report questionnaires and also by researchers who called or visited patients every other week.

While ginseng did not appear to significantly increase the change in fatigue scores over placebo at 4 weeks (14.4 vs 8.2; P=.07), fatigue scores at 8 weeks were significantly improved (20 vs 10.3; P=.003). Interestingly, though, there was a significant improvement in fatigue scores with ginseng at both 4 weeks (P=.02) and 8 weeks (P=.01) when researchers looked at only those patients who were currently receiving cancer treatment. On the other hand, those patients who were not currently undergoing treatment did not show a significant improvement at either time cutoff.

There was no statistically significant difference in adverse events between the ginseng and placebo groups over the 8-week study.

WHAT'S NEW: The first evidence-based therapy for cancer-related fatigue

We now have good evidence that American ginseng 1000 mg twice daily is safe and effective for ameliorating cancer-related fatigue. Before this study, no other effective treatments had been identified.

CAVEATS: Ginseng may not help patients who've finished cancer treatment

In this study, ginseng did not improve fatigue at 4 weeks, which was the primary outcome, although benefits were noted after 8 weeks of treatment. Interestingly, though, participants who were receiving radiation and/or chemotherapy during the study experienced significant improvements at 4 and 8 weeks, while those with previous (but not current) treatment did not significantly improve at either time point.

Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient's INR.It may be that ginseng works best to ameliorate cancer-related fatigue in patients simultaneously receiving cancer treatment, but not in those who have completed treatment. The findings also suggest that patients who have completed treatment may wish to try ginseng for longer than 8 weeks to see if it offers any benefit.

Because this study excluded patients with brain cancer, CNS lymphoma, moderate to severe pain, or insomnia and those taking steroids, it is not known if ginseng would help them.

In one study, a low-dose methanolic extract of American ginseng caused a breast cancer cell line to proliferate; however, it was later discovered that this extract had been contaminated with Fusarium fungi containing zearalenone, which has strong estrogenic activity.^9,10 However, higher doses of a similar methanolic extract, as well as other water-based extracts, have reduced proliferation of breast cancer cells.¹¹

Proceed carefully if a patient is taking warfarin. Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient’s international normalized ratio (INR).¹² Therefore, carefully monitor INR in patients concurrently taking ginseng and warfarin. Furthermore, ginseng may lower blood glucose in patients with diabetes, so carefully monitor blood glucose in these patients when initiating or discontinuing ginseng.¹³

CHALLENGES TO IMPLEMENTATION: With ginseng, it's hard to know exactly what you're getting

Advise patients to obtain American ginseng products that contain at least 3% ginsenosides.Regulating dietary supplements has been a challenge for the US Food and Drug Administration, especially verifying ingredients and potency. Although ginseng commonly is adulterated, much of the adulteration occurs with the Asian species (Panax ginseng) rather than the American species (Panax quinquefolius) used in this study.¹⁰ Physicians who want to recommend ginseng for cancer-related fatigue should advise patients to use American ginseng root products produced in the United States. Additionally, ginseng products should contain at least 3% ginsenosides to match the dose used in this study.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

A 54-year-old woman is receiving chemotherapy for adenocarcinoma of the right breast (T2N1M0) and has persistent, disabling fatigue. She has been unable to work or care for her family since starting chemotherapy. She says she gets enough sleep and denies being depressed or in pain. Lab testing for anemia and thyroid dysfunction is negative.

Is there a safe and effective intervention that can reduce her fatigue?

Cancer-related fatigue is a common, distressing symptom that occurs in more than half of all patients undergoing chemotherapy and over two-thirds of those receiving radiation therapy.² For many cancer survivors, fatigue can persist for 5 to 10 years after treatment._³ Because no treatments have been effective, many clinicians and patients accept it as inevitable. In RCTs, psychostimulants such as methylphenidate and antidepressants such as donepezil and paroxetine have not been found effective.^4-6 Dietary supplements such as coenzyme Q10 and L-Carnitine also have not been found effective in placebo-controlled trials.^7,8 The double-blind RCT reported on here looked at whether American ginseng might be effective in relieving cancer-related fatigue.

STUDY SUMMARY: Ginseng reduced fatigue after 8 weeks of treatment

There are 2 major species of ginseng—Asian and American—and they have varying amounts, strengths, and varieties of ginsenosides, which are the active ingredients. In this 8-week, double-blind RCT, Barton et al¹ randomized more than 300 patients from 40 US cancer facilities to receive either 1000 mg of American ginseng twice daily (in the morning and at noon) or matched placebo capsules. Patients were either currently receiving treatment for cancer or were posttreatment, but within 2 years of receiving a cancer diagnosis. All participants had experienced fatigue for at least a month that they rated as ≥4 or higher on a scale of 0 to 10. Patients with other causes of fatigue were excluded, as were those who had pain or insomnia rated ≥4 on a scale of 0 to 10, those with brain cancer or central nervous system (CNS) lymphoma, those taking systemic steroids or opioids, and those who were using, or had used, ginseng or other agents for fatigue.

