Take note, ObGyns: A number of changes in Current Procedural Terminology (CPT) 2009—those changes took effect January 1—are going to modify the way you bill and will have an impact on your reimbursement. Most of these changes are minor, although renumbering of infusion codes will require changes to the encounter form. And I have good and bad news for urogynecologists who perform vaginal paravaginal repairs and sling procedures for stress urinary incontinence. Read on for details!

Mesh for vaginal paravaginal defect repair—
code error corrected

Code 57267 is an add-on code that describes the insertion of mesh, or other prosthesis, through a vaginal approach when native tissues have been determined to be weak and inadequate for repair—especially in patients who have undergone a previous attempt at repair. As an add-on code, it can be billed only in addition to other, specific procedures.

Before January 1, code 57267 could only be reported with an anterior or posterior colporrhaphy, or both, or with a rectocele repair without colporrhaphy.

When performing a vaginal approach paravaginal defect repair, however, the same weakened tissues also require use of the mesh, yet code 57825 (paravaginal defect repair [including repair of cystocele, if performed]) was not included as one of the allowed codes. This error is rectified in 2009.

You must still be aware that reporting the 57267 add-on code requires that you establish medical necessity for its use. Documentation of weakened, attenuated, or incompetent pubocervical tissue in the case of a paravaginal repair (International Classification of Diseases Clinical Modification [ICD-9-CM] code 618.81) or rectovaginal tissue for rectocele/enterocele repair (618.82) continues to be important when reporting the add-on mesh code.

A reminder about anesthesia

Until January 1, codes 57400 (dilation of vagina), 57410 (pelvic examination), and 57415 (removal of impacted vaginal foreign body) read “under anesthesia.” In a move to standardize terminology, these codes will be revised to add the wording “other than local.” The revision clarifies that 1) all surgical codes include administration of a local anesthetic and 2) codes designated with “under anesthesia” refer to regional blocks and general anesthesia.

New human papillomavirus vaccine, new code

A new code, 90650, has been added to report the newer bivalent human papillomavirus (HPV) vaccine, which contains an adjuvant formulation and is intended to protect against infection by high-risk HPV types 16 and 18. The existing HPV vaccine code, 90649, targets those high-risk types of HPV and two low-risk types (6 and 11).

Coverage recommendations for the new vaccine match those of the existing, quadrivalent vaccine, but not all payers are covering the HPV vaccine based on those recommendations. The new vaccine offers a less costly alternative for patients whose health-care insurance does not cover the vaccine or who are uninsured.

Wholesale reorganization of injection and infusion codes

Codes 90760–90779 (covering therapeutic, prophylactic, and diagnostic injections and infusions) are deleted in 2009 and renumbered, with the same descriptors, to 96360–96379. This was done to organize all infusions and injections together. The biggest change for you and every other ObGyn? You must revise the practice’s encounter form to reflect the requirement that intramuscular and subcutaneous injections are now coded 96372 instead of 90772.

Modifier -21 and prolonged E/M services

Now deleted is Modifier -21 (prolonged evaluation and management [E/M] service). This modifier represented acknowledgment that a continuous face-to-face E/M service could exceed the maximum time allowed by the highest level of E/M service for the type being billed.

In other words, before January 1, 2009, if a patient’s condition was such that you documented an established or new patient visit (99215 or 99205) but in fact spent more time with her than the 45 or 60 minutes that typically accompanies these codes, you added modifier -21 in the hope of receiving higher reimbursement. Now the modifier is deleted because there is already a mechanism in place to report such prolonged service.

Add-on codes 99354–99357 are used to report face-to-face outpatient and inpatient prolonged E/M services. Guidelines for these codes mandate cumulative time rather than continuous time, and using the add-on codes is contingent on the additional time spent being 30 or more minutes above the typical time allotted for the basic E/M service that you are billing.

Here’s a case that exemplifies how coding works in these circumstances:

CASE

You evaluate a patient for severe uterine bleeding, and report a level-4 visit (99214), which has a typical time of 25 minutes. At the same visit, you determine that endometrial biopsy is required, and you perform it during the visit. But the patient faints during the procedure—and you spend an additional 35 minutes (cumulative time) with her before you send her home.

Because the typical time of 25 minutes was exceeded by at least 30 minutes, you should report 99354 (prolonged physician service in the office or other outpatient setting requiring direct [face-to-face] patient contact beyond the usual service; first hour [list separately in addition to code for office or other outpatient Evaluation and Management service]) in addition to 99214.

Guidelines for correct use of these codes are also being revised to emphasize that only outpatient prolonged services codes are intended to be used to report total duration of face-to-face time; on the other hand, inpatient codes are intended to report the total duration of the time spent (whether continuous or noncontinuous) by the physician on the unit actively involved in caring for the patient.

Take note, ObGyns: A number of changes in Current Procedural Terminology (CPT) 2009—those changes took effect January 1—are going to modify the way you bill and will have an impact on your reimbursement. Most of these changes are minor, although renumbering of infusion codes will require changes to the encounter form. And I have good and bad news for urogynecologists who perform vaginal paravaginal repairs and sling procedures for stress urinary incontinence. Read on for details!

Mesh for vaginal paravaginal defect repair—
code error corrected

Code 57267 is an add-on code that describes the insertion of mesh, or other prosthesis, through a vaginal approach when native tissues have been determined to be weak and inadequate for repair—especially in patients who have undergone a previous attempt at repair. As an add-on code, it can be billed only in addition to other, specific procedures.

Before January 1, code 57267 could only be reported with an anterior or posterior colporrhaphy, or both, or with a rectocele repair without colporrhaphy.

When performing a vaginal approach paravaginal defect repair, however, the same weakened tissues also require use of the mesh, yet code 57825 (paravaginal defect repair [including repair of cystocele, if performed]) was not included as one of the allowed codes. This error is rectified in 2009.

You must still be aware that reporting the 57267 add-on code requires that you establish medical necessity for its use. Documentation of weakened, attenuated, or incompetent pubocervical tissue in the case of a paravaginal repair (International Classification of Diseases Clinical Modification [ICD-9-CM] code 618.81) or rectovaginal tissue for rectocele/enterocele repair (618.82) continues to be important when reporting the add-on mesh code.

A reminder about anesthesia

Until January 1, codes 57400 (dilation of vagina), 57410 (pelvic examination), and 57415 (removal of impacted vaginal foreign body) read “under anesthesia.” In a move to standardize terminology, these codes will be revised to add the wording “other than local.” The revision clarifies that 1) all surgical codes include administration of a local anesthetic and 2) codes designated with “under anesthesia” refer to regional blocks and general anesthesia.

New human papillomavirus vaccine, new code

A new code, 90650, has been added to report the newer bivalent human papillomavirus (HPV) vaccine, which contains an adjuvant formulation and is intended to protect against infection by high-risk HPV types 16 and 18. The existing HPV vaccine code, 90649, targets those high-risk types of HPV and two low-risk types (6 and 11).

Coverage recommendations for the new vaccine match those of the existing, quadrivalent vaccine, but not all payers are covering the HPV vaccine based on those recommendations. The new vaccine offers a less costly alternative for patients whose health-care insurance does not cover the vaccine or who are uninsured.

Wholesale reorganization of injection and infusion codes

Codes 90760–90779 (covering therapeutic, prophylactic, and diagnostic injections and infusions) are deleted in 2009 and renumbered, with the same descriptors, to 96360–96379. This was done to organize all infusions and injections together. The biggest change for you and every other ObGyn? You must revise the practice’s encounter form to reflect the requirement that intramuscular and subcutaneous injections are now coded 96372 instead of 90772.

Modifier -21 and prolonged E/M services

Now deleted is Modifier -21 (prolonged evaluation and management [E/M] service). This modifier represented acknowledgment that a continuous face-to-face E/M service could exceed the maximum time allowed by the highest level of E/M service for the type being billed.

In other words, before January 1, 2009, if a patient’s condition was such that you documented an established or new patient visit (99215 or 99205) but in fact spent more time with her than the 45 or 60 minutes that typically accompanies these codes, you added modifier -21 in the hope of receiving higher reimbursement. Now the modifier is deleted because there is already a mechanism in place to report such prolonged service.

Add-on codes 99354–99357 are used to report face-to-face outpatient and inpatient prolonged E/M services. Guidelines for these codes mandate cumulative time rather than continuous time, and using the add-on codes is contingent on the additional time spent being 30 or more minutes above the typical time allotted for the basic E/M service that you are billing.

Here’s a case that exemplifies how coding works in these circumstances:

CASE

You evaluate a patient for severe uterine bleeding, and report a level-4 visit (99214), which has a typical time of 25 minutes. At the same visit, you determine that endometrial biopsy is required, and you perform it during the visit. But the patient faints during the procedure—and you spend an additional 35 minutes (cumulative time) with her before you send her home.

Because the typical time of 25 minutes was exceeded by at least 30 minutes, you should report 99354 (prolonged physician service in the office or other outpatient setting requiring direct [face-to-face] patient contact beyond the usual service; first hour [list separately in addition to code for office or other outpatient Evaluation and Management service]) in addition to 99214.

Guidelines for correct use of these codes are also being revised to emphasize that only outpatient prolonged services codes are intended to be used to report total duration of face-to-face time; on the other hand, inpatient codes are intended to report the total duration of the time spent (whether continuous or noncontinuous) by the physician on the unit actively involved in caring for the patient.

Take note, ObGyns: A number of changes in Current Procedural Terminology (CPT) 2009—those changes took effect January 1—are going to modify the way you bill and will have an impact on your reimbursement. Most of these changes are minor, although renumbering of infusion codes will require changes to the encounter form. And I have good and bad news for urogynecologists who perform vaginal paravaginal repairs and sling procedures for stress urinary incontinence. Read on for details!

Mesh for vaginal paravaginal defect repair—
code error corrected

Code 57267 is an add-on code that describes the insertion of mesh, or other prosthesis, through a vaginal approach when native tissues have been determined to be weak and inadequate for repair—especially in patients who have undergone a previous attempt at repair. As an add-on code, it can be billed only in addition to other, specific procedures.

Before January 1, code 57267 could only be reported with an anterior or posterior colporrhaphy, or both, or with a rectocele repair without colporrhaphy.

When performing a vaginal approach paravaginal defect repair, however, the same weakened tissues also require use of the mesh, yet code 57825 (paravaginal defect repair [including repair of cystocele, if performed]) was not included as one of the allowed codes. This error is rectified in 2009.

You must still be aware that reporting the 57267 add-on code requires that you establish medical necessity for its use. Documentation of weakened, attenuated, or incompetent pubocervical tissue in the case of a paravaginal repair (International Classification of Diseases Clinical Modification [ICD-9-CM] code 618.81) or rectovaginal tissue for rectocele/enterocele repair (618.82) continues to be important when reporting the add-on mesh code.

