Role of ACE Inhibitors in Preventing Scleroderma Renal Crisis Remains Unclear

CANCUN, MEXICO - Scleroderma patients on angiotensin-converting enzyme inhibitors at the onset of scleroderma renal crisis do not appear to have worse outcomes than do those not taking the antihypertensive agents prior to the acute renal function deterioration, according to preliminary data from the largest prospective cohort study of incident scleroderma renal crisis to date.

The finding further fuels the ongoing debate over the role of angiotensin-converting enzyme (ACE) inhibitors as prophylaxis for scleroderma renal crisis (SRC), lead investigator Dr. Marie Hudson reported at the annual meeting of the Canadian Rheumatology.

Although the use of ACE inhibitors since the 1980s has dramatically improved the outcome of SRC patients – prior to their widespread use for this indication, SRC mortality was more than 80% – there is still room for substantial improvement, explained Dr. Hudson, noting that the 1- and 5-year survival rates hover around 75% and 65%, respectively, and approximately 19% die within 3 months of diagnosis. It is possible that earlier intervention with ACE inhibitors might improve SRC outcomes. Most likely to benefit are individuals considered at risk for the complication, including those with diffuse and rapidly progressing skin involvement, history of glucocorticoid use, and positive analysis of anti-RNA polymerase III antibodies. But not everyone agrees, she said. "[Opponents] have suggested that prophylactic ACE inhibition could delay the diagnosis [of SRC] because of normalized blood pressure and as a result lead to worse outcomes."

Because a trial of ACE inhibitors in non-SRC patients could carry some risk for participants, Dr. Hudson, a rheumatologist at the Jewish General Hospital and a faculty member at McGill University, Montreal, and her colleagues in the International Scleroderma Renal Crisis study instead sought to evaluate the outcomes of scleroderma patients who presented with incident SRC while taking ACE inhibitors immediately prior to the onset of the condition. To date, they have identified 94 cases of incident SRC nationwide using an ongoing, Internet-based survey in which the investigators e-mail nearly 600 participating physicians worldwide every other week to ask about new cases of SRC, she said. For each new case identified, the investigators collect data on patient demographics, disease characteristics, and exposure to ACE inhibitors. The investigators send recruiting physicians a follow-up case report form 1 year after a patient is identified, she explained, noting that the primary outcome measure is death or dialysis dependence at 1 year after SRC onset.

Of the 94 cases identified so far, 90% had hypertensive SRC and 10% had normotensive SRC; 47% had a history of glucocorticoid use immediately prior to SRC onset, at a mean dose of 17 mg prednisone/day; 15% had anti-RNA polymerase III antibodies; and 23% were on ACE inhibitors prior to the onset of disease, said Dr. Hudson. "Proportionally, more of the normotensive SRC patients were on ACE inhibitors than hypotensive SRC patients."

An analysis of the 1-year follow up data that have been collected to date showed that more than 50% of the patients have died or remain on dialysis at 1 year, Dr. Hudson reported. "So far, there is no evidence that those exposed to ACE inhibitors prior to SRC had worse outcomes," she said, stressing that the findings are preliminary as the collection of 1-year follow-up data is ongoing.

As new data are collected and the findings are validated through additional studies, "we hope to offer new insight into the role of ACE inhibitors in patients with scleroderma," said Dr. Hudson. The use of the Internet-survey technology, in particular, has streamlined the research process because it has facilitated international collaboration and allowed the collection of a substantial amount of information on a rare condition in a short period of time, she said.

Dr. Hudson disclosed a financial relationship with Pfizer, which manufactures several ACE inhibitors.

CANCUN, MEXICO - Scleroderma patients on angiotensin-converting enzyme inhibitors at the onset of scleroderma renal crisis do not appear to have worse outcomes than do those not taking the antihypertensive agents prior to the acute renal function deterioration, according to preliminary data from the largest prospective cohort study of incident scleroderma renal crisis to date.

The finding further fuels the ongoing debate over the role of angiotensin-converting enzyme (ACE) inhibitors as prophylaxis for scleroderma renal crisis (SRC), lead investigator Dr. Marie Hudson reported at the annual meeting of the Canadian Rheumatology.

Although the use of ACE inhibitors since the 1980s has dramatically improved the outcome of SRC patients – prior to their widespread use for this indication, SRC mortality was more than 80% – there is still room for substantial improvement, explained Dr. Hudson, noting that the 1- and 5-year survival rates hover around 75% and 65%, respectively, and approximately 19% die within 3 months of diagnosis. It is possible that earlier intervention with ACE inhibitors might improve SRC outcomes. Most likely to benefit are individuals considered at risk for the complication, including those with diffuse and rapidly progressing skin involvement, history of glucocorticoid use, and positive analysis of anti-RNA polymerase III antibodies. But not everyone agrees, she said. "[Opponents] have suggested that prophylactic ACE inhibition could delay the diagnosis [of SRC] because of normalized blood pressure and as a result lead to worse outcomes."