Of the 364 randomized participants, 300 (147 ginseng patients, 153 placebo patients) remained in the study through the primary endpoint at 4 weeks, and 261 completed the entire 8-week study. There were no baseline differences between groups in demographic characteristics, time since cancer diagnosis, cancer type, current or prior treatment, and fatigue at baseline.

The primary outcome was a change in score on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) at 4 weeks. Secondary outcomes included a change in MFSI-SF score at 8 weeks. The authors also conducted a subset analysis comparing ginseng vs placebo in just those patients currently undergoing cancer treatment vs those who had completed treatment. To make it easier to compare results, all scores were converted to a 100-point scale; higher scores indicated less fatigue. Adverse events were documented by patient self-report questionnaires and also by researchers who called or visited patients every other week.

While ginseng did not appear to significantly increase the change in fatigue scores over placebo at 4 weeks (14.4 vs 8.2; P=.07), fatigue scores at 8 weeks were significantly improved (20 vs 10.3; P=.003). Interestingly, though, there was a significant improvement in fatigue scores with ginseng at both 4 weeks (P=.02) and 8 weeks (P=.01) when researchers looked at only those patients who were currently receiving cancer treatment. On the other hand, those patients who were not currently undergoing treatment did not show a significant improvement at either time cutoff.

There was no statistically significant difference in adverse events between the ginseng and placebo groups over the 8-week study.

WHAT'S NEW: The first evidence-based therapy for cancer-related fatigue

We now have good evidence that American ginseng 1000 mg twice daily is safe and effective for ameliorating cancer-related fatigue. Before this study, no other effective treatments had been identified.

CAVEATS: Ginseng may not help patients who've finished cancer treatment

In this study, ginseng did not improve fatigue at 4 weeks, which was the primary outcome, although benefits were noted after 8 weeks of treatment. Interestingly, though, participants who were receiving radiation and/or chemotherapy during the study experienced significant improvements at 4 and 8 weeks, while those with previous (but not current) treatment did not significantly improve at either time point.

Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient's INR.It may be that ginseng works best to ameliorate cancer-related fatigue in patients simultaneously receiving cancer treatment, but not in those who have completed treatment. The findings also suggest that patients who have completed treatment may wish to try ginseng for longer than 8 weeks to see if it offers any benefit.

Because this study excluded patients with brain cancer, CNS lymphoma, moderate to severe pain, or insomnia and those taking steroids, it is not known if ginseng would help them.

In one study, a low-dose methanolic extract of American ginseng caused a breast cancer cell line to proliferate; however, it was later discovered that this extract had been contaminated with Fusarium fungi containing zearalenone, which has strong estrogenic activity.^9,10 However, higher doses of a similar methanolic extract, as well as other water-based extracts, have reduced proliferation of breast cancer cells.¹¹

Proceed carefully if a patient is taking warfarin. Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient’s international normalized ratio (INR).¹² Therefore, carefully monitor INR in patients concurrently taking ginseng and warfarin. Furthermore, ginseng may lower blood glucose in patients with diabetes, so carefully monitor blood glucose in these patients when initiating or discontinuing ginseng.¹³

CHALLENGES TO IMPLEMENTATION: With ginseng, it's hard to know exactly what you're getting

Advise patients to obtain American ginseng products that contain at least 3% ginsenosides.Regulating dietary supplements has been a challenge for the US Food and Drug Administration, especially verifying ingredients and potency. Although ginseng commonly is adulterated, much of the adulteration occurs with the Asian species (Panax ginseng) rather than the American species (Panax quinquefolius) used in this study.¹⁰ Physicians who want to recommend ginseng for cancer-related fatigue should advise patients to use American ginseng root products produced in the United States. Additionally, ginseng products should contain at least 3% ginsenosides to match the dose used in this study.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

A 54-year-old woman is receiving chemotherapy for adenocarcinoma of the right breast (T2N1M0) and has persistent, disabling fatigue. She has been unable to work or care for her family since starting chemotherapy. She says she gets enough sleep and denies being depressed or in pain. Lab testing for anemia and thyroid dysfunction is negative.

Is there a safe and effective intervention that can reduce her fatigue?

Cancer-related fatigue is a common, distressing symptom that occurs in more than half of all patients undergoing chemotherapy and over two-thirds of those receiving radiation therapy.² For many cancer survivors, fatigue can persist for 5 to 10 years after treatment._³ Because no treatments have been effective, many clinicians and patients accept it as inevitable. In RCTs, psychostimulants such as methylphenidate and antidepressants such as donepezil and paroxetine have not been found effective.^4-6 Dietary supplements such as coenzyme Q10 and L-Carnitine also have not been found effective in placebo-controlled trials.^7,8 The double-blind RCT reported on here looked at whether American ginseng might be effective in relieving cancer-related fatigue.