A reminder about anesthesia

Until January 1, codes 57400 (dilation of vagina), 57410 (pelvic examination), and 57415 (removal of impacted vaginal foreign body) read “under anesthesia.” In a move to standardize terminology, these codes will be revised to add the wording “other than local.” The revision clarifies that 1) all surgical codes include administration of a local anesthetic and 2) codes designated with “under anesthesia” refer to regional blocks and general anesthesia.

New human papillomavirus vaccine, new code

A new code, 90650, has been added to report the newer bivalent human papillomavirus (HPV) vaccine, which contains an adjuvant formulation and is intended to protect against infection by high-risk HPV types 16 and 18. The existing HPV vaccine code, 90649, targets those high-risk types of HPV and two low-risk types (6 and 11).

Coverage recommendations for the new vaccine match those of the existing, quadrivalent vaccine, but not all payers are covering the HPV vaccine based on those recommendations. The new vaccine offers a less costly alternative for patients whose health-care insurance does not cover the vaccine or who are uninsured.

Wholesale reorganization of injection and infusion codes

Codes 90760–90779 (covering therapeutic, prophylactic, and diagnostic injections and infusions) are deleted in 2009 and renumbered, with the same descriptors, to 96360–96379. This was done to organize all infusions and injections together. The biggest change for you and every other ObGyn? You must revise the practice’s encounter form to reflect the requirement that intramuscular and subcutaneous injections are now coded 96372 instead of 90772.

Modifier -21 and prolonged E/M services

Now deleted is Modifier -21 (prolonged evaluation and management [E/M] service). This modifier represented acknowledgment that a continuous face-to-face E/M service could exceed the maximum time allowed by the highest level of E/M service for the type being billed.

In other words, before January 1, 2009, if a patient’s condition was such that you documented an established or new patient visit (99215 or 99205) but in fact spent more time with her than the 45 or 60 minutes that typically accompanies these codes, you added modifier -21 in the hope of receiving higher reimbursement. Now the modifier is deleted because there is already a mechanism in place to report such prolonged service.

Add-on codes 99354–99357 are used to report face-to-face outpatient and inpatient prolonged E/M services. Guidelines for these codes mandate cumulative time rather than continuous time, and using the add-on codes is contingent on the additional time spent being 30 or more minutes above the typical time allotted for the basic E/M service that you are billing.

Here’s a case that exemplifies how coding works in these circumstances:

CASE

You evaluate a patient for severe uterine bleeding, and report a level-4 visit (99214), which has a typical time of 25 minutes. At the same visit, you determine that endometrial biopsy is required, and you perform it during the visit. But the patient faints during the procedure—and you spend an additional 35 minutes (cumulative time) with her before you send her home.

Because the typical time of 25 minutes was exceeded by at least 30 minutes, you should report 99354 (prolonged physician service in the office or other outpatient setting requiring direct [face-to-face] patient contact beyond the usual service; first hour [list separately in addition to code for office or other outpatient Evaluation and Management service]) in addition to 99214.

Guidelines for correct use of these codes are also being revised to emphasize that only outpatient prolonged services codes are intended to be used to report total duration of face-to-face time; on the other hand, inpatient codes are intended to report the total duration of the time spent (whether continuous or noncontinuous) by the physician on the unit actively involved in caring for the patient.

Man treated for asthma dies of undiagnosed heart disease

A MONTH AFTER HE BEGAN RECEIVING ASTHMA TREATMENT from his physician, a 50-year-old man suffered a heart attack and died. An autopsy revealed idiopathic dilated cardiomyopathy.

PLAINTIFF’S CLAIM: The doctor negligently failed to examine the patient for heart disease; the patient was in congestive heart failure during treatment.

DOCTOR’S DEFENSE: The physician claimed that he twice recommended that the patient see a cardiologist. The plaintiff countered that the doctor didn’t make a referral, despite chart notes to that effect.

VERDICT: California defense verdict.

COMMENT: Clear documentation of the history, physical, and differential diagnostic thinking helps fend off unwarranted lawsuits.

Failure to confirm Echo result leads to cardiac arrest

SUDDEN ONSET OF CHEST PAIN radiating to the back, which had started during rest, brought a 49-year-old woman to the hospital. The patient also complained of pain radiating to her left jaw and ear, which became worse when she inhaled or moved. She had no shortness of breath, palpitations, diaphoresis, or history of trauma. She did have a history of gastroesophageal reflux disease (GERD), but said that the pain didn’t resemble the pain of GERD. While in the triage area, she vomited.

Two electrocardiograms (EKGs) done in the emergency room showed sinus bradycardia and nonspecific T-wave abnormalities. A chest radiograph was reported as normal, but with a note of borderline heart enlargement and a tortuous aorta. A gastrointestinal (GI) cocktail of Nitropaste and Toradol didn’t relieve the pain, nor did Ativan. No workup for aortic dissection was done.

After consultation with a doctor covering for the patient’s primary care physician, the patient was hospitalized with orders for laboratory studies, a chest radiograph, and an EKG the next morning. The EKG again showed abnormalities, including a nonspecific T-wave abnormality, as did the chest radiograph (moderate cardiomegaly, tortuous aorta, mild prominence of the pulmonary vasculature without evidence of congestive failure, and small left pleural effusion or slight blunting of the left lateral costophrenic angle). But the radiograph wasn’t compared to the one taken the night before. A GI consult—by which time the patient’s hematocrit had dropped from 32 to 26—attributed the pain to GERD and recommended outpatient esophagogastroduodenoscopy.

The results of a routine echocardiogram—faxed to the patient’s floor the same day—were worrisome: a dilated aortic root and ascending aorta accompanied by at least moderately severe aortic insufficiency and normal ventricular function.

The patient’s primary care physician saw the patient and discharged her that evening. Fewer than 2 hours later, the patient suffered a cardiac arrest at home and couldn’t be resuscitated after transport to the hospital. An autopsy found the cause of death to be cardiac tamponade resulting from dissection of an aortic aneurysm.

PLAINTIFF’S CLAIM: The patient shouldn’t have been discharged without clarification of the echocardiogram results.

DOCTOR’S DEFENSE: The primary care physician’s understanding was that the cardiologist had ruled out heart-related problems, including aortic dissection, and that the patient had been diagnosed with a stomach illness, which would be followed on an outpatient basis. Even if a diagnosis of aortic dissection had been made, the outcome would have been the same.

VERDICT: $560,000 Massachusetts settlement.

COMMENT: Inadequate follow-up of testing—in this case, an inpatient echocardiogram—can have catastrophic results. Before discharge, each inpatient test should be reviewed and adjudicated, and a clear plan for follow-up delineated.

Cancer missed in patient with rectal bleeding

A 44-YEAR-OLD MAN went to his family physician, an internist, with complaints that included rectal bleeding. The physician performed a flexible sigmoidoscopy, which found hemorrhoids that weren’t inflamed or bleeding. A hemoccult test at a physical exam before the sigmoidoscopy was positive for bleeding.

A year later, the patient returned to the doctor complaining of blood in his underwear almost every other day. The doctor noted a “slightly inflamed hemorrhoid” on anoscopy, but no bleeding from the hemorrhoid; he didn’t test for occult bleeding.

Early the next year, the patient saw the physician for a complaint of blood in the stool and changes in bowel habits. A hemoccult test was positive, and the doctor diagnosed irritable bowel syndrome. The patient returned 6 months later with the same complaints and, he said, requested referral to a gastroenterologist. The doctor again attributed the complaints to irritable bowel syndrome.

Early the following year, the patient went to another internist because his insurance changed. This internist immediately diagnosed stage-3 rectal cancer. The patient underwent radiation, chemotherapy, and 2 surgeries, one to remove part of his rectum and a second to reverse an ileostomy done during the first operation. The patient was left impotent, with permanent, variable bowel dysfunction.

PLAINTIFF’S CLAIM: The diagnosis of hemorrhoids wasn’t reasonable; the patient should have been referred to a gastroenterologist or for colorectal cancer surgery. Early detection and diagnosis would have resulted in removal of a polyp or early cancer, which could have been done during a colonoscopy or by transanal excision.

DOCTOR’S DEFENSE: The patient’s doctor denied that the patient had requested a referral to a gastroenterologist and maintained that he believed the flexible sigmoidoscopy had ruled out a serious cause of bleeding.

VERDICT: $1 million Virginia verdict.

COMMENT: When a patient has persistent rectal bleeding without a clear cause, no matter what the patient’s age, further evaluation or referral is prudent.

Man treated for asthma dies of undiagnosed heart disease

A MONTH AFTER HE BEGAN RECEIVING ASTHMA TREATMENT from his physician, a 50-year-old man suffered a heart attack and died. An autopsy revealed idiopathic dilated cardiomyopathy.

PLAINTIFF’S CLAIM: The doctor negligently failed to examine the patient for heart disease; the patient was in congestive heart failure during treatment.

DOCTOR’S DEFENSE: The physician claimed that he twice recommended that the patient see a cardiologist. The plaintiff countered that the doctor didn’t make a referral, despite chart notes to that effect.

VERDICT: California defense verdict.

COMMENT: Clear documentation of the history, physical, and differential diagnostic thinking helps fend off unwarranted lawsuits.

Failure to confirm Echo result leads to cardiac arrest

SUDDEN ONSET OF CHEST PAIN radiating to the back, which had started during rest, brought a 49-year-old woman to the hospital. The patient also complained of pain radiating to her left jaw and ear, which became worse when she inhaled or moved. She had no shortness of breath, palpitations, diaphoresis, or history of trauma. She did have a history of gastroesophageal reflux disease (GERD), but said that the pain didn’t resemble the pain of GERD. While in the triage area, she vomited.

Two electrocardiograms (EKGs) done in the emergency room showed sinus bradycardia and nonspecific T-wave abnormalities. A chest radiograph was reported as normal, but with a note of borderline heart enlargement and a tortuous aorta. A gastrointestinal (GI) cocktail of Nitropaste and Toradol didn’t relieve the pain, nor did Ativan. No workup for aortic dissection was done.

After consultation with a doctor covering for the patient’s primary care physician, the patient was hospitalized with orders for laboratory studies, a chest radiograph, and an EKG the next morning. The EKG again showed abnormalities, including a nonspecific T-wave abnormality, as did the chest radiograph (moderate cardiomegaly, tortuous aorta, mild prominence of the pulmonary vasculature without evidence of congestive failure, and small left pleural effusion or slight blunting of the left lateral costophrenic angle). But the radiograph wasn’t compared to the one taken the night before. A GI consult—by which time the patient’s hematocrit had dropped from 32 to 26—attributed the pain to GERD and recommended outpatient esophagogastroduodenoscopy.

The results of a routine echocardiogram—faxed to the patient’s floor the same day—were worrisome: a dilated aortic root and ascending aorta accompanied by at least moderately severe aortic insufficiency and normal ventricular function.

The patient’s primary care physician saw the patient and discharged her that evening. Fewer than 2 hours later, the patient suffered a cardiac arrest at home and couldn’t be resuscitated after transport to the hospital. An autopsy found the cause of death to be cardiac tamponade resulting from dissection of an aortic aneurysm.

PLAINTIFF’S CLAIM: The patient shouldn’t have been discharged without clarification of the echocardiogram results.

DOCTOR’S DEFENSE: The primary care physician’s understanding was that the cardiologist had ruled out heart-related problems, including aortic dissection, and that the patient had been diagnosed with a stomach illness, which would be followed on an outpatient basis. Even if a diagnosis of aortic dissection had been made, the outcome would have been the same.

VERDICT: $560,000 Massachusetts settlement.

COMMENT: Inadequate follow-up of testing—in this case, an inpatient echocardiogram—can have catastrophic results. Before discharge, each inpatient test should be reviewed and adjudicated, and a clear plan for follow-up delineated.

Cancer missed in patient with rectal bleeding

A 44-YEAR-OLD MAN went to his family physician, an internist, with complaints that included rectal bleeding. The physician performed a flexible sigmoidoscopy, which found hemorrhoids that weren’t inflamed or bleeding. A hemoccult test at a physical exam before the sigmoidoscopy was positive for bleeding.

A year later, the patient returned to the doctor complaining of blood in his underwear almost every other day. The doctor noted a “slightly inflamed hemorrhoid” on anoscopy, but no bleeding from the hemorrhoid; he didn’t test for occult bleeding.

Early the next year, the patient saw the physician for a complaint of blood in the stool and changes in bowel habits. A hemoccult test was positive, and the doctor diagnosed irritable bowel syndrome. The patient returned 6 months later with the same complaints and, he said, requested referral to a gastroenterologist. The doctor again attributed the complaints to irritable bowel syndrome.

Early the following year, the patient went to another internist because his insurance changed. This internist immediately diagnosed stage-3 rectal cancer. The patient underwent radiation, chemotherapy, and 2 surgeries, one to remove part of his rectum and a second to reverse an ileostomy done during the first operation. The patient was left impotent, with permanent, variable bowel dysfunction.

PLAINTIFF’S CLAIM: The diagnosis of hemorrhoids wasn’t reasonable; the patient should have been referred to a gastroenterologist or for colorectal cancer surgery. Early detection and diagnosis would have resulted in removal of a polyp or early cancer, which could have been done during a colonoscopy or by transanal excision.

DOCTOR’S DEFENSE: The patient’s doctor denied that the patient had requested a referral to a gastroenterologist and maintained that he believed the flexible sigmoidoscopy had ruled out a serious cause of bleeding.

VERDICT: $1 million Virginia verdict.

COMMENT: When a patient has persistent rectal bleeding without a clear cause, no matter what the patient’s age, further evaluation or referral is prudent.

Man treated for asthma dies of undiagnosed heart disease

A MONTH AFTER HE BEGAN RECEIVING ASTHMA TREATMENT from his physician, a 50-year-old man suffered a heart attack and died. An autopsy revealed idiopathic dilated cardiomyopathy.

PLAINTIFF’S CLAIM: The doctor negligently failed to examine the patient for heart disease; the patient was in congestive heart failure during treatment.

DOCTOR’S DEFENSE: The physician claimed that he twice recommended that the patient see a cardiologist. The plaintiff countered that the doctor didn’t make a referral, despite chart notes to that effect.

VERDICT: California defense verdict.

COMMENT: Clear documentation of the history, physical, and differential diagnostic thinking helps fend off unwarranted lawsuits.

Failure to confirm Echo result leads to cardiac arrest

SUDDEN ONSET OF CHEST PAIN radiating to the back, which had started during rest, brought a 49-year-old woman to the hospital. The patient also complained of pain radiating to her left jaw and ear, which became worse when she inhaled or moved. She had no shortness of breath, palpitations, diaphoresis, or history of trauma. She did have a history of gastroesophageal reflux disease (GERD), but said that the pain didn’t resemble the pain of GERD. While in the triage area, she vomited.

Two electrocardiograms (EKGs) done in the emergency room showed sinus bradycardia and nonspecific T-wave abnormalities. A chest radiograph was reported as normal, but with a note of borderline heart enlargement and a tortuous aorta. A gastrointestinal (GI) cocktail of Nitropaste and Toradol didn’t relieve the pain, nor did Ativan. No workup for aortic dissection was done.

After consultation with a doctor covering for the patient’s primary care physician, the patient was hospitalized with orders for laboratory studies, a chest radiograph, and an EKG the next morning. The EKG again showed abnormalities, including a nonspecific T-wave abnormality, as did the chest radiograph (moderate cardiomegaly, tortuous aorta, mild prominence of the pulmonary vasculature without evidence of congestive failure, and small left pleural effusion or slight blunting of the left lateral costophrenic angle). But the radiograph wasn’t compared to the one taken the night before. A GI consult—by which time the patient’s hematocrit had dropped from 32 to 26—attributed the pain to GERD and recommended outpatient esophagogastroduodenoscopy.

The results of a routine echocardiogram—faxed to the patient’s floor the same day—were worrisome: a dilated aortic root and ascending aorta accompanied by at least moderately severe aortic insufficiency and normal ventricular function.

The patient’s primary care physician saw the patient and discharged her that evening. Fewer than 2 hours later, the patient suffered a cardiac arrest at home and couldn’t be resuscitated after transport to the hospital. An autopsy found the cause of death to be cardiac tamponade resulting from dissection of an aortic aneurysm.

PLAINTIFF’S CLAIM: The patient shouldn’t have been discharged without clarification of the echocardiogram results.

DOCTOR’S DEFENSE: The primary care physician’s understanding was that the cardiologist had ruled out heart-related problems, including aortic dissection, and that the patient had been diagnosed with a stomach illness, which would be followed on an outpatient basis. Even if a diagnosis of aortic dissection had been made, the outcome would have been the same.

VERDICT: $560,000 Massachusetts settlement.

COMMENT: Inadequate follow-up of testing—in this case, an inpatient echocardiogram—can have catastrophic results. Before discharge, each inpatient test should be reviewed and adjudicated, and a clear plan for follow-up delineated.

Cancer missed in patient with rectal bleeding

A 44-YEAR-OLD MAN went to his family physician, an internist, with complaints that included rectal bleeding. The physician performed a flexible sigmoidoscopy, which found hemorrhoids that weren’t inflamed or bleeding. A hemoccult test at a physical exam before the sigmoidoscopy was positive for bleeding.

A year later, the patient returned to the doctor complaining of blood in his underwear almost every other day. The doctor noted a “slightly inflamed hemorrhoid” on anoscopy, but no bleeding from the hemorrhoid; he didn’t test for occult bleeding.

Early the next year, the patient saw the physician for a complaint of blood in the stool and changes in bowel habits. A hemoccult test was positive, and the doctor diagnosed irritable bowel syndrome. The patient returned 6 months later with the same complaints and, he said, requested referral to a gastroenterologist. The doctor again attributed the complaints to irritable bowel syndrome.

Early the following year, the patient went to another internist because his insurance changed. This internist immediately diagnosed stage-3 rectal cancer. The patient underwent radiation, chemotherapy, and 2 surgeries, one to remove part of his rectum and a second to reverse an ileostomy done during the first operation. The patient was left impotent, with permanent, variable bowel dysfunction.

PLAINTIFF’S CLAIM: The diagnosis of hemorrhoids wasn’t reasonable; the patient should have been referred to a gastroenterologist or for colorectal cancer surgery. Early detection and diagnosis would have resulted in removal of a polyp or early cancer, which could have been done during a colonoscopy or by transanal excision.

DOCTOR’S DEFENSE: The patient’s doctor denied that the patient had requested a referral to a gastroenterologist and maintained that he believed the flexible sigmoidoscopy had ruled out a serious cause of bleeding.

VERDICT: $1 million Virginia verdict.

COMMENT: When a patient has persistent rectal bleeding without a clear cause, no matter what the patient’s age, further evaluation or referral is prudent.

ILLUSTRATIVE CASE

A 56-year-old patient with well-controlled type 2 diabetes and hypertension comes to see you for routine follow up. His blood pressure is controlled with lisinopril 40 mg/d. But his albumin-to-creatinine ratio is 75 mg/g, and your records reveal that his albuminuria is getting progressively worse.

You’re aware of the potential benefits of a dual angiotensin blockade, and are considering adding an angiotensin receptor blocker (ARB) to your patient’s medication regimen. You wonder whether the combination of an angiotensin-converting enzyme (ACE) inhibitor and an ARB will slow the decline of renal function. You also wonder whether the combination will reduce your patient’s cardiovascular risk.

ACE inhibitors are known to reduce cardiovascular morbidity and mortality, as well as proteinuria in patients with vascular disease or diabetes, whether or not they have heart failure.² But few studies have compared the effects of ACE inhibitors and ARBs in high-risk patients without heart failure. Nor has there been a definitive study of the effects of an ACE inhibitor–ARB combination on proteinuria and cardiovascular risk.

Are 2 drugs better than 1?

In a recent meta-analysis, researchers reported that combination therapy had a beneficial effect on proteinuria.³ But that observation was based on a small number of patients (N=309 from 10 studies), short follow up, and a lack of data on key clinical end points such as decline of the glomerular filtration rate (GFR) and the onset of dialysis.

Other evidence comes from a study of 199 patients with diabetes and microalbuminuria, in which the ACE inhibitor-ARB combination reduced proteinuria more than either agent alone.⁴ And in a study of 336 patients with nondiabetic nephropathy, the 2-drug combination slowed the decline in renal function more than monotherapy.⁵

Small studies raise hopes. These preliminary findings, along with the theoretical benefits of dual angiotensin blockade, suggested that the benefits of taking both agents together could be significant. A large, well-done randomized controlled trial (RCT) was needed to determine the following: (1) whether an ARB is as effective as an ACE inhibitor in reducing morbidity and mortality in high-risk patients who don’t have heart failure, and (2) whether the ACE inhibitor–ARB combination is better than monotherapy for patients at high risk.

Key findings

The ONTARGET study:

 

• established that telmisartan, an ARB, is not inferior to ramipril, an ACE inhibitor, in reducing cardiovascular and renal events in high-risk patients without heart failure.
• found that either drug alone is more effective than combination therapy for this patient population.
• cast fresh doubt on the assumption that proteinuria is an accurate surrogate marker for progressive renal dysfunction.

STUDY SUMMARY: Vascular outcomes same for ACE inhibitors, ARBs

The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a multi-year study of thousands of patients, addressed both of those questions. The researchers compared the effects of both telmisartan (Micardis, an ARB) alone and a telmisartan + ramipril (Altace, an ACE inhibitor) combination with the effects of the ACE inhibitor alone in patients ≥55 years of age with established atherosclerotic vascular disease or diabetes with end-organ damage.¹ Exclusion criteria included major renal artery stenosis, uncorrected volume or sodium depletion, a serum creatinine concentration of ≥3 mg/dL, and uncontrolled hypertension (>160 mm Hg systolic or >100 mm Hg diastolic).

After a 3-week run-in period to eliminate those who were unable to tolerate either medication or were nonadherent, a total of 25,620 patients remained. They were randomly assigned to take ramipril 10 mg/d, telmisartan 80 mg/d, or both the ACE inhibitor and the ARB. The researchers followed the patients for a median of 56 months.

The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure;¹ the main renal outcome was a composite of first dialysis, doubling of serum creatinine, or death.⁶

The percentage of patients with the primary outcome was the same in all 3 groups (~16.5%). This finding was somewhat surprising because the blood pressure of patients in the combination therapy group was 2 to 3 mm Hg lower overall (both systolic and diastolic) than the blood pressure of patients on monotherapy—a difference that in other studies has been associated with an estimated 4% to 5% reduction in risk.^1,2 Patients in the combination group had more hypotensive symptoms compared with those in the ramipril group (4.8% vs 1.7%, number needed to harm [NNH]=32, P<.001).

Renal dysfunction was highest in dual therapy group

Patients in the combination therapy group had higher rates of renal dysfunction than either the ramipril group (13.5% vs 10.2%, NNH=30, P<.001) or the telmisartan group (10.6%), despite a decrease in proteinuria among those on dual therapy. Patients taking the 2-drug combination also had higher rates of hyperkalemia.

While telmisartan proved to be equal to ramipril in reducing vascular events in high-risk patients, patients taking the ACE inhibitor experienced more cough (NNH=32, P<.001) and angioedema (NNH=500, P=.01). In both monotherapy groups, the rates of adverse drug reactions were probably lower than what we typically see in clinical practice because after the run-in period, only patients who were better able to tolerate both medications remained.

WHAT’S NEW: Combination causes renal impairment

This study established that telmisartan, an ARB, is not inferior to ramipril, an ACE inhibitor, in reducing cardiovascular and renal events in patients without heart failure. In addition, as the largest RCT to explore the effects of a dual blockade of the renin-angiotensin system with an ACE inhibitor and an ARB, it casts fresh doubt on the assumption that proteinuria is an accurate surrogate marker for progressive renal dysfunction. The reduction in proteinuria seen in patients in the combination therapy group came at a cost of increased renal impairment.

CAVEATS: Findings do not apply to heart failure patients

More than 11% of potential subjects were excluded from this study during the run-in period. This suggests that physicians in practice are likely to find a significant number of patients who are unable to tolerate (or fail to adhere to) monotherapy with ACE inhibitors or ARBs.

At baseline, only a small subgroup—13%—had overt diabetic nephropathy, the hallmark for a substantial continuous decline of GFR. However, 38% of the study group had diabetes, and almost 30% of these diabetes patients had microalbuminuria. Subgroup analysis found results consistent with the overall group, and the large sample size reduces the likelihood that these findings were due to low power. The overall rate of dialysis and doubling of serum creatinine was low, but still statistically significant, due to the large size of this study.

In determining treatment for high-risk patients with vascular disease or diabetes, it is important to keep the study population in mind. Studies of patients with poorly controlled congestive heart failure (CHF) have shown potential benefits from an ACE inhibitor–ARB combination.⁷ The ONTARGET trial specifically excluded individuals with CHF, and its findings—and recommendations to avoid combination therapy—should not be applied to heart failure patients.

CHALLENGES TO IMPLEMENTATION: Best microalbuminuria Tx remains elusive

Although albuminuria has been considered an early sign of the onset of diabetic nephropathy, the ONTARGET study demonstrated that combination therapy may cause further reduction in albuminuria but still adversely affect renal function. Thus, this study raises important questions about the best treatment for patients with diabetes who have microalbuminuria and are already on either an ACE inhibitor or an ARB. We wonder, too, whether we should continue to test for microalbuminuria in patients who are taking one of these agents, given the lack of guidance regarding further treatment.

Acknowledgements

The PURLs Surveillance System is 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.

PURLs methodology

This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

A 56-year-old patient with well-controlled type 2 diabetes and hypertension comes to see you for routine follow up. His blood pressure is controlled with lisinopril 40 mg/d. But his albumin-to-creatinine ratio is 75 mg/g, and your records reveal that his albuminuria is getting progressively worse.

You’re aware of the potential benefits of a dual angiotensin blockade, and are considering adding an angiotensin receptor blocker (ARB) to your patient’s medication regimen. You wonder whether the combination of an angiotensin-converting enzyme (ACE) inhibitor and an ARB will slow the decline of renal function. You also wonder whether the combination will reduce your patient’s cardiovascular risk.

ACE inhibitors are known to reduce cardiovascular morbidity and mortality, as well as proteinuria in patients with vascular disease or diabetes, whether or not they have heart failure.² But few studies have compared the effects of ACE inhibitors and ARBs in high-risk patients without heart failure. Nor has there been a definitive study of the effects of an ACE inhibitor–ARB combination on proteinuria and cardiovascular risk.

Are 2 drugs better than 1?

In a recent meta-analysis, researchers reported that combination therapy had a beneficial effect on proteinuria.³ But that observation was based on a small number of patients (N=309 from 10 studies), short follow up, and a lack of data on key clinical end points such as decline of the glomerular filtration rate (GFR) and the onset of dialysis.

Other evidence comes from a study of 199 patients with diabetes and microalbuminuria, in which the ACE inhibitor-ARB combination reduced proteinuria more than either agent alone.⁴ And in a study of 336 patients with nondiabetic nephropathy, the 2-drug combination slowed the decline in renal function more than monotherapy.⁵

Small studies raise hopes. These preliminary findings, along with the theoretical benefits of dual angiotensin blockade, suggested that the benefits of taking both agents together could be significant. A large, well-done randomized controlled trial (RCT) was needed to determine the following: (1) whether an ARB is as effective as an ACE inhibitor in reducing morbidity and mortality in high-risk patients who don’t have heart failure, and (2) whether the ACE inhibitor–ARB combination is better than monotherapy for patients at high risk.

Key findings

The ONTARGET study:

 

• established that telmisartan, an ARB, is not inferior to ramipril, an ACE inhibitor, in reducing cardiovascular and renal events in high-risk patients without heart failure.
• found that either drug alone is more effective than combination therapy for this patient population.
• cast fresh doubt on the assumption that proteinuria is an accurate surrogate marker for progressive renal dysfunction.

STUDY SUMMARY: Vascular outcomes same for ACE inhibitors, ARBs

The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a multi-year study of thousands of patients, addressed both of those questions. The researchers compared the effects of both telmisartan (Micardis, an ARB) alone and a telmisartan + ramipril (Altace, an ACE inhibitor) combination with the effects of the ACE inhibitor alone in patients ≥55 years of age with established atherosclerotic vascular disease or diabetes with end-organ damage.¹ Exclusion criteria included major renal artery stenosis, uncorrected volume or sodium depletion, a serum creatinine concentration of ≥3 mg/dL, and uncontrolled hypertension (>160 mm Hg systolic or >100 mm Hg diastolic).

After a 3-week run-in period to eliminate those who were unable to tolerate either medication or were nonadherent, a total of 25,620 patients remained. They were randomly assigned to take ramipril 10 mg/d, telmisartan 80 mg/d, or both the ACE inhibitor and the ARB. The researchers followed the patients for a median of 56 months.

The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure;¹ the main renal outcome was a composite of first dialysis, doubling of serum creatinine, or death.⁶

The percentage of patients with the primary outcome was the same in all 3 groups (~16.5%). This finding was somewhat surprising because the blood pressure of patients in the combination therapy group was 2 to 3 mm Hg lower overall (both systolic and diastolic) than the blood pressure of patients on monotherapy—a difference that in other studies has been associated with an estimated 4% to 5% reduction in risk.^1,2 Patients in the combination group had more hypotensive symptoms compared with those in the ramipril group (4.8% vs 1.7%, number needed to harm [NNH]=32, P<.001).

Renal dysfunction was highest in dual therapy group

Patients in the combination therapy group had higher rates of renal dysfunction than either the ramipril group (13.5% vs 10.2%, NNH=30, P<.001) or the telmisartan group (10.6%), despite a decrease in proteinuria among those on dual therapy. Patients taking the 2-drug combination also had higher rates of hyperkalemia.

While telmisartan proved to be equal to ramipril in reducing vascular events in high-risk patients, patients taking the ACE inhibitor experienced more cough (NNH=32, P<.001) and angioedema (NNH=500, P=.01). In both monotherapy groups, the rates of adverse drug reactions were probably lower than what we typically see in clinical practice because after the run-in period, only patients who were better able to tolerate both medications remained.

WHAT’S NEW: Combination causes renal impairment

This study established that telmisartan, an ARB, is not inferior to ramipril, an ACE inhibitor, in reducing cardiovascular and renal events in patients without heart failure. In addition, as the largest RCT to explore the effects of a dual blockade of the renin-angiotensin system with an ACE inhibitor and an ARB, it casts fresh doubt on the assumption that proteinuria is an accurate surrogate marker for progressive renal dysfunction. The reduction in proteinuria seen in patients in the combination therapy group came at a cost of increased renal impairment.

CAVEATS: Findings do not apply to heart failure patients

More than 11% of potential subjects were excluded from this study during the run-in period. This suggests that physicians in practice are likely to find a significant number of patients who are unable to tolerate (or fail to adhere to) monotherapy with ACE inhibitors or ARBs.

At baseline, only a small subgroup—13%—had overt diabetic nephropathy, the hallmark for a substantial continuous decline of GFR. However, 38% of the study group had diabetes, and almost 30% of these diabetes patients had microalbuminuria. Subgroup analysis found results consistent with the overall group, and the large sample size reduces the likelihood that these findings were due to low power. The overall rate of dialysis and doubling of serum creatinine was low, but still statistically significant, due to the large size of this study.

In determining treatment for high-risk patients with vascular disease or diabetes, it is important to keep the study population in mind. Studies of patients with poorly controlled congestive heart failure (CHF) have shown potential benefits from an ACE inhibitor–ARB combination.⁷ The ONTARGET trial specifically excluded individuals with CHF, and its findings—and recommendations to avoid combination therapy—should not be applied to heart failure patients.

CHALLENGES TO IMPLEMENTATION: Best microalbuminuria Tx remains elusive

Although albuminuria has been considered an early sign of the onset of diabetic nephropathy, the ONTARGET study demonstrated that combination therapy may cause further reduction in albuminuria but still adversely affect renal function. Thus, this study raises important questions about the best treatment for patients with diabetes who have microalbuminuria and are already on either an ACE inhibitor or an ARB. We wonder, too, whether we should continue to test for microalbuminuria in patients who are taking one of these agents, given the lack of guidance regarding further treatment.

Acknowledgements

The PURLs Surveillance System is 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.

PURLs methodology

This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

A 56-year-old patient with well-controlled type 2 diabetes and hypertension comes to see you for routine follow up. His blood pressure is controlled with lisinopril 40 mg/d. But his albumin-to-creatinine ratio is 75 mg/g, and your records reveal that his albuminuria is getting progressively worse.

You’re aware of the potential benefits of a dual angiotensin blockade, and are considering adding an angiotensin receptor blocker (ARB) to your patient’s medication regimen. You wonder whether the combination of an angiotensin-converting enzyme (ACE) inhibitor and an ARB will slow the decline of renal function. You also wonder whether the combination will reduce your patient’s cardiovascular risk.

ACE inhibitors are known to reduce cardiovascular morbidity and mortality, as well as proteinuria in patients with vascular disease or diabetes, whether or not they have heart failure.² But few studies have compared the effects of ACE inhibitors and ARBs in high-risk patients without heart failure. Nor has there been a definitive study of the effects of an ACE inhibitor–ARB combination on proteinuria and cardiovascular risk.

Are 2 drugs better than 1?

In a recent meta-analysis, researchers reported that combination therapy had a beneficial effect on proteinuria.³ But that observation was based on a small number of patients (N=309 from 10 studies), short follow up, and a lack of data on key clinical end points such as decline of the glomerular filtration rate (GFR) and the onset of dialysis.

Other evidence comes from a study of 199 patients with diabetes and microalbuminuria, in which the ACE inhibitor-ARB combination reduced proteinuria more than either agent alone.⁴ And in a study of 336 patients with nondiabetic nephropathy, the 2-drug combination slowed the decline in renal function more than monotherapy.⁵

Small studies raise hopes. These preliminary findings, along with the theoretical benefits of dual angiotensin blockade, suggested that the benefits of taking both agents together could be significant. A large, well-done randomized controlled trial (RCT) was needed to determine the following: (1) whether an ARB is as effective as an ACE inhibitor in reducing morbidity and mortality in high-risk patients who don’t have heart failure, and (2) whether the ACE inhibitor–ARB combination is better than monotherapy for patients at high risk.

Key findings

The ONTARGET study:

 

• established that telmisartan, an ARB, is not inferior to ramipril, an ACE inhibitor, in reducing cardiovascular and renal events in high-risk patients without heart failure.
• found that either drug alone is more effective than combination therapy for this patient population.
• cast fresh doubt on the assumption that proteinuria is an accurate surrogate marker for progressive renal dysfunction.

STUDY SUMMARY: Vascular outcomes same for ACE inhibitors, ARBs

The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a multi-year study of thousands of patients, addressed both of those questions. The researchers compared the effects of both telmisartan (Micardis, an ARB) alone and a telmisartan + ramipril (Altace, an ACE inhibitor) combination with the effects of the ACE inhibitor alone in patients ≥55 years of age with established atherosclerotic vascular disease or diabetes with end-organ damage.¹ Exclusion criteria included major renal artery stenosis, uncorrected volume or sodium depletion, a serum creatinine concentration of ≥3 mg/dL, and uncontrolled hypertension (>160 mm Hg systolic or >100 mm Hg diastolic).

After a 3-week run-in period to eliminate those who were unable to tolerate either medication or were nonadherent, a total of 25,620 patients remained. They were randomly assigned to take ramipril 10 mg/d, telmisartan 80 mg/d, or both the ACE inhibitor and the ARB. The researchers followed the patients for a median of 56 months.

The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure;¹ the main renal outcome was a composite of first dialysis, doubling of serum creatinine, or death.⁶

The percentage of patients with the primary outcome was the same in all 3 groups (~16.5%). This finding was somewhat surprising because the blood pressure of patients in the combination therapy group was 2 to 3 mm Hg lower overall (both systolic and diastolic) than the blood pressure of patients on monotherapy—a difference that in other studies has been associated with an estimated 4% to 5% reduction in risk.^1,2 Patients in the combination group had more hypotensive symptoms compared with those in the ramipril group (4.8% vs 1.7%, number needed to harm [NNH]=32, P<.001).

Renal dysfunction was highest in dual therapy group

Patients in the combination therapy group had higher rates of renal dysfunction than either the ramipril group (13.5% vs 10.2%, NNH=30, P<.001) or the telmisartan group (10.6%), despite a decrease in proteinuria among those on dual therapy. Patients taking the 2-drug combination also had higher rates of hyperkalemia.

While telmisartan proved to be equal to ramipril in reducing vascular events in high-risk patients, patients taking the ACE inhibitor experienced more cough (NNH=32, P<.001) and angioedema (NNH=500, P=.01). In both monotherapy groups, the rates of adverse drug reactions were probably lower than what we typically see in clinical practice because after the run-in period, only patients who were better able to tolerate both medications remained.

WHAT’S NEW: Combination causes renal impairment

This study established that telmisartan, an ARB, is not inferior to ramipril, an ACE inhibitor, in reducing cardiovascular and renal events in patients without heart failure. In addition, as the largest RCT to explore the effects of a dual blockade of the renin-angiotensin system with an ACE inhibitor and an ARB, it casts fresh doubt on the assumption that proteinuria is an accurate surrogate marker for progressive renal dysfunction. The reduction in proteinuria seen in patients in the combination therapy group came at a cost of increased renal impairment.

CAVEATS: Findings do not apply to heart failure patients

More than 11% of potential subjects were excluded from this study during the run-in period. This suggests that physicians in practice are likely to find a significant number of patients who are unable to tolerate (or fail to adhere to) monotherapy with ACE inhibitors or ARBs.

At baseline, only a small subgroup—13%—had overt diabetic nephropathy, the hallmark for a substantial continuous decline of GFR. However, 38% of the study group had diabetes, and almost 30% of these diabetes patients had microalbuminuria. Subgroup analysis found results consistent with the overall group, and the large sample size reduces the likelihood that these findings were due to low power. The overall rate of dialysis and doubling of serum creatinine was low, but still statistically significant, due to the large size of this study.

In determining treatment for high-risk patients with vascular disease or diabetes, it is important to keep the study population in mind. Studies of patients with poorly controlled congestive heart failure (CHF) have shown potential benefits from an ACE inhibitor–ARB combination.⁷ The ONTARGET trial specifically excluded individuals with CHF, and its findings—and recommendations to avoid combination therapy—should not be applied to heart failure patients.

CHALLENGES TO IMPLEMENTATION: Best microalbuminuria Tx remains elusive

Although albuminuria has been considered an early sign of the onset of diabetic nephropathy, the ONTARGET study demonstrated that combination therapy may cause further reduction in albuminuria but still adversely affect renal function. Thus, this study raises important questions about the best treatment for patients with diabetes who have microalbuminuria and are already on either an ACE inhibitor or an ARB. We wonder, too, whether we should continue to test for microalbuminuria in patients who are taking one of these agents, given the lack of guidance regarding further treatment.

Acknowledgements

The PURLs Surveillance System is 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.

PURLs methodology

This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Click here to view PURL METHODOLOGY

Please do a follow-up to your article on billing and coding—specifically, on 99215. I realize many physicians are trying to work up from 99213 to 99214. But we have a mature practice with many complex patients and need help working up to 99215.

Here’s an example: A patient comes in with an asthmatic exacerbation due to sinusitis, and it’s likely a level 4. But the original purpose of the visit was a lipid panel review and follow-up for abnormal liver enzymes—another level 4. The patient also wants to discuss his colonoscopy report, which shows the presence of polyps.

Yes, I know I can make such patients schedule 3 separate appointments. But they’ll get mad, their boss will fire them, and it’s inefficient besides. I also know I can spend nearly 40 minutes with them and code for “counseling.” But suppose I can treat the asthma and infection in 6 minutes, discuss and alter the lipid Rx in 4 minutes, and review the colonoscopy results in 2. Now I have a 12-minute visit that I’m stuck billing at the rate of a 99214, which is “typically 25 minutes.”

I know I’m supposed to feel guilty, but I’m not going to do all that “free” work just because I can do it quickly and efficiently. So how do I go from 99214 to 99215 for such complex cases? I’m not going to call other physicians, chat for 40 minutes, or order unneeded tests just so I can “code up,” but I want to be paid for more than the asthma exacerbation because I’m doing more than that.

Andrew Johnstone, MD, Indianapolis

Please do a follow-up to your article on billing and coding—specifically, on 99215. I realize many physicians are trying to work up from 99213 to 99214. But we have a mature practice with many complex patients and need help working up to 99215.

Here’s an example: A patient comes in with an asthmatic exacerbation due to sinusitis, and it’s likely a level 4. But the original purpose of the visit was a lipid panel review and follow-up for abnormal liver enzymes—another level 4. The patient also wants to discuss his colonoscopy report, which shows the presence of polyps.

Yes, I know I can make such patients schedule 3 separate appointments. But they’ll get mad, their boss will fire them, and it’s inefficient besides. I also know I can spend nearly 40 minutes with them and code for “counseling.” But suppose I can treat the asthma and infection in 6 minutes, discuss and alter the lipid Rx in 4 minutes, and review the colonoscopy results in 2. Now I have a 12-minute visit that I’m stuck billing at the rate of a 99214, which is “typically 25 minutes.”

I know I’m supposed to feel guilty, but I’m not going to do all that “free” work just because I can do it quickly and efficiently. So how do I go from 99214 to 99215 for such complex cases? I’m not going to call other physicians, chat for 40 minutes, or order unneeded tests just so I can “code up,” but I want to be paid for more than the asthma exacerbation because I’m doing more than that.

Andrew Johnstone, MD, Indianapolis

Please do a follow-up to your article on billing and coding—specifically, on 99215. I realize many physicians are trying to work up from 99213 to 99214. But we have a mature practice with many complex patients and need help working up to 99215.

Here’s an example: A patient comes in with an asthmatic exacerbation due to sinusitis, and it’s likely a level 4. But the original purpose of the visit was a lipid panel review and follow-up for abnormal liver enzymes—another level 4. The patient also wants to discuss his colonoscopy report, which shows the presence of polyps.

Yes, I know I can make such patients schedule 3 separate appointments. But they’ll get mad, their boss will fire them, and it’s inefficient besides. I also know I can spend nearly 40 minutes with them and code for “counseling.” But suppose I can treat the asthma and infection in 6 minutes, discuss and alter the lipid Rx in 4 minutes, and review the colonoscopy results in 2. Now I have a 12-minute visit that I’m stuck billing at the rate of a 99214, which is “typically 25 minutes.”

I know I’m supposed to feel guilty, but I’m not going to do all that “free” work just because I can do it quickly and efficiently. So how do I go from 99214 to 99215 for such complex cases? I’m not going to call other physicians, chat for 40 minutes, or order unneeded tests just so I can “code up,” but I want to be paid for more than the asthma exacerbation because I’m doing more than that.

Andrew Johnstone, MD, Indianapolis

Jaxon Hernandes, MD, a hospitalist with Apogee Physicians at Clara Maass Medical Center in Belleville, N.J., believes he and his colleagues are positioned perfectly to help properly diagnose asthma, a timely opinion given new Canadian research suggesting the bronchial condition routinely is over-diagnosed.

The study in the Canadian Medical Association Journal (2008;179(11):1121-1131) found up to 30% of adults diagnosed with asthma had no evidence of the condition. It included 496 people from eight Canadian cities who reported a diagnosis of asthma from their physician. The researchers' goal was to determine whether obese people were more likely to be misdiagnosed with asthma, but researchers found the issue was just as prevalent in people of normal weight.

Henderson notes hospitalists rarely make initial diagnoses when a patient is first encountered in the hospital, but once they are admitted, a hospitalist can order peak-flow-rate and spirometric tests. Clinical guidelines recommend using a spirometer to objectively measure long volume and airway flow.

"The hospitalist is in a position where he can get the pulmonologist to do what he needs to do," Dr. Hernandes says. "He can force a diagnosis being made."

Dr. Hernandes adds hospitalists have an onus to order the tests because doctors "may be under-diagnosing the primary issue with a patient or over-diagnosing and psychologically scarring them."

Jaxon Hernandes, MD, a hospitalist with Apogee Physicians at Clara Maass Medical Center in Belleville, N.J., believes he and his colleagues are positioned perfectly to help properly diagnose asthma, a timely opinion given new Canadian research suggesting the bronchial condition routinely is over-diagnosed.

The study in the Canadian Medical Association Journal (2008;179(11):1121-1131) found up to 30% of adults diagnosed with asthma had no evidence of the condition. It included 496 people from eight Canadian cities who reported a diagnosis of asthma from their physician. The researchers' goal was to determine whether obese people were more likely to be misdiagnosed with asthma, but researchers found the issue was just as prevalent in people of normal weight.

Henderson notes hospitalists rarely make initial diagnoses when a patient is first encountered in the hospital, but once they are admitted, a hospitalist can order peak-flow-rate and spirometric tests. Clinical guidelines recommend using a spirometer to objectively measure long volume and airway flow.

"The hospitalist is in a position where he can get the pulmonologist to do what he needs to do," Dr. Hernandes says. "He can force a diagnosis being made."

Dr. Hernandes adds hospitalists have an onus to order the tests because doctors "may be under-diagnosing the primary issue with a patient or over-diagnosing and psychologically scarring them."

Jaxon Hernandes, MD, a hospitalist with Apogee Physicians at Clara Maass Medical Center in Belleville, N.J., believes he and his colleagues are positioned perfectly to help properly diagnose asthma, a timely opinion given new Canadian research suggesting the bronchial condition routinely is over-diagnosed.

The study in the Canadian Medical Association Journal (2008;179(11):1121-1131) found up to 30% of adults diagnosed with asthma had no evidence of the condition. It included 496 people from eight Canadian cities who reported a diagnosis of asthma from their physician. The researchers' goal was to determine whether obese people were more likely to be misdiagnosed with asthma, but researchers found the issue was just as prevalent in people of normal weight.

Henderson notes hospitalists rarely make initial diagnoses when a patient is first encountered in the hospital, but once they are admitted, a hospitalist can order peak-flow-rate and spirometric tests. Clinical guidelines recommend using a spirometer to objectively measure long volume and airway flow.

"The hospitalist is in a position where he can get the pulmonologist to do what he needs to do," Dr. Hernandes says. "He can force a diagnosis being made."

Dr. Hernandes adds hospitalists have an onus to order the tests because doctors "may be under-diagnosing the primary issue with a patient or over-diagnosing and psychologically scarring them."

A small Illinois hospital has joined the ranks of facilities—including its neighbors—in adding a hospital medicine (HM) program. The Genesis Medical Center, Illini Campus, in Silvas, Ill., began providing full-time hospitalist coverage on Dec. 1.

As the influx of hospitalists allowed local primary care physicians to stop making hospital visits, the Illini Campus rushed to fill the gap with its own HM program. "We were the last acute care hospital to implement a hospitalist program," says Chuck Bruhn, CEO of Illini Campus. "It had become a medical community issue."

Illini Campus, located near the Quad Cities on the western Illinois-eastern Iowa border, is a 149-bed facility with an average daily census of 50 to 55 patients. Its sister facility, the Genesis Medical Center in Davenport, Iowa, has had a successful hospital medicine program since 2005. Genesis' agreement with Cogent Healthcare, Inc., recently expanded to manage the program at Illini Campus, with round-the-clock coverage, including one full-time hospitalist.

Just two weeks after implementation, "the hospitalist program is growing much more rapidly than we had anticipated," Bruhn says. "They’re already covering a census of 14 patients a day. We're already talking about adding a physician extender."

Bruhn is pleased with the way the fledgling program has taken root. "We see it as a definite improvement, not only to quality and continuity of care, but to expediency of care. And the hospitalists provide additional support; they provide education to our clinical staff."

A small Illinois hospital has joined the ranks of facilities—including its neighbors—in adding a hospital medicine (HM) program. The Genesis Medical Center, Illini Campus, in Silvas, Ill., began providing full-time hospitalist coverage on Dec. 1.

As the influx of hospitalists allowed local primary care physicians to stop making hospital visits, the Illini Campus rushed to fill the gap with its own HM program. "We were the last acute care hospital to implement a hospitalist program," says Chuck Bruhn, CEO of Illini Campus. "It had become a medical community issue."

Illini Campus, located near the Quad Cities on the western Illinois-eastern Iowa border, is a 149-bed facility with an average daily census of 50 to 55 patients. Its sister facility, the Genesis Medical Center in Davenport, Iowa, has had a successful hospital medicine program since 2005. Genesis' agreement with Cogent Healthcare, Inc., recently expanded to manage the program at Illini Campus, with round-the-clock coverage, including one full-time hospitalist.

Just two weeks after implementation, "the hospitalist program is growing much more rapidly than we had anticipated," Bruhn says. "They’re already covering a census of 14 patients a day. We're already talking about adding a physician extender."

Bruhn is pleased with the way the fledgling program has taken root. "We see it as a definite improvement, not only to quality and continuity of care, but to expediency of care. And the hospitalists provide additional support; they provide education to our clinical staff."

A small Illinois hospital has joined the ranks of facilities—including its neighbors—in adding a hospital medicine (HM) program. The Genesis Medical Center, Illini Campus, in Silvas, Ill., began providing full-time hospitalist coverage on Dec. 1.

As the influx of hospitalists allowed local primary care physicians to stop making hospital visits, the Illini Campus rushed to fill the gap with its own HM program. "We were the last acute care hospital to implement a hospitalist program," says Chuck Bruhn, CEO of Illini Campus. "It had become a medical community issue."

Illini Campus, located near the Quad Cities on the western Illinois-eastern Iowa border, is a 149-bed facility with an average daily census of 50 to 55 patients. Its sister facility, the Genesis Medical Center in Davenport, Iowa, has had a successful hospital medicine program since 2005. Genesis' agreement with Cogent Healthcare, Inc., recently expanded to manage the program at Illini Campus, with round-the-clock coverage, including one full-time hospitalist.

Just two weeks after implementation, "the hospitalist program is growing much more rapidly than we had anticipated," Bruhn says. "They’re already covering a census of 14 patients a day. We're already talking about adding a physician extender."

Bruhn is pleased with the way the fledgling program has taken root. "We see it as a definite improvement, not only to quality and continuity of care, but to expediency of care. And the hospitalists provide additional support; they provide education to our clinical staff."

The recent suspension of a New York City doctor who failed to report a gunshot wound suffered by a football star is an opportunity for hospitalists to revisit their own reporting requirements, the president of SHM's NYC chapter says.

Josyann Abisaab, MD, of New York-Presbyterian Hospital/Weill Cornell Medical Center, was suspended after treating New York Giants wide receiver Plaxico Burress on Nov. 29. Less than a year after catching the winning touchdown pass in the Giants' Super Bowl victory, Burress, who told police he accidentally shot himself in the thigh at a NYC nightclub, has been suspended by the league and charged with criminal possession of a gun.

"I was not aware that something like this needed a report to the police," says Bradley Flansbaum, DO, MPH, chief of hospitalist services at Lenox Hill Hospital in Manhattan and president of SHM’s NYC chapter. "It opened up space in my brain. If I were confronted with this, when would I know when to and when not to call the police?"

Complicating matters is the fact hospitalists may have to report issues to more than just law enforcement; depending on diagnoses and patient histories, doctors may have to notify state and federal health agencies or social service departments. Rules vary by state, so Dr. Flansbaum says hospitalists would do well to brush up on their requirements and liabilities.

"I may not know the rules," Dr. Flansbaum said, "but I certainly would speak to the right people here and ask them: 'What are my obligations? How do I protect myself and the patient?' " He recommends hospitalists verify local requirements with their hospital administration.

The recent suspension of a New York City doctor who failed to report a gunshot wound suffered by a football star is an opportunity for hospitalists to revisit their own reporting requirements, the president of SHM's NYC chapter says.

Josyann Abisaab, MD, of New York-Presbyterian Hospital/Weill Cornell Medical Center, was suspended after treating New York Giants wide receiver Plaxico Burress on Nov. 29. Less than a year after catching the winning touchdown pass in the Giants' Super Bowl victory, Burress, who told police he accidentally shot himself in the thigh at a NYC nightclub, has been suspended by the league and charged with criminal possession of a gun.

"I was not aware that something like this needed a report to the police," says Bradley Flansbaum, DO, MPH, chief of hospitalist services at Lenox Hill Hospital in Manhattan and president of SHM’s NYC chapter. "It opened up space in my brain. If I were confronted with this, when would I know when to and when not to call the police?"

Complicating matters is the fact hospitalists may have to report issues to more than just law enforcement; depending on diagnoses and patient histories, doctors may have to notify state and federal health agencies or social service departments. Rules vary by state, so Dr. Flansbaum says hospitalists would do well to brush up on their requirements and liabilities.

"I may not know the rules," Dr. Flansbaum said, "but I certainly would speak to the right people here and ask them: 'What are my obligations? How do I protect myself and the patient?' " He recommends hospitalists verify local requirements with their hospital administration.

The recent suspension of a New York City doctor who failed to report a gunshot wound suffered by a football star is an opportunity for hospitalists to revisit their own reporting requirements, the president of SHM's NYC chapter says.

Josyann Abisaab, MD, of New York-Presbyterian Hospital/Weill Cornell Medical Center, was suspended after treating New York Giants wide receiver Plaxico Burress on Nov. 29. Less than a year after catching the winning touchdown pass in the Giants' Super Bowl victory, Burress, who told police he accidentally shot himself in the thigh at a NYC nightclub, has been suspended by the league and charged with criminal possession of a gun.

"I was not aware that something like this needed a report to the police," says Bradley Flansbaum, DO, MPH, chief of hospitalist services at Lenox Hill Hospital in Manhattan and president of SHM’s NYC chapter. "It opened up space in my brain. If I were confronted with this, when would I know when to and when not to call the police?"

Complicating matters is the fact hospitalists may have to report issues to more than just law enforcement; depending on diagnoses and patient histories, doctors may have to notify state and federal health agencies or social service departments. Rules vary by state, so Dr. Flansbaum says hospitalists would do well to brush up on their requirements and liabilities.

"I may not know the rules," Dr. Flansbaum said, "but I certainly would speak to the right people here and ask them: 'What are my obligations? How do I protect myself and the patient?' " He recommends hospitalists verify local requirements with their hospital administration.

Question: Is sodium bicarbonate superior to sodium chloride in preventing contrast-induced nephropathy in patients with chronic kidney disease (CKD) undergoing coronary angiography?

Background: Sodium bicarbonate has been suggested as a possible strategy to prevent contrast-induced nephropathy—a condition that can lead to prolonged hospitalization, increased healthcare costs, and substantial morbidity and mortality.

Study design: Randomized, controlled, single-blind study.

Setting: Kaiser Permanente Medical Center, Los Angeles.

Synopsis: Data were collected over 12 months by selecting 353 patients with stable CKD undergoing coronary angiography who were 18 or older and had an estimated glomerular filtration rate (GFR) of 60mL/min/1.73m² or less and one or more of diabetes mellitus, congestive heart failure, hypertension, or age older than 75 years. Patients were randomized to received sodium chloride (n=178) and sodium bicarbonate (n=175) at the same rate and duration.

There was no statistical difference in the primary endpoint (p=0.82), which was a 25% or greater decrease in the GFR on days 1 through 4 after contrast exposure.

Study results were limited by several factors; most importantly, it was not a double-blinded study and was performed at a single center. Also, the sodium content of the two fluids varied; normal saline carried 154mEq and sodium bicarbonate 130mEq of sodium, respectively.

Bottom line: Hydration with sodium bicarbonate is not superior to sodium chloride in preventing contrast-induced nephropathy in patients with moderate to severe CKD undergoing coronary angiography.

Citation: JAMA. 2008;300(9):1038-1046

—Reviewed for the e-wire by Elbert Chun, MD, John Vazquez, MD, Larry Beer, MD, Maged Doss, MD, Vana Bollineni, MD, Mohammed S. Singapuri, MD, Dan Dressler, MD, MsCR, Emory University Hospital, Atlanta

Question: Is sodium bicarbonate superior to sodium chloride in preventing contrast-induced nephropathy in patients with chronic kidney disease (CKD) undergoing coronary angiography?

Background: Sodium bicarbonate has been suggested as a possible strategy to prevent contrast-induced nephropathy—a condition that can lead to prolonged hospitalization, increased healthcare costs, and substantial morbidity and mortality.

Study design: Randomized, controlled, single-blind study.

Setting: Kaiser Permanente Medical Center, Los Angeles.

Synopsis: Data were collected over 12 months by selecting 353 patients with stable CKD undergoing coronary angiography who were 18 or older and had an estimated glomerular filtration rate (GFR) of 60mL/min/1.73m² or less and one or more of diabetes mellitus, congestive heart failure, hypertension, or age older than 75 years. Patients were randomized to received sodium chloride (n=178) and sodium bicarbonate (n=175) at the same rate and duration.

There was no statistical difference in the primary endpoint (p=0.82), which was a 25% or greater decrease in the GFR on days 1 through 4 after contrast exposure.

Study results were limited by several factors; most importantly, it was not a double-blinded study and was performed at a single center. Also, the sodium content of the two fluids varied; normal saline carried 154mEq and sodium bicarbonate 130mEq of sodium, respectively.

Bottom line: Hydration with sodium bicarbonate is not superior to sodium chloride in preventing contrast-induced nephropathy in patients with moderate to severe CKD undergoing coronary angiography.

Citation: JAMA. 2008;300(9):1038-1046

—Reviewed for the e-wire by Elbert Chun, MD, John Vazquez, MD, Larry Beer, MD, Maged Doss, MD, Vana Bollineni, MD, Mohammed S. Singapuri, MD, Dan Dressler, MD, MsCR, Emory University Hospital, Atlanta

Question: Is sodium bicarbonate superior to sodium chloride in preventing contrast-induced nephropathy in patients with chronic kidney disease (CKD) undergoing coronary angiography?

Background: Sodium bicarbonate has been suggested as a possible strategy to prevent contrast-induced nephropathy—a condition that can lead to prolonged hospitalization, increased healthcare costs, and substantial morbidity and mortality.

Study design: Randomized, controlled, single-blind study.

Setting: Kaiser Permanente Medical Center, Los Angeles.

Synopsis: Data were collected over 12 months by selecting 353 patients with stable CKD undergoing coronary angiography who were 18 or older and had an estimated glomerular filtration rate (GFR) of 60mL/min/1.73m² or less and one or more of diabetes mellitus, congestive heart failure, hypertension, or age older than 75 years. Patients were randomized to received sodium chloride (n=178) and sodium bicarbonate (n=175) at the same rate and duration.

There was no statistical difference in the primary endpoint (p=0.82), which was a 25% or greater decrease in the GFR on days 1 through 4 after contrast exposure.

Study results were limited by several factors; most importantly, it was not a double-blinded study and was performed at a single center. Also, the sodium content of the two fluids varied; normal saline carried 154mEq and sodium bicarbonate 130mEq of sodium, respectively.

Bottom line: Hydration with sodium bicarbonate is not superior to sodium chloride in preventing contrast-induced nephropathy in patients with moderate to severe CKD undergoing coronary angiography.

Citation: JAMA. 2008;300(9):1038-1046

—Reviewed for the e-wire by Elbert Chun, MD, John Vazquez, MD, Larry Beer, MD, Maged Doss, MD, Vana Bollineni, MD, Mohammed S. Singapuri, MD, Dan Dressler, MD, MsCR, Emory University Hospital, Atlanta

Imatinib tablet

SAN FRANCISCO—The longest duration study of imatinib treatment for patients with Ph+ CML shows 86% of patients are still alive 7 years after beginning therapy.

The International Randomized Interferon versus STI571 (IRIS) study revealed only 1 early chronic-phase patient progressed to a more advanced phase between years 6 and 7, Stephen O’Brien, MD, PhD, of Newcastle University in the UK, said at the 50th Annual Meeting of the American Society of Hematology.

IRIS is an open-label, phase 3 clinical trial enrolling 1106 newly diagnosed patients with chronic phase Ph+ CML in 177 centers across 16 countries. One group of 553 patients received imatinib 400 mg per day. Another group of 553 patients received a target dose of interferon (IFN) of 5 MIU/m²/day in combination with cytarabine at 20 mg/m²/day for 10 days each month.

Because of tolerability issues, lack of response, or loss of response, 65% of patients in the IFN/cytarabine arm crossed over to the imatinib arm. Only 3% of patients in the imatinib arm crossed over to the IFN/cytarabine arm.

A low rate of progression has been reported every year since this trial began in 2001. Seven percent of patients treated with imatinib progressed to advanced phases of CML after 7 years. Of the 456 patients (82%) who achieved a complete cytogenetic response, 17% lost their response and 3% progressed to advanced phases. 

“After 1 year of treatment, there is a small risk of progression,” Dr O’Brien said. “If patients achieve and maintain a complete cytogenetic response after 3 years, they are fairly safe.”

Treatment with imatinib in the IRIS study was well tolerated, he said. No new serious adverse events occurred between the sixth and seventh year of treatment.

The results from the IRIS study also reveal that, by year 6, 85% to 90% of patients still taking imatinib achieved a major molecular response. This key milestone indicates a reduction in the abnormal protein responsible for the uncontrolled production of abnormal white blood cells and may be a sensitive predictor of long-term progression-free survival.

“There was a steady improvement in major molecular responses between 4 and 7 years of treatment,” said Timothy Hughes, MD, of the Institute of Medical and Veterinary Science in Adelaide, Australia. “By 7 years, the vast majority of patients who achieved a complete cytogenetic response also achieved a major molecular response.”

A major molecular response at any time point represents a “safe haven” for patients, Dr Hughes said. Both molecular and cytogenetic evaluations should be used to guide treatment decisions until a complete cytogenetic response is achieved, followed by measurements of molecular assessments.

“In this, the seventh year of the IRIS study, CML patients treated with imatinib continue to demonstrate impressive long-term survival,” Dr O’Brien said. “Imatinib 400 mg daily is confirmed as the standard of care for the initial therapy of chronic-phase CML.”

Imatinib, the first therapy to inhibit the activity of Bcr-Abl, revolutionized the treatment of Ph+ CML, Dr O’Brien said. Prior to imatinib, about 50% of patients with Ph+ CML progressed from the initial phase to more advanced stages after 3 to 5 years. Once patients reached the final blast crisis phase, survival was generally 3 to 6 months.

Imatinib tablet

SAN FRANCISCO—The longest duration study of imatinib treatment for patients with Ph+ CML shows 86% of patients are still alive 7 years after beginning therapy.

The International Randomized Interferon versus STI571 (IRIS) study revealed only 1 early chronic-phase patient progressed to a more advanced phase between years 6 and 7, Stephen O’Brien, MD, PhD, of Newcastle University in the UK, said at the 50th Annual Meeting of the American Society of Hematology.

IRIS is an open-label, phase 3 clinical trial enrolling 1106 newly diagnosed patients with chronic phase Ph+ CML in 177 centers across 16 countries. One group of 553 patients received imatinib 400 mg per day. Another group of 553 patients received a target dose of interferon (IFN) of 5 MIU/m²/day in combination with cytarabine at 20 mg/m²/day for 10 days each month.

Because of tolerability issues, lack of response, or loss of response, 65% of patients in the IFN/cytarabine arm crossed over to the imatinib arm. Only 3% of patients in the imatinib arm crossed over to the IFN/cytarabine arm.

A low rate of progression has been reported every year since this trial began in 2001. Seven percent of patients treated with imatinib progressed to advanced phases of CML after 7 years. Of the 456 patients (82%) who achieved a complete cytogenetic response, 17% lost their response and 3% progressed to advanced phases. 

“After 1 year of treatment, there is a small risk of progression,” Dr O’Brien said. “If patients achieve and maintain a complete cytogenetic response after 3 years, they are fairly safe.”

Treatment with imatinib in the IRIS study was well tolerated, he said. No new serious adverse events occurred between the sixth and seventh year of treatment.

The results from the IRIS study also reveal that, by year 6, 85% to 90% of patients still taking imatinib achieved a major molecular response. This key milestone indicates a reduction in the abnormal protein responsible for the uncontrolled production of abnormal white blood cells and may be a sensitive predictor of long-term progression-free survival.

“There was a steady improvement in major molecular responses between 4 and 7 years of treatment,” said Timothy Hughes, MD, of the Institute of Medical and Veterinary Science in Adelaide, Australia. “By 7 years, the vast majority of patients who achieved a complete cytogenetic response also achieved a major molecular response.”

A major molecular response at any time point represents a “safe haven” for patients, Dr Hughes said. Both molecular and cytogenetic evaluations should be used to guide treatment decisions until a complete cytogenetic response is achieved, followed by measurements of molecular assessments.

“In this, the seventh year of the IRIS study, CML patients treated with imatinib continue to demonstrate impressive long-term survival,” Dr O’Brien said. “Imatinib 400 mg daily is confirmed as the standard of care for the initial therapy of chronic-phase CML.”

Imatinib, the first therapy to inhibit the activity of Bcr-Abl, revolutionized the treatment of Ph+ CML, Dr O’Brien said. Prior to imatinib, about 50% of patients with Ph+ CML progressed from the initial phase to more advanced stages after 3 to 5 years. Once patients reached the final blast crisis phase, survival was generally 3 to 6 months.

Imatinib tablet

SAN FRANCISCO—The longest duration study of imatinib treatment for patients with Ph+ CML shows 86% of patients are still alive 7 years after beginning therapy.

The International Randomized Interferon versus STI571 (IRIS) study revealed only 1 early chronic-phase patient progressed to a more advanced phase between years 6 and 7, Stephen O’Brien, MD, PhD, of Newcastle University in the UK, said at the 50th Annual Meeting of the American Society of Hematology.

IRIS is an open-label, phase 3 clinical trial enrolling 1106 newly diagnosed patients with chronic phase Ph+ CML in 177 centers across 16 countries. One group of 553 patients received imatinib 400 mg per day. Another group of 553 patients received a target dose of interferon (IFN) of 5 MIU/m²/day in combination with cytarabine at 20 mg/m²/day for 10 days each month.

Because of tolerability issues, lack of response, or loss of response, 65% of patients in the IFN/cytarabine arm crossed over to the imatinib arm. Only 3% of patients in the imatinib arm crossed over to the IFN/cytarabine arm.

A low rate of progression has been reported every year since this trial began in 2001. Seven percent of patients treated with imatinib progressed to advanced phases of CML after 7 years. Of the 456 patients (82%) who achieved a complete cytogenetic response, 17% lost their response and 3% progressed to advanced phases. 

“After 1 year of treatment, there is a small risk of progression,” Dr O’Brien said. “If patients achieve and maintain a complete cytogenetic response after 3 years, they are fairly safe.”

Treatment with imatinib in the IRIS study was well tolerated, he said. No new serious adverse events occurred between the sixth and seventh year of treatment.

The results from the IRIS study also reveal that, by year 6, 85% to 90% of patients still taking imatinib achieved a major molecular response. This key milestone indicates a reduction in the abnormal protein responsible for the uncontrolled production of abnormal white blood cells and may be a sensitive predictor of long-term progression-free survival.

“There was a steady improvement in major molecular responses between 4 and 7 years of treatment,” said Timothy Hughes, MD, of the Institute of Medical and Veterinary Science in Adelaide, Australia. “By 7 years, the vast majority of patients who achieved a complete cytogenetic response also achieved a major molecular response.”

A major molecular response at any time point represents a “safe haven” for patients, Dr Hughes said. Both molecular and cytogenetic evaluations should be used to guide treatment decisions until a complete cytogenetic response is achieved, followed by measurements of molecular assessments.

“In this, the seventh year of the IRIS study, CML patients treated with imatinib continue to demonstrate impressive long-term survival,” Dr O’Brien said. “Imatinib 400 mg daily is confirmed as the standard of care for the initial therapy of chronic-phase CML.”

Imatinib, the first therapy to inhibit the activity of Bcr-Abl, revolutionized the treatment of Ph+ CML, Dr O’Brien said. Prior to imatinib, about 50% of patients with Ph+ CML progressed from the initial phase to more advanced stages after 3 to 5 years. Once patients reached the final blast crisis phase, survival was generally 3 to 6 months.

San Francisco—Researchers confirmed the safety and efficacy of a lower dose of dabigatran etexilate in elderly hip and total knee replacement surgery patients.

Dabigatran is a new oral thrombin inhibitor recently approved in Europe for the prevention of VTE in patients undergoing this surgery. Ola E. Dahl, MD, of the Thrombosis Research Institute in London, reported the results of a post hoc pooled analysis of 2 pivotal trials comparing dabigatran with enoxaparin at the 50th Annual Meeting of the American Society of Hematology.

Dr Dahl and colleagues analyzed 883 patients older than 75 years who were enrolled in the RE-MODEL and RE-NOVATE trials. Researchers evaluated 220 mg and 150 mg once-daily doses of dabigatran compared to a 40 mg daily dose of enoxaparin.

The primary efficacy endpoint was total number of VTEs and all-cause mortality. Both doses of dabigatran reduced total VTEs compared to enoxaparin, though not significantly.

However, the higher dose of dabigatran produced a significant difference in the secondary endpoint, major VTEs and VTE-related mortality. Four of 216 patients (1.9%) receiving the 220 mg dose had a major VTE, compared with 13 of 218 patients receiving enoxaparin (P=0.045).

The safety endpoint was the difference in major bleeding events, including surgical site bleeding, which accounts for up to 90% of bleeding in these patients. Major bleeding events occurred in 3.7% of the patients receiving dabigatran at 220 mg and 1.4% receiving 150 mg, compared to 2.9% in the enoxaparin group. The study was not powered to show significance in the safety endpoint.

“If you look into the dabigatran regimens versus enoxaparin, you see that we have more efficacious 200 mg dosing with slightly increased bleeding,” Dr Dahl said. “The 150 mg dose has the same efficacy level, but with a little less bleeding. And that is exactly the profile we are looking for in the elderly.”

San Francisco—Researchers confirmed the safety and efficacy of a lower dose of dabigatran etexilate in elderly hip and total knee replacement surgery patients.

Dabigatran is a new oral thrombin inhibitor recently approved in Europe for the prevention of VTE in patients undergoing this surgery. Ola E. Dahl, MD, of the Thrombosis Research Institute in London, reported the results of a post hoc pooled analysis of 2 pivotal trials comparing dabigatran with enoxaparin at the 50th Annual Meeting of the American Society of Hematology.

Dr Dahl and colleagues analyzed 883 patients older than 75 years who were enrolled in the RE-MODEL and RE-NOVATE trials. Researchers evaluated 220 mg and 150 mg once-daily doses of dabigatran compared to a 40 mg daily dose of enoxaparin.

The primary efficacy endpoint was total number of VTEs and all-cause mortality. Both doses of dabigatran reduced total VTEs compared to enoxaparin, though not significantly.

However, the higher dose of dabigatran produced a significant difference in the secondary endpoint, major VTEs and VTE-related mortality. Four of 216 patients (1.9%) receiving the 220 mg dose had a major VTE, compared with 13 of 218 patients receiving enoxaparin (P=0.045).

The safety endpoint was the difference in major bleeding events, including surgical site bleeding, which accounts for up to 90% of bleeding in these patients. Major bleeding events occurred in 3.7% of the patients receiving dabigatran at 220 mg and 1.4% receiving 150 mg, compared to 2.9% in the enoxaparin group. The study was not powered to show significance in the safety endpoint.

“If you look into the dabigatran regimens versus enoxaparin, you see that we have more efficacious 200 mg dosing with slightly increased bleeding,” Dr Dahl said. “The 150 mg dose has the same efficacy level, but with a little less bleeding. And that is exactly the profile we are looking for in the elderly.”

San Francisco—Researchers confirmed the safety and efficacy of a lower dose of dabigatran etexilate in elderly hip and total knee replacement surgery patients.

Dabigatran is a new oral thrombin inhibitor recently approved in Europe for the prevention of VTE in patients undergoing this surgery. Ola E. Dahl, MD, of the Thrombosis Research Institute in London, reported the results of a post hoc pooled analysis of 2 pivotal trials comparing dabigatran with enoxaparin at the 50th Annual Meeting of the American Society of Hematology.

Dr Dahl and colleagues analyzed 883 patients older than 75 years who were enrolled in the RE-MODEL and RE-NOVATE trials. Researchers evaluated 220 mg and 150 mg once-daily doses of dabigatran compared to a 40 mg daily dose of enoxaparin.

The primary efficacy endpoint was total number of VTEs and all-cause mortality. Both doses of dabigatran reduced total VTEs compared to enoxaparin, though not significantly.

However, the higher dose of dabigatran produced a significant difference in the secondary endpoint, major VTEs and VTE-related mortality. Four of 216 patients (1.9%) receiving the 220 mg dose had a major VTE, compared with 13 of 218 patients receiving enoxaparin (P=0.045).

The safety endpoint was the difference in major bleeding events, including surgical site bleeding, which accounts for up to 90% of bleeding in these patients. Major bleeding events occurred in 3.7% of the patients receiving dabigatran at 220 mg and 1.4% receiving 150 mg, compared to 2.9% in the enoxaparin group. The study was not powered to show significance in the safety endpoint.

“If you look into the dabigatran regimens versus enoxaparin, you see that we have more efficacious 200 mg dosing with slightly increased bleeding,” Dr Dahl said. “The 150 mg dose has the same efficacy level, but with a little less bleeding. And that is exactly the profile we are looking for in the elderly.”