Betsy Bates

NEW ORLEANS — Rosuvastatin slowed the progression of carotid intima-media thickness in asymptomatic subjects at low risk of cardiovascular events but who nonetheless had subclinical atherosclerosis, Dr. John R. Crouse III reported at a conference sponsored by the American College of Cardiology.

The agent “basically halted progression” of intima-media thickness, Dr. Crouse said during a late-breaking clinical trials session at the meeting.

Unlike previous clinical trials of the drug involving high-risk subjects or patients with known cardiovascular disease, the METEOR (Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin) trial assessed asymptomatic people aged 45–70 years who were at low cardiovascular risk and had only moderately elevated cholesterol, but were found to have a relatively high carotid wall thickness on ultrasound examination.

The low-risk population was intentionally chosen for the study so that a placebo arm could ethically be included, said Dr. Crouse, professor of medicine and public health sciences at Wake Forest University in Winston-Salem, N.C.

A total of 984 subjects were enrolled in the study in August 2002-March 2004 at 61 medical centers throughout the United States and Europe, and were followed with serial carotid imaging for 2 years. The study was funded by AstraZeneca Pharmaceuticals LP, maker of rosuvastatin (Crestor).

Ultrasound measurements of carotid intima-media thickness were performed at enrollment and at 6-month intervals for 2 years. Measurements were made at 12 carotid artery sites in each patient, including the near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery.

Results were available for 252 subjects who had been randomly assigned to receive placebo and 624 who had been assigned to receive 40 mg of rosuvastatin daily. This is not the recommended starting dosage but was selected “to provide the maximum efficacy expected to slow or delay progression of atherosclerosis,” Dr. Crouse wrote in a report that was published at the time of the presentation (JAMA 2007;297:1344–53).

Carotid intima-media thickness progressed in the placebo group and regressed in the rosuvastatin group. The difference from baseline did not reach significance except at the common carotid artery.

The significant difference in progression between the placebo and rosuvastatin groups persisted across all clinical subgroups, regardless of subject age, sex, geographical location, race, body mass index, risk factors, blood pressure levels, or lipid levels, Dr. Crouse said.

Rosuvastatin did not induce regression of carotid atherosclerosis, as it has been shown to do in previous studies involving patients with more advanced disease, they added.

“This was focused on low-risk participants without advanced atherosclerosis, and this may have limited the opportunity to achieve disease regression,” Dr. Crouse said at the meeting, which was also sponsored by the Society for Cardiovascular Angiography and Intervention.

LDL cholesterol declined by 49% and HDL cholesterol increased by 8% among patients taking rosuvastatin.

The frequency of adverse events was similar between the two groups, and most effects were of mild or moderate severity.

In an editorial comment accompanying the published report, Dr. Michael S. Lauer of the Cleveland Clinic Heart Center said, “At first glance, the METEOR findings suggest that there may be a role for routine arterial imaging” in low-risk people, and that routine rosuvastatin therapy may be warranted for those found to have increased carotid intima-media thickness.

But this would be “a radically different approach to primary prevention than what is recommended by current guidelines,” and the METEOR results clearly do not justify such a change, he noted (JAMA 2007;297:1376–8).

For one thing, carotid intima-media thickness is merely a surrogate end point for clinical events, and the medical literature is rife with “numerous bad experiences whereby agents that improved surrogate end points yielded no benefit or were even found to cause harm when tested for their ability to prevent clinical events,” Dr. Lauer wrote.

Moreover, there is only limited evidence that statin-induced changes in carotid intima-media thickness actually correlate with a decrease in atherosclerotic events.

The METEOR study had two additional weaknesses. “A fair number of enrolled patients failed to complete the protocol and were lost to follow-up. … [A] higher rate of follow-up clearly would have increased the credibility of the findings,” he noted.

And the study was not powered to evaluate the drug's effect on clinical events. Among nearly 1,000 subjects, only six ischemic events occurred—all of them, “curiously,” in subjects taking the study drug. “Ambitious event-based randomized trials involving large numbers of patients and communities must be done,” Dr. Lauer said.

On the other hand, panel discussant Dr. Paul Ridker, of Brigham and Women's Hospital, Boston, told Dr. Crouse that the cholesterol changes and slowing of atherosclerosis progression in low-risk patients taking rosuvastatin was “very exciting. … This is not a group we normally think about [in terms of risk reduction].”

Dr. Crouse replied that caution should be used in extrapolating study findings with regard to screening and early treatment implications.

NEW ORLEANS — Rosuvastatin slowed the progression of carotid intima-media thickness in asymptomatic subjects at low risk of cardiovascular events but who nonetheless had subclinical atherosclerosis, Dr. John R. Crouse III reported at a conference sponsored by the American College of Cardiology.

The agent “basically halted progression” of intima-media thickness, Dr. Crouse said during a late-breaking clinical trials session at the meeting.

Unlike previous clinical trials of the drug involving high-risk subjects or patients with known cardiovascular disease, the METEOR (Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin) trial assessed asymptomatic people aged 45–70 years who were at low cardiovascular risk and had only moderately elevated cholesterol, but were found to have a relatively high carotid wall thickness on ultrasound examination.

The low-risk population was intentionally chosen for the study so that a placebo arm could ethically be included, said Dr. Crouse, professor of medicine and public health sciences at Wake Forest University in Winston-Salem, N.C.

A total of 984 subjects were enrolled in the study in August 2002-March 2004 at 61 medical centers throughout the United States and Europe, and were followed with serial carotid imaging for 2 years. The study was funded by AstraZeneca Pharmaceuticals LP, maker of rosuvastatin (Crestor).

Ultrasound measurements of carotid intima-media thickness were performed at enrollment and at 6-month intervals for 2 years. Measurements were made at 12 carotid artery sites in each patient, including the near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery.

Results were available for 252 subjects who had been randomly assigned to receive placebo and 624 who had been assigned to receive 40 mg of rosuvastatin daily. This is not the recommended starting dosage but was selected “to provide the maximum efficacy expected to slow or delay progression of atherosclerosis,” Dr. Crouse wrote in a report that was published at the time of the presentation (JAMA 2007;297:1344–53).

Carotid intima-media thickness progressed in the placebo group and regressed in the rosuvastatin group. The difference from baseline did not reach significance except at the common carotid artery.

