LONDON — Despite concerns that the polyvalent pneumococcal vaccine may be inadequately protective in patients with lupus, most patients with severe disease can benefit from receiving it, Catherine Naveau, M.D., said at the Sixth European Lupus Meeting.

Invasive infections by common pathogens and opportunistic agents are frequent in patients with systemic lupus erythematosus and remain one of the leading causes of death, said Dr. Naveau of the rheumatology department, University Clinics Saint-Luc, Catholic University of Louvain, Brussels.

A review of the files of 208 patients from the Louvain lupus cohort identified 5 (2.5%) who had a history of pneumococcal septicemia prior to 1999.

“Since 1999 we have been vaccinating all our severe lupus patients with a polyvalent pneumococcal polysaccharide vaccine, and 5 years later we have not observed a single case of pneumococcal septicemia in vaccinated patients,” the rheumatologist said.

The five infected patients were female and ranged in age from 13 to 54 years. All had septic shock and unequivocal evidence on blood cultures of systemic Streptococcus pneumoniae infections, she said.

Three of the patients had infections of the central nervous system—two meningitis and one meningoencephalitis—one had bilateral pneumonia, and one had septic arthritis of the hip.

At the time of their infectious episode four of the five were being treated with corticosteroids, though at low to moderate doses ranging from the equivalent of 5 mg to 20 mg of prednisolone per day, Dr. Naveau reported in a poster session at the meeting, which was sponsored by the British Society for Rheumatology.

Only one was receiving a cytotoxic agent—intravenous cyclophosphamide.

All required treatment in the intensive care unit and survived without major organ damage, except for permanent bilateral hearing loss in one patient. “This series emphasizes the unusual incidence and severity of pneumococcal sepsis in systemic lupus erythematosus and suggests that vaccination should be offered to severe lupus patients,” Dr. Naveau said.

The U.S. Advisory Committee on Immunization Practices, while not mentioning lupus specifically, recommends the pneumococcal vaccine for patients who are immunocompromised or are being treated with immunosuppressive therapies.

The Lupus Foundation of America has acknowledged that the antibody response to the vaccine is inadequate in patients with severe lupus and in those being treated with corticosteroids and alkylating agents, but recommends it as being highly effective in the majority of lupus patients.

There have been reports of disease flares after vaccination with the pneumococcal vaccine, but in one of the largest reported series, no changes in lupus disease activity were seen in 73 patients following immunization with pneumococcal, tetanus toxoid (TT), and Haemophilus influenzae type B (HIB) vaccines (Arthritis Rheum. 1998;41:1828-34).

In addition, that study showed that the majority of patients developed protective levels of antibody to TT (90%) and HIB (88%). Protective antibody levels could not be determined for pneumococcus but almost half of the patients developed a fourfold antibody response. Antibody responses tended to be lower in patients with active disease who were being treated with immunosuppressive therapy.

LONDON — Despite concerns that the polyvalent pneumococcal vaccine may be inadequately protective in patients with lupus, most patients with severe disease can benefit from receiving it, Catherine Naveau, M.D., said at the Sixth European Lupus Meeting.

Invasive infections by common pathogens and opportunistic agents are frequent in patients with systemic lupus erythematosus and remain one of the leading causes of death, said Dr. Naveau of the rheumatology department, University Clinics Saint-Luc, Catholic University of Louvain, Brussels.

A review of the files of 208 patients from the Louvain lupus cohort identified 5 (2.5%) who had a history of pneumococcal septicemia prior to 1999.

“Since 1999 we have been vaccinating all our severe lupus patients with a polyvalent pneumococcal polysaccharide vaccine, and 5 years later we have not observed a single case of pneumococcal septicemia in vaccinated patients,” the rheumatologist said.

The five infected patients were female and ranged in age from 13 to 54 years. All had septic shock and unequivocal evidence on blood cultures of systemic Streptococcus pneumoniae infections, she said.

Three of the patients had infections of the central nervous system—two meningitis and one meningoencephalitis—one had bilateral pneumonia, and one had septic arthritis of the hip.

At the time of their infectious episode four of the five were being treated with corticosteroids, though at low to moderate doses ranging from the equivalent of 5 mg to 20 mg of prednisolone per day, Dr. Naveau reported in a poster session at the meeting, which was sponsored by the British Society for Rheumatology.

Only one was receiving a cytotoxic agent—intravenous cyclophosphamide.

All required treatment in the intensive care unit and survived without major organ damage, except for permanent bilateral hearing loss in one patient. “This series emphasizes the unusual incidence and severity of pneumococcal sepsis in systemic lupus erythematosus and suggests that vaccination should be offered to severe lupus patients,” Dr. Naveau said.

The U.S. Advisory Committee on Immunization Practices, while not mentioning lupus specifically, recommends the pneumococcal vaccine for patients who are immunocompromised or are being treated with immunosuppressive therapies.

The Lupus Foundation of America has acknowledged that the antibody response to the vaccine is inadequate in patients with severe lupus and in those being treated with corticosteroids and alkylating agents, but recommends it as being highly effective in the majority of lupus patients.

There have been reports of disease flares after vaccination with the pneumococcal vaccine, but in one of the largest reported series, no changes in lupus disease activity were seen in 73 patients following immunization with pneumococcal, tetanus toxoid (TT), and Haemophilus influenzae type B (HIB) vaccines (Arthritis Rheum. 1998;41:1828-34).

In addition, that study showed that the majority of patients developed protective levels of antibody to TT (90%) and HIB (88%). Protective antibody levels could not be determined for pneumococcus but almost half of the patients developed a fourfold antibody response. Antibody responses tended to be lower in patients with active disease who were being treated with immunosuppressive therapy.

LONDON — Despite concerns that the polyvalent pneumococcal vaccine may be inadequately protective in patients with lupus, most patients with severe disease can benefit from receiving it, Catherine Naveau, M.D., said at the Sixth European Lupus Meeting.

Invasive infections by common pathogens and opportunistic agents are frequent in patients with systemic lupus erythematosus and remain one of the leading causes of death, said Dr. Naveau of the rheumatology department, University Clinics Saint-Luc, Catholic University of Louvain, Brussels.

A review of the files of 208 patients from the Louvain lupus cohort identified 5 (2.5%) who had a history of pneumococcal septicemia prior to 1999.

“Since 1999 we have been vaccinating all our severe lupus patients with a polyvalent pneumococcal polysaccharide vaccine, and 5 years later we have not observed a single case of pneumococcal septicemia in vaccinated patients,” the rheumatologist said.

The five infected patients were female and ranged in age from 13 to 54 years. All had septic shock and unequivocal evidence on blood cultures of systemic Streptococcus pneumoniae infections, she said.

Three of the patients had infections of the central nervous system—two meningitis and one meningoencephalitis—one had bilateral pneumonia, and one had septic arthritis of the hip.

At the time of their infectious episode four of the five were being treated with corticosteroids, though at low to moderate doses ranging from the equivalent of 5 mg to 20 mg of prednisolone per day, Dr. Naveau reported in a poster session at the meeting, which was sponsored by the British Society for Rheumatology.

Only one was receiving a cytotoxic agent—intravenous cyclophosphamide.

All required treatment in the intensive care unit and survived without major organ damage, except for permanent bilateral hearing loss in one patient. “This series emphasizes the unusual incidence and severity of pneumococcal sepsis in systemic lupus erythematosus and suggests that vaccination should be offered to severe lupus patients,” Dr. Naveau said.

The U.S. Advisory Committee on Immunization Practices, while not mentioning lupus specifically, recommends the pneumococcal vaccine for patients who are immunocompromised or are being treated with immunosuppressive therapies.

The Lupus Foundation of America has acknowledged that the antibody response to the vaccine is inadequate in patients with severe lupus and in those being treated with corticosteroids and alkylating agents, but recommends it as being highly effective in the majority of lupus patients.

There have been reports of disease flares after vaccination with the pneumococcal vaccine, but in one of the largest reported series, no changes in lupus disease activity were seen in 73 patients following immunization with pneumococcal, tetanus toxoid (TT), and Haemophilus influenzae type B (HIB) vaccines (Arthritis Rheum. 1998;41:1828-34).

In addition, that study showed that the majority of patients developed protective levels of antibody to TT (90%) and HIB (88%). Protective antibody levels could not be determined for pneumococcus but almost half of the patients developed a fourfold antibody response. Antibody responses tended to be lower in patients with active disease who were being treated with immunosuppressive therapy.

SNOWMASS, COLO. — Admonitions persist against patients with polymyositis and dermatomyositis engaging in exercise, despite research showing it can be beneficial, Ingrid E. Lundberg, M.D., said at a symposium sponsored by the American College of Rheumatology.

Creatine supplements may also help improve function.

The notion that exercise could aggravate myositis stems in part from observations of muscle inflammation among marathon runners, Dr. Lundberg explained.

No study has ever shown harm with exercise in polymyositis or dermatomyositis patients, and yet medical textbook articles continued to suggest that such patients should avoid exercise, said Dr. Lundberg of the rheumatology unit at Karolinska University Hospital, Stockholm.

Now, a group of researchers including Dr. Lundberg and her colleagues are conducting small studies whose findings challenge the idea that exercise increases inflammation. In fact, many have found that exercise actually improves function.

In one observational study involving 10 patients with stable chronic polymyositis or dermatomyositis following an exercise program, none of the participants developed signs of aggravated disease activity as measured by MRI, plasma creatine phosphokinase level, and biopsy. Instead, all participants had improvements in their muscle function, according to an index test; among six of the patients the improvement was significant, Dr. Lundberg said at the symposium.

The 12-week program involved 15 minutes of resistance strength training and 15 minutes of walking 5 days a week.

In addition, the patients experienced reductions in their “bodily pain,” according to measures on the Short Form 36 health survey questionnaire (Rheumatology 1999;38:608-11).

Another study conducted around the same time assessed the effects of aerobic training rather than strength training. In that investigation, eight patients were assigned to a program that included stationary cycling and step aerobics. They were compared with five control patients given no intervention. At the end of 6 months, the patients who trained had a mean 28% increase in aerobic capacity and a 34% increase in muscle torque strength. They also had a mean 8% decrease in their resting heart rate (Br. J. Rheumatol. 1998;37:1338-42). There was no change in the controls.

Findings from another study, conducted by Dr. Lundberg and her colleagues, suggest that exercise may even be beneficial in early active disease.

In a study presented at the American College of Rheumatology last year, they found that creatine paired with exercise significantly improved muscle function over exercise alone. For that study, 18 patients were assigned to a combination program of creatine and exercise, and 19 patients to exercise alone. The patients assigned to creatine took a loading dose of 30 g/kg a day for 8 days and then a daily dose of 3 g/kg for 6 months.

At follow-up, the patients who took creatine had an average 13% improvement on a test of physical activity that included a 5-minute walking test and climbing stairs. That compared with an average 3% improvement for those in the control group.

Corticosteroid treatment remains the standard initial therapy for polymyositis and dermatomyositis, but physicians should keep in mind that it's not an evidence-based approach, she said. Controlled clinical trials of corticosteroids in these patients have never been conducted, so there are no data on optimal starting dosages, or on how long one should treat before attempting to taper, she said.

Most experts recommend starting prednisone at 40-60 mg daily for about 1 month, and then slowly tapering the corticosteroid while monitoring plasma creatine phosphokinase levels.

Dr. Lundberg, however, said she recommends following muscle function before tapering because muscle function returns more slowly than do normal levels of creatine phosphokinase, and the return of muscle strength may take more than a month.

Studies have shown that 75% of patients respond to corticosteroid therapy, but few recover muscle function fully, and there is a high rate of adverse effects.

Azathioprine, 2 mg/kg a day, can be added to the prednisone to decrease corticosteroid exposure; methotrexate, 7.5-25 mg/wk, also can be effective for patients who do not respond to prednisone.

Any patient who doesn't respond to corticosteroid treatment should have their diagnosis reevaluated before continuing treatment, with either a repeat MRI or a new muscle biopsy, she advised.

Cyclosporine has been shown to be as effective as methotrexate and may even be preferable for those patients with concurrent interstitial lung disease.

Experimental treatments for myositis include tacrolimus, which showed “impressive” results in a small, open-label trial of eight patients who were not responsive to corticosteroids and anti-tumor necrosis factor therapy. However, outcomes involving 13 similar patients at Dr. Lundberg's institution were not as favorable. Of those patients, three had some improvement, but not in muscle function, two worsened, and the rest did not respond. Moreover, muscle inflammation did not appear to be impacted.

SNOWMASS, COLO. — Admonitions persist against patients with polymyositis and dermatomyositis engaging in exercise, despite research showing it can be beneficial, Ingrid E. Lundberg, M.D., said at a symposium sponsored by the American College of Rheumatology.

Creatine supplements may also help improve function.

The notion that exercise could aggravate myositis stems in part from observations of muscle inflammation among marathon runners, Dr. Lundberg explained.

No study has ever shown harm with exercise in polymyositis or dermatomyositis patients, and yet medical textbook articles continued to suggest that such patients should avoid exercise, said Dr. Lundberg of the rheumatology unit at Karolinska University Hospital, Stockholm.

