NEW ORLEANS — Thrombolysis was safe and effective for treating acute ischemic stroke in patients who recently underwent cardiac catheterization in a review of 48 cases.

Many physicians have been reluctant to use thrombolysis in such patients because of the erroneous presumptions that the intracranial thrombus would not be dissolved by treatment and that postcatheterization patients are especially vulnerable to intracranial hemorrhage. But these concerns were not borne out by this case review, Pooja Khatri, M.D., said while presenting a poster at the 30th International Stroke Conference.

“This is a great population of patients to treat,” said Dr. Khatri, a neurologist at the University of Cincinnati.

Because these patients are still hospitalized when their strokes occur, they can be quickly diagnosed and treated, she explained.

Dr. Khatri and her associates collected case information on 48 consecutive, eligible patients who were treated at several U.S. academic centers since 2001. All patients had an ischemic stroke within 36 hours of cardiac catheterization. Of them, 10 were treated with tissue plasminogen activator (TPA), and the other 38 received only supportive care.

The median National Institutes of Health Stroke Scale (NIHSS) score at the time of diagnosis was 12 in the patients treated with TPA and 6 in those who did not receive thrombolytic therapy. The study's primary outcome was the median improvement in the NIHSS score at 24 hours after initial diagnosis. The median improvement in NIHSS score was 6 points in the patients who got TPA, compared with 0 points in those who did not, a statistically significant difference, reported Dr. Khatri at the conference, which was sponsored by the American Stroke Association.

By 7 days after diagnosis, scores had improved by a median of 6.5 points in those who got TPA and by a median of 2 points in those who did not, also a statistically significant difference.

Substantially better improvement was seen in patients treated with TPA even when the analysis excluded patients with mild strokes, defined as a NIHSS score of 5 or lower at the time of diagnosis. “This will hopefully lead to a substantial change in patient treatment,” she told CARDIOLOGY NEWS.

None of the 48 patients in the study had a symptomatic, intracranial hemorrhage. Six patients had minor, asymptomatic, intracranial hemorrhages, three in the group that received TPA and three in the group that did not get thrombolysis. A total of five patients had minor bleeding at their catheterization puncture sites; one of these patients had received TPA.

None of the patients in either group required a transfusion. No patient had a retroperitoneal hemorrhage, hemopericardium, or other sites of bleeding, Dr. Khatri said.

NEW ORLEANS — Thrombolysis was safe and effective for treating acute ischemic stroke in patients who recently underwent cardiac catheterization in a review of 48 cases.

Many physicians have been reluctant to use thrombolysis in such patients because of the erroneous presumptions that the intracranial thrombus would not be dissolved by treatment and that postcatheterization patients are especially vulnerable to intracranial hemorrhage. But these concerns were not borne out by this case review, Pooja Khatri, M.D., said while presenting a poster at the 30th International Stroke Conference.

“This is a great population of patients to treat,” said Dr. Khatri, a neurologist at the University of Cincinnati.

Because these patients are still hospitalized when their strokes occur, they can be quickly diagnosed and treated, she explained.

Dr. Khatri and her associates collected case information on 48 consecutive, eligible patients who were treated at several U.S. academic centers since 2001. All patients had an ischemic stroke within 36 hours of cardiac catheterization. Of them, 10 were treated with tissue plasminogen activator (TPA), and the other 38 received only supportive care.

The median National Institutes of Health Stroke Scale (NIHSS) score at the time of diagnosis was 12 in the patients treated with TPA and 6 in those who did not receive thrombolytic therapy. The study's primary outcome was the median improvement in the NIHSS score at 24 hours after initial diagnosis. The median improvement in NIHSS score was 6 points in the patients who got TPA, compared with 0 points in those who did not, a statistically significant difference, reported Dr. Khatri at the conference, which was sponsored by the American Stroke Association.

By 7 days after diagnosis, scores had improved by a median of 6.5 points in those who got TPA and by a median of 2 points in those who did not, also a statistically significant difference.

Substantially better improvement was seen in patients treated with TPA even when the analysis excluded patients with mild strokes, defined as a NIHSS score of 5 or lower at the time of diagnosis. “This will hopefully lead to a substantial change in patient treatment,” she told CARDIOLOGY NEWS.

None of the 48 patients in the study had a symptomatic, intracranial hemorrhage. Six patients had minor, asymptomatic, intracranial hemorrhages, three in the group that received TPA and three in the group that did not get thrombolysis. A total of five patients had minor bleeding at their catheterization puncture sites; one of these patients had received TPA.

None of the patients in either group required a transfusion. No patient had a retroperitoneal hemorrhage, hemopericardium, or other sites of bleeding, Dr. Khatri said.

NEW ORLEANS — Thrombolysis was safe and effective for treating acute ischemic stroke in patients who recently underwent cardiac catheterization in a review of 48 cases.

Many physicians have been reluctant to use thrombolysis in such patients because of the erroneous presumptions that the intracranial thrombus would not be dissolved by treatment and that postcatheterization patients are especially vulnerable to intracranial hemorrhage. But these concerns were not borne out by this case review, Pooja Khatri, M.D., said while presenting a poster at the 30th International Stroke Conference.

“This is a great population of patients to treat,” said Dr. Khatri, a neurologist at the University of Cincinnati.

Because these patients are still hospitalized when their strokes occur, they can be quickly diagnosed and treated, she explained.

Dr. Khatri and her associates collected case information on 48 consecutive, eligible patients who were treated at several U.S. academic centers since 2001. All patients had an ischemic stroke within 36 hours of cardiac catheterization. Of them, 10 were treated with tissue plasminogen activator (TPA), and the other 38 received only supportive care.

The median National Institutes of Health Stroke Scale (NIHSS) score at the time of diagnosis was 12 in the patients treated with TPA and 6 in those who did not receive thrombolytic therapy. The study's primary outcome was the median improvement in the NIHSS score at 24 hours after initial diagnosis. The median improvement in NIHSS score was 6 points in the patients who got TPA, compared with 0 points in those who did not, a statistically significant difference, reported Dr. Khatri at the conference, which was sponsored by the American Stroke Association.

By 7 days after diagnosis, scores had improved by a median of 6.5 points in those who got TPA and by a median of 2 points in those who did not, also a statistically significant difference.

Substantially better improvement was seen in patients treated with TPA even when the analysis excluded patients with mild strokes, defined as a NIHSS score of 5 or lower at the time of diagnosis. “This will hopefully lead to a substantial change in patient treatment,” she told CARDIOLOGY NEWS.

None of the 48 patients in the study had a symptomatic, intracranial hemorrhage. Six patients had minor, asymptomatic, intracranial hemorrhages, three in the group that received TPA and three in the group that did not get thrombolysis. A total of five patients had minor bleeding at their catheterization puncture sites; one of these patients had received TPA.

None of the patients in either group required a transfusion. No patient had a retroperitoneal hemorrhage, hemopericardium, or other sites of bleeding, Dr. Khatri said.

Patients with systemic lupus erythematosus who are under the age of 50 have a high rate of fragility fractures, osteoporosis, and poor bone mineral density, according to new research.

And as expected, steroid use was found to be significantly linked to reduced bone mineral density (BMD), reported C-S Yee of the University of Birmingham and colleagues (Ann. Rheum. Dis. 2005;64:111–113).

Although bisphosphonates are the only class of drugs that have shown efficacy in the treatment and prevention of corticosteroid-induced osteoporosis, their use in premenopausal women poses serious risks of birth defects in the event of an unplanned pregnancy, noted the authors.

The investigation included 242 participants with systemic lupus erythematosus (SLE), 231 (95%) of whom were female.

Study participants were asked to complete a questionnaire about risk factors for osteoporosis, including details about previous fractures and family history of fractures. There were also asked about drug use and in particular about the use of glucocorticoids, oral contraceptives, hormone therapy, calcium and vitamin D supplementation, and bisphosphonates.

Bone mineral densitometry screening was also performed.

Among the women, 126 (54%) were premenopausal, 39 (17%) had experienced premature menopause, and 64 (28%) had experienced normal menopause. The menopausal status of two patients was unknown because they did not fully complete the questionnaire.

A total of 123 patients (51%) had reduced BMD (T score less than −1.0), and 25 were in the osteoporotic range (T score less than −2.5).