The significant difference in progression between the placebo and rosuvastatin groups persisted across all clinical subgroups, regardless of subject age, sex, geographical location, race, body mass index, risk factors, blood pressure levels, or lipid levels, Dr. Crouse said.

Rosuvastatin did not induce regression of carotid atherosclerosis, as it has been shown to do in previous studies involving patients with more advanced disease, they added.

“This was focused on low-risk participants without advanced atherosclerosis, and this may have limited the opportunity to achieve disease regression,” Dr. Crouse said at the meeting, which was also sponsored by the Society for Cardiovascular Angiography and Intervention.

LDL cholesterol declined by 49% and HDL cholesterol increased by 8% among patients taking rosuvastatin.

The frequency of adverse events was similar between the two groups, and most effects were of mild or moderate severity.

In an editorial comment accompanying the published report, Dr. Michael S. Lauer of the Cleveland Clinic Heart Center said, “At first glance, the METEOR findings suggest that there may be a role for routine arterial imaging” in low-risk people, and that routine rosuvastatin therapy may be warranted for those found to have increased carotid intima-media thickness.

But this would be “a radically different approach to primary prevention than what is recommended by current guidelines,” and the METEOR results clearly do not justify such a change, he noted (JAMA 2007;297:1376–8).

For one thing, carotid intima-media thickness is merely a surrogate end point for clinical events, and the medical literature is rife with “numerous bad experiences whereby agents that improved surrogate end points yielded no benefit or were even found to cause harm when tested for their ability to prevent clinical events,” Dr. Lauer wrote.

Moreover, there is only limited evidence that statin-induced changes in carotid intima-media thickness actually correlate with a decrease in atherosclerotic events.

The METEOR study had two additional weaknesses. “A fair number of enrolled patients failed to complete the protocol and were lost to follow-up. … [A] higher rate of follow-up clearly would have increased the credibility of the findings,” he noted.

And the study was not powered to evaluate the drug's effect on clinical events. Among nearly 1,000 subjects, only six ischemic events occurred—all of them, “curiously,” in subjects taking the study drug. “Ambitious event-based randomized trials involving large numbers of patients and communities must be done,” Dr. Lauer said.

On the other hand, panel discussant Dr. Paul Ridker, of Brigham and Women's Hospital, Boston, told Dr. Crouse that the cholesterol changes and slowing of atherosclerosis progression in low-risk patients taking rosuvastatin was “very exciting. … This is not a group we normally think about [in terms of risk reduction].”

Dr. Crouse replied that caution should be used in extrapolating study findings with regard to screening and early treatment implications.

NEW ORLEANS — Rosuvastatin slowed the progression of carotid intima-media thickness in asymptomatic subjects at low risk of cardiovascular events but who nonetheless had subclinical atherosclerosis, Dr. John R. Crouse III reported at a conference sponsored by the American College of Cardiology.

The agent “basically halted progression” of intima-media thickness, Dr. Crouse said during a late-breaking clinical trials session at the meeting.

Unlike previous clinical trials of the drug involving high-risk subjects or patients with known cardiovascular disease, the METEOR (Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin) trial assessed asymptomatic people aged 45–70 years who were at low cardiovascular risk and had only moderately elevated cholesterol, but were found to have a relatively high carotid wall thickness on ultrasound examination.

The low-risk population was intentionally chosen for the study so that a placebo arm could ethically be included, said Dr. Crouse, professor of medicine and public health sciences at Wake Forest University in Winston-Salem, N.C.

A total of 984 subjects were enrolled in the study in August 2002-March 2004 at 61 medical centers throughout the United States and Europe, and were followed with serial carotid imaging for 2 years. The study was funded by AstraZeneca Pharmaceuticals LP, maker of rosuvastatin (Crestor).

Ultrasound measurements of carotid intima-media thickness were performed at enrollment and at 6-month intervals for 2 years. Measurements were made at 12 carotid artery sites in each patient, including the near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery.

Results were available for 252 subjects who had been randomly assigned to receive placebo and 624 who had been assigned to receive 40 mg of rosuvastatin daily. This is not the recommended starting dosage but was selected “to provide the maximum efficacy expected to slow or delay progression of atherosclerosis,” Dr. Crouse wrote in a report that was published at the time of the presentation (JAMA 2007;297:1344–53).

Carotid intima-media thickness progressed in the placebo group and regressed in the rosuvastatin group. The difference from baseline did not reach significance except at the common carotid artery.

The significant difference in progression between the placebo and rosuvastatin groups persisted across all clinical subgroups, regardless of subject age, sex, geographical location, race, body mass index, risk factors, blood pressure levels, or lipid levels, Dr. Crouse said.

Rosuvastatin did not induce regression of carotid atherosclerosis, as it has been shown to do in previous studies involving patients with more advanced disease, they added.

“This was focused on low-risk participants without advanced atherosclerosis, and this may have limited the opportunity to achieve disease regression,” Dr. Crouse said at the meeting, which was also sponsored by the Society for Cardiovascular Angiography and Intervention.

LDL cholesterol declined by 49% and HDL cholesterol increased by 8% among patients taking rosuvastatin.

The frequency of adverse events was similar between the two groups, and most effects were of mild or moderate severity.

In an editorial comment accompanying the published report, Dr. Michael S. Lauer of the Cleveland Clinic Heart Center said, “At first glance, the METEOR findings suggest that there may be a role for routine arterial imaging” in low-risk people, and that routine rosuvastatin therapy may be warranted for those found to have increased carotid intima-media thickness.

But this would be “a radically different approach to primary prevention than what is recommended by current guidelines,” and the METEOR results clearly do not justify such a change, he noted (JAMA 2007;297:1376–8).

For one thing, carotid intima-media thickness is merely a surrogate end point for clinical events, and the medical literature is rife with “numerous bad experiences whereby agents that improved surrogate end points yielded no benefit or were even found to cause harm when tested for their ability to prevent clinical events,” Dr. Lauer wrote.

Moreover, there is only limited evidence that statin-induced changes in carotid intima-media thickness actually correlate with a decrease in atherosclerotic events.

The METEOR study had two additional weaknesses. “A fair number of enrolled patients failed to complete the protocol and were lost to follow-up. … [A] higher rate of follow-up clearly would have increased the credibility of the findings,” he noted.