Now, a group of researchers including Dr. Lundberg and her colleagues are conducting small studies whose findings challenge the idea that exercise increases inflammation. In fact, many have found that exercise actually improves function.

In one observational study involving 10 patients with stable chronic polymyositis or dermatomyositis following an exercise program, none of the participants developed signs of aggravated disease activity as measured by MRI, plasma creatine phosphokinase level, and biopsy. Instead, all participants had improvements in their muscle function, according to an index test; among six of the patients the improvement was significant, Dr. Lundberg said at the symposium.

The 12-week program involved 15 minutes of resistance strength training and 15 minutes of walking 5 days a week.

In addition, the patients experienced reductions in their “bodily pain,” according to measures on the Short Form 36 health survey questionnaire (Rheumatology 1999;38:608-11).

Another study conducted around the same time assessed the effects of aerobic training rather than strength training. In that investigation, eight patients were assigned to a program that included stationary cycling and step aerobics. They were compared with five control patients given no intervention. At the end of 6 months, the patients who trained had a mean 28% increase in aerobic capacity and a 34% increase in muscle torque strength. They also had a mean 8% decrease in their resting heart rate (Br. J. Rheumatol. 1998;37:1338-42). There was no change in the controls.

Findings from another study, conducted by Dr. Lundberg and her colleagues, suggest that exercise may even be beneficial in early active disease.

In a study presented at the American College of Rheumatology last year, they found that creatine paired with exercise significantly improved muscle function over exercise alone. For that study, 18 patients were assigned to a combination program of creatine and exercise, and 19 patients to exercise alone. The patients assigned to creatine took a loading dose of 30 g/kg a day for 8 days and then a daily dose of 3 g/kg for 6 months.

At follow-up, the patients who took creatine had an average 13% improvement on a test of physical activity that included a 5-minute walking test and climbing stairs. That compared with an average 3% improvement for those in the control group.

Corticosteroid treatment remains the standard initial therapy for polymyositis and dermatomyositis, but physicians should keep in mind that it's not an evidence-based approach, she said. Controlled clinical trials of corticosteroids in these patients have never been conducted, so there are no data on optimal starting dosages, or on how long one should treat before attempting to taper, she said.

Most experts recommend starting prednisone at 40-60 mg daily for about 1 month, and then slowly tapering the corticosteroid while monitoring plasma creatine phosphokinase levels.

Dr. Lundberg, however, said she recommends following muscle function before tapering because muscle function returns more slowly than do normal levels of creatine phosphokinase, and the return of muscle strength may take more than a month.

Studies have shown that 75% of patients respond to corticosteroid therapy, but few recover muscle function fully, and there is a high rate of adverse effects.

Azathioprine, 2 mg/kg a day, can be added to the prednisone to decrease corticosteroid exposure; methotrexate, 7.5-25 mg/wk, also can be effective for patients who do not respond to prednisone.

Any patient who doesn't respond to corticosteroid treatment should have their diagnosis reevaluated before continuing treatment, with either a repeat MRI or a new muscle biopsy, she advised.

Cyclosporine has been shown to be as effective as methotrexate and may even be preferable for those patients with concurrent interstitial lung disease.

Experimental treatments for myositis include tacrolimus, which showed “impressive” results in a small, open-label trial of eight patients who were not responsive to corticosteroids and anti-tumor necrosis factor therapy. However, outcomes involving 13 similar patients at Dr. Lundberg's institution were not as favorable. Of those patients, three had some improvement, but not in muscle function, two worsened, and the rest did not respond. Moreover, muscle inflammation did not appear to be impacted.

SNOWMASS, COLO. — Admonitions persist against patients with polymyositis and dermatomyositis engaging in exercise, despite research showing it can be beneficial, Ingrid E. Lundberg, M.D., said at a symposium sponsored by the American College of Rheumatology.

Creatine supplements may also help improve function.

The notion that exercise could aggravate myositis stems in part from observations of muscle inflammation among marathon runners, Dr. Lundberg explained.

No study has ever shown harm with exercise in polymyositis or dermatomyositis patients, and yet medical textbook articles continued to suggest that such patients should avoid exercise, said Dr. Lundberg of the rheumatology unit at Karolinska University Hospital, Stockholm.

Now, a group of researchers including Dr. Lundberg and her colleagues are conducting small studies whose findings challenge the idea that exercise increases inflammation. In fact, many have found that exercise actually improves function.

In one observational study involving 10 patients with stable chronic polymyositis or dermatomyositis following an exercise program, none of the participants developed signs of aggravated disease activity as measured by MRI, plasma creatine phosphokinase level, and biopsy. Instead, all participants had improvements in their muscle function, according to an index test; among six of the patients the improvement was significant, Dr. Lundberg said at the symposium.

The 12-week program involved 15 minutes of resistance strength training and 15 minutes of walking 5 days a week.

In addition, the patients experienced reductions in their “bodily pain,” according to measures on the Short Form 36 health survey questionnaire (Rheumatology 1999;38:608-11).

Another study conducted around the same time assessed the effects of aerobic training rather than strength training. In that investigation, eight patients were assigned to a program that included stationary cycling and step aerobics. They were compared with five control patients given no intervention. At the end of 6 months, the patients who trained had a mean 28% increase in aerobic capacity and a 34% increase in muscle torque strength. They also had a mean 8% decrease in their resting heart rate (Br. J. Rheumatol. 1998;37:1338-42). There was no change in the controls.

Findings from another study, conducted by Dr. Lundberg and her colleagues, suggest that exercise may even be beneficial in early active disease.

In a study presented at the American College of Rheumatology last year, they found that creatine paired with exercise significantly improved muscle function over exercise alone. For that study, 18 patients were assigned to a combination program of creatine and exercise, and 19 patients to exercise alone. The patients assigned to creatine took a loading dose of 30 g/kg a day for 8 days and then a daily dose of 3 g/kg for 6 months.

At follow-up, the patients who took creatine had an average 13% improvement on a test of physical activity that included a 5-minute walking test and climbing stairs. That compared with an average 3% improvement for those in the control group.

Corticosteroid treatment remains the standard initial therapy for polymyositis and dermatomyositis, but physicians should keep in mind that it's not an evidence-based approach, she said. Controlled clinical trials of corticosteroids in these patients have never been conducted, so there are no data on optimal starting dosages, or on how long one should treat before attempting to taper, she said.

Most experts recommend starting prednisone at 40-60 mg daily for about 1 month, and then slowly tapering the corticosteroid while monitoring plasma creatine phosphokinase levels.

Dr. Lundberg, however, said she recommends following muscle function before tapering because muscle function returns more slowly than do normal levels of creatine phosphokinase, and the return of muscle strength may take more than a month.

Studies have shown that 75% of patients respond to corticosteroid therapy, but few recover muscle function fully, and there is a high rate of adverse effects.

Azathioprine, 2 mg/kg a day, can be added to the prednisone to decrease corticosteroid exposure; methotrexate, 7.5-25 mg/wk, also can be effective for patients who do not respond to prednisone.

Any patient who doesn't respond to corticosteroid treatment should have their diagnosis reevaluated before continuing treatment, with either a repeat MRI or a new muscle biopsy, she advised.

Cyclosporine has been shown to be as effective as methotrexate and may even be preferable for those patients with concurrent interstitial lung disease.

Experimental treatments for myositis include tacrolimus, which showed “impressive” results in a small, open-label trial of eight patients who were not responsive to corticosteroids and anti-tumor necrosis factor therapy. However, outcomes involving 13 similar patients at Dr. Lundberg's institution were not as favorable. Of those patients, three had some improvement, but not in muscle function, two worsened, and the rest did not respond. Moreover, muscle inflammation did not appear to be impacted.

LONDON — Patients with systemic lupus erythematosus should be evaluated on an annual basis for cardiovascular risk until such time as specific recommendations are formulated, Heiko Schotte, M.D., said at the Sixth European Lupus Meeting.

Results of procedures that detect coronary insufficiency, surrogates of atherosclerotic burden, and echocardiographic findings are often abnormal in SLE, but evidence to support routine screening is not currently available. “Therefore, based on the recommendations that have been proposed for other conditions associated with cardiovascular disease, we suggest annual assessment of traditional risk factors including diabetes mellitus, dyslipidemia, hypertension, smoking, and family history of premature coronary disease,” Dr. Schotte said in a poster session at the meeting, which was sponsored by the British Society for Rheumatology.

If two or more risk factors are present, an exercise ECG should be done, he said.

The cardiac manifestations of SLE can involve almost all components of the heart—pericardium, myocardium, and valves—and pulmonary hypertension also often develops during the course of disease. Echocardiography also should be done each year to look for any of these abnormalities, even for patients who are asymptomatic, he said.

These recommendations must be confirmed in prospective studies, and should be enlarged to include other SLE-specific risk factors such as antiphospholipid antibodies and long-term corticosteroid therapy, said Dr. Schotte of the department of medicine, Muenster (Germany) University Hospital.

LONDON — Patients with systemic lupus erythematosus should be evaluated on an annual basis for cardiovascular risk until such time as specific recommendations are formulated, Heiko Schotte, M.D., said at the Sixth European Lupus Meeting.

Results of procedures that detect coronary insufficiency, surrogates of atherosclerotic burden, and echocardiographic findings are often abnormal in SLE, but evidence to support routine screening is not currently available. “Therefore, based on the recommendations that have been proposed for other conditions associated with cardiovascular disease, we suggest annual assessment of traditional risk factors including diabetes mellitus, dyslipidemia, hypertension, smoking, and family history of premature coronary disease,” Dr. Schotte said in a poster session at the meeting, which was sponsored by the British Society for Rheumatology.

If two or more risk factors are present, an exercise ECG should be done, he said.

The cardiac manifestations of SLE can involve almost all components of the heart—pericardium, myocardium, and valves—and pulmonary hypertension also often develops during the course of disease. Echocardiography also should be done each year to look for any of these abnormalities, even for patients who are asymptomatic, he said.

These recommendations must be confirmed in prospective studies, and should be enlarged to include other SLE-specific risk factors such as antiphospholipid antibodies and long-term corticosteroid therapy, said Dr. Schotte of the department of medicine, Muenster (Germany) University Hospital.

LONDON — Patients with systemic lupus erythematosus should be evaluated on an annual basis for cardiovascular risk until such time as specific recommendations are formulated, Heiko Schotte, M.D., said at the Sixth European Lupus Meeting.

Results of procedures that detect coronary insufficiency, surrogates of atherosclerotic burden, and echocardiographic findings are often abnormal in SLE, but evidence to support routine screening is not currently available. “Therefore, based on the recommendations that have been proposed for other conditions associated with cardiovascular disease, we suggest annual assessment of traditional risk factors including diabetes mellitus, dyslipidemia, hypertension, smoking, and family history of premature coronary disease,” Dr. Schotte said in a poster session at the meeting, which was sponsored by the British Society for Rheumatology.

If two or more risk factors are present, an exercise ECG should be done, he said.

The cardiac manifestations of SLE can involve almost all components of the heart—pericardium, myocardium, and valves—and pulmonary hypertension also often develops during the course of disease. Echocardiography also should be done each year to look for any of these abnormalities, even for patients who are asymptomatic, he said.

These recommendations must be confirmed in prospective studies, and should be enlarged to include other SLE-specific risk factors such as antiphospholipid antibodies and long-term corticosteroid therapy, said Dr. Schotte of the department of medicine, Muenster (Germany) University Hospital.

NEW ORLEANS — Patients with refractory systemic lupus erythematosus have had “substantial improvements” following autologous stem cell transplants in an uncontrolled, phase I-II study.

The next step is to test the treatment in a randomized, controlled trial, Richard Burt, M.D., said at the southern regional meeting of the American Federation for Medical Research.

As of February, Dr. Burt had followed 48 patients treated with nonmyeloablative stem cell transplants and found that they stayed in remission for as long as 88 months and for an average of 33 months.

Among patients followed for at least 2 years, 70% were in remission; after at least 5 years, 50% were in remission, said Dr. Burt, chief of the division of immunotherapy and autoimmune diseases at Northwestern University in Chicago. He defined remission as requiring less than 10 mg/day of prednisone. Before receiving stem cell transplants, these patients required 50-100 mg of prednisone daily.

The treatment aims to ablate a patient's dysfunctional immune system and then regenerate immunity with autologous stem cells. In patients with systemic lupus erythematosus (SLE), as well as other autoimmune diseases, the pathologic defect is presumed to be environmental and not genetic, and hence the patient's stem cells should be able to regenerate a more normally functioning immune system.

A key to the success of this program is that patients receive a conditioning regimen that is immunoablative but not myeloablative. This makes the treatment safer, Dr. Burt said.

The series enrolled patients who had steroid-dependent SLE, with an average age of 26 years; 87% were women.

Stem cells were mobilized by using a combination of low-dose cyclophosphamide and granulocyte colony-stimulating factor. Stem cells were harvested 10 days later. Patients were then immunoablated with a combination regimen of high-dose cyclophosphamide, a total of 200 mg/kg, along with equine antithymocyte globulin to eliminate T cells. After the ablative regimen was complete, patients received an infusion of their autologous stem cells.