Because a trial of ACE inhibitors in non-SRC patients could carry some risk for participants, Dr. Hudson, a rheumatologist at the Jewish General Hospital and a faculty member at McGill University, Montreal, and her colleagues in the International Scleroderma Renal Crisis study instead sought to evaluate the outcomes of scleroderma patients who presented with incident SRC while taking ACE inhibitors immediately prior to the onset of the condition. To date, they have identified 94 cases of incident SRC nationwide using an ongoing, Internet-based survey in which the investigators e-mail nearly 600 participating physicians worldwide every other week to ask about new cases of SRC, she said. For each new case identified, the investigators collect data on patient demographics, disease characteristics, and exposure to ACE inhibitors. The investigators send recruiting physicians a follow-up case report form 1 year after a patient is identified, she explained, noting that the primary outcome measure is death or dialysis dependence at 1 year after SRC onset.

Of the 94 cases identified so far, 90% had hypertensive SRC and 10% had normotensive SRC; 47% had a history of glucocorticoid use immediately prior to SRC onset, at a mean dose of 17 mg prednisone/day; 15% had anti-RNA polymerase III antibodies; and 23% were on ACE inhibitors prior to the onset of disease, said Dr. Hudson. "Proportionally, more of the normotensive SRC patients were on ACE inhibitors than hypotensive SRC patients."

An analysis of the 1-year follow up data that have been collected to date showed that more than 50% of the patients have died or remain on dialysis at 1 year, Dr. Hudson reported. "So far, there is no evidence that those exposed to ACE inhibitors prior to SRC had worse outcomes," she said, stressing that the findings are preliminary as the collection of 1-year follow-up data is ongoing.

As new data are collected and the findings are validated through additional studies, "we hope to offer new insight into the role of ACE inhibitors in patients with scleroderma," said Dr. Hudson. The use of the Internet-survey technology, in particular, has streamlined the research process because it has facilitated international collaboration and allowed the collection of a substantial amount of information on a rare condition in a short period of time, she said.

Dr. Hudson disclosed a financial relationship with Pfizer, which manufactures several ACE inhibitors.

CANCUN, MEXICO - Scleroderma patients on angiotensin-converting enzyme inhibitors at the onset of scleroderma renal crisis do not appear to have worse outcomes than do those not taking the antihypertensive agents prior to the acute renal function deterioration, according to preliminary data from the largest prospective cohort study of incident scleroderma renal crisis to date.

The finding further fuels the ongoing debate over the role of angiotensin-converting enzyme (ACE) inhibitors as prophylaxis for scleroderma renal crisis (SRC), lead investigator Dr. Marie Hudson reported at the annual meeting of the Canadian Rheumatology.

Although the use of ACE inhibitors since the 1980s has dramatically improved the outcome of SRC patients – prior to their widespread use for this indication, SRC mortality was more than 80% – there is still room for substantial improvement, explained Dr. Hudson, noting that the 1- and 5-year survival rates hover around 75% and 65%, respectively, and approximately 19% die within 3 months of diagnosis. It is possible that earlier intervention with ACE inhibitors might improve SRC outcomes. Most likely to benefit are individuals considered at risk for the complication, including those with diffuse and rapidly progressing skin involvement, history of glucocorticoid use, and positive analysis of anti-RNA polymerase III antibodies. But not everyone agrees, she said. "[Opponents] have suggested that prophylactic ACE inhibition could delay the diagnosis [of SRC] because of normalized blood pressure and as a result lead to worse outcomes."

Because a trial of ACE inhibitors in non-SRC patients could carry some risk for participants, Dr. Hudson, a rheumatologist at the Jewish General Hospital and a faculty member at McGill University, Montreal, and her colleagues in the International Scleroderma Renal Crisis study instead sought to evaluate the outcomes of scleroderma patients who presented with incident SRC while taking ACE inhibitors immediately prior to the onset of the condition. To date, they have identified 94 cases of incident SRC nationwide using an ongoing, Internet-based survey in which the investigators e-mail nearly 600 participating physicians worldwide every other week to ask about new cases of SRC, she said. For each new case identified, the investigators collect data on patient demographics, disease characteristics, and exposure to ACE inhibitors. The investigators send recruiting physicians a follow-up case report form 1 year after a patient is identified, she explained, noting that the primary outcome measure is death or dialysis dependence at 1 year after SRC onset.

Of the 94 cases identified so far, 90% had hypertensive SRC and 10% had normotensive SRC; 47% had a history of glucocorticoid use immediately prior to SRC onset, at a mean dose of 17 mg prednisone/day; 15% had anti-RNA polymerase III antibodies; and 23% were on ACE inhibitors prior to the onset of disease, said Dr. Hudson. "Proportionally, more of the normotensive SRC patients were on ACE inhibitors than hypotensive SRC patients."

An analysis of the 1-year follow up data that have been collected to date showed that more than 50% of the patients have died or remain on dialysis at 1 year, Dr. Hudson reported. "So far, there is no evidence that those exposed to ACE inhibitors prior to SRC had worse outcomes," she said, stressing that the findings are preliminary as the collection of 1-year follow-up data is ongoing.

As new data are collected and the findings are validated through additional studies, "we hope to offer new insight into the role of ACE inhibitors in patients with scleroderma," said Dr. Hudson. The use of the Internet-survey technology, in particular, has streamlined the research process because it has facilitated international collaboration and allowed the collection of a substantial amount of information on a rare condition in a short period of time, she said.

Dr. Hudson disclosed a financial relationship with Pfizer, which manufactures several ACE inhibitors.