STUDY SUMMARY: Ginseng reduced fatigue after 8 weeks of treatment

There are 2 major species of ginseng—Asian and American—and they have varying amounts, strengths, and varieties of ginsenosides, which are the active ingredients. In this 8-week, double-blind RCT, Barton et al¹ randomized more than 300 patients from 40 US cancer facilities to receive either 1000 mg of American ginseng twice daily (in the morning and at noon) or matched placebo capsules. Patients were either currently receiving treatment for cancer or were posttreatment, but within 2 years of receiving a cancer diagnosis. All participants had experienced fatigue for at least a month that they rated as ≥4 or higher on a scale of 0 to 10. Patients with other causes of fatigue were excluded, as were those who had pain or insomnia rated ≥4 on a scale of 0 to 10, those with brain cancer or central nervous system (CNS) lymphoma, those taking systemic steroids or opioids, and those who were using, or had used, ginseng or other agents for fatigue.

Of the 364 randomized participants, 300 (147 ginseng patients, 153 placebo patients) remained in the study through the primary endpoint at 4 weeks, and 261 completed the entire 8-week study. There were no baseline differences between groups in demographic characteristics, time since cancer diagnosis, cancer type, current or prior treatment, and fatigue at baseline.

The primary outcome was a change in score on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) at 4 weeks. Secondary outcomes included a change in MFSI-SF score at 8 weeks. The authors also conducted a subset analysis comparing ginseng vs placebo in just those patients currently undergoing cancer treatment vs those who had completed treatment. To make it easier to compare results, all scores were converted to a 100-point scale; higher scores indicated less fatigue. Adverse events were documented by patient self-report questionnaires and also by researchers who called or visited patients every other week.

While ginseng did not appear to significantly increase the change in fatigue scores over placebo at 4 weeks (14.4 vs 8.2; P=.07), fatigue scores at 8 weeks were significantly improved (20 vs 10.3; P=.003). Interestingly, though, there was a significant improvement in fatigue scores with ginseng at both 4 weeks (P=.02) and 8 weeks (P=.01) when researchers looked at only those patients who were currently receiving cancer treatment. On the other hand, those patients who were not currently undergoing treatment did not show a significant improvement at either time cutoff.

There was no statistically significant difference in adverse events between the ginseng and placebo groups over the 8-week study.

WHAT'S NEW: The first evidence-based therapy for cancer-related fatigue

We now have good evidence that American ginseng 1000 mg twice daily is safe and effective for ameliorating cancer-related fatigue. Before this study, no other effective treatments had been identified.

CAVEATS: Ginseng may not help patients who've finished cancer treatment

In this study, ginseng did not improve fatigue at 4 weeks, which was the primary outcome, although benefits were noted after 8 weeks of treatment. Interestingly, though, participants who were receiving radiation and/or chemotherapy during the study experienced significant improvements at 4 and 8 weeks, while those with previous (but not current) treatment did not significantly improve at either time point.

Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient's INR.It may be that ginseng works best to ameliorate cancer-related fatigue in patients simultaneously receiving cancer treatment, but not in those who have completed treatment. The findings also suggest that patients who have completed treatment may wish to try ginseng for longer than 8 weeks to see if it offers any benefit.

Because this study excluded patients with brain cancer, CNS lymphoma, moderate to severe pain, or insomnia and those taking steroids, it is not known if ginseng would help them.

In one study, a low-dose methanolic extract of American ginseng caused a breast cancer cell line to proliferate; however, it was later discovered that this extract had been contaminated with Fusarium fungi containing zearalenone, which has strong estrogenic activity.^9,10 However, higher doses of a similar methanolic extract, as well as other water-based extracts, have reduced proliferation of breast cancer cells.¹¹

Proceed carefully if a patient is taking warfarin. Coadministration of ginseng and warfarin may reduce both warfarin concentrations and a patient’s international normalized ratio (INR).¹² Therefore, carefully monitor INR in patients concurrently taking ginseng and warfarin. Furthermore, ginseng may lower blood glucose in patients with diabetes, so carefully monitor blood glucose in these patients when initiating or discontinuing ginseng.¹³

CHALLENGES TO IMPLEMENTATION: With ginseng, it's hard to know exactly what you're getting

Advise patients to obtain American ginseng products that contain at least 3% ginsenosides.Regulating dietary supplements has been a challenge for the US Food and Drug Administration, especially verifying ingredients and potency. Although ginseng commonly is adulterated, much of the adulteration occurs with the Asian species (Panax ginseng) rather than the American species (Panax quinquefolius) used in this study.¹⁰ Physicians who want to recommend ginseng for cancer-related fatigue should advise patients to use American ginseng root products produced in the United States. Additionally, ginseng products should contain at least 3% ginsenosides to match the dose used in this study.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

PRACTICE CHANGER

Recommend aspirin 975 mg (three adult tablets) as a viable firstline treatment for acute migraine. Consider prescribing metoclopramide 10 mg to be taken with aspirin to markedly decrease associated nausea and help achieve maximum symptom relief.¹

STRENGTH OF RECOMMENDATION

B: Based on a Cochrane meta-analysis of 13 good-quality, randomized controlled trials (RCTs).¹

ILLUSTRATIVE CASE

During a routine physical, a 37-year-old patient asks you what she should take for occasional migraine. She describes a unilateral headache with associated nausea, vomiting, phonophobia, and photophobia. What medication should you recommend?

Migraine headache affects more than 37 million Americans.² Women are three times more likely than men to experience migraine, with the highest prevalence among those ages 30 to 50.^3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of four to six workdays each year due to migraine.^5,6

Do you recommend this low-cost option?

Although many patients try OTC headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care provider.⁷ But despite a 2010 Cochrane review showing aspirin’s efficacy for acute migraine,⁸ our experience—based on discussions with physicians at numerous residency programs—suggests that family practice providers are not likely to recommend it.

Further evidence of the underuse of aspirin for migraine comes from a 2013 review of national surveillance studies,⁵ which found that in 2009, triptans accounted for nearly 80% of antimigraine ­analgesics prescribed during office visits.⁵ Thus, when the Cochrane reviewers issued this update of the earlier meta-analysis, we welcomed the opportunity to feature a practice changer that might not be getting the “traction” it deserves.

Continue reading for the study summary... 

STUDY SUMMARY

Multiple RCTs highlight aspirin’s efficacy

The 2013 Cochrane reviewers used the same 13 good-quality, double-blind RCTs involving 4,222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5,261 episodes of moderate-to-severe migraine were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.¹

Five studies had placebo controls, four had active controls (eg, sumatriptan, zolmitriptan, ibuprofen, acetaminophen plus codeine, and ergotamine plus caffeine), and four had both active and placebo controls. Primary outcomes were painfree status at two hours and headache relief (defined as a reduction in pain from moderate/severe to none/mild without the use of rescue medication) at two hours. Sustained headache relief at 24 hours was a secondary outcome.

Patients self-assessed their headache pain, using either a four-point categorical scale (none, mild, moderate, or severe) or a 100-mm visual analog scale. On the analog scale, less than 30 mm was considered mild or no pain; 30 mm or more was considered moderate or severe.

Study participants were ages 18 to 65 (mean age range, 37 to 44), and their symptoms met International Headache Society criteria for migraine with or without aura.⁹ All participants had migraine symptoms for at least 12 months, with one to six attacks of moderate to severe intensity per month prior to the study period.

In six studies (n = 2,027), investigators compared either 900- or 1,000-mg aspirin alone with placebo. For both primary outcomes, aspirin alone was superior to placebo, with a number needed to treat (NNT) of 8.1 for two-hour painfree status and 4.9 for two-hour headache relief. In three studies (n = 1,142), aspirin was superior to placebo for 24-hour headache relief, with an NNT of 6.6.

Aspirin plus metoclopramide was also better than placebo for primary and secondary outcomes, with an NNT of 8.8 for two-hour painfree status, 3.3 for two-hour headache relief, and 6.2 for 24-hour headache relief. Based on subgroup analysis, aspirin plus metoclopramide was more effective than aspirin alone for two-hour headache relief but equivalent for two-hour painfree status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea and vomiting.

In two studies (n = 726), aspirin alone was equivalent to sumatriptan 50 mg for reaching painfree and headache relief status at two hours. Two additional studies (n = 523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for two-hour headache relief, but the aspirin combination was inferior to the triptan for painfree status at two hours (n = 528). Data were insufficient to compare the efficacy of aspirin with zolmitriptan, ibuprofen, or acetaminophen plus codeine.

There were no reports of gastrointestinal bleeding or other serious adverse events attributable to aspirin therapy. Most adverse effects were mild or moderate disturbances of the digestive and nervous systems, with a number needed to harm of 34 for aspirin (with or without metoclopramide) versus placebo.

WHAT’S NEW?

A reminder of aspirin’s efficacy in treating migraine

The update of this meta-analysis confirms that high-dose aspirin (900 to 1,000 mg) is an effective treatment for migraine headache in adults ages 18 to 65. The addition of metoclopramide reduces nausea and vomiting but offers little if any benefit for headache/pain relief.

Continue reading for the caveats and challenges to implementation... 

CAVEATS

Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other NSAIDs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients who have chronic renal disease and/or a history of peptic ulcer disease.

CHALLENGES TO IMPLEMENTATION

Patients want a prescription

Patients often expect a prescription when they present with complaints of migraine headache and may feel shortchanged if they’re told to take an aspirin. Providing a prescription for the antiemetic metoclopramide, as well as a brief explanation of the evidence indicating that aspirin is effective for migraine, may adequately address such expectations.

Continue reading for the references... 

REFERENCES

1. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008041.

2. National Headache Foundation. Migraine. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed February 14, 2014.

3. Lipton RB, Stewart WF, Diamond S, et. al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646-657.

4. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalagia. 2010; 9:1065-1072.

5. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

6. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818.

7. Gibbs TS, Fleischer AB Jr, Feldman SR, et al. Health care utilization in patients with migraine: demographics and patterns of care in the ambulatory setting. Headache. 2003;43:330-335.

8. Kirthi V, Derry S, Moore RA, et al. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041.

9. The international classification of headache disorders. 2nd ed. Cephalalgia. 2004; 24 (suppl 1):S9-S160.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. 

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(2):94-96.

PRACTICE CHANGER

Recommend aspirin 975 mg (three adult tablets) as a viable firstline treatment for acute migraine. Consider prescribing metoclopramide 10 mg to be taken with aspirin to markedly decrease associated nausea and help achieve maximum symptom relief.¹

STRENGTH OF RECOMMENDATION

B: Based on a Cochrane meta-analysis of 13 good-quality, randomized controlled trials (RCTs).¹

ILLUSTRATIVE CASE

During a routine physical, a 37-year-old patient asks you what she should take for occasional migraine. She describes a unilateral headache with associated nausea, vomiting, phonophobia, and photophobia. What medication should you recommend?

Migraine headache affects more than 37 million Americans.² Women are three times more likely than men to experience migraine, with the highest prevalence among those ages 30 to 50.^3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of four to six workdays each year due to migraine.^5,6

Do you recommend this low-cost option?

Although many patients try OTC headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care provider.⁷ But despite a 2010 Cochrane review showing aspirin’s efficacy for acute migraine,⁸ our experience—based on discussions with physicians at numerous residency programs—suggests that family practice providers are not likely to recommend it.

Further evidence of the underuse of aspirin for migraine comes from a 2013 review of national surveillance studies,⁵ which found that in 2009, triptans accounted for nearly 80% of antimigraine ­analgesics prescribed during office visits.⁵ Thus, when the Cochrane reviewers issued this update of the earlier meta-analysis, we welcomed the opportunity to feature a practice changer that might not be getting the “traction” it deserves.

Continue reading for the study summary... 

STUDY SUMMARY

Multiple RCTs highlight aspirin’s efficacy

The 2013 Cochrane reviewers used the same 13 good-quality, double-blind RCTs involving 4,222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5,261 episodes of moderate-to-severe migraine were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.¹

Five studies had placebo controls, four had active controls (eg, sumatriptan, zolmitriptan, ibuprofen, acetaminophen plus codeine, and ergotamine plus caffeine), and four had both active and placebo controls. Primary outcomes were painfree status at two hours and headache relief (defined as a reduction in pain from moderate/severe to none/mild without the use of rescue medication) at two hours. Sustained headache relief at 24 hours was a secondary outcome.

Patients self-assessed their headache pain, using either a four-point categorical scale (none, mild, moderate, or severe) or a 100-mm visual analog scale. On the analog scale, less than 30 mm was considered mild or no pain; 30 mm or more was considered moderate or severe.

Study participants were ages 18 to 65 (mean age range, 37 to 44), and their symptoms met International Headache Society criteria for migraine with or without aura.⁹ All participants had migraine symptoms for at least 12 months, with one to six attacks of moderate to severe intensity per month prior to the study period.

In six studies (n = 2,027), investigators compared either 900- or 1,000-mg aspirin alone with placebo. For both primary outcomes, aspirin alone was superior to placebo, with a number needed to treat (NNT) of 8.1 for two-hour painfree status and 4.9 for two-hour headache relief. In three studies (n = 1,142), aspirin was superior to placebo for 24-hour headache relief, with an NNT of 6.6.

Aspirin plus metoclopramide was also better than placebo for primary and secondary outcomes, with an NNT of 8.8 for two-hour painfree status, 3.3 for two-hour headache relief, and 6.2 for 24-hour headache relief. Based on subgroup analysis, aspirin plus metoclopramide was more effective than aspirin alone for two-hour headache relief but equivalent for two-hour painfree status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea and vomiting.

In two studies (n = 726), aspirin alone was equivalent to sumatriptan 50 mg for reaching painfree and headache relief status at two hours. Two additional studies (n = 523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for two-hour headache relief, but the aspirin combination was inferior to the triptan for painfree status at two hours (n = 528). Data were insufficient to compare the efficacy of aspirin with zolmitriptan, ibuprofen, or acetaminophen plus codeine.

There were no reports of gastrointestinal bleeding or other serious adverse events attributable to aspirin therapy. Most adverse effects were mild or moderate disturbances of the digestive and nervous systems, with a number needed to harm of 34 for aspirin (with or without metoclopramide) versus placebo.

WHAT’S NEW?

A reminder of aspirin’s efficacy in treating migraine

The update of this meta-analysis confirms that high-dose aspirin (900 to 1,000 mg) is an effective treatment for migraine headache in adults ages 18 to 65. The addition of metoclopramide reduces nausea and vomiting but offers little if any benefit for headache/pain relief.

Continue reading for the caveats and challenges to implementation... 

CAVEATS

Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other NSAIDs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients who have chronic renal disease and/or a history of peptic ulcer disease.

CHALLENGES TO IMPLEMENTATION

Patients want a prescription

Patients often expect a prescription when they present with complaints of migraine headache and may feel shortchanged if they’re told to take an aspirin. Providing a prescription for the antiemetic metoclopramide, as well as a brief explanation of the evidence indicating that aspirin is effective for migraine, may adequately address such expectations.

Continue reading for the references... 

REFERENCES

1. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008041.

2. National Headache Foundation. Migraine. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed February 14, 2014.

3. Lipton RB, Stewart WF, Diamond S, et. al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646-657.

4. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalagia. 2010; 9:1065-1072.

5. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

6. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818.

7. Gibbs TS, Fleischer AB Jr, Feldman SR, et al. Health care utilization in patients with migraine: demographics and patterns of care in the ambulatory setting. Headache. 2003;43:330-335.

8. Kirthi V, Derry S, Moore RA, et al. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041.

9. The international classification of headache disorders. 2nd ed. Cephalalgia. 2004; 24 (suppl 1):S9-S160.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. 

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(2):94-96.

PRACTICE CHANGER

Recommend aspirin 975 mg (three adult tablets) as a viable firstline treatment for acute migraine. Consider prescribing metoclopramide 10 mg to be taken with aspirin to markedly decrease associated nausea and help achieve maximum symptom relief.¹

STRENGTH OF RECOMMENDATION

B: Based on a Cochrane meta-analysis of 13 good-quality, randomized controlled trials (RCTs).¹

ILLUSTRATIVE CASE

During a routine physical, a 37-year-old patient asks you what she should take for occasional migraine. She describes a unilateral headache with associated nausea, vomiting, phonophobia, and photophobia. What medication should you recommend?

Migraine headache affects more than 37 million Americans.² Women are three times more likely than men to experience migraine, with the highest prevalence among those ages 30 to 50.^3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of four to six workdays each year due to migraine.^5,6

Do you recommend this low-cost option?

Although many patients try OTC headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care provider.⁷ But despite a 2010 Cochrane review showing aspirin’s efficacy for acute migraine,⁸ our experience—based on discussions with physicians at numerous residency programs—suggests that family practice providers are not likely to recommend it.

Further evidence of the underuse of aspirin for migraine comes from a 2013 review of national surveillance studies,⁵ which found that in 2009, triptans accounted for nearly 80% of antimigraine ­analgesics prescribed during office visits.⁵ Thus, when the Cochrane reviewers issued this update of the earlier meta-analysis, we welcomed the opportunity to feature a practice changer that might not be getting the “traction” it deserves.

Continue reading for the study summary... 

STUDY SUMMARY

Multiple RCTs highlight aspirin’s efficacy

The 2013 Cochrane reviewers used the same 13 good-quality, double-blind RCTs involving 4,222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5,261 episodes of moderate-to-severe migraine were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.¹

Five studies had placebo controls, four had active controls (eg, sumatriptan, zolmitriptan, ibuprofen, acetaminophen plus codeine, and ergotamine plus caffeine), and four had both active and placebo controls. Primary outcomes were painfree status at two hours and headache relief (defined as a reduction in pain from moderate/severe to none/mild without the use of rescue medication) at two hours. Sustained headache relief at 24 hours was a secondary outcome.

Patients self-assessed their headache pain, using either a four-point categorical scale (none, mild, moderate, or severe) or a 100-mm visual analog scale. On the analog scale, less than 30 mm was considered mild or no pain; 30 mm or more was considered moderate or severe.

Study participants were ages 18 to 65 (mean age range, 37 to 44), and their symptoms met International Headache Society criteria for migraine with or without aura.⁹ All participants had migraine symptoms for at least 12 months, with one to six attacks of moderate to severe intensity per month prior to the study period.

In six studies (n = 2,027), investigators compared either 900- or 1,000-mg aspirin alone with placebo. For both primary outcomes, aspirin alone was superior to placebo, with a number needed to treat (NNT) of 8.1 for two-hour painfree status and 4.9 for two-hour headache relief. In three studies (n = 1,142), aspirin was superior to placebo for 24-hour headache relief, with an NNT of 6.6.

Aspirin plus metoclopramide was also better than placebo for primary and secondary outcomes, with an NNT of 8.8 for two-hour painfree status, 3.3 for two-hour headache relief, and 6.2 for 24-hour headache relief. Based on subgroup analysis, aspirin plus metoclopramide was more effective than aspirin alone for two-hour headache relief but equivalent for two-hour painfree status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea and vomiting.

In two studies (n = 726), aspirin alone was equivalent to sumatriptan 50 mg for reaching painfree and headache relief status at two hours. Two additional studies (n = 523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for two-hour headache relief, but the aspirin combination was inferior to the triptan for painfree status at two hours (n = 528). Data were insufficient to compare the efficacy of aspirin with zolmitriptan, ibuprofen, or acetaminophen plus codeine.

There were no reports of gastrointestinal bleeding or other serious adverse events attributable to aspirin therapy. Most adverse effects were mild or moderate disturbances of the digestive and nervous systems, with a number needed to harm of 34 for aspirin (with or without metoclopramide) versus placebo.

WHAT’S NEW?

A reminder of aspirin’s efficacy in treating migraine

The update of this meta-analysis confirms that high-dose aspirin (900 to 1,000 mg) is an effective treatment for migraine headache in adults ages 18 to 65. The addition of metoclopramide reduces nausea and vomiting but offers little if any benefit for headache/pain relief.

Continue reading for the caveats and challenges to implementation... 

CAVEATS

Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other NSAIDs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients who have chronic renal disease and/or a history of peptic ulcer disease.

CHALLENGES TO IMPLEMENTATION

Patients want a prescription

Patients often expect a prescription when they present with complaints of migraine headache and may feel shortchanged if they’re told to take an aspirin. Providing a prescription for the antiemetic metoclopramide, as well as a brief explanation of the evidence indicating that aspirin is effective for migraine, may adequately address such expectations.

Continue reading for the references... 

REFERENCES

1. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008041.

2. National Headache Foundation. Migraine. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed February 14, 2014.

3. Lipton RB, Stewart WF, Diamond S, et. al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646-657.

4. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalagia. 2010; 9:1065-1072.

5. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

6. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818.

7. Gibbs TS, Fleischer AB Jr, Feldman SR, et al. Health care utilization in patients with migraine: demographics and patterns of care in the ambulatory setting. Headache. 2003;43:330-335.

8. Kirthi V, Derry S, Moore RA, et al. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041.

9. The international classification of headache disorders. 2nd ed. Cephalalgia. 2004; 24 (suppl 1):S9-S160.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. 

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(2):94-96.

EVIDENCE SUMMARY
Troponin I and T proteins are specific to cardiac myocytes and, unlike CK-MB, aren’t elevated by damage to skeletal muscle.

Measuring troponin levels increased the number of patients diagnosed with AMI

A multinational prospective cohort study of patients with suspected ACS (N=10,719) found that measuring troponin levels in addition to CK-MB levels improved the diagnosis of AMI.¹ Investigators used elevation of any biomarker (CK, CK-MB, or troponin I or T) above the upper limit of normal as their diagnostic criterion. They found that measuring troponin increased the number of patients diagnosed with AMI by 10.4% over patients diagnosed using CK and CK-MB levels. Elevated troponin levels were associated with an inpatient mortality rate 1.5 to 3 times higher, regardless of the patient’s CK-MB status.

Troponin levels are more sensitive and specific than CK-MB

A prospective cohort study of 718 patients with suspected AMI calculated the area under curve (AUC) of the receiver operator curve—a measure of diagnostic accuracy in which an AUC value of 1 indicates 100% sensitivity and specificity—for troponin and CK-MB levels at initial presentation.² Two independent cardiologists reviewed all available medical records and made the final diagnosis. The AUCs for troponin levels ranged from 0.94 to 0.96 compared with 0.88 for CK-MB.

Troponin levels and odds of MI or death

A prospective study of 1852 patients with suspected ACS from 3 trial populations evaluated the prognostic value of increased troponin levels vs CK-MB levels at initial presentation, compared with a reference group with normal troponin and CK-MB levels.³ Patients with isolated troponin elevation had an increased odds of MI or death at 24 hours (odds ratio [OR]=5.2; 95% confidence interval [CI], 2.2-11.9) and 30 days (OR=2.1; 95% CI, 1.4-3.0), whereas patients with isolated CK-MB elevations didn't. At 30 days, patients with isolated CK-MB elevations equaled the reference group odds for MI and death (OR=1.0; 95% CI, 0.6-1.6).

Serial troponin assessment boosts diagnostic sensitivity

A prospective cohort study found that serial measurements of troponin increased the diagnostic sensitivity for AMI.⁴ Investigators evaluated 1818 consecutive patients with new onset chest pain in 3 German chest-pain units with troponin levels on admission and at 3 and 6 hours later. The gold standard was diagnosis of AMI by 2 independent cardiologists. Troponin measurement produced an AUC of 0.96 at admission, increasing to 0.98 and 0.99 at 3 and 6 hours after admission, respectively.

Recommendations
The American College of Cardiology and American Heart Association recommend measuring biomarkers of cardiac injury in all patients who present with chest discomfort consistent with ACS.⁵ A cardiac-specific troponin is the preferred marker and should be measured in all patients. If troponin is not available, CK-MB is the best alternative. Cardiac biomarkers should be repeated 6 to 9 hours after presentation and, in patients with a high clinical suspicion of AMI, at 12 to 24 hours.^6,7

EVIDENCE SUMMARY
Troponin I and T proteins are specific to cardiac myocytes and, unlike CK-MB, aren’t elevated by damage to skeletal muscle.

Measuring troponin levels increased the number of patients diagnosed with AMI

A multinational prospective cohort study of patients with suspected ACS (N=10,719) found that measuring troponin levels in addition to CK-MB levels improved the diagnosis of AMI.¹ Investigators used elevation of any biomarker (CK, CK-MB, or troponin I or T) above the upper limit of normal as their diagnostic criterion. They found that measuring troponin increased the number of patients diagnosed with AMI by 10.4% over patients diagnosed using CK and CK-MB levels. Elevated troponin levels were associated with an inpatient mortality rate 1.5 to 3 times higher, regardless of the patient’s CK-MB status.

Troponin levels are more sensitive and specific than CK-MB

A prospective cohort study of 718 patients with suspected AMI calculated the area under curve (AUC) of the receiver operator curve—a measure of diagnostic accuracy in which an AUC value of 1 indicates 100% sensitivity and specificity—for troponin and CK-MB levels at initial presentation.² Two independent cardiologists reviewed all available medical records and made the final diagnosis. The AUCs for troponin levels ranged from 0.94 to 0.96 compared with 0.88 for CK-MB.

Troponin levels and odds of MI or death

A prospective study of 1852 patients with suspected ACS from 3 trial populations evaluated the prognostic value of increased troponin levels vs CK-MB levels at initial presentation, compared with a reference group with normal troponin and CK-MB levels.³ Patients with isolated troponin elevation had an increased odds of MI or death at 24 hours (odds ratio [OR]=5.2; 95% confidence interval [CI], 2.2-11.9) and 30 days (OR=2.1; 95% CI, 1.4-3.0), whereas patients with isolated CK-MB elevations didn't. At 30 days, patients with isolated CK-MB elevations equaled the reference group odds for MI and death (OR=1.0; 95% CI, 0.6-1.6).

Serial troponin assessment boosts diagnostic sensitivity

A prospective cohort study found that serial measurements of troponin increased the diagnostic sensitivity for AMI.⁴ Investigators evaluated 1818 consecutive patients with new onset chest pain in 3 German chest-pain units with troponin levels on admission and at 3 and 6 hours later. The gold standard was diagnosis of AMI by 2 independent cardiologists. Troponin measurement produced an AUC of 0.96 at admission, increasing to 0.98 and 0.99 at 3 and 6 hours after admission, respectively.

Recommendations
The American College of Cardiology and American Heart Association recommend measuring biomarkers of cardiac injury in all patients who present with chest discomfort consistent with ACS.⁵ A cardiac-specific troponin is the preferred marker and should be measured in all patients. If troponin is not available, CK-MB is the best alternative. Cardiac biomarkers should be repeated 6 to 9 hours after presentation and, in patients with a high clinical suspicion of AMI, at 12 to 24 hours.^6,7

EVIDENCE SUMMARY
Troponin I and T proteins are specific to cardiac myocytes and, unlike CK-MB, aren’t elevated by damage to skeletal muscle.

Measuring troponin levels increased the number of patients diagnosed with AMI

A multinational prospective cohort study of patients with suspected ACS (N=10,719) found that measuring troponin levels in addition to CK-MB levels improved the diagnosis of AMI.¹ Investigators used elevation of any biomarker (CK, CK-MB, or troponin I or T) above the upper limit of normal as their diagnostic criterion. They found that measuring troponin increased the number of patients diagnosed with AMI by 10.4% over patients diagnosed using CK and CK-MB levels. Elevated troponin levels were associated with an inpatient mortality rate 1.5 to 3 times higher, regardless of the patient’s CK-MB status.

Troponin levels are more sensitive and specific than CK-MB

A prospective cohort study of 718 patients with suspected AMI calculated the area under curve (AUC) of the receiver operator curve—a measure of diagnostic accuracy in which an AUC value of 1 indicates 100% sensitivity and specificity—for troponin and CK-MB levels at initial presentation.² Two independent cardiologists reviewed all available medical records and made the final diagnosis. The AUCs for troponin levels ranged from 0.94 to 0.96 compared with 0.88 for CK-MB.

Troponin levels and odds of MI or death

A prospective study of 1852 patients with suspected ACS from 3 trial populations evaluated the prognostic value of increased troponin levels vs CK-MB levels at initial presentation, compared with a reference group with normal troponin and CK-MB levels.³ Patients with isolated troponin elevation had an increased odds of MI or death at 24 hours (odds ratio [OR]=5.2; 95% confidence interval [CI], 2.2-11.9) and 30 days (OR=2.1; 95% CI, 1.4-3.0), whereas patients with isolated CK-MB elevations didn't. At 30 days, patients with isolated CK-MB elevations equaled the reference group odds for MI and death (OR=1.0; 95% CI, 0.6-1.6).

Serial troponin assessment boosts diagnostic sensitivity

A prospective cohort study found that serial measurements of troponin increased the diagnostic sensitivity for AMI.⁴ Investigators evaluated 1818 consecutive patients with new onset chest pain in 3 German chest-pain units with troponin levels on admission and at 3 and 6 hours later. The gold standard was diagnosis of AMI by 2 independent cardiologists. Troponin measurement produced an AUC of 0.96 at admission, increasing to 0.98 and 0.99 at 3 and 6 hours after admission, respectively.

Recommendations
The American College of Cardiology and American Heart Association recommend measuring biomarkers of cardiac injury in all patients who present with chest discomfort consistent with ACS.⁵ A cardiac-specific troponin is the preferred marker and should be measured in all patients. If troponin is not available, CK-MB is the best alternative. Cardiac biomarkers should be repeated 6 to 9 hours after presentation and, in patients with a high clinical suspicion of AMI, at 12 to 24 hours.^6,7