And the study was not powered to evaluate the drug's effect on clinical events. Among nearly 1,000 subjects, only six ischemic events occurred—all of them, “curiously,” in subjects taking the study drug. “Ambitious event-based randomized trials involving large numbers of patients and communities must be done,” Dr. Lauer said.

On the other hand, panel discussant Dr. Paul Ridker, of Brigham and Women's Hospital, Boston, told Dr. Crouse that the cholesterol changes and slowing of atherosclerosis progression in low-risk patients taking rosuvastatin was “very exciting. … This is not a group we normally think about [in terms of risk reduction].”

Dr. Crouse replied that caution should be used in extrapolating study findings with regard to screening and early treatment implications.

NEW ORLEANS — Torcetrapib profoundly raised HDL cholesterol values and decreased LDL cholesterol levels, yet failed to halt the progress of atherosclerosis in two separate international trials, Dr. Steven Nissen said at the annual meeting of the American College of Cardiology.

The combined conclusions of the studies led Dr. Nissen, one of the trial investigators and president of the ACC, to conclude, “At this point, obviously, this molecule is dead.”

Investigators remain puzzled why the investigational cholesterol ester transfer protein inhibitor, which led to unparalleled increases in HDL cholesterol, failed to reduce atheroma volume on carotid ultrasounds.

In a late-breaking clinical trial session at the meeting, Dr. Nissen cited three possible explanations for the findings: An increase in blood pressure may have “counterbalanced” beneficial lipid effects, blood pressure may be a marker for an unknown toxicity associated with the drug, or cholesterol ester transfer protein (CETP) inhibition “may not generate HDL particles that function normally in facilitating reverse cholesterol transport,” Dr. Nissen said.

Whatever the mechanism, the resulting antiatherogenic outcomes with torcetrapib reminded Dr. John J.P. Kastelein of “Dutch pancake—you can't get it any flatter. There was no difference whatsoever.”

Dr. Nissen held out hope that other agents in the CETP class might prove beneficial. “My view is, you can't slam the door on the whole class when the only data we have are for a drug that had this unusual toxicity,” he said at a press briefing.

The trials presented by Dr. Nissen and Dr. Kastelein were part of a huge development program of the first CETP inhibitor by Pfizer, manufacturer of torcetrapib. In December 2006, a third clinical trial was terminated early because of an excess of deaths and cardiovascular events among subjects who received torcetrapib. Pfizer immediately suspended the entire program.

Serious cardiovascular events also were higher with torcetrapib in the trials presented at the meeting; however, these were relatively small trials and not statistically powered to show a significant increase in adverse clinical events.

In the ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation) trial, investigators at 137 medical centers throughout North America and Europe used intravascular ultrasound to assess coronary atheroma volume in 910 patients with known coronary atherosclerosis. The subjects were randomly assigned to receive either atorvastatin plus torcetrapib (464 subjects) or atorvastatin plus placebo (446 subjects) for 2 years, said Dr. Nissen of the Cleveland Clinic.

Adding torcetrapib to the statin induced an unparalleled 60% rise in HDL cholesterol and a 20% decline in LDL cholesterol, relative to atorvastatin alone.

“Thus, at the end of 24 months, treatment with torcetrapib resulted in an average HDL level that was actually higher than the LDL level, with an LDL to HDL ratio of 0.93: a ratio never before achieved in any major clinical trial,” Dr. Nissen said in his presentation. However, it also induced a “substantial” increase in systolic blood pressure of 4.6 mm Hg, he said.

Further, percent atheroma volume, the primary efficacy measure, was not affected. Neither was progression of atherosclerosis in the most diseased segment of the target artery, a secondary measure. Another secondary measure—progression in total atheroma volume—improved with torcetrapib, but “the treatment difference was relatively small, particularly considering the long duration of the trial,” wrote Dr. Nissen and his associates in an article published simultaneously with the presentation (N. Engl. J. Med. 2007; 356:1304–16).

In the RADIANCE 1 trial (Rating Atherosclerotic Disease Change by Imaging with a New DETP Inhibitor), investigators used ultrasound to assess the progression of carotid intima-media thickness over 2 years in 850 patients with familial hypercholesterolemia who were treated at 37 medical centers in North America, Europe, and South Africa. A total of 423 subjects were randomly assigned to receive torcetrapib and atorvastatin, while 427 received atorvastatin plus placebo.

“The net effect of torcetrapib was a 51.9% relative increase in HDL cholesterol and a 20.6% relative decrease in LDL cholesterol,” wrote Dr. John J. P. Kastelein of the University of Amsterdam and his associates in an article published at the time of the meeting (N. Engl. J. Med. 2007 March 29 [Epub doi:10.1056/NEJMoa071359]).

Yet the drug failed to halt progression of carotid intima-media thickness and actually appeared to accelerate the atherosclerotic process in one segment of the artery. As in the study by Dr. Nissen and colleagues, torcetrapib significantly raised systolic blood pressure. It also induced more adverse cardiovascular events, particularly those related to increased blood pressure, than did placebo, Dr. Kastelein and his associates said.

The RADIANCE 2 study, which studied torcetrapib in 752 patients with mixed hyperlipidemia, showed “strikingly similar results,” Dr. Kastelein said at the meeting.

Although torcetrapib led to unparalleled increases in HDL cholesterol, it failed to reduce atheroma volume. DR. NISSEN

NEW ORLEANS — Torcetrapib profoundly raised HDL cholesterol values and decreased LDL cholesterol levels, yet failed to halt the progress of atherosclerosis in two separate international trials, Dr. Steven Nissen said at the annual meeting of the American College of Cardiology.

The combined conclusions of the studies led Dr. Nissen, one of the trial investigators and president of the ACC, to conclude, “At this point, obviously, this molecule is dead.”

Investigators remain puzzled why the investigational cholesterol ester transfer protein inhibitor, which led to unparalleled increases in HDL cholesterol, failed to reduce atheroma volume on carotid ultrasounds.

In a late-breaking clinical trial session at the meeting, Dr. Nissen cited three possible explanations for the findings: An increase in blood pressure may have “counterbalanced” beneficial lipid effects, blood pressure may be a marker for an unknown toxicity associated with the drug, or cholesterol ester transfer protein (CETP) inhibition “may not generate HDL particles that function normally in facilitating reverse cholesterol transport,” Dr. Nissen said.