During recovery, patients required an average of six red blood cell transfusions and seven platelet transfusions. Adequate neurophil recovery usually occurred within 9 days after completion of the immunoablative treatment, and platelets usually recovered by day 12.

Patients generally were discharged from the hospital 14 days after immunoablation.

Following treatment, patients had a marked reduction in their level of antinuclear antibody and an increase in complement, so that levels returned to the normal range. Proteinuria severity also improved markedly, with reductions of about 75%. Many patients have also had resolution of pneumonitis or alveolar hemorrhage.

Antiphospholipid antibody levels dropped, enabling about 80% of patients to stop chronic treatment with anticoagulants without the occurrence of thrombotic events during a mean of 17 months.

Since the start of this study 7 years ago, four patients have died from disease relapse, one has died following a traumatic accident, and one has died from an unrelated, late infection.

Dr. Burt believes this treatment is probably applicable to several different autoimmune diseases. He and his associates have already used it safely and with encouraging results in patients with other autoimmune disorders, including Crohn's disease and multiple sclerosis.

NEW ORLEANS — Patients with refractory systemic lupus erythematosus have had “substantial improvements” following autologous stem cell transplants in an uncontrolled, phase I-II study.

The next step is to test the treatment in a randomized, controlled trial, Richard Burt, M.D., said at the southern regional meeting of the American Federation for Medical Research.

As of February, Dr. Burt had followed 48 patients treated with nonmyeloablative stem cell transplants and found that they stayed in remission for as long as 88 months and for an average of 33 months.

Among patients followed for at least 2 years, 70% were in remission; after at least 5 years, 50% were in remission, said Dr. Burt, chief of the division of immunotherapy and autoimmune diseases at Northwestern University in Chicago. He defined remission as requiring less than 10 mg/day of prednisone. Before receiving stem cell transplants, these patients required 50-100 mg of prednisone daily.

The treatment aims to ablate a patient's dysfunctional immune system and then regenerate immunity with autologous stem cells. In patients with systemic lupus erythematosus (SLE), as well as other autoimmune diseases, the pathologic defect is presumed to be environmental and not genetic, and hence the patient's stem cells should be able to regenerate a more normally functioning immune system.

A key to the success of this program is that patients receive a conditioning regimen that is immunoablative but not myeloablative. This makes the treatment safer, Dr. Burt said.

The series enrolled patients who had steroid-dependent SLE, with an average age of 26 years; 87% were women.

Stem cells were mobilized by using a combination of low-dose cyclophosphamide and granulocyte colony-stimulating factor. Stem cells were harvested 10 days later. Patients were then immunoablated with a combination regimen of high-dose cyclophosphamide, a total of 200 mg/kg, along with equine antithymocyte globulin to eliminate T cells. After the ablative regimen was complete, patients received an infusion of their autologous stem cells.

During recovery, patients required an average of six red blood cell transfusions and seven platelet transfusions. Adequate neurophil recovery usually occurred within 9 days after completion of the immunoablative treatment, and platelets usually recovered by day 12.

Patients generally were discharged from the hospital 14 days after immunoablation.

Following treatment, patients had a marked reduction in their level of antinuclear antibody and an increase in complement, so that levels returned to the normal range. Proteinuria severity also improved markedly, with reductions of about 75%. Many patients have also had resolution of pneumonitis or alveolar hemorrhage.

Antiphospholipid antibody levels dropped, enabling about 80% of patients to stop chronic treatment with anticoagulants without the occurrence of thrombotic events during a mean of 17 months.

Since the start of this study 7 years ago, four patients have died from disease relapse, one has died following a traumatic accident, and one has died from an unrelated, late infection.

Dr. Burt believes this treatment is probably applicable to several different autoimmune diseases. He and his associates have already used it safely and with encouraging results in patients with other autoimmune disorders, including Crohn's disease and multiple sclerosis.

NEW ORLEANS — Patients with refractory systemic lupus erythematosus have had “substantial improvements” following autologous stem cell transplants in an uncontrolled, phase I-II study.

The next step is to test the treatment in a randomized, controlled trial, Richard Burt, M.D., said at the southern regional meeting of the American Federation for Medical Research.

As of February, Dr. Burt had followed 48 patients treated with nonmyeloablative stem cell transplants and found that they stayed in remission for as long as 88 months and for an average of 33 months.

Among patients followed for at least 2 years, 70% were in remission; after at least 5 years, 50% were in remission, said Dr. Burt, chief of the division of immunotherapy and autoimmune diseases at Northwestern University in Chicago. He defined remission as requiring less than 10 mg/day of prednisone. Before receiving stem cell transplants, these patients required 50-100 mg of prednisone daily.

The treatment aims to ablate a patient's dysfunctional immune system and then regenerate immunity with autologous stem cells. In patients with systemic lupus erythematosus (SLE), as well as other autoimmune diseases, the pathologic defect is presumed to be environmental and not genetic, and hence the patient's stem cells should be able to regenerate a more normally functioning immune system.

A key to the success of this program is that patients receive a conditioning regimen that is immunoablative but not myeloablative. This makes the treatment safer, Dr. Burt said.

The series enrolled patients who had steroid-dependent SLE, with an average age of 26 years; 87% were women.

Stem cells were mobilized by using a combination of low-dose cyclophosphamide and granulocyte colony-stimulating factor. Stem cells were harvested 10 days later. Patients were then immunoablated with a combination regimen of high-dose cyclophosphamide, a total of 200 mg/kg, along with equine antithymocyte globulin to eliminate T cells. After the ablative regimen was complete, patients received an infusion of their autologous stem cells.

During recovery, patients required an average of six red blood cell transfusions and seven platelet transfusions. Adequate neurophil recovery usually occurred within 9 days after completion of the immunoablative treatment, and platelets usually recovered by day 12.

Patients generally were discharged from the hospital 14 days after immunoablation.

Following treatment, patients had a marked reduction in their level of antinuclear antibody and an increase in complement, so that levels returned to the normal range. Proteinuria severity also improved markedly, with reductions of about 75%. Many patients have also had resolution of pneumonitis or alveolar hemorrhage.

Antiphospholipid antibody levels dropped, enabling about 80% of patients to stop chronic treatment with anticoagulants without the occurrence of thrombotic events during a mean of 17 months.

Since the start of this study 7 years ago, four patients have died from disease relapse, one has died following a traumatic accident, and one has died from an unrelated, late infection.

Dr. Burt believes this treatment is probably applicable to several different autoimmune diseases. He and his associates have already used it safely and with encouraging results in patients with other autoimmune disorders, including Crohn's disease and multiple sclerosis.

LONDON — Women with lupus face an elevated risk of having cervical dysplasia, but the underlying cause of such pathology is still unclear, Michelle T. McHenry, M.B., said at the Sixth European Lupus Meeting.

Unlike the situation for healthy women, there appeared to be no association between cervical dysplasia and other traditional risk factors, such as a history of sexually transmitted disease, in a cohort of 221 women with systemic lupus erythematosus (SLE) identified through hospital records and the Northern Ireland pathology database.

Among this entire cohort, 74 (33%) had a lifetime history of having had at least one abnormal cervical smear, Dr. McHenry reported.

Of those, 45% had had more than one abnormal smear and 26% had had a high-grade abnormality, she said.

From the entire cohort, 141 patients agreed to participate in a study that involved answering a risk factor questionnaire and providing a current cervical smear. Adequate smears were obtained from 133 patients.

Low-grade abnormalities were found on 22 (17%) of these smears, which is twice the expected incidence, according to the Northern Ireland department of health statistics. High-grade abnormalities were identified on six (5%), which is three times the expected incidence, said Dr. McHenry, a rheumatologist at Queen's University Musculoskeletal Education and Research Unit, Belfast.

The abnormality was detected after the time of diagnosis of lupus in 63% of patients.

“Patients with SLE are at increased risk of cervical cancer but the reasons why are unclear, whether it is related to having the disease itself, to having active disease, [or] to the treatments we administer, or if traditional cervical cancer risk factors have a part to play,” Dr. McHenry said.

“When we assessed these patients for traditional cervical cancer risk factors, we found they were more likely to have had more sexual partners and more children,” she said at the meeting, which was sponsored by the British Society for Rheumatology.

There also was an increased risk of having a cervical smear abnormality among patients who had more active disease as reflected by the Systemic Lupus Activity Measure (SLAM) score, she said.

Other risk factors, including age at first sexual contact and history of ever having used oral contraceptives, were not associated with increased risk of cervical dysplasia. “And surprisingly, there was no association between abnormal cervical smear history and tobacco smoking,” she said. (See chart.)

Although a correlation was seen between high disease activity scores and history of cervical smear abnormality, there was no correlation with lupus damage scores or duration of disease.

Exposure to corticosteroids and immunosuppressive agents also did not differ between patients with and without abnormal cervical smear histories.

Further analyses will consider cumulative immunosuppressive doses and will compare human papillomavirus DNA findings between lupus patients and controls.

LONDON — Women with lupus face an elevated risk of having cervical dysplasia, but the underlying cause of such pathology is still unclear, Michelle T. McHenry, M.B., said at the Sixth European Lupus Meeting.

Unlike the situation for healthy women, there appeared to be no association between cervical dysplasia and other traditional risk factors, such as a history of sexually transmitted disease, in a cohort of 221 women with systemic lupus erythematosus (SLE) identified through hospital records and the Northern Ireland pathology database.

Among this entire cohort, 74 (33%) had a lifetime history of having had at least one abnormal cervical smear, Dr. McHenry reported.

Of those, 45% had had more than one abnormal smear and 26% had had a high-grade abnormality, she said.

From the entire cohort, 141 patients agreed to participate in a study that involved answering a risk factor questionnaire and providing a current cervical smear. Adequate smears were obtained from 133 patients.

Low-grade abnormalities were found on 22 (17%) of these smears, which is twice the expected incidence, according to the Northern Ireland department of health statistics. High-grade abnormalities were identified on six (5%), which is three times the expected incidence, said Dr. McHenry, a rheumatologist at Queen's University Musculoskeletal Education and Research Unit, Belfast.

The abnormality was detected after the time of diagnosis of lupus in 63% of patients.

“Patients with SLE are at increased risk of cervical cancer but the reasons why are unclear, whether it is related to having the disease itself, to having active disease, [or] to the treatments we administer, or if traditional cervical cancer risk factors have a part to play,” Dr. McHenry said.

“When we assessed these patients for traditional cervical cancer risk factors, we found they were more likely to have had more sexual partners and more children,” she said at the meeting, which was sponsored by the British Society for Rheumatology.

There also was an increased risk of having a cervical smear abnormality among patients who had more active disease as reflected by the Systemic Lupus Activity Measure (SLAM) score, she said.

Other risk factors, including age at first sexual contact and history of ever having used oral contraceptives, were not associated with increased risk of cervical dysplasia. “And surprisingly, there was no association between abnormal cervical smear history and tobacco smoking,” she said. (See chart.)

Although a correlation was seen between high disease activity scores and history of cervical smear abnormality, there was no correlation with lupus damage scores or duration of disease.

Exposure to corticosteroids and immunosuppressive agents also did not differ between patients with and without abnormal cervical smear histories.

Further analyses will consider cumulative immunosuppressive doses and will compare human papillomavirus DNA findings between lupus patients and controls.

LONDON — Women with lupus face an elevated risk of having cervical dysplasia, but the underlying cause of such pathology is still unclear, Michelle T. McHenry, M.B., said at the Sixth European Lupus Meeting.

Unlike the situation for healthy women, there appeared to be no association between cervical dysplasia and other traditional risk factors, such as a history of sexually transmitted disease, in a cohort of 221 women with systemic lupus erythematosus (SLE) identified through hospital records and the Northern Ireland pathology database.

Among this entire cohort, 74 (33%) had a lifetime history of having had at least one abnormal cervical smear, Dr. McHenry reported.

Of those, 45% had had more than one abnormal smear and 26% had had a high-grade abnormality, she said.

From the entire cohort, 141 patients agreed to participate in a study that involved answering a risk factor questionnaire and providing a current cervical smear. Adequate smears were obtained from 133 patients.

Low-grade abnormalities were found on 22 (17%) of these smears, which is twice the expected incidence, according to the Northern Ireland department of health statistics. High-grade abnormalities were identified on six (5%), which is three times the expected incidence, said Dr. McHenry, a rheumatologist at Queen's University Musculoskeletal Education and Research Unit, Belfast.

The abnormality was detected after the time of diagnosis of lupus in 63% of patients.

“Patients with SLE are at increased risk of cervical cancer but the reasons why are unclear, whether it is related to having the disease itself, to having active disease, [or] to the treatments we administer, or if traditional cervical cancer risk factors have a part to play,” Dr. McHenry said.

“When we assessed these patients for traditional cervical cancer risk factors, we found they were more likely to have had more sexual partners and more children,” she said at the meeting, which was sponsored by the British Society for Rheumatology.

There also was an increased risk of having a cervical smear abnormality among patients who had more active disease as reflected by the Systemic Lupus Activity Measure (SLAM) score, she said.

Other risk factors, including age at first sexual contact and history of ever having used oral contraceptives, were not associated with increased risk of cervical dysplasia. “And surprisingly, there was no association between abnormal cervical smear history and tobacco smoking,” she said. (See chart.)

Although a correlation was seen between high disease activity scores and history of cervical smear abnormality, there was no correlation with lupus damage scores or duration of disease.

Exposure to corticosteroids and immunosuppressive agents also did not differ between patients with and without abnormal cervical smear histories.

Further analyses will consider cumulative immunosuppressive doses and will compare human papillomavirus DNA findings between lupus patients and controls.

LONDON — The incidence of coronary heart disease among young women with systemic lupus erythematosus is “startlingly worrying,” Ian Bruce, M.D., said at the Sixth European Lupus Meeting.

Studies have shown that the annual incidence of ischemic heart disease in lupus patients is 1.3%-1.5%. In comparison, the incidence among those with newly diagnosed type 2 diabetes and among those who have had a first myocardial infarction is 2%-2.2% per annum. “This latter number may be higher, but you have to remember that these are men in their mid- to late 50s, while the lupus patients in these studies are women whose average age is 35-37,” said Dr. Bruce, of the University of Manchester (England).

The prevalence of myocardial infarction or angina in lupus cohorts ranges from 7% to 10%, depending on patient age and duration of follow-up, he said.

Moreover, as survival improves, the prevalence of the disease increases, as does the proportion of lupus patients who are older and at even greater risk for cardiovascular disease, he said.

Some epidemiologic work has suggested that the peak age of onset also is increasing and now occurs between the fifth to seventh decades. Damage accrues more quickly among patients who are older at onset, he added.

Atherosclerosis also occurs much earlier in women with lupus than in healthy women. “In women younger than 45 in the general population, you virtually do not see plaque, whereas women with lupus are beginning to acquire plaque at that early age,” Dr. Bruce said.

Classic risk factors clearly are implicated in the premature atherosclerosis and coronary heart disease seen in lupus. There is a much higher prevalence of hypertension, diabetes, and renal impairment, and lupus patients typically have other risk factors such as higher levels of LDL cholesterol and triglycerides (Arthritis Rheum. 2003;48:3159-67).

And these risk factors do have an impact. “In a cohort study, we stratified patients according to their total cholesterol levels and found that among those with persistently elevated cholesterol, 24% developed a cardiac event during 12 years of follow-up, compared with 3% whose cholesterol level was normal or varied only slightly with disease flares,” Dr. Bruce said at the meeting, sponsored by the British Society for Rheumatology.

But classic risk factors do not tell the whole story. (See box.) In the general population, risk for a cardiac event increases as risk factors accumulate. “Lupus patients, however, seem to be set at an intrinsically higher baseline, and the accumulation of risk factors has an even more devastating effect,” he said.

A great need exists for properly conducted clinical trials of potential interventions for these patients. “We need to see if what we think will work actually does work and what the magnitude of risk reduction is with a particular intervention,” he said.

Statins are an example. “Everywhere they have been used so far, they have been associated with a reduction in risk of coronary-disease events by about 30%. You could assume that also might be the case in lupus, but that could be a dangerous assumption, because these drugs might not be as well tolerated by lupus patients,” he said.

The larger scope of the disease also must be addressed. Future work must focus on the worldwide burden of atherosclerosis in lupus and consider the ethnic gradient of risk, which might reveal some interesting things about the pathogenesis, he said.

Classic Risk Factors Don't Tell the Whole Story

As the magnitude and severity of atherosclerosis and heart disease in systemic lupus erythematosus (SLE) become clearer, so do some possible mediators and markers. A series of posters presented at the meeting by researchers from the Karolinska Institute, Stockholm, explored various potential contributing factors:

▸ LDL cholesterol. Increased LDL-cholesterol oxidation contributes to lupus-related cardiovascular disease, reported Anna Cederholm, M.D. She compared levels of several risk and protective factors in three groups: 26 women with lupus plus cardiovascular disease, 26 women with lupus but no clinical manifestations of cardiovascular disease, and 26 normal controls. Circulating levels of oxidized LDL cholesterol were increased in both lupus groups, as was platelet-activating factor acetylhydrolase (PAF-AH). Levels of oxidized LDL cholesterol and PAF-AH also were significantly higher in the lupus patients with cardiovascular disease than in those with lupus and no heart disease. Because PAF-AH binds to LDL cholesterol, it also may contribute to atherogenesis, Dr. Cederholm said.

▸ Anti-HDL cholesterol antibodies. SLE-related dyslipidemia showed a surprising pattern in a study of women with a history of cardiovascular disease, reported J. Su, M.D. Large, rather than small, LDL- and HDL-cholesterol particles characterized the dyslipidemia profile. This was not an expected atherogenic lipid profile, Dr. Su explained.

Antibodies against apolipoprotein A1 in HDL cholesterol also were elevated and were associated with the presence of tumor necrosis factor. Whether these anti-apo A1 antibodies play a pathogenic role—for example, by inhibiting the anti-inflammatory properties of HDL—is under investigation, Dr. Su said.

▸ Homocysteine. Hyperhomocysteinemia in patients with lupus correlates with markers of inflammatory activity and is a risk factor for cardiovascular disease, said Elisabet Svenungsson, M.D. In fasting blood samples obtained from a cohort of 208 patients, homocysteine levels were associated with acute phase reactants including C-reactive protein, serum amyloid A protein, fibrinogen, and complement.

Hyperhomocysteinemia also correlated with the presence of arterial disease and nephritis. “It may cause endothelial activation and damage and thus adds to the inflammatory burden that we believe renders SLE patients highly susceptible to cardiovascular disease,” she said.

—Nancy Walsh

LONDON — The incidence of coronary heart disease among young women with systemic lupus erythematosus is “startlingly worrying,” Ian Bruce, M.D., said at the Sixth European Lupus Meeting.

Studies have shown that the annual incidence of ischemic heart disease in lupus patients is 1.3%-1.5%. In comparison, the incidence among those with newly diagnosed type 2 diabetes and among those who have had a first myocardial infarction is 2%-2.2% per annum. “This latter number may be higher, but you have to remember that these are men in their mid- to late 50s, while the lupus patients in these studies are women whose average age is 35-37,” said Dr. Bruce, of the University of Manchester (England).

The prevalence of myocardial infarction or angina in lupus cohorts ranges from 7% to 10%, depending on patient age and duration of follow-up, he said.

Moreover, as survival improves, the prevalence of the disease increases, as does the proportion of lupus patients who are older and at even greater risk for cardiovascular disease, he said.

Some epidemiologic work has suggested that the peak age of onset also is increasing and now occurs between the fifth to seventh decades. Damage accrues more quickly among patients who are older at onset, he added.

Atherosclerosis also occurs much earlier in women with lupus than in healthy women. “In women younger than 45 in the general population, you virtually do not see plaque, whereas women with lupus are beginning to acquire plaque at that early age,” Dr. Bruce said.

Classic risk factors clearly are implicated in the premature atherosclerosis and coronary heart disease seen in lupus. There is a much higher prevalence of hypertension, diabetes, and renal impairment, and lupus patients typically have other risk factors such as higher levels of LDL cholesterol and triglycerides (Arthritis Rheum. 2003;48:3159-67).

And these risk factors do have an impact. “In a cohort study, we stratified patients according to their total cholesterol levels and found that among those with persistently elevated cholesterol, 24% developed a cardiac event during 12 years of follow-up, compared with 3% whose cholesterol level was normal or varied only slightly with disease flares,” Dr. Bruce said at the meeting, sponsored by the British Society for Rheumatology.

But classic risk factors do not tell the whole story. (See box.) In the general population, risk for a cardiac event increases as risk factors accumulate. “Lupus patients, however, seem to be set at an intrinsically higher baseline, and the accumulation of risk factors has an even more devastating effect,” he said.

A great need exists for properly conducted clinical trials of potential interventions for these patients. “We need to see if what we think will work actually does work and what the magnitude of risk reduction is with a particular intervention,” he said.

Statins are an example. “Everywhere they have been used so far, they have been associated with a reduction in risk of coronary-disease events by about 30%. You could assume that also might be the case in lupus, but that could be a dangerous assumption, because these drugs might not be as well tolerated by lupus patients,” he said.

The larger scope of the disease also must be addressed. Future work must focus on the worldwide burden of atherosclerosis in lupus and consider the ethnic gradient of risk, which might reveal some interesting things about the pathogenesis, he said.

Classic Risk Factors Don't Tell the Whole Story

As the magnitude and severity of atherosclerosis and heart disease in systemic lupus erythematosus (SLE) become clearer, so do some possible mediators and markers. A series of posters presented at the meeting by researchers from the Karolinska Institute, Stockholm, explored various potential contributing factors:

▸ LDL cholesterol. Increased LDL-cholesterol oxidation contributes to lupus-related cardiovascular disease, reported Anna Cederholm, M.D. She compared levels of several risk and protective factors in three groups: 26 women with lupus plus cardiovascular disease, 26 women with lupus but no clinical manifestations of cardiovascular disease, and 26 normal controls. Circulating levels of oxidized LDL cholesterol were increased in both lupus groups, as was platelet-activating factor acetylhydrolase (PAF-AH). Levels of oxidized LDL cholesterol and PAF-AH also were significantly higher in the lupus patients with cardiovascular disease than in those with lupus and no heart disease. Because PAF-AH binds to LDL cholesterol, it also may contribute to atherogenesis, Dr. Cederholm said.

▸ Anti-HDL cholesterol antibodies. SLE-related dyslipidemia showed a surprising pattern in a study of women with a history of cardiovascular disease, reported J. Su, M.D. Large, rather than small, LDL- and HDL-cholesterol particles characterized the dyslipidemia profile. This was not an expected atherogenic lipid profile, Dr. Su explained.

Antibodies against apolipoprotein A1 in HDL cholesterol also were elevated and were associated with the presence of tumor necrosis factor. Whether these anti-apo A1 antibodies play a pathogenic role—for example, by inhibiting the anti-inflammatory properties of HDL—is under investigation, Dr. Su said.

▸ Homocysteine. Hyperhomocysteinemia in patients with lupus correlates with markers of inflammatory activity and is a risk factor for cardiovascular disease, said Elisabet Svenungsson, M.D. In fasting blood samples obtained from a cohort of 208 patients, homocysteine levels were associated with acute phase reactants including C-reactive protein, serum amyloid A protein, fibrinogen, and complement.

Hyperhomocysteinemia also correlated with the presence of arterial disease and nephritis. “It may cause endothelial activation and damage and thus adds to the inflammatory burden that we believe renders SLE patients highly susceptible to cardiovascular disease,” she said.

—Nancy Walsh

LONDON — The incidence of coronary heart disease among young women with systemic lupus erythematosus is “startlingly worrying,” Ian Bruce, M.D., said at the Sixth European Lupus Meeting.

Studies have shown that the annual incidence of ischemic heart disease in lupus patients is 1.3%-1.5%. In comparison, the incidence among those with newly diagnosed type 2 diabetes and among those who have had a first myocardial infarction is 2%-2.2% per annum. “This latter number may be higher, but you have to remember that these are men in their mid- to late 50s, while the lupus patients in these studies are women whose average age is 35-37,” said Dr. Bruce, of the University of Manchester (England).

The prevalence of myocardial infarction or angina in lupus cohorts ranges from 7% to 10%, depending on patient age and duration of follow-up, he said.

Moreover, as survival improves, the prevalence of the disease increases, as does the proportion of lupus patients who are older and at even greater risk for cardiovascular disease, he said.

Some epidemiologic work has suggested that the peak age of onset also is increasing and now occurs between the fifth to seventh decades. Damage accrues more quickly among patients who are older at onset, he added.

Atherosclerosis also occurs much earlier in women with lupus than in healthy women. “In women younger than 45 in the general population, you virtually do not see plaque, whereas women with lupus are beginning to acquire plaque at that early age,” Dr. Bruce said.

Classic risk factors clearly are implicated in the premature atherosclerosis and coronary heart disease seen in lupus. There is a much higher prevalence of hypertension, diabetes, and renal impairment, and lupus patients typically have other risk factors such as higher levels of LDL cholesterol and triglycerides (Arthritis Rheum. 2003;48:3159-67).

And these risk factors do have an impact. “In a cohort study, we stratified patients according to their total cholesterol levels and found that among those with persistently elevated cholesterol, 24% developed a cardiac event during 12 years of follow-up, compared with 3% whose cholesterol level was normal or varied only slightly with disease flares,” Dr. Bruce said at the meeting, sponsored by the British Society for Rheumatology.

But classic risk factors do not tell the whole story. (See box.) In the general population, risk for a cardiac event increases as risk factors accumulate. “Lupus patients, however, seem to be set at an intrinsically higher baseline, and the accumulation of risk factors has an even more devastating effect,” he said.

A great need exists for properly conducted clinical trials of potential interventions for these patients. “We need to see if what we think will work actually does work and what the magnitude of risk reduction is with a particular intervention,” he said.

Statins are an example. “Everywhere they have been used so far, they have been associated with a reduction in risk of coronary-disease events by about 30%. You could assume that also might be the case in lupus, but that could be a dangerous assumption, because these drugs might not be as well tolerated by lupus patients,” he said.

The larger scope of the disease also must be addressed. Future work must focus on the worldwide burden of atherosclerosis in lupus and consider the ethnic gradient of risk, which might reveal some interesting things about the pathogenesis, he said.

Classic Risk Factors Don't Tell the Whole Story

As the magnitude and severity of atherosclerosis and heart disease in systemic lupus erythematosus (SLE) become clearer, so do some possible mediators and markers. A series of posters presented at the meeting by researchers from the Karolinska Institute, Stockholm, explored various potential contributing factors:

▸ LDL cholesterol. Increased LDL-cholesterol oxidation contributes to lupus-related cardiovascular disease, reported Anna Cederholm, M.D. She compared levels of several risk and protective factors in three groups: 26 women with lupus plus cardiovascular disease, 26 women with lupus but no clinical manifestations of cardiovascular disease, and 26 normal controls. Circulating levels of oxidized LDL cholesterol were increased in both lupus groups, as was platelet-activating factor acetylhydrolase (PAF-AH). Levels of oxidized LDL cholesterol and PAF-AH also were significantly higher in the lupus patients with cardiovascular disease than in those with lupus and no heart disease. Because PAF-AH binds to LDL cholesterol, it also may contribute to atherogenesis, Dr. Cederholm said.

▸ Anti-HDL cholesterol antibodies. SLE-related dyslipidemia showed a surprising pattern in a study of women with a history of cardiovascular disease, reported J. Su, M.D. Large, rather than small, LDL- and HDL-cholesterol particles characterized the dyslipidemia profile. This was not an expected atherogenic lipid profile, Dr. Su explained.

Antibodies against apolipoprotein A1 in HDL cholesterol also were elevated and were associated with the presence of tumor necrosis factor. Whether these anti-apo A1 antibodies play a pathogenic role—for example, by inhibiting the anti-inflammatory properties of HDL—is under investigation, Dr. Su said.

▸ Homocysteine. Hyperhomocysteinemia in patients with lupus correlates with markers of inflammatory activity and is a risk factor for cardiovascular disease, said Elisabet Svenungsson, M.D. In fasting blood samples obtained from a cohort of 208 patients, homocysteine levels were associated with acute phase reactants including C-reactive protein, serum amyloid A protein, fibrinogen, and complement.

Hyperhomocysteinemia also correlated with the presence of arterial disease and nephritis. “It may cause endothelial activation and damage and thus adds to the inflammatory burden that we believe renders SLE patients highly susceptible to cardiovascular disease,” she said.

—Nancy Walsh

NEW ORLEANS — Real world experience with warfarin suggests that it is not as good at preventing strokes in patients with atrial fibrillation as clinical trial results have suggested, especially among African Americans.

A review of more than 23,000 Medicare patients with atrial fibrillation showed that overall, warfarin prophylaxis cut the stroke rate by 34%, compared with a 65% cut in strokes that's been consistently seen in clinical trials, Brian F. Gage, M.D., reported at the 30th International Stroke Conference.

This lower efficacy in a real-world setting is “disappointing,” said Dr. Gage, an internist at Washington University in St. Louis.

But warfarin performed even worse in the African Americans in the study. In this group, warfarin use was associated with a trend toward more strokes, although this increase was not statistically significant, compared with African Americans not on warfarin.

In this analysis, the 95% confidence interval showed that, at best, warfarin prophylaxis in African Americans produced an 18% reduction in strokes, compared with untreated patients. This benefit is close to the 22% stroke reduction from aspirin prophylaxis in all patients, a suggestion that aspirin prophylaxis may be just as good as or better than warfarin prophylaxis in African Americans. This hypothesis should be tested by analyzing results already collected in prior randomized, controlled studies, Dr. Gage told this newspaper.

The study used a national sample of 23,657 Medicare patients with atrial fibrillation who were treated during April 1998 through March 1999. Warfarin prophylaxis was used by 43% of African Americans in the study and by 50% of white patients.

Information culled from the medical records of the patients on warfarin therapy showed that this prophylaxis was often used in a less-than-ideal manner. Patients who regularly receive warfarin should have their dosage adjusted based on their international normalized ratio (INR), a measure of clotting time. Ideally, INRs should be measured about every 28 days in patients who regularly take warfarin.

Among all white patients, the average time between INR measurements was 26 days, and among African Americans the average interval was 30 days. But 25% of the white patients on warfarin had an interval of 39 days or longer between INR measurements. Among African Americans on warfarin, 25% had an interval of 57 days or longer between measurements, Dr. Gage said at the conference, sponsored by the American Stroke Association. For these subgroups, the interval between INR measurements was “way too long,” he said.

But substandard INR monitoring was not the only reason patients got less benefit from warfarin prophylaxis, compared with the benchmark of clinical trials. The rate of protection from stroke remained unexpectedly low among African Americans even in an analysis that controlled for the frequency of INR monitoring as well as clinical variables that predispose patients to strokes.

Other factors that were not controlled for in this analysis, and that may help explain warfarin's underachievement, include poor compliance with the warfarin regimen, inadequacies in the health care setting, and inadequate access to anticoagulant services, said Dr. Gage, who is also medical director of the Blood Thinner Clinic at Barnes-Jewish Hospital in St. Louis.

The clinical trials that assessed warfarin's efficacy for preventing strokes in patients with atrial fibrillation were highly selective; more than 90% of patients who were initially assessed for these trials were eventually excluded. The clinical trial results therefore came from patients that were mostly white, less than age 75 years, and followed very closely, and these results may not be generalizable to other health care settings, Dr. Gage said.

NEW ORLEANS — Real world experience with warfarin suggests that it is not as good at preventing strokes in patients with atrial fibrillation as clinical trial results have suggested, especially among African Americans.

A review of more than 23,000 Medicare patients with atrial fibrillation showed that overall, warfarin prophylaxis cut the stroke rate by 34%, compared with a 65% cut in strokes that's been consistently seen in clinical trials, Brian F. Gage, M.D., reported at the 30th International Stroke Conference.

This lower efficacy in a real-world setting is “disappointing,” said Dr. Gage, an internist at Washington University in St. Louis.

But warfarin performed even worse in the African Americans in the study. In this group, warfarin use was associated with a trend toward more strokes, although this increase was not statistically significant, compared with African Americans not on warfarin.

In this analysis, the 95% confidence interval showed that, at best, warfarin prophylaxis in African Americans produced an 18% reduction in strokes, compared with untreated patients. This benefit is close to the 22% stroke reduction from aspirin prophylaxis in all patients, a suggestion that aspirin prophylaxis may be just as good as or better than warfarin prophylaxis in African Americans. This hypothesis should be tested by analyzing results already collected in prior randomized, controlled studies, Dr. Gage told this newspaper.

The study used a national sample of 23,657 Medicare patients with atrial fibrillation who were treated during April 1998 through March 1999. Warfarin prophylaxis was used by 43% of African Americans in the study and by 50% of white patients.

Information culled from the medical records of the patients on warfarin therapy showed that this prophylaxis was often used in a less-than-ideal manner. Patients who regularly receive warfarin should have their dosage adjusted based on their international normalized ratio (INR), a measure of clotting time. Ideally, INRs should be measured about every 28 days in patients who regularly take warfarin.

Among all white patients, the average time between INR measurements was 26 days, and among African Americans the average interval was 30 days. But 25% of the white patients on warfarin had an interval of 39 days or longer between INR measurements. Among African Americans on warfarin, 25% had an interval of 57 days or longer between measurements, Dr. Gage said at the conference, sponsored by the American Stroke Association. For these subgroups, the interval between INR measurements was “way too long,” he said.

But substandard INR monitoring was not the only reason patients got less benefit from warfarin prophylaxis, compared with the benchmark of clinical trials. The rate of protection from stroke remained unexpectedly low among African Americans even in an analysis that controlled for the frequency of INR monitoring as well as clinical variables that predispose patients to strokes.

Other factors that were not controlled for in this analysis, and that may help explain warfarin's underachievement, include poor compliance with the warfarin regimen, inadequacies in the health care setting, and inadequate access to anticoagulant services, said Dr. Gage, who is also medical director of the Blood Thinner Clinic at Barnes-Jewish Hospital in St. Louis.

The clinical trials that assessed warfarin's efficacy for preventing strokes in patients with atrial fibrillation were highly selective; more than 90% of patients who were initially assessed for these trials were eventually excluded. The clinical trial results therefore came from patients that were mostly white, less than age 75 years, and followed very closely, and these results may not be generalizable to other health care settings, Dr. Gage said.

NEW ORLEANS — Real world experience with warfarin suggests that it is not as good at preventing strokes in patients with atrial fibrillation as clinical trial results have suggested, especially among African Americans.

A review of more than 23,000 Medicare patients with atrial fibrillation showed that overall, warfarin prophylaxis cut the stroke rate by 34%, compared with a 65% cut in strokes that's been consistently seen in clinical trials, Brian F. Gage, M.D., reported at the 30th International Stroke Conference.

This lower efficacy in a real-world setting is “disappointing,” said Dr. Gage, an internist at Washington University in St. Louis.

But warfarin performed even worse in the African Americans in the study. In this group, warfarin use was associated with a trend toward more strokes, although this increase was not statistically significant, compared with African Americans not on warfarin.

In this analysis, the 95% confidence interval showed that, at best, warfarin prophylaxis in African Americans produced an 18% reduction in strokes, compared with untreated patients. This benefit is close to the 22% stroke reduction from aspirin prophylaxis in all patients, a suggestion that aspirin prophylaxis may be just as good as or better than warfarin prophylaxis in African Americans. This hypothesis should be tested by analyzing results already collected in prior randomized, controlled studies, Dr. Gage told this newspaper.

The study used a national sample of 23,657 Medicare patients with atrial fibrillation who were treated during April 1998 through March 1999. Warfarin prophylaxis was used by 43% of African Americans in the study and by 50% of white patients.

Information culled from the medical records of the patients on warfarin therapy showed that this prophylaxis was often used in a less-than-ideal manner. Patients who regularly receive warfarin should have their dosage adjusted based on their international normalized ratio (INR), a measure of clotting time. Ideally, INRs should be measured about every 28 days in patients who regularly take warfarin.

Among all white patients, the average time between INR measurements was 26 days, and among African Americans the average interval was 30 days. But 25% of the white patients on warfarin had an interval of 39 days or longer between INR measurements. Among African Americans on warfarin, 25% had an interval of 57 days or longer between measurements, Dr. Gage said at the conference, sponsored by the American Stroke Association. For these subgroups, the interval between INR measurements was “way too long,” he said.

But substandard INR monitoring was not the only reason patients got less benefit from warfarin prophylaxis, compared with the benchmark of clinical trials. The rate of protection from stroke remained unexpectedly low among African Americans even in an analysis that controlled for the frequency of INR monitoring as well as clinical variables that predispose patients to strokes.

Other factors that were not controlled for in this analysis, and that may help explain warfarin's underachievement, include poor compliance with the warfarin regimen, inadequacies in the health care setting, and inadequate access to anticoagulant services, said Dr. Gage, who is also medical director of the Blood Thinner Clinic at Barnes-Jewish Hospital in St. Louis.

The clinical trials that assessed warfarin's efficacy for preventing strokes in patients with atrial fibrillation were highly selective; more than 90% of patients who were initially assessed for these trials were eventually excluded. The clinical trial results therefore came from patients that were mostly white, less than age 75 years, and followed very closely, and these results may not be generalizable to other health care settings, Dr. Gage said.

ORLANDO, FLA. — Three more salvos were fired in the battle of competing drug-eluting coronary stents. When the smoke cleared and findings from the new head-to-head trials were reported at the annual meeting of the American College of Cardiology, the sirolimus-eluting stent, Cypher, had edged the paclitaxel stent, Taxus, in two studies, with the third and largest trial ending in a draw.

With the results from at least four head-to-head studies now reported (results from the fourth were reported in January), the sirolimus-eluting stent has shown some consistent advantages.

The biggest difference between the two types of stents was seen in a study with 1,012 patients who were randomized to treatment with either sirolimus- or paclitaxel-eluting stents at two Swiss university hospitals. The study, named SIRTAX, was completely funded by the hospitals and received no industry sponsorship, said Stephan Windecker, M.D., a cardiologist at the University Hospital in Bern.

The study randomized all comers who required coronary stenting. Slightly more than half of the patients had acute coronary syndrome, almost a quarter had triple-vessel disease, and about 20% had diabetes. About 8% had ostial lesions, another 8% had lesions at bifurcations, 35% had calcified lesions, 37% had lesions of moderate or excessive tortuosity, and 2% of lesions were in saphenous vein grafts.

All patients were treated with 75 mg clopidogrel daily for a year following stenting, and all received 100 mg aspirin daily indefinitely.

The study's primary end point was the combined incidence of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization (TLR) within 9 months of treatment. The rate of this end point was 6.2% in the 503 patients who received sirolimus-eluting stents and 10.8% in the 509 who received paclitaxel-eluting stents, a statistically significant difference.

This outcome was driven largely by the difference in the need for TLR: 4.8% in patients who received sirolimus-eluting stents and 8.3% in those who got paclitaxel-eluting stents, also a statistically significant difference. All of the secondary end points also favored the sirolimus-eluting stent, although some of these were not statistically significant.

The advantage in the primary, combined end point for the sirolimus-eluting stents was especially dramatic in patients with diabetes. In this subgroup, sirolimus-eluting stents were associated with a better than threefold reduction in events, compared with the paclitaxel-eluting stents. The advantage was half as large in patients without diabetes. The two groups had identical rates of stent thrombosis.

An even larger, higher-profile trial failed to show a clear advantage for either type of stent. The highly anticipated prospective randomized multicenter head-to-head comparison of the two stents, named REALITY, was done at 90 centers in Europe, Asia, South America, and Mexico (but not in the United States), enrolled 1,353 patients, and was sponsored by Cordis, the company that makes and markets the sirolimus-eluting coronary stent.

This study involved a more highly selected group of patients, excluding those with ostial lesions, recent MIs, total occlusions, and certain other high-risk conditions. But 28% of patients had diabetes. After stenting, all patients received 100 mg of aspirin indefinitely. Daily treatment with a thienopyridine (clopidogrel or ticlopidine) was used for at least 2 months in all patients who received sirolimus-eluting stents and for at least 6 months in all patients who got paclitaxel-eluting stents.

The study's primary end point was the rate of in-lesion binary restenosis at 8 months after stenting, as measured by angiography. This rate was 9.6% in the sirolimus-eluting stents and 11.1% in the paclitaxel-eluting stents, a difference that was not statistically significant, reported Marie-Claude Morice, M.D., a cardiologist at the Cardiovascular Institute in Paris.

Other important clinical end points also failed to show a statistically significant difference between the two stent types. The combined rate of major coronary end points—cardiac death, MI, and TLR, was 9.2% in the patients who received sirolimus-eluting stents and 10.6% in those who received paclitaxel-eluting stents. The difference in the revascularization rate only was even tighter: 5.0% in the sirolimus-eluting stent group and 5.4% in those who got paclitaxel-eluting stents.

The only major differences between stent types in this study were in late in-stent lumen loss after 8 months, and in the rate of stent thrombosis during the first 30 days of treatment. Late loss averaged 0.1 mm with the sirolimus stents and 0.3 mm with the paclitaxel stents. Stent thrombosis occurred in 0.4% of patients who received sirolimus stents and in 1.8% of those who received paclitaxel stents. But the rate of stent thrombosis was not a prespecified end point for this study and a difference between the two stent types for this measure was unexpected. As a result, the clinical significance of this finding was unclear, Dr. Morice said.

The third set of study results presented at the meeting came from a single-center study with a total of 250 patients, all of whom had diabetes. Like the larger Swiss trial, this study, called ISAR-DIABETES, had no commercial funding and was sponsored solely by the German Heart Center in Munich.

This study had fewer exclusion criteria than the REALITY study. Exclusions were limited to patients with acute MI, left-main disease, in-stent restenosis, or an allergy to one of the study drugs.

The study's primary end point was the rate of in-segment, late lumen loss at 6-8 months after stenting, as measured by angiography. The average amount of late loss was 0.43 mm in patients who received sirolimus stents and 0.67 mm in those who got paclitaxel stents, a difference that was statistically significant, reported Adnan Kastrati, M.D., professor of cardiology at the German Heart Center.

Patients who received sirolimus stents also had significantly less angiographic restenosis than did those who got paclitaxel stents, 6.9% vs. 16.5%, respectively. But there were no statistically significant differences in clinical end points, including clinical restenosis and the rates of death and MI at 9 months after stenting.

Although the results from this third study showed differences only for angiographic end points, Dr. Kastrati said that he was convinced by the outcome. “The results will push us to select sirolimus-eluting stents for patients with diabetes,” he said.

In January, results were reported from a fourth study by Dr. Kastrati and associates that compared the two stent types, in 200 patients with in-stent restenosis. In that study, patients who received sirolimus-eluting stents had significantly less clinical restenosis compared with the patients who received paclitaxel-eluting stents (JAMA 2005;293:165-71).

ORLANDO, FLA. — Three more salvos were fired in the battle of competing drug-eluting coronary stents. When the smoke cleared and findings from the new head-to-head trials were reported at the annual meeting of the American College of Cardiology, the sirolimus-eluting stent, Cypher, had edged the paclitaxel stent, Taxus, in two studies, with the third and largest trial ending in a draw.

With the results from at least four head-to-head studies now reported (results from the fourth were reported in January), the sirolimus-eluting stent has shown some consistent advantages.

The biggest difference between the two types of stents was seen in a study with 1,012 patients who were randomized to treatment with either sirolimus- or paclitaxel-eluting stents at two Swiss university hospitals. The study, named SIRTAX, was completely funded by the hospitals and received no industry sponsorship, said Stephan Windecker, M.D., a cardiologist at the University Hospital in Bern.

The study randomized all comers who required coronary stenting. Slightly more than half of the patients had acute coronary syndrome, almost a quarter had triple-vessel disease, and about 20% had diabetes. About 8% had ostial lesions, another 8% had lesions at bifurcations, 35% had calcified lesions, 37% had lesions of moderate or excessive tortuosity, and 2% of lesions were in saphenous vein grafts.

All patients were treated with 75 mg clopidogrel daily for a year following stenting, and all received 100 mg aspirin daily indefinitely.

The study's primary end point was the combined incidence of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization (TLR) within 9 months of treatment. The rate of this end point was 6.2% in the 503 patients who received sirolimus-eluting stents and 10.8% in the 509 who received paclitaxel-eluting stents, a statistically significant difference.

This outcome was driven largely by the difference in the need for TLR: 4.8% in patients who received sirolimus-eluting stents and 8.3% in those who got paclitaxel-eluting stents, also a statistically significant difference. All of the secondary end points also favored the sirolimus-eluting stent, although some of these were not statistically significant.

The advantage in the primary, combined end point for the sirolimus-eluting stents was especially dramatic in patients with diabetes. In this subgroup, sirolimus-eluting stents were associated with a better than threefold reduction in events, compared with the paclitaxel-eluting stents. The advantage was half as large in patients without diabetes. The two groups had identical rates of stent thrombosis.

An even larger, higher-profile trial failed to show a clear advantage for either type of stent. The highly anticipated prospective randomized multicenter head-to-head comparison of the two stents, named REALITY, was done at 90 centers in Europe, Asia, South America, and Mexico (but not in the United States), enrolled 1,353 patients, and was sponsored by Cordis, the company that makes and markets the sirolimus-eluting coronary stent.

This study involved a more highly selected group of patients, excluding those with ostial lesions, recent MIs, total occlusions, and certain other high-risk conditions. But 28% of patients had diabetes. After stenting, all patients received 100 mg of aspirin indefinitely. Daily treatment with a thienopyridine (clopidogrel or ticlopidine) was used for at least 2 months in all patients who received sirolimus-eluting stents and for at least 6 months in all patients who got paclitaxel-eluting stents.

The study's primary end point was the rate of in-lesion binary restenosis at 8 months after stenting, as measured by angiography. This rate was 9.6% in the sirolimus-eluting stents and 11.1% in the paclitaxel-eluting stents, a difference that was not statistically significant, reported Marie-Claude Morice, M.D., a cardiologist at the Cardiovascular Institute in Paris.

Other important clinical end points also failed to show a statistically significant difference between the two stent types. The combined rate of major coronary end points—cardiac death, MI, and TLR, was 9.2% in the patients who received sirolimus-eluting stents and 10.6% in those who received paclitaxel-eluting stents. The difference in the revascularization rate only was even tighter: 5.0% in the sirolimus-eluting stent group and 5.4% in those who got paclitaxel-eluting stents.

The only major differences between stent types in this study were in late in-stent lumen loss after 8 months, and in the rate of stent thrombosis during the first 30 days of treatment. Late loss averaged 0.1 mm with the sirolimus stents and 0.3 mm with the paclitaxel stents. Stent thrombosis occurred in 0.4% of patients who received sirolimus stents and in 1.8% of those who received paclitaxel stents. But the rate of stent thrombosis was not a prespecified end point for this study and a difference between the two stent types for this measure was unexpected. As a result, the clinical significance of this finding was unclear, Dr. Morice said.

The third set of study results presented at the meeting came from a single-center study with a total of 250 patients, all of whom had diabetes. Like the larger Swiss trial, this study, called ISAR-DIABETES, had no commercial funding and was sponsored solely by the German Heart Center in Munich.

This study had fewer exclusion criteria than the REALITY study. Exclusions were limited to patients with acute MI, left-main disease, in-stent restenosis, or an allergy to one of the study drugs.

The study's primary end point was the rate of in-segment, late lumen loss at 6-8 months after stenting, as measured by angiography. The average amount of late loss was 0.43 mm in patients who received sirolimus stents and 0.67 mm in those who got paclitaxel stents, a difference that was statistically significant, reported Adnan Kastrati, M.D., professor of cardiology at the German Heart Center.

Patients who received sirolimus stents also had significantly less angiographic restenosis than did those who got paclitaxel stents, 6.9% vs. 16.5%, respectively. But there were no statistically significant differences in clinical end points, including clinical restenosis and the rates of death and MI at 9 months after stenting.

Although the results from this third study showed differences only for angiographic end points, Dr. Kastrati said that he was convinced by the outcome. “The results will push us to select sirolimus-eluting stents for patients with diabetes,” he said.

In January, results were reported from a fourth study by Dr. Kastrati and associates that compared the two stent types, in 200 patients with in-stent restenosis. In that study, patients who received sirolimus-eluting stents had significantly less clinical restenosis compared with the patients who received paclitaxel-eluting stents (JAMA 2005;293:165-71).

ORLANDO, FLA. — Three more salvos were fired in the battle of competing drug-eluting coronary stents. When the smoke cleared and findings from the new head-to-head trials were reported at the annual meeting of the American College of Cardiology, the sirolimus-eluting stent, Cypher, had edged the paclitaxel stent, Taxus, in two studies, with the third and largest trial ending in a draw.

With the results from at least four head-to-head studies now reported (results from the fourth were reported in January), the sirolimus-eluting stent has shown some consistent advantages.

The biggest difference between the two types of stents was seen in a study with 1,012 patients who were randomized to treatment with either sirolimus- or paclitaxel-eluting stents at two Swiss university hospitals. The study, named SIRTAX, was completely funded by the hospitals and received no industry sponsorship, said Stephan Windecker, M.D., a cardiologist at the University Hospital in Bern.

The study randomized all comers who required coronary stenting. Slightly more than half of the patients had acute coronary syndrome, almost a quarter had triple-vessel disease, and about 20% had diabetes. About 8% had ostial lesions, another 8% had lesions at bifurcations, 35% had calcified lesions, 37% had lesions of moderate or excessive tortuosity, and 2% of lesions were in saphenous vein grafts.

All patients were treated with 75 mg clopidogrel daily for a year following stenting, and all received 100 mg aspirin daily indefinitely.

The study's primary end point was the combined incidence of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization (TLR) within 9 months of treatment. The rate of this end point was 6.2% in the 503 patients who received sirolimus-eluting stents and 10.8% in the 509 who received paclitaxel-eluting stents, a statistically significant difference.

This outcome was driven largely by the difference in the need for TLR: 4.8% in patients who received sirolimus-eluting stents and 8.3% in those who got paclitaxel-eluting stents, also a statistically significant difference. All of the secondary end points also favored the sirolimus-eluting stent, although some of these were not statistically significant.

The advantage in the primary, combined end point for the sirolimus-eluting stents was especially dramatic in patients with diabetes. In this subgroup, sirolimus-eluting stents were associated with a better than threefold reduction in events, compared with the paclitaxel-eluting stents. The advantage was half as large in patients without diabetes. The two groups had identical rates of stent thrombosis.

An even larger, higher-profile trial failed to show a clear advantage for either type of stent. The highly anticipated prospective randomized multicenter head-to-head comparison of the two stents, named REALITY, was done at 90 centers in Europe, Asia, South America, and Mexico (but not in the United States), enrolled 1,353 patients, and was sponsored by Cordis, the company that makes and markets the sirolimus-eluting coronary stent.

This study involved a more highly selected group of patients, excluding those with ostial lesions, recent MIs, total occlusions, and certain other high-risk conditions. But 28% of patients had diabetes. After stenting, all patients received 100 mg of aspirin indefinitely. Daily treatment with a thienopyridine (clopidogrel or ticlopidine) was used for at least 2 months in all patients who received sirolimus-eluting stents and for at least 6 months in all patients who got paclitaxel-eluting stents.

The study's primary end point was the rate of in-lesion binary restenosis at 8 months after stenting, as measured by angiography. This rate was 9.6% in the sirolimus-eluting stents and 11.1% in the paclitaxel-eluting stents, a difference that was not statistically significant, reported Marie-Claude Morice, M.D., a cardiologist at the Cardiovascular Institute in Paris.

Other important clinical end points also failed to show a statistically significant difference between the two stent types. The combined rate of major coronary end points—cardiac death, MI, and TLR, was 9.2% in the patients who received sirolimus-eluting stents and 10.6% in those who received paclitaxel-eluting stents. The difference in the revascularization rate only was even tighter: 5.0% in the sirolimus-eluting stent group and 5.4% in those who got paclitaxel-eluting stents.

The only major differences between stent types in this study were in late in-stent lumen loss after 8 months, and in the rate of stent thrombosis during the first 30 days of treatment. Late loss averaged 0.1 mm with the sirolimus stents and 0.3 mm with the paclitaxel stents. Stent thrombosis occurred in 0.4% of patients who received sirolimus stents and in 1.8% of those who received paclitaxel stents. But the rate of stent thrombosis was not a prespecified end point for this study and a difference between the two stent types for this measure was unexpected. As a result, the clinical significance of this finding was unclear, Dr. Morice said.

The third set of study results presented at the meeting came from a single-center study with a total of 250 patients, all of whom had diabetes. Like the larger Swiss trial, this study, called ISAR-DIABETES, had no commercial funding and was sponsored solely by the German Heart Center in Munich.

This study had fewer exclusion criteria than the REALITY study. Exclusions were limited to patients with acute MI, left-main disease, in-stent restenosis, or an allergy to one of the study drugs.

The study's primary end point was the rate of in-segment, late lumen loss at 6-8 months after stenting, as measured by angiography. The average amount of late loss was 0.43 mm in patients who received sirolimus stents and 0.67 mm in those who got paclitaxel stents, a difference that was statistically significant, reported Adnan Kastrati, M.D., professor of cardiology at the German Heart Center.

Patients who received sirolimus stents also had significantly less angiographic restenosis than did those who got paclitaxel stents, 6.9% vs. 16.5%, respectively. But there were no statistically significant differences in clinical end points, including clinical restenosis and the rates of death and MI at 9 months after stenting.

Although the results from this third study showed differences only for angiographic end points, Dr. Kastrati said that he was convinced by the outcome. “The results will push us to select sirolimus-eluting stents for patients with diabetes,” he said.

In January, results were reported from a fourth study by Dr. Kastrati and associates that compared the two stent types, in 200 patients with in-stent restenosis. In that study, patients who received sirolimus-eluting stents had significantly less clinical restenosis compared with the patients who received paclitaxel-eluting stents (JAMA 2005;293:165-71).

Despite their higher cost, and despite recent concerns about late thrombosis, drug-eluting stents now dominate.

In the final 3 months of 2004, drug-eluting stents were estimated to have been used for 87% of all interventional coronary procedures in the United States, Martin B. Leon, M.D., said last November at the American Heart Association's scientific sessions in New Orleans. Less than 2 years earlier, not a single drug-eluting stent had been used in the United States outside of a clinical trial. The Food and Drug Administration first approved a drug-eluting stent in April 2003.

“We have not yet identified any subsets of patients who don't benefit from receiving drug-eluting stents [by having less restenosis] compared with bare metal stents,” said David J. Cohen, M.D., associate director of interventional cardiology at Beth Israel Deaconess Medical Center in Boston. “De facto practice in the United States today is to use drug-eluting stents whenever the available stent lengths and diameters fit. At Beth Israel Deaconess, most of the time when patients [who are undergoing coronary stenting] don't receive drug-eluting stents it's because the vessel is too small or too large to accommodate available stent sizes,” he told this newspaper.

They are so widespread that medicolegal concerns may now drive their use even more than purely clinical factors. “When the risk of restenosis is low, operators must balance the need for drug-eluting stents with the medicolegal risk of avoiding what has become the de facto standard of care for all patients,” said Herbert D. Aronow, M.D., director of the cardiac catheterization laboratories at the Veterans Affairs Medical Center in Philadelphia.

According to one study, in 2003, about a third of all sirolimus-eluting (Cypher) stents used in the United States were for off-label coronary artery indications (CARDIOLOGY NEWS, February 2005, p. 15).

As of early this year, no cardiology society had issued formal recommendations on the appropriate uses of drug-eluting stents, although these are expected soon. In the meantime, some experts have given their personal opinions.

One set of standards was laid out by Gregg W. Stone, M.D., in a talk at the AHA scientific session. “In workhorse lesions, in patients undergoing elective coronary interventions with de novo lesions up to 46 mm in length and in vessels with reference diameters of 2.5-3.75 mm without acute coronary syndrome or acute MI, in general the safety and efficacy of two drug-eluting stents, Cypher and Taxus [paclitaxel-eluting], has been proved,” said Dr. Stone, an interventional cardiologist at Columbia University in New York. “Using drug-eluting stents over bare metal stents in these lesions is the appropriate thing to do.”

But, he added, “we desperately need more data regarding the safety and efficacy of drug-eluting stents in unapproved and high-risk indications before their use should be considered routine. … You need to be aware of the evidence so you know what you are doing.”

A step was taken this past March to better define the safety and efficacy of drug-eluting stents in more complex vessels and lesions, with reports from two studies at the annual meeting of the American College of Cardiology. A Danish study with 322 patients compared sirolimus-eluting with bare-metal stents in patients with total occlusions, lesions at bifurcations, ostial lesions, and lesions in angulated arteries. Patients who received drug-eluting stents had better angiographic and clinical outcomes. A second report involved more than 1,100 patients who were treated with either paclitaxel-eluting or bare metal stents. The results showed that the drug-eluting stents were superior in coronaries narrower than 2.25 mm and in wide arteries.

According to Dr. Stone last November, there are also grounds for using a single drug-eluting stent to treat in-stent restenosis within a bare metal stent. But he cautioned physicians to “think twice” about using drug-eluting stents outside of a study for unprotected left main disease, in-stent restenosis following failed brachytherapy, and in patients with acute myocardial infarction. There is even less evidence on using drug-eluting stents for V-stenting of a bifurcation, and it is completely unclear how cardiologists should manage restenosis within a drug-eluting stent.

Despite their higher cost, and despite recent concerns about late thrombosis, drug-eluting stents now dominate.

In the final 3 months of 2004, drug-eluting stents were estimated to have been used for 87% of all interventional coronary procedures in the United States, Martin B. Leon, M.D., said last November at the American Heart Association's scientific sessions in New Orleans. Less than 2 years earlier, not a single drug-eluting stent had been used in the United States outside of a clinical trial. The Food and Drug Administration first approved a drug-eluting stent in April 2003.

“We have not yet identified any subsets of patients who don't benefit from receiving drug-eluting stents [by having less restenosis] compared with bare metal stents,” said David J. Cohen, M.D., associate director of interventional cardiology at Beth Israel Deaconess Medical Center in Boston. “De facto practice in the United States today is to use drug-eluting stents whenever the available stent lengths and diameters fit. At Beth Israel Deaconess, most of the time when patients [who are undergoing coronary stenting] don't receive drug-eluting stents it's because the vessel is too small or too large to accommodate available stent sizes,” he told this newspaper.

They are so widespread that medicolegal concerns may now drive their use even more than purely clinical factors. “When the risk of restenosis is low, operators must balance the need for drug-eluting stents with the medicolegal risk of avoiding what has become the de facto standard of care for all patients,” said Herbert D. Aronow, M.D., director of the cardiac catheterization laboratories at the Veterans Affairs Medical Center in Philadelphia.

According to one study, in 2003, about a third of all sirolimus-eluting (Cypher) stents used in the United States were for off-label coronary artery indications (CARDIOLOGY NEWS, February 2005, p. 15).

As of early this year, no cardiology society had issued formal recommendations on the appropriate uses of drug-eluting stents, although these are expected soon. In the meantime, some experts have given their personal opinions.

One set of standards was laid out by Gregg W. Stone, M.D., in a talk at the AHA scientific session. “In workhorse lesions, in patients undergoing elective coronary interventions with de novo lesions up to 46 mm in length and in vessels with reference diameters of 2.5-3.75 mm without acute coronary syndrome or acute MI, in general the safety and efficacy of two drug-eluting stents, Cypher and Taxus [paclitaxel-eluting], has been proved,” said Dr. Stone, an interventional cardiologist at Columbia University in New York. “Using drug-eluting stents over bare metal stents in these lesions is the appropriate thing to do.”

But, he added, “we desperately need more data regarding the safety and efficacy of drug-eluting stents in unapproved and high-risk indications before their use should be considered routine. … You need to be aware of the evidence so you know what you are doing.”

A step was taken this past March to better define the safety and efficacy of drug-eluting stents in more complex vessels and lesions, with reports from two studies at the annual meeting of the American College of Cardiology. A Danish study with 322 patients compared sirolimus-eluting with bare-metal stents in patients with total occlusions, lesions at bifurcations, ostial lesions, and lesions in angulated arteries. Patients who received drug-eluting stents had better angiographic and clinical outcomes. A second report involved more than 1,100 patients who were treated with either paclitaxel-eluting or bare metal stents. The results showed that the drug-eluting stents were superior in coronaries narrower than 2.25 mm and in wide arteries.

According to Dr. Stone last November, there are also grounds for using a single drug-eluting stent to treat in-stent restenosis within a bare metal stent. But he cautioned physicians to “think twice” about using drug-eluting stents outside of a study for unprotected left main disease, in-stent restenosis following failed brachytherapy, and in patients with acute myocardial infarction. There is even less evidence on using drug-eluting stents for V-stenting of a bifurcation, and it is completely unclear how cardiologists should manage restenosis within a drug-eluting stent.

Despite their higher cost, and despite recent concerns about late thrombosis, drug-eluting stents now dominate.

In the final 3 months of 2004, drug-eluting stents were estimated to have been used for 87% of all interventional coronary procedures in the United States, Martin B. Leon, M.D., said last November at the American Heart Association's scientific sessions in New Orleans. Less than 2 years earlier, not a single drug-eluting stent had been used in the United States outside of a clinical trial. The Food and Drug Administration first approved a drug-eluting stent in April 2003.

“We have not yet identified any subsets of patients who don't benefit from receiving drug-eluting stents [by having less restenosis] compared with bare metal stents,” said David J. Cohen, M.D., associate director of interventional cardiology at Beth Israel Deaconess Medical Center in Boston. “De facto practice in the United States today is to use drug-eluting stents whenever the available stent lengths and diameters fit. At Beth Israel Deaconess, most of the time when patients [who are undergoing coronary stenting] don't receive drug-eluting stents it's because the vessel is too small or too large to accommodate available stent sizes,” he told this newspaper.

They are so widespread that medicolegal concerns may now drive their use even more than purely clinical factors. “When the risk of restenosis is low, operators must balance the need for drug-eluting stents with the medicolegal risk of avoiding what has become the de facto standard of care for all patients,” said Herbert D. Aronow, M.D., director of the cardiac catheterization laboratories at the Veterans Affairs Medical Center in Philadelphia.

According to one study, in 2003, about a third of all sirolimus-eluting (Cypher) stents used in the United States were for off-label coronary artery indications (CARDIOLOGY NEWS, February 2005, p. 15).

As of early this year, no cardiology society had issued formal recommendations on the appropriate uses of drug-eluting stents, although these are expected soon. In the meantime, some experts have given their personal opinions.

One set of standards was laid out by Gregg W. Stone, M.D., in a talk at the AHA scientific session. “In workhorse lesions, in patients undergoing elective coronary interventions with de novo lesions up to 46 mm in length and in vessels with reference diameters of 2.5-3.75 mm without acute coronary syndrome or acute MI, in general the safety and efficacy of two drug-eluting stents, Cypher and Taxus [paclitaxel-eluting], has been proved,” said Dr. Stone, an interventional cardiologist at Columbia University in New York. “Using drug-eluting stents over bare metal stents in these lesions is the appropriate thing to do.”

But, he added, “we desperately need more data regarding the safety and efficacy of drug-eluting stents in unapproved and high-risk indications before their use should be considered routine. … You need to be aware of the evidence so you know what you are doing.”

A step was taken this past March to better define the safety and efficacy of drug-eluting stents in more complex vessels and lesions, with reports from two studies at the annual meeting of the American College of Cardiology. A Danish study with 322 patients compared sirolimus-eluting with bare-metal stents in patients with total occlusions, lesions at bifurcations, ostial lesions, and lesions in angulated arteries. Patients who received drug-eluting stents had better angiographic and clinical outcomes. A second report involved more than 1,100 patients who were treated with either paclitaxel-eluting or bare metal stents. The results showed that the drug-eluting stents were superior in coronaries narrower than 2.25 mm and in wide arteries.

According to Dr. Stone last November, there are also grounds for using a single drug-eluting stent to treat in-stent restenosis within a bare metal stent. But he cautioned physicians to “think twice” about using drug-eluting stents outside of a study for unprotected left main disease, in-stent restenosis following failed brachytherapy, and in patients with acute myocardial infarction. There is even less evidence on using drug-eluting stents for V-stenting of a bifurcation, and it is completely unclear how cardiologists should manage restenosis within a drug-eluting stent.

The vision of a re-engineered hospital with patient-centered care, delivered by a fully empowered team of professionals, which is data driven with clear quality measurements, where better performance is rewarded by better compensation is coming to a hospital near you during your professional career. And SHM and hospitalists are at the center of this revolution in the care of the acutely ill patient.

Hospitals are complex organizations with many moving parts and many unique constituencies often with different and, at times, competing definitions of success. What is clear is that even though many people have been talking about rewarding quality or making the hospital work for the patient, the current system is primarily physician centered and driven by increasing units of activity rather than how well a job is done. If we had the ideal system the patient would be able to demand that the physician appear when he wanted him to and we would be paying more for the best quality of care.

In order to change this complex system many institutions will need to be overhauled. The physical plant of the hospital may need to change from the noisy centralized nurses’ station where the health professionals congregate to a place designed to have data and nurses and doctors at the bedside. This would be the first concrete step to get the important members of the team (physicians, nurses, pharmacists, therapists) closer to the patient and closer to each other. The next step is to figure out how best to use everyone’s knowledge and perspective of the patient to provide more efficient and more effective care. SHM is working with Robert Wood Johnson Foundation and others on this initiative.

We will need to shift the data we collect from being mostly about getting paid to more about measuring how good a job we are doing. And while we are at it, it would be good if we could agree on what should be measured and if we could create a constant format so we can compare performance between institutions and groups. It would also be nice if physicians would agree to even be measured, and even better if physicians would be active participants in validating and responding to the data.

Then we would need to get the payers, the businesses and the insurers, and the government to care enough about quality to put their money where their measurements are and start paying for better performance rather than for more units of service (e.g., more visits, procedures, or surgeries, no matter the indications or the outcomes).

Before you start thinking this is the raving of someone who wants manna from heaven, let me point out what is happening right now in 2005.

SHM has partnered with the Critical Care Institute of the American College of Chest Physicians (ACCP), the American Association of Critical Care Nurses (AACCN), the American Society of Health System Pharmacists (ASHP), and others to form a Critical Care Collaborative. Together these organizations represent over 100,000 healthcare professionals and through their leadership will work towards designing a more patient-focused approach that relies on communication and cooperation from the entire team responsible for delivering patient care. The goal will be to design and test models of care, as well as to increase recognition and awareness of existing models by tapping into the resources of the participating organizations. Efforts will be directed at all elements of the system including the point of care, support systems (IT), administration, payers, and regulatory bodies.

SHM is also actively participating in quality and team-based initiatives with the endocrine societies and the cardiology communities. This will lead to a new way of managing care in diabetes, heart failure, coronary artery disease, and deep vein thrombosis and pulmonary embolism.

On a national level President Bush has appointed David Brailler as the “health IT czar” with the charge to expand and integrate the information capabilities in health care. This coupled with the work being done at the National Quality Forum by Ken Kizer and others will lead to practical front line applications of standards of care and the ability to measure our performance in the reality of today’s hospital.

And even the payers are getting into the mix. The new buzz words are “pay for performance” and it is all the rage. CMS and others are well into beta test programs to see just how this would play out. Peer pressure and restriction of privileges have been the only concrete drivers to improve quality in the past. The prospect that demonstrable, measurable better care will translate into more compensation or greater market share is being tested in today’s hospital.

This is not a pipe dream or a Ralph Waldo Emerson essay. These initiatives are being driven by capable action oriented leaders who have a history of making change happen. And hospitalists, who for the most part are in the beginning of a 20 to 30-year professional career, are primed to play significant roles in this changing dynamic.

In the most basic way, today’s 12,000 hospitalists and the next 20,000 who will join us in the coming years must be much more than just willing participants to make this fly. Sure hospitalists will be the effector arm of health system change in their hospitals, but hospitalists must have

the skills and the vision to help shape this better day in health care. Hospitalists need to embrace the patient-centered, performance-driven acute care system. Hospitalists need to demand care delivered by teams and have the leadership skills to help these teams manage and lead change.

This wasn’t taught in medical school or residency, but that doesn’t matter. Hospital medicine as a new specialty has arrived coincident to (or by design at) a special moment in health care. Our patients have expectations of excellent care. There are plenty of resources available to do the best job. We just aren’t organized to be the best that we can be. But this will all be sorted out in the coming years. It is an exciting time to be a health professional, and hospitalists are at the center. And SHM has the vision and will have the programs to help our hospitalists be an important part in creating this new era of health care.

The vision of a re-engineered hospital with patient-centered care, delivered by a fully empowered team of professionals, which is data driven with clear quality measurements, where better performance is rewarded by better compensation is coming to a hospital near you during your professional career. And SHM and hospitalists are at the center of this revolution in the care of the acutely ill patient.

Hospitals are complex organizations with many moving parts and many unique constituencies often with different and, at times, competing definitions of success. What is clear is that even though many people have been talking about rewarding quality or making the hospital work for the patient, the current system is primarily physician centered and driven by increasing units of activity rather than how well a job is done. If we had the ideal system the patient would be able to demand that the physician appear when he wanted him to and we would be paying more for the best quality of care.

In order to change this complex system many institutions will need to be overhauled. The physical plant of the hospital may need to change from the noisy centralized nurses’ station where the health professionals congregate to a place designed to have data and nurses and doctors at the bedside. This would be the first concrete step to get the important members of the team (physicians, nurses, pharmacists, therapists) closer to the patient and closer to each other. The next step is to figure out how best to use everyone’s knowledge and perspective of the patient to provide more efficient and more effective care. SHM is working with Robert Wood Johnson Foundation and others on this initiative.

We will need to shift the data we collect from being mostly about getting paid to more about measuring how good a job we are doing. And while we are at it, it would be good if we could agree on what should be measured and if we could create a constant format so we can compare performance between institutions and groups. It would also be nice if physicians would agree to even be measured, and even better if physicians would be active participants in validating and responding to the data.

Then we would need to get the payers, the businesses and the insurers, and the government to care enough about quality to put their money where their measurements are and start paying for better performance rather than for more units of service (e.g., more visits, procedures, or surgeries, no matter the indications or the outcomes).

Before you start thinking this is the raving of someone who wants manna from heaven, let me point out what is happening right now in 2005.

SHM has partnered with the Critical Care Institute of the American College of Chest Physicians (ACCP), the American Association of Critical Care Nurses (AACCN), the American Society of Health System Pharmacists (ASHP), and others to form a Critical Care Collaborative. Together these organizations represent over 100,000 healthcare professionals and through their leadership will work towards designing a more patient-focused approach that relies on communication and cooperation from the entire team responsible for delivering patient care. The goal will be to design and test models of care, as well as to increase recognition and awareness of existing models by tapping into the resources of the participating organizations. Efforts will be directed at all elements of the system including the point of care, support systems (IT), administration, payers, and regulatory bodies.

SHM is also actively participating in quality and team-based initiatives with the endocrine societies and the cardiology communities. This will lead to a new way of managing care in diabetes, heart failure, coronary artery disease, and deep vein thrombosis and pulmonary embolism.

On a national level President Bush has appointed David Brailler as the “health IT czar” with the charge to expand and integrate the information capabilities in health care. This coupled with the work being done at the National Quality Forum by Ken Kizer and others will lead to practical front line applications of standards of care and the ability to measure our performance in the reality of today’s hospital.

And even the payers are getting into the mix. The new buzz words are “pay for performance” and it is all the rage. CMS and others are well into beta test programs to see just how this would play out. Peer pressure and restriction of privileges have been the only concrete drivers to improve quality in the past. The prospect that demonstrable, measurable better care will translate into more compensation or greater market share is being tested in today’s hospital.

This is not a pipe dream or a Ralph Waldo Emerson essay. These initiatives are being driven by capable action oriented leaders who have a history of making change happen. And hospitalists, who for the most part are in the beginning of a 20 to 30-year professional career, are primed to play significant roles in this changing dynamic.

In the most basic way, today’s 12,000 hospitalists and the next 20,000 who will join us in the coming years must be much more than just willing participants to make this fly. Sure hospitalists will be the effector arm of health system change in their hospitals, but hospitalists must have

the skills and the vision to help shape this better day in health care. Hospitalists need to embrace the patient-centered, performance-driven acute care system. Hospitalists need to demand care delivered by teams and have the leadership skills to help these teams manage and lead change.

This wasn’t taught in medical school or residency, but that doesn’t matter. Hospital medicine as a new specialty has arrived coincident to (or by design at) a special moment in health care. Our patients have expectations of excellent care. There are plenty of resources available to do the best job. We just aren’t organized to be the best that we can be. But this will all be sorted out in the coming years. It is an exciting time to be a health professional, and hospitalists are at the center. And SHM has the vision and will have the programs to help our hospitalists be an important part in creating this new era of health care.

The vision of a re-engineered hospital with patient-centered care, delivered by a fully empowered team of professionals, which is data driven with clear quality measurements, where better performance is rewarded by better compensation is coming to a hospital near you during your professional career. And SHM and hospitalists are at the center of this revolution in the care of the acutely ill patient.

Hospitals are complex organizations with many moving parts and many unique constituencies often with different and, at times, competing definitions of success. What is clear is that even though many people have been talking about rewarding quality or making the hospital work for the patient, the current system is primarily physician centered and driven by increasing units of activity rather than how well a job is done. If we had the ideal system the patient would be able to demand that the physician appear when he wanted him to and we would be paying more for the best quality of care.

In order to change this complex system many institutions will need to be overhauled. The physical plant of the hospital may need to change from the noisy centralized nurses’ station where the health professionals congregate to a place designed to have data and nurses and doctors at the bedside. This would be the first concrete step to get the important members of the team (physicians, nurses, pharmacists, therapists) closer to the patient and closer to each other. The next step is to figure out how best to use everyone’s knowledge and perspective of the patient to provide more efficient and more effective care. SHM is working with Robert Wood Johnson Foundation and others on this initiative.

We will need to shift the data we collect from being mostly about getting paid to more about measuring how good a job we are doing. And while we are at it, it would be good if we could agree on what should be measured and if we could create a constant format so we can compare performance between institutions and groups. It would also be nice if physicians would agree to even be measured, and even better if physicians would be active participants in validating and responding to the data.

Then we would need to get the payers, the businesses and the insurers, and the government to care enough about quality to put their money where their measurements are and start paying for better performance rather than for more units of service (e.g., more visits, procedures, or surgeries, no matter the indications or the outcomes).

Before you start thinking this is the raving of someone who wants manna from heaven, let me point out what is happening right now in 2005.

SHM has partnered with the Critical Care Institute of the American College of Chest Physicians (ACCP), the American Association of Critical Care Nurses (AACCN), the American Society of Health System Pharmacists (ASHP), and others to form a Critical Care Collaborative. Together these organizations represent over 100,000 healthcare professionals and through their leadership will work towards designing a more patient-focused approach that relies on communication and cooperation from the entire team responsible for delivering patient care. The goal will be to design and test models of care, as well as to increase recognition and awareness of existing models by tapping into the resources of the participating organizations. Efforts will be directed at all elements of the system including the point of care, support systems (IT), administration, payers, and regulatory bodies.

SHM is also actively participating in quality and team-based initiatives with the endocrine societies and the cardiology communities. This will lead to a new way of managing care in diabetes, heart failure, coronary artery disease, and deep vein thrombosis and pulmonary embolism.

On a national level President Bush has appointed David Brailler as the “health IT czar” with the charge to expand and integrate the information capabilities in health care. This coupled with the work being done at the National Quality Forum by Ken Kizer and others will lead to practical front line applications of standards of care and the ability to measure our performance in the reality of today’s hospital.

And even the payers are getting into the mix. The new buzz words are “pay for performance” and it is all the rage. CMS and others are well into beta test programs to see just how this would play out. Peer pressure and restriction of privileges have been the only concrete drivers to improve quality in the past. The prospect that demonstrable, measurable better care will translate into more compensation or greater market share is being tested in today’s hospital.

This is not a pipe dream or a Ralph Waldo Emerson essay. These initiatives are being driven by capable action oriented leaders who have a history of making change happen. And hospitalists, who for the most part are in the beginning of a 20 to 30-year professional career, are primed to play significant roles in this changing dynamic.

In the most basic way, today’s 12,000 hospitalists and the next 20,000 who will join us in the coming years must be much more than just willing participants to make this fly. Sure hospitalists will be the effector arm of health system change in their hospitals, but hospitalists must have

the skills and the vision to help shape this better day in health care. Hospitalists need to embrace the patient-centered, performance-driven acute care system. Hospitalists need to demand care delivered by teams and have the leadership skills to help these teams manage and lead change.

This wasn’t taught in medical school or residency, but that doesn’t matter. Hospital medicine as a new specialty has arrived coincident to (or by design at) a special moment in health care. Our patients have expectations of excellent care. There are plenty of resources available to do the best job. We just aren’t organized to be the best that we can be. But this will all be sorted out in the coming years. It is an exciting time to be a health professional, and hospitalists are at the center. And SHM has the vision and will have the programs to help our hospitalists be an important part in creating this new era of health care.