Ten of the patients with reduced BMD and 3 in the osteoporotic range were taking bisphosphonates at the time of the scan.

There were 22 patients (9%) who had experienced fragility fractures since their diagnosis of SLE, all of whom were female. Of these, 2 (9%) had normal BMD, while the other 20 (91%) had reduced BMD, with 7 of these women were in the osteoporotic range.

Most of the patients with fragility fractures (82%) were menopausal, and only 3 were taking bisphosphonates at the time of the scan.

Non-Afro-Caribbean race and exposure to prednisolone (more than 10mg/day) were associated with reduced BMD, while age and menopause were associated with osteoporosis, according to the findings of a regression analysis.

Only low BMD and advanced age predicted fractures. Steroid exposure did not predict fracture rates, noted the authors. However, they noted that “it is likely that the effect of steroids on fractures is mediated predominantly by reduction in bone density in susceptible individuals.”

Despite a high prevalence of fractures in this cohort, the authors noted a low prevalence among the premenopausal women (3%).

Because the teratogenic risks of bisphosphonates are most relevant in premenopausal women, “we recommend bisphosphonates only in those premenopausal SLE patients with osteopenia or osteoporosis who require long-term, high-dose steroids. Bisphosphonates with the least evidence of persistence in the skeleton should be used,” they said.

Patients with systemic lupus erythematosus who are under the age of 50 have a high rate of fragility fractures, osteoporosis, and poor bone mineral density, according to new research.

And as expected, steroid use was found to be significantly linked to reduced bone mineral density (BMD), reported C-S Yee of the University of Birmingham and colleagues (Ann. Rheum. Dis. 2005;64:111–113).

Although bisphosphonates are the only class of drugs that have shown efficacy in the treatment and prevention of corticosteroid-induced osteoporosis, their use in premenopausal women poses serious risks of birth defects in the event of an unplanned pregnancy, noted the authors.

The investigation included 242 participants with systemic lupus erythematosus (SLE), 231 (95%) of whom were female.

Study participants were asked to complete a questionnaire about risk factors for osteoporosis, including details about previous fractures and family history of fractures. There were also asked about drug use and in particular about the use of glucocorticoids, oral contraceptives, hormone therapy, calcium and vitamin D supplementation, and bisphosphonates.

Bone mineral densitometry screening was also performed.

Among the women, 126 (54%) were premenopausal, 39 (17%) had experienced premature menopause, and 64 (28%) had experienced normal menopause. The menopausal status of two patients was unknown because they did not fully complete the questionnaire.

A total of 123 patients (51%) had reduced BMD (T score less than −1.0), and 25 were in the osteoporotic range (T score less than −2.5).

Ten of the patients with reduced BMD and 3 in the osteoporotic range were taking bisphosphonates at the time of the scan.

There were 22 patients (9%) who had experienced fragility fractures since their diagnosis of SLE, all of whom were female. Of these, 2 (9%) had normal BMD, while the other 20 (91%) had reduced BMD, with 7 of these women were in the osteoporotic range.

Most of the patients with fragility fractures (82%) were menopausal, and only 3 were taking bisphosphonates at the time of the scan.

Non-Afro-Caribbean race and exposure to prednisolone (more than 10mg/day) were associated with reduced BMD, while age and menopause were associated with osteoporosis, according to the findings of a regression analysis.

Only low BMD and advanced age predicted fractures. Steroid exposure did not predict fracture rates, noted the authors. However, they noted that “it is likely that the effect of steroids on fractures is mediated predominantly by reduction in bone density in susceptible individuals.”

Despite a high prevalence of fractures in this cohort, the authors noted a low prevalence among the premenopausal women (3%).

Because the teratogenic risks of bisphosphonates are most relevant in premenopausal women, “we recommend bisphosphonates only in those premenopausal SLE patients with osteopenia or osteoporosis who require long-term, high-dose steroids. Bisphosphonates with the least evidence of persistence in the skeleton should be used,” they said.

Patients with systemic lupus erythematosus who are under the age of 50 have a high rate of fragility fractures, osteoporosis, and poor bone mineral density, according to new research.

And as expected, steroid use was found to be significantly linked to reduced bone mineral density (BMD), reported C-S Yee of the University of Birmingham and colleagues (Ann. Rheum. Dis. 2005;64:111–113).

Although bisphosphonates are the only class of drugs that have shown efficacy in the treatment and prevention of corticosteroid-induced osteoporosis, their use in premenopausal women poses serious risks of birth defects in the event of an unplanned pregnancy, noted the authors.

The investigation included 242 participants with systemic lupus erythematosus (SLE), 231 (95%) of whom were female.

Study participants were asked to complete a questionnaire about risk factors for osteoporosis, including details about previous fractures and family history of fractures. There were also asked about drug use and in particular about the use of glucocorticoids, oral contraceptives, hormone therapy, calcium and vitamin D supplementation, and bisphosphonates.

Bone mineral densitometry screening was also performed.

Among the women, 126 (54%) were premenopausal, 39 (17%) had experienced premature menopause, and 64 (28%) had experienced normal menopause. The menopausal status of two patients was unknown because they did not fully complete the questionnaire.

A total of 123 patients (51%) had reduced BMD (T score less than −1.0), and 25 were in the osteoporotic range (T score less than −2.5).

Ten of the patients with reduced BMD and 3 in the osteoporotic range were taking bisphosphonates at the time of the scan.

There were 22 patients (9%) who had experienced fragility fractures since their diagnosis of SLE, all of whom were female. Of these, 2 (9%) had normal BMD, while the other 20 (91%) had reduced BMD, with 7 of these women were in the osteoporotic range.

Most of the patients with fragility fractures (82%) were menopausal, and only 3 were taking bisphosphonates at the time of the scan.

Non-Afro-Caribbean race and exposure to prednisolone (more than 10mg/day) were associated with reduced BMD, while age and menopause were associated with osteoporosis, according to the findings of a regression analysis.

Only low BMD and advanced age predicted fractures. Steroid exposure did not predict fracture rates, noted the authors. However, they noted that “it is likely that the effect of steroids on fractures is mediated predominantly by reduction in bone density in susceptible individuals.”

Despite a high prevalence of fractures in this cohort, the authors noted a low prevalence among the premenopausal women (3%).

Because the teratogenic risks of bisphosphonates are most relevant in premenopausal women, “we recommend bisphosphonates only in those premenopausal SLE patients with osteopenia or osteoporosis who require long-term, high-dose steroids. Bisphosphonates with the least evidence of persistence in the skeleton should be used,” they said.

The Food and Drug administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. The randomized clinical trial leading to approval enrolled 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6–9 inhalations per day) was 19% vs. 4% for the placebo group. The rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost comes in single-use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Iloprost should not be inhaled more than once every 2 hours and is not effective in sleeping patients. Vital signs should be monitored when starting iloprost because of the risk of syncope.

Iloprost, not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, the drug's marketer in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA, in August 2004.

The Food and Drug administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. The randomized clinical trial leading to approval enrolled 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6–9 inhalations per day) was 19% vs. 4% for the placebo group. The rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost comes in single-use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Iloprost should not be inhaled more than once every 2 hours and is not effective in sleeping patients. Vital signs should be monitored when starting iloprost because of the risk of syncope.

Iloprost, not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, the drug's marketer in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA, in August 2004.

The Food and Drug administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. The randomized clinical trial leading to approval enrolled 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6–9 inhalations per day) was 19% vs. 4% for the placebo group. The rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost comes in single-use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Iloprost should not be inhaled more than once every 2 hours and is not effective in sleeping patients. Vital signs should be monitored when starting iloprost because of the risk of syncope.

Iloprost, not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, the drug's marketer in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA, in August 2004.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of hydroxychloroquine, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus.

Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy. In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

No unusual side effects occurred in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of hydroxychloroquine, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus.

Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy. In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

No unusual side effects occurred in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of hydroxychloroquine, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus.

Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy. In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

No unusual side effects occurred in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children.

SAN ANTONIO — The use of high-dose pulsed intravenous glucocorticoid infusions may provide a means of effectively inducing remission in patients with giant cell arteritis, Mehrdad Mazlumzadeh, M.D., said at the annual meeting of the American College of Rheumatology.

First-line treatment for this condition, in which the arteries of the head and neck become inflamed, is with oral prednisone. This approach leads to rapid suppression of the inflammatory processes and resulting symptoms, which can include headache, fatigue, and even blindness. Inflammatory infiltrates persist in the temporal arteries, however, and many patients relapse.

And because extended courses of oral therapy typically are needed, patients are at risk for the many adverse effects associated with long-term steroid exposure, said Dr. Mazlumzadeh, a rheumatologist at the Mayo Clinic, Rochester, Minn.

In a study that included 27 patients with biopsy-proven giant cell arteritis, all participants received oral prednisone in a dose of 40 mg/day. They also were randomized to receive either pulse IV methylprednisolone, 15 mg/kg per day for 3 days, or intravenous saline.

The goal was to determine if high-dose pulse methylprednisolone as the initial treatment of giant cell arteritis would allow for more rapid tapering of oral prednisone without increasing the number of relapses. The primary outcome was reduction in the oral prednisone dose to no more than 5 mg/day after 34 weeks of therapy. “The results were impressive,” Dr. Mazlumzadeh said.

Of the 14 patients in the intravenous treatment group, 10 achieved the primary outcome vs. 2 of 13 in the control group—71% vs. 15%, a statistically significant difference.

Remission was defined as being off prednisone altogether with no recurrences for at least 2 months. Six of the active treatment patients were in remission at 18 months. None of the control patients achieved remission, he said.

There were 21 disease flares in the active treatment group and 34 in the control group. The rate of relapses per 100 person-months of treatment in the control group was 14.5, compared with 8.3 in the active treatment group.

The median cumulative dose of prednisone in the active treatment group was 4,853 mg, compared with 7,215 mg in the control group.

There were no differences between the groups in terms of the development of steroid-associated complications including osteoporosis, hypertension, hyperlipidemia, and diabetes.

No life-threatening disease-associated complications or vision loss occurred. One patient in the intravenous treatment group developed pyelonephritis 11 days after starting therapy.

SAN ANTONIO — The use of high-dose pulsed intravenous glucocorticoid infusions may provide a means of effectively inducing remission in patients with giant cell arteritis, Mehrdad Mazlumzadeh, M.D., said at the annual meeting of the American College of Rheumatology.

First-line treatment for this condition, in which the arteries of the head and neck become inflamed, is with oral prednisone. This approach leads to rapid suppression of the inflammatory processes and resulting symptoms, which can include headache, fatigue, and even blindness. Inflammatory infiltrates persist in the temporal arteries, however, and many patients relapse.

And because extended courses of oral therapy typically are needed, patients are at risk for the many adverse effects associated with long-term steroid exposure, said Dr. Mazlumzadeh, a rheumatologist at the Mayo Clinic, Rochester, Minn.

In a study that included 27 patients with biopsy-proven giant cell arteritis, all participants received oral prednisone in a dose of 40 mg/day. They also were randomized to receive either pulse IV methylprednisolone, 15 mg/kg per day for 3 days, or intravenous saline.

The goal was to determine if high-dose pulse methylprednisolone as the initial treatment of giant cell arteritis would allow for more rapid tapering of oral prednisone without increasing the number of relapses. The primary outcome was reduction in the oral prednisone dose to no more than 5 mg/day after 34 weeks of therapy. “The results were impressive,” Dr. Mazlumzadeh said.

Of the 14 patients in the intravenous treatment group, 10 achieved the primary outcome vs. 2 of 13 in the control group—71% vs. 15%, a statistically significant difference.

Remission was defined as being off prednisone altogether with no recurrences for at least 2 months. Six of the active treatment patients were in remission at 18 months. None of the control patients achieved remission, he said.

There were 21 disease flares in the active treatment group and 34 in the control group. The rate of relapses per 100 person-months of treatment in the control group was 14.5, compared with 8.3 in the active treatment group.

The median cumulative dose of prednisone in the active treatment group was 4,853 mg, compared with 7,215 mg in the control group.

There were no differences between the groups in terms of the development of steroid-associated complications including osteoporosis, hypertension, hyperlipidemia, and diabetes.

No life-threatening disease-associated complications or vision loss occurred. One patient in the intravenous treatment group developed pyelonephritis 11 days after starting therapy.

SAN ANTONIO — The use of high-dose pulsed intravenous glucocorticoid infusions may provide a means of effectively inducing remission in patients with giant cell arteritis, Mehrdad Mazlumzadeh, M.D., said at the annual meeting of the American College of Rheumatology.

First-line treatment for this condition, in which the arteries of the head and neck become inflamed, is with oral prednisone. This approach leads to rapid suppression of the inflammatory processes and resulting symptoms, which can include headache, fatigue, and even blindness. Inflammatory infiltrates persist in the temporal arteries, however, and many patients relapse.

And because extended courses of oral therapy typically are needed, patients are at risk for the many adverse effects associated with long-term steroid exposure, said Dr. Mazlumzadeh, a rheumatologist at the Mayo Clinic, Rochester, Minn.

In a study that included 27 patients with biopsy-proven giant cell arteritis, all participants received oral prednisone in a dose of 40 mg/day. They also were randomized to receive either pulse IV methylprednisolone, 15 mg/kg per day for 3 days, or intravenous saline.

The goal was to determine if high-dose pulse methylprednisolone as the initial treatment of giant cell arteritis would allow for more rapid tapering of oral prednisone without increasing the number of relapses. The primary outcome was reduction in the oral prednisone dose to no more than 5 mg/day after 34 weeks of therapy. “The results were impressive,” Dr. Mazlumzadeh said.

Of the 14 patients in the intravenous treatment group, 10 achieved the primary outcome vs. 2 of 13 in the control group—71% vs. 15%, a statistically significant difference.

Remission was defined as being off prednisone altogether with no recurrences for at least 2 months. Six of the active treatment patients were in remission at 18 months. None of the control patients achieved remission, he said.

There were 21 disease flares in the active treatment group and 34 in the control group. The rate of relapses per 100 person-months of treatment in the control group was 14.5, compared with 8.3 in the active treatment group.

The median cumulative dose of prednisone in the active treatment group was 4,853 mg, compared with 7,215 mg in the control group.

There were no differences between the groups in terms of the development of steroid-associated complications including osteoporosis, hypertension, hyperlipidemia, and diabetes.

No life-threatening disease-associated complications or vision loss occurred. One patient in the intravenous treatment group developed pyelonephritis 11 days after starting therapy.

SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.

In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.

Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.

Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.

To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m

All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.

Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).

Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.

Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.

Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.

Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.

But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.

“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.

For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.

On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.

This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.

Only three cases of serum sickness after rituximab treatment have been reported previously, he said.

SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.

In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.

Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.

Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.

To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m

All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.

Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).

Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.

Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.

Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.

Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.

But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.

“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.

For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.

On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.

This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.

Only three cases of serum sickness after rituximab treatment have been reported previously, he said.

SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.

In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.

Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.

Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.

To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m

All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.

Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).

Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.

Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.

Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.

Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.

But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.

“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.

For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.

On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.

This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.

Only three cases of serum sickness after rituximab treatment have been reported previously, he said.

NEW ORLEANS — More than a third of the drug‐eluting stents placed in the first 9 months following marketing approval of the Cypher stent were for off‐label indications, according to data from the American College of Cardiology‐National Cardiovascular Data Registry.

The use of drug‐eluting stents rose rapidly during this period, and growth in the off‐label uses kept pace with the increase for the approved indication, Sunil V. Rao, M.D., said at the annual scientific sessions of the American Heart Association.

Dr. Rao presented a unique picture of the clinical adoption of a major new medical technology as reflected in a large national registry experience. The American College of Cardiology‐National Cardiovascular Data Registry (ACC‐NCDR) is an ACC‐initiated quality improvement project that to date includes more than 2 million admissions and 800,000 percutaneous coronary interventions (PCIs) at 528 participating U.S. sites.

The registry data are reassuring in that off‐label use of drug‐eluting stents (DESs) appeared to be safe, at least in terms of the very low associated periprocedural adverse event rate, said Dr. Rao of the Duke Clinical Research Institute, Durham, N.C. “However, long‐term safety and efficacy of drug‐eluting stent use in off‐label situations really should be evaluated in appropriately powered, randomized controlled trials,” he said.

For purposes of his study, Dr. Rao focused on PCIs involving only the Cypher stent, the first DES to reach the U.S. market between the device's April 2003 approval through the end of that year. PCIs involving placement of both a Cypher stent and one or more bare metal stents were excluded from consideration. Cypher‐only procedures comprised 30% of the nearly 163,000 PCIs entered into the registry during the study period.

The official Food and Drug Administration‐approved indication for the Cypher DES is for use in improving coronary luminal diameter in patients with symptomatic ischemic heart disease due to discrete de novo coronary lesions less than 30 mm long in native arteries having a reference vessel diameter of 2.5‐3.5 mm, Dr. Rao said.

Dr. Rao focused on four specific off‐label applications: ST‐segment elevation MI, in‐stent restenosis, saphenous vein grafts, and chronic total occlusions. These four off‐label uses accounted for 33% of all DES procedures during the study period. This figure is actually an underestimate of the true proportion of DES procedures that were off label, since it doesn't include other possible off‐label indications, such as long lesions or bifurcations.

The fastest growth in off‐label use of the DES during the 9‐month study period was in cases of ST‐segment elevation MI, followed by in‐stent restenosis.

The incidences of in‐hospital mortality and unplanned coronary artery bypass surgery in connection with off‐label use of the Cypher stent were both well below 1%. Moreover, the postprocedural acute MI rate was similar to that seen with bare metal stents, Dr. Rao said.

Several audience members took issue with his call for randomized trials designed to expand the approved indications for DEs. Some observed that companies have little incentive to conduct such trials, since business is already booming. Others argued that at this point it would be unethical to randomize patients to bare metal stents for most off‐label uses and said that the FDA should rely on registry data to evaluate possible expanded indications for drug‐eluting stents.

Dr. Rao replied that it's highly unlikely the FDA would expand the indications on the basis of registry data, which after all are inferior to information gained from randomized trials. “The registry data have a tremendous amount of residual confounding that cannot be accounted for regardless of the statistical analyses used. I think registries are highly valuable for safety data. I don't think, however, we can accept efficacy data as reliable,” he said.

NEW ORLEANS — More than a third of the drug‐eluting stents placed in the first 9 months following marketing approval of the Cypher stent were for off‐label indications, according to data from the American College of Cardiology‐National Cardiovascular Data Registry.

The use of drug‐eluting stents rose rapidly during this period, and growth in the off‐label uses kept pace with the increase for the approved indication, Sunil V. Rao, M.D., said at the annual scientific sessions of the American Heart Association.

Dr. Rao presented a unique picture of the clinical adoption of a major new medical technology as reflected in a large national registry experience. The American College of Cardiology‐National Cardiovascular Data Registry (ACC‐NCDR) is an ACC‐initiated quality improvement project that to date includes more than 2 million admissions and 800,000 percutaneous coronary interventions (PCIs) at 528 participating U.S. sites.

The registry data are reassuring in that off‐label use of drug‐eluting stents (DESs) appeared to be safe, at least in terms of the very low associated periprocedural adverse event rate, said Dr. Rao of the Duke Clinical Research Institute, Durham, N.C. “However, long‐term safety and efficacy of drug‐eluting stent use in off‐label situations really should be evaluated in appropriately powered, randomized controlled trials,” he said.

For purposes of his study, Dr. Rao focused on PCIs involving only the Cypher stent, the first DES to reach the U.S. market between the device's April 2003 approval through the end of that year. PCIs involving placement of both a Cypher stent and one or more bare metal stents were excluded from consideration. Cypher‐only procedures comprised 30% of the nearly 163,000 PCIs entered into the registry during the study period.

The official Food and Drug Administration‐approved indication for the Cypher DES is for use in improving coronary luminal diameter in patients with symptomatic ischemic heart disease due to discrete de novo coronary lesions less than 30 mm long in native arteries having a reference vessel diameter of 2.5‐3.5 mm, Dr. Rao said.

Dr. Rao focused on four specific off‐label applications: ST‐segment elevation MI, in‐stent restenosis, saphenous vein grafts, and chronic total occlusions. These four off‐label uses accounted for 33% of all DES procedures during the study period. This figure is actually an underestimate of the true proportion of DES procedures that were off label, since it doesn't include other possible off‐label indications, such as long lesions or bifurcations.

The fastest growth in off‐label use of the DES during the 9‐month study period was in cases of ST‐segment elevation MI, followed by in‐stent restenosis.

The incidences of in‐hospital mortality and unplanned coronary artery bypass surgery in connection with off‐label use of the Cypher stent were both well below 1%. Moreover, the postprocedural acute MI rate was similar to that seen with bare metal stents, Dr. Rao said.

Several audience members took issue with his call for randomized trials designed to expand the approved indications for DEs. Some observed that companies have little incentive to conduct such trials, since business is already booming. Others argued that at this point it would be unethical to randomize patients to bare metal stents for most off‐label uses and said that the FDA should rely on registry data to evaluate possible expanded indications for drug‐eluting stents.

Dr. Rao replied that it's highly unlikely the FDA would expand the indications on the basis of registry data, which after all are inferior to information gained from randomized trials. “The registry data have a tremendous amount of residual confounding that cannot be accounted for regardless of the statistical analyses used. I think registries are highly valuable for safety data. I don't think, however, we can accept efficacy data as reliable,” he said.

NEW ORLEANS — More than a third of the drug‐eluting stents placed in the first 9 months following marketing approval of the Cypher stent were for off‐label indications, according to data from the American College of Cardiology‐National Cardiovascular Data Registry.

The use of drug‐eluting stents rose rapidly during this period, and growth in the off‐label uses kept pace with the increase for the approved indication, Sunil V. Rao, M.D., said at the annual scientific sessions of the American Heart Association.

Dr. Rao presented a unique picture of the clinical adoption of a major new medical technology as reflected in a large national registry experience. The American College of Cardiology‐National Cardiovascular Data Registry (ACC‐NCDR) is an ACC‐initiated quality improvement project that to date includes more than 2 million admissions and 800,000 percutaneous coronary interventions (PCIs) at 528 participating U.S. sites.

The registry data are reassuring in that off‐label use of drug‐eluting stents (DESs) appeared to be safe, at least in terms of the very low associated periprocedural adverse event rate, said Dr. Rao of the Duke Clinical Research Institute, Durham, N.C. “However, long‐term safety and efficacy of drug‐eluting stent use in off‐label situations really should be evaluated in appropriately powered, randomized controlled trials,” he said.

For purposes of his study, Dr. Rao focused on PCIs involving only the Cypher stent, the first DES to reach the U.S. market between the device's April 2003 approval through the end of that year. PCIs involving placement of both a Cypher stent and one or more bare metal stents were excluded from consideration. Cypher‐only procedures comprised 30% of the nearly 163,000 PCIs entered into the registry during the study period.

The official Food and Drug Administration‐approved indication for the Cypher DES is for use in improving coronary luminal diameter in patients with symptomatic ischemic heart disease due to discrete de novo coronary lesions less than 30 mm long in native arteries having a reference vessel diameter of 2.5‐3.5 mm, Dr. Rao said.

Dr. Rao focused on four specific off‐label applications: ST‐segment elevation MI, in‐stent restenosis, saphenous vein grafts, and chronic total occlusions. These four off‐label uses accounted for 33% of all DES procedures during the study period. This figure is actually an underestimate of the true proportion of DES procedures that were off label, since it doesn't include other possible off‐label indications, such as long lesions or bifurcations.

The fastest growth in off‐label use of the DES during the 9‐month study period was in cases of ST‐segment elevation MI, followed by in‐stent restenosis.

The incidences of in‐hospital mortality and unplanned coronary artery bypass surgery in connection with off‐label use of the Cypher stent were both well below 1%. Moreover, the postprocedural acute MI rate was similar to that seen with bare metal stents, Dr. Rao said.

Several audience members took issue with his call for randomized trials designed to expand the approved indications for DEs. Some observed that companies have little incentive to conduct such trials, since business is already booming. Others argued that at this point it would be unethical to randomize patients to bare metal stents for most off‐label uses and said that the FDA should rely on registry data to evaluate possible expanded indications for drug‐eluting stents.

Dr. Rao replied that it's highly unlikely the FDA would expand the indications on the basis of registry data, which after all are inferior to information gained from randomized trials. “The registry data have a tremendous amount of residual confounding that cannot be accounted for regardless of the statistical analyses used. I think registries are highly valuable for safety data. I don't think, however, we can accept efficacy data as reliable,” he said.