Whatever the mechanism, the resulting antiatherogenic outcomes with torcetrapib reminded Dr. John J.P. Kastelein of “Dutch pancake—you can't get it any flatter. There was no difference whatsoever.”

Dr. Nissen held out hope that other agents in the CETP class might prove beneficial. “My view is, you can't slam the door on the whole class when the only data we have are for a drug that had this unusual toxicity,” he said at a press briefing.

The trials presented by Dr. Nissen and Dr. Kastelein were part of a huge development program of the first CETP inhibitor by Pfizer, manufacturer of torcetrapib. In December 2006, a third clinical trial was terminated early because of an excess of deaths and cardiovascular events among subjects who received torcetrapib. Pfizer immediately suspended the entire program.

Serious cardiovascular events also were higher with torcetrapib in the trials presented at the meeting; however, these were relatively small trials and not statistically powered to show a significant increase in adverse clinical events.

In the ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation) trial, investigators at 137 medical centers throughout North America and Europe used intravascular ultrasound to assess coronary atheroma volume in 910 patients with known coronary atherosclerosis. The subjects were randomly assigned to receive either atorvastatin plus torcetrapib (464 subjects) or atorvastatin plus placebo (446 subjects) for 2 years, said Dr. Nissen of the Cleveland Clinic.

Adding torcetrapib to the statin induced an unparalleled 60% rise in HDL cholesterol and a 20% decline in LDL cholesterol, relative to atorvastatin alone.

“Thus, at the end of 24 months, treatment with torcetrapib resulted in an average HDL level that was actually higher than the LDL level, with an LDL to HDL ratio of 0.93: a ratio never before achieved in any major clinical trial,” Dr. Nissen said in his presentation. However, it also induced a “substantial” increase in systolic blood pressure of 4.6 mm Hg, he said.

Further, percent atheroma volume, the primary efficacy measure, was not affected. Neither was progression of atherosclerosis in the most diseased segment of the target artery, a secondary measure. Another secondary measure—progression in total atheroma volume—improved with torcetrapib, but “the treatment difference was relatively small, particularly considering the long duration of the trial,” wrote Dr. Nissen and his associates in an article published simultaneously with the presentation (N. Engl. J. Med. 2007; 356:1304–16).

In the RADIANCE 1 trial (Rating Atherosclerotic Disease Change by Imaging with a New DETP Inhibitor), investigators used ultrasound to assess the progression of carotid intima-media thickness over 2 years in 850 patients with familial hypercholesterolemia who were treated at 37 medical centers in North America, Europe, and South Africa. A total of 423 subjects were randomly assigned to receive torcetrapib and atorvastatin, while 427 received atorvastatin plus placebo.

“The net effect of torcetrapib was a 51.9% relative increase in HDL cholesterol and a 20.6% relative decrease in LDL cholesterol,” wrote Dr. John J. P. Kastelein of the University of Amsterdam and his associates in an article published at the time of the meeting (N. Engl. J. Med. 2007 March 29 [Epub doi:10.1056/NEJMoa071359]).

Yet the drug failed to halt progression of carotid intima-media thickness and actually appeared to accelerate the atherosclerotic process in one segment of the artery. As in the study by Dr. Nissen and colleagues, torcetrapib significantly raised systolic blood pressure. It also induced more adverse cardiovascular events, particularly those related to increased blood pressure, than did placebo, Dr. Kastelein and his associates said.

The RADIANCE 2 study, which studied torcetrapib in 752 patients with mixed hyperlipidemia, showed “strikingly similar results,” Dr. Kastelein said at the meeting.

Although torcetrapib led to unparalleled increases in HDL cholesterol, it failed to reduce atheroma volume. DR. NISSEN

NEW ORLEANS — Torcetrapib profoundly raised HDL cholesterol values and decreased LDL cholesterol levels, yet failed to halt the progress of atherosclerosis in two separate international trials, Dr. Steven Nissen said at the annual meeting of the American College of Cardiology.

The combined conclusions of the studies led Dr. Nissen, one of the trial investigators and president of the ACC, to conclude, “At this point, obviously, this molecule is dead.”

Investigators remain puzzled why the investigational cholesterol ester transfer protein inhibitor, which led to unparalleled increases in HDL cholesterol, failed to reduce atheroma volume on carotid ultrasounds.

In a late-breaking clinical trial session at the meeting, Dr. Nissen cited three possible explanations for the findings: An increase in blood pressure may have “counterbalanced” beneficial lipid effects, blood pressure may be a marker for an unknown toxicity associated with the drug, or cholesterol ester transfer protein (CETP) inhibition “may not generate HDL particles that function normally in facilitating reverse cholesterol transport,” Dr. Nissen said.

Whatever the mechanism, the resulting antiatherogenic outcomes with torcetrapib reminded Dr. John J.P. Kastelein of “Dutch pancake—you can't get it any flatter. There was no difference whatsoever.”

Dr. Nissen held out hope that other agents in the CETP class might prove beneficial. “My view is, you can't slam the door on the whole class when the only data we have are for a drug that had this unusual toxicity,” he said at a press briefing.

The trials presented by Dr. Nissen and Dr. Kastelein were part of a huge development program of the first CETP inhibitor by Pfizer, manufacturer of torcetrapib. In December 2006, a third clinical trial was terminated early because of an excess of deaths and cardiovascular events among subjects who received torcetrapib. Pfizer immediately suspended the entire program.

Serious cardiovascular events also were higher with torcetrapib in the trials presented at the meeting; however, these were relatively small trials and not statistically powered to show a significant increase in adverse clinical events.

In the ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation) trial, investigators at 137 medical centers throughout North America and Europe used intravascular ultrasound to assess coronary atheroma volume in 910 patients with known coronary atherosclerosis. The subjects were randomly assigned to receive either atorvastatin plus torcetrapib (464 subjects) or atorvastatin plus placebo (446 subjects) for 2 years, said Dr. Nissen of the Cleveland Clinic.

Adding torcetrapib to the statin induced an unparalleled 60% rise in HDL cholesterol and a 20% decline in LDL cholesterol, relative to atorvastatin alone.

“Thus, at the end of 24 months, treatment with torcetrapib resulted in an average HDL level that was actually higher than the LDL level, with an LDL to HDL ratio of 0.93: a ratio never before achieved in any major clinical trial,” Dr. Nissen said in his presentation. However, it also induced a “substantial” increase in systolic blood pressure of 4.6 mm Hg, he said.

Further, percent atheroma volume, the primary efficacy measure, was not affected. Neither was progression of atherosclerosis in the most diseased segment of the target artery, a secondary measure. Another secondary measure—progression in total atheroma volume—improved with torcetrapib, but “the treatment difference was relatively small, particularly considering the long duration of the trial,” wrote Dr. Nissen and his associates in an article published simultaneously with the presentation (N. Engl. J. Med. 2007; 356:1304–16).

In the RADIANCE 1 trial (Rating Atherosclerotic Disease Change by Imaging with a New DETP Inhibitor), investigators used ultrasound to assess the progression of carotid intima-media thickness over 2 years in 850 patients with familial hypercholesterolemia who were treated at 37 medical centers in North America, Europe, and South Africa. A total of 423 subjects were randomly assigned to receive torcetrapib and atorvastatin, while 427 received atorvastatin plus placebo.

“The net effect of torcetrapib was a 51.9% relative increase in HDL cholesterol and a 20.6% relative decrease in LDL cholesterol,” wrote Dr. John J. P. Kastelein of the University of Amsterdam and his associates in an article published at the time of the meeting (N. Engl. J. Med. 2007 March 29 [Epub doi:10.1056/NEJMoa071359]).

Yet the drug failed to halt progression of carotid intima-media thickness and actually appeared to accelerate the atherosclerotic process in one segment of the artery. As in the study by Dr. Nissen and colleagues, torcetrapib significantly raised systolic blood pressure. It also induced more adverse cardiovascular events, particularly those related to increased blood pressure, than did placebo, Dr. Kastelein and his associates said.

The RADIANCE 2 study, which studied torcetrapib in 752 patients with mixed hyperlipidemia, showed “strikingly similar results,” Dr. Kastelein said at the meeting.

Although torcetrapib led to unparalleled increases in HDL cholesterol, it failed to reduce atheroma volume. DR. NISSEN

RENO, NEV. — Cervical dilatation at presentation and over the 6 hours following admission was highly predictive of preterm birth in women admitted with preterm labor, but obstetric history also contributed important information about which mothers were likely to deliver before 34 weeks' or 37 weeks' gestation.

Dr. Jamie A. Bastek and associates in the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, reviewed the records of 400 women with singleton pregnancies who were admitted in preterm labor before 34 weeks' gestation.

The researchers sought to determine whether the risk of preterm birth could be stratified based on a number of easily identifiable variables, including cervical dilatation and a prior history of preterm or full-term birth.

Dr. Bastek presented their results at the annual meeting of the Society for Gynecologic Investigation.

“As tocolytics are not without harm, we felt it was important to see if we could identify women with a low likelihood of preterm birth who could be managed without admission and/or tocolytic agents” she said in an interview at the meeting, where the study was presented in poster form.

As expected, the total cohort had a significant risk of early delivery.

Nearly 45% delivered before 34 weeks, and 63% delivered before 37 weeks' gestation.

In trying to determine what distinguished the women who delivered after 37 weeks, Dr. Bastek and associates found a number of features conferring protection, including later gestational age at presentation, less cervical dilatation at presentation, smaller rates of change in cervical dilatation, and obstetric history.

Presentation at fewer than 25 weeks' gestation conferred more than a 15-fold increase in the odds of delivering before 34 weeks, compared with women who presented at 32 weeks' gestation. Presentation before 28 weeks was also a noteworthy risk, bestowing 3.5 times the risk of delivering before 34 weeks.

However, presenting at more than 30 weeks' gestation did not demonstrate elevated odds of delivering before 34 weeks or before 37 weeks, compared with presentation at 32 weeks' gestation.

Cervical dilatation—both on presentation and over the course of 6 hours following admission—was significantly predictive of preterm birth, even after controlling for multiple other variables such as maternal age, race, prenatal care, and gestational age on admission.

Each 1-cm increase in cervical dilatation on presentation more than doubled the odds of delivering before 37 weeks, a significant finding (P less than .0001). However, this risk was modified depending on obstetric history.

At a dilatation of 2 cm on admission, for example, the patients who were at highest risk of a preterm birth before 37 weeks were those with no previous births, followed by those with one or more prior preterm deliveries. Rates were lower for mothers who had a history of both preterm and full-term deliveries, and for those who previously had only had full-term deliveries.

The interaction between obstetric history and cervical dilatation was complex.

Patients with a previous preterm birth had the highest baseline risk of another preterm delivery before 37 weeks if cervical dilatation was not taken into consideration.

Within each obstetric history cohort, advancing cervical dilatation was significantly associated with preterm birth before 34 and 37 weeks. Advancing cervical dilatation had the greatest impact on patients with no prior preterm birth and the least impact on those with only a prior preterm birth.

Notably, more than 60% of women with a history of one or more full-term deliveries and no preterm deliveries carried their pregnancies beyond 34 weeks.

What happened after admission was also very relevant to the risk of preterm delivery.

Just 17.8% of the cohort (71 patients) delivered within 6 hours of admission.

Among the remaining 329 women, a 1- to 2-cm change in cervical dilatation after admission conferred almost a threefold risk of delivery before 34 weeks and a twofold risk of delivering before 37 weeks.

A 3-cm or greater change in cervical dilatation was associated with a nearly 12-fold increase in risk of a preterm birth before 34 weeks and a sevenfold increase in the odds of delivering before 37 weeks.

All eight women with more than a 4-cm change in dilatation over the first 6 hours post admission delivered at fewer than 34 weeks.

The research pointed to a number of factors that should be considered in the management of women with preterm labor, especially gestational age at presentation; cervical dilatation on presentation and cervical change over the 6 hours following admission; and obstetric history.

Further research is planned to randomize women with no previous preterm births and a low-risk cervical dilatation profile to tocolysis or expectant management.

“Our goal is to use this information to move into a trial that examines whether women with a low baseline risk can be managed without exposing them to magnesium or other tocolytics,” she said.

Dr. Bastek's coresearchers included principal investigator Dr. Michal A. Elovitz, Dr. Sindhu Srinivas, and biostatistician Mary D. Sammel.

RENO, NEV. — Cervical dilatation at presentation and over the 6 hours following admission was highly predictive of preterm birth in women admitted with preterm labor, but obstetric history also contributed important information about which mothers were likely to deliver before 34 weeks' or 37 weeks' gestation.

Dr. Jamie A. Bastek and associates in the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, reviewed the records of 400 women with singleton pregnancies who were admitted in preterm labor before 34 weeks' gestation.

The researchers sought to determine whether the risk of preterm birth could be stratified based on a number of easily identifiable variables, including cervical dilatation and a prior history of preterm or full-term birth.

Dr. Bastek presented their results at the annual meeting of the Society for Gynecologic Investigation.

“As tocolytics are not without harm, we felt it was important to see if we could identify women with a low likelihood of preterm birth who could be managed without admission and/or tocolytic agents” she said in an interview at the meeting, where the study was presented in poster form.

As expected, the total cohort had a significant risk of early delivery.

Nearly 45% delivered before 34 weeks, and 63% delivered before 37 weeks' gestation.

In trying to determine what distinguished the women who delivered after 37 weeks, Dr. Bastek and associates found a number of features conferring protection, including later gestational age at presentation, less cervical dilatation at presentation, smaller rates of change in cervical dilatation, and obstetric history.

Presentation at fewer than 25 weeks' gestation conferred more than a 15-fold increase in the odds of delivering before 34 weeks, compared with women who presented at 32 weeks' gestation. Presentation before 28 weeks was also a noteworthy risk, bestowing 3.5 times the risk of delivering before 34 weeks.

However, presenting at more than 30 weeks' gestation did not demonstrate elevated odds of delivering before 34 weeks or before 37 weeks, compared with presentation at 32 weeks' gestation.

Cervical dilatation—both on presentation and over the course of 6 hours following admission—was significantly predictive of preterm birth, even after controlling for multiple other variables such as maternal age, race, prenatal care, and gestational age on admission.

Each 1-cm increase in cervical dilatation on presentation more than doubled the odds of delivering before 37 weeks, a significant finding (P less than .0001). However, this risk was modified depending on obstetric history.

At a dilatation of 2 cm on admission, for example, the patients who were at highest risk of a preterm birth before 37 weeks were those with no previous births, followed by those with one or more prior preterm deliveries. Rates were lower for mothers who had a history of both preterm and full-term deliveries, and for those who previously had only had full-term deliveries.

The interaction between obstetric history and cervical dilatation was complex.

Patients with a previous preterm birth had the highest baseline risk of another preterm delivery before 37 weeks if cervical dilatation was not taken into consideration.

Within each obstetric history cohort, advancing cervical dilatation was significantly associated with preterm birth before 34 and 37 weeks. Advancing cervical dilatation had the greatest impact on patients with no prior preterm birth and the least impact on those with only a prior preterm birth.

Notably, more than 60% of women with a history of one or more full-term deliveries and no preterm deliveries carried their pregnancies beyond 34 weeks.

What happened after admission was also very relevant to the risk of preterm delivery.

Just 17.8% of the cohort (71 patients) delivered within 6 hours of admission.

Among the remaining 329 women, a 1- to 2-cm change in cervical dilatation after admission conferred almost a threefold risk of delivery before 34 weeks and a twofold risk of delivering before 37 weeks.

A 3-cm or greater change in cervical dilatation was associated with a nearly 12-fold increase in risk of a preterm birth before 34 weeks and a sevenfold increase in the odds of delivering before 37 weeks.

All eight women with more than a 4-cm change in dilatation over the first 6 hours post admission delivered at fewer than 34 weeks.

The research pointed to a number of factors that should be considered in the management of women with preterm labor, especially gestational age at presentation; cervical dilatation on presentation and cervical change over the 6 hours following admission; and obstetric history.

Further research is planned to randomize women with no previous preterm births and a low-risk cervical dilatation profile to tocolysis or expectant management.

“Our goal is to use this information to move into a trial that examines whether women with a low baseline risk can be managed without exposing them to magnesium or other tocolytics,” she said.

Dr. Bastek's coresearchers included principal investigator Dr. Michal A. Elovitz, Dr. Sindhu Srinivas, and biostatistician Mary D. Sammel.

RENO, NEV. — Cervical dilatation at presentation and over the 6 hours following admission was highly predictive of preterm birth in women admitted with preterm labor, but obstetric history also contributed important information about which mothers were likely to deliver before 34 weeks' or 37 weeks' gestation.

Dr. Jamie A. Bastek and associates in the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, reviewed the records of 400 women with singleton pregnancies who were admitted in preterm labor before 34 weeks' gestation.

The researchers sought to determine whether the risk of preterm birth could be stratified based on a number of easily identifiable variables, including cervical dilatation and a prior history of preterm or full-term birth.

Dr. Bastek presented their results at the annual meeting of the Society for Gynecologic Investigation.

“As tocolytics are not without harm, we felt it was important to see if we could identify women with a low likelihood of preterm birth who could be managed without admission and/or tocolytic agents” she said in an interview at the meeting, where the study was presented in poster form.

As expected, the total cohort had a significant risk of early delivery.

Nearly 45% delivered before 34 weeks, and 63% delivered before 37 weeks' gestation.

In trying to determine what distinguished the women who delivered after 37 weeks, Dr. Bastek and associates found a number of features conferring protection, including later gestational age at presentation, less cervical dilatation at presentation, smaller rates of change in cervical dilatation, and obstetric history.

Presentation at fewer than 25 weeks' gestation conferred more than a 15-fold increase in the odds of delivering before 34 weeks, compared with women who presented at 32 weeks' gestation. Presentation before 28 weeks was also a noteworthy risk, bestowing 3.5 times the risk of delivering before 34 weeks.

However, presenting at more than 30 weeks' gestation did not demonstrate elevated odds of delivering before 34 weeks or before 37 weeks, compared with presentation at 32 weeks' gestation.

Cervical dilatation—both on presentation and over the course of 6 hours following admission—was significantly predictive of preterm birth, even after controlling for multiple other variables such as maternal age, race, prenatal care, and gestational age on admission.

Each 1-cm increase in cervical dilatation on presentation more than doubled the odds of delivering before 37 weeks, a significant finding (P less than .0001). However, this risk was modified depending on obstetric history.

At a dilatation of 2 cm on admission, for example, the patients who were at highest risk of a preterm birth before 37 weeks were those with no previous births, followed by those with one or more prior preterm deliveries. Rates were lower for mothers who had a history of both preterm and full-term deliveries, and for those who previously had only had full-term deliveries.

The interaction between obstetric history and cervical dilatation was complex.

Patients with a previous preterm birth had the highest baseline risk of another preterm delivery before 37 weeks if cervical dilatation was not taken into consideration.

Within each obstetric history cohort, advancing cervical dilatation was significantly associated with preterm birth before 34 and 37 weeks. Advancing cervical dilatation had the greatest impact on patients with no prior preterm birth and the least impact on those with only a prior preterm birth.

Notably, more than 60% of women with a history of one or more full-term deliveries and no preterm deliveries carried their pregnancies beyond 34 weeks.

What happened after admission was also very relevant to the risk of preterm delivery.

Just 17.8% of the cohort (71 patients) delivered within 6 hours of admission.

Among the remaining 329 women, a 1- to 2-cm change in cervical dilatation after admission conferred almost a threefold risk of delivery before 34 weeks and a twofold risk of delivering before 37 weeks.

A 3-cm or greater change in cervical dilatation was associated with a nearly 12-fold increase in risk of a preterm birth before 34 weeks and a sevenfold increase in the odds of delivering before 37 weeks.

All eight women with more than a 4-cm change in dilatation over the first 6 hours post admission delivered at fewer than 34 weeks.

The research pointed to a number of factors that should be considered in the management of women with preterm labor, especially gestational age at presentation; cervical dilatation on presentation and cervical change over the 6 hours following admission; and obstetric history.

Further research is planned to randomize women with no previous preterm births and a low-risk cervical dilatation profile to tocolysis or expectant management.

“Our goal is to use this information to move into a trial that examines whether women with a low baseline risk can be managed without exposing them to magnesium or other tocolytics,” she said.

Dr. Bastek's coresearchers included principal investigator Dr. Michal A. Elovitz, Dr. Sindhu Srinivas, and biostatistician Mary D. Sammel.

Mary Ann Moon contributed to this report.

NEW ORLEANS — Percutaneous coronary intervention adds no benefit to optimal medical therapy for extensive but stable coronary artery disease, according to results of the COURAGE trial, and that finding has set off a debate about the medical necessity of PCI in many patients.

As an initial management strategy, PCI added to optimal medical therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial did not reduce the rates of death, nonfatal MI, or hospitalization for acute coronary syndromes during a mean follow-up of 4.6 years, Dr. William E. Boden reported at the annual meeting of the American College of Cardiology.

“I think we can say with some degree of conviction that if you opt for an initial strategy of medical therapy, you are not putting patients in harm's way,” Dr. Boden said at a press briefing preceding his formal presentation. “What was remarkable was how well optimal medical therapy did in this trial.”

At the press briefing, Dr. Boden said, “Historically, there has been an unproven assumption that if you have significant angiographic coronary disease or if you have inducible ischemia that you must proceed to revascularization. … Lost in the shuffle in all this has been medical therapy. It has gotten a bad rap over the years. It sort of seems old-fashioned.”

But he said the COURAGE trial clearly shows that physicians who help patients meet targets for cholesterol, blood pressure, diabetes control, and lifestyle modification can have a strong and favorable impact on prognosis.

The findings fly in the face of what has become standard practice in the United States. As many as 85% of more than a million PCI procedures performed each year are done electively in patients with stable CAD, according to Dr. Boden and colleagues in an article published online at the time of the press briefing (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa070829]).

COURAGE assessed 2,287 patients enrolled during 1999–2004 at 50 U.S. and Canadian medical centers and followed for a mean of 4.6 years. The subjects showed stenosis of at least 70% in at least one proximal coronary artery, plus either objective evidence of myocardial ischemia or classic angina.

A total of 1,138 patients were randomly assigned to receive optimal medical therapy alone and 1,149 were randomized to optimal medical therapy plus PCI. The entire study population showed high rates of adherence to medications and a regimen of diet, regular exercise, and smoking cessation. Seventy percent achieved target cholesterol levels, 65% reached target systolic blood pressure, 94% reached target diastolic blood pressure, and 45% of those with diabetes achieved target glycolated hemoglobin levels.

The estimated cumulative event rate, a composite outcome of death from any cause and nonfatal MI, was 19.0% in the PCI group and 18.5% in the medical therapy group, a nonsignificant difference. Similarly, there were no significant differences in rates of stroke, hospitalization for acute coronary syndromes, MI alone, death alone, or coronary artery bypass surgery, reported Dr. Boden of the Veterans Affairs Western New York Healthcare System, Buffalo.

Both study groups showed a substantial reduction in the prevalence of angina, and there was a significant difference in favor of PCI for the first few years of follow-up. But by 5 years, that difference had dwindled to the point that 74% of subjects in the PCI group and 72% of those in the medical therapy group were free of angina.

“Our findings reinforce existing clinical practice guidelines, which state that PCI can be safely deferred in patients with stable CAD, even in those with extensive, multivessel involvement and inducible ischemia, provided that intensive, multifaceted medical therapy is instituted and maintained,” the researchers noted.

But those guidelines have not been followed, according to Dr. Salim Yusuf, a panelist at the late-breaking trials session where the study was presented. For too long, the belief has persisted that stenosis is directly related to MI risk, or that PCI would prevent MIs and save lives if only its imperfections could be remedied by better stents, he said.

“We would all have liked to see PCI prevent MIs, prevent death, because surely spreading somebody's chest open is not a nice thing to do,” he said. “Unfortunately, the truth doesn't go that way.”

“The time has come to confront ourselves about why these myths have persisted,” he said. Sometimes, PCI is performed because “the referring doctor wants it,” maintained Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

Dr. Gregory J. Dehmer, president of the Society for Cardiovascular Angiography and Interventions (SCAI), said that the proportion of PCI procedures in patients with stable CAD is far lower than the COURAGE researchers' estimate. Most PCI procedures are performed in patients having severe acute MIs, those with unstable angina, and those with high-risk disease characteristics that would have made them ineligible for inclusion for the COURAGE trial, he said in an interview.

Also at the press briefing, Dr. William S. Weintraub of Christiana Hospital in Wilmington, Del., released lifestyle and economic findings of the study. Both optimal medical therapy and PCI quickly and markedly improved patients' angina frequency and quality of life.

Over most of the course of the study, PCI held a slight edge over medication in terms of reducing angina symptoms, leading to a significant but “very slight trend” to improved quality-of-life-years, he said.

The incremental cost-effectiveness ratio at 3 years favored PCI by $217,000, meaning that the cost of the procedure was beneficial in terms of quality of life gained.

The COURAGE study was funded by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institute of Health, and unrestricted grants from Merck & Co., Pfizer, Bristol-Myers Squibb, Fujisawa Healthcare Inc., Kos Pharmaceuticals Inc., Datascope Corp., Astra-Zeneca Pharmaceuticals, Key Pharmaceuticals, Sanofi-Aventis, First Horizon Pharmaceutical Corp, and GE Healthcare.

Mary Ann Moon contributed to this report.

NEW ORLEANS — Percutaneous coronary intervention adds no benefit to optimal medical therapy for extensive but stable coronary artery disease, according to results of the COURAGE trial, and that finding has set off a debate about the medical necessity of PCI in many patients.

As an initial management strategy, PCI added to optimal medical therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial did not reduce the rates of death, nonfatal MI, or hospitalization for acute coronary syndromes during a mean follow-up of 4.6 years, Dr. William E. Boden reported at the annual meeting of the American College of Cardiology.

“I think we can say with some degree of conviction that if you opt for an initial strategy of medical therapy, you are not putting patients in harm's way,” Dr. Boden said at a press briefing preceding his formal presentation. “What was remarkable was how well optimal medical therapy did in this trial.”

At the press briefing, Dr. Boden said, “Historically, there has been an unproven assumption that if you have significant angiographic coronary disease or if you have inducible ischemia that you must proceed to revascularization. … Lost in the shuffle in all this has been medical therapy. It has gotten a bad rap over the years. It sort of seems old-fashioned.”

But he said the COURAGE trial clearly shows that physicians who help patients meet targets for cholesterol, blood pressure, diabetes control, and lifestyle modification can have a strong and favorable impact on prognosis.

The findings fly in the face of what has become standard practice in the United States. As many as 85% of more than a million PCI procedures performed each year are done electively in patients with stable CAD, according to Dr. Boden and colleagues in an article published online at the time of the press briefing (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa070829]).

COURAGE assessed 2,287 patients enrolled during 1999–2004 at 50 U.S. and Canadian medical centers and followed for a mean of 4.6 years. The subjects showed stenosis of at least 70% in at least one proximal coronary artery, plus either objective evidence of myocardial ischemia or classic angina.

A total of 1,138 patients were randomly assigned to receive optimal medical therapy alone and 1,149 were randomized to optimal medical therapy plus PCI. The entire study population showed high rates of adherence to medications and a regimen of diet, regular exercise, and smoking cessation. Seventy percent achieved target cholesterol levels, 65% reached target systolic blood pressure, 94% reached target diastolic blood pressure, and 45% of those with diabetes achieved target glycolated hemoglobin levels.

The estimated cumulative event rate, a composite outcome of death from any cause and nonfatal MI, was 19.0% in the PCI group and 18.5% in the medical therapy group, a nonsignificant difference. Similarly, there were no significant differences in rates of stroke, hospitalization for acute coronary syndromes, MI alone, death alone, or coronary artery bypass surgery, reported Dr. Boden of the Veterans Affairs Western New York Healthcare System, Buffalo.

Both study groups showed a substantial reduction in the prevalence of angina, and there was a significant difference in favor of PCI for the first few years of follow-up. But by 5 years, that difference had dwindled to the point that 74% of subjects in the PCI group and 72% of those in the medical therapy group were free of angina.

“Our findings reinforce existing clinical practice guidelines, which state that PCI can be safely deferred in patients with stable CAD, even in those with extensive, multivessel involvement and inducible ischemia, provided that intensive, multifaceted medical therapy is instituted and maintained,” the researchers noted.

But those guidelines have not been followed, according to Dr. Salim Yusuf, a panelist at the late-breaking trials session where the study was presented. For too long, the belief has persisted that stenosis is directly related to MI risk, or that PCI would prevent MIs and save lives if only its imperfections could be remedied by better stents, he said.

“We would all have liked to see PCI prevent MIs, prevent death, because surely spreading somebody's chest open is not a nice thing to do,” he said. “Unfortunately, the truth doesn't go that way.”

“The time has come to confront ourselves about why these myths have persisted,” he said. Sometimes, PCI is performed because “the referring doctor wants it,” maintained Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

Dr. Gregory J. Dehmer, president of the Society for Cardiovascular Angiography and Interventions (SCAI), said that the proportion of PCI procedures in patients with stable CAD is far lower than the COURAGE researchers' estimate. Most PCI procedures are performed in patients having severe acute MIs, those with unstable angina, and those with high-risk disease characteristics that would have made them ineligible for inclusion for the COURAGE trial, he said in an interview.

Also at the press briefing, Dr. William S. Weintraub of Christiana Hospital in Wilmington, Del., released lifestyle and economic findings of the study. Both optimal medical therapy and PCI quickly and markedly improved patients' angina frequency and quality of life.

Over most of the course of the study, PCI held a slight edge over medication in terms of reducing angina symptoms, leading to a significant but “very slight trend” to improved quality-of-life-years, he said.

The incremental cost-effectiveness ratio at 3 years favored PCI by $217,000, meaning that the cost of the procedure was beneficial in terms of quality of life gained.

The COURAGE study was funded by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institute of Health, and unrestricted grants from Merck & Co., Pfizer, Bristol-Myers Squibb, Fujisawa Healthcare Inc., Kos Pharmaceuticals Inc., Datascope Corp., Astra-Zeneca Pharmaceuticals, Key Pharmaceuticals, Sanofi-Aventis, First Horizon Pharmaceutical Corp, and GE Healthcare.

Mary Ann Moon contributed to this report.

NEW ORLEANS — Percutaneous coronary intervention adds no benefit to optimal medical therapy for extensive but stable coronary artery disease, according to results of the COURAGE trial, and that finding has set off a debate about the medical necessity of PCI in many patients.

As an initial management strategy, PCI added to optimal medical therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial did not reduce the rates of death, nonfatal MI, or hospitalization for acute coronary syndromes during a mean follow-up of 4.6 years, Dr. William E. Boden reported at the annual meeting of the American College of Cardiology.

“I think we can say with some degree of conviction that if you opt for an initial strategy of medical therapy, you are not putting patients in harm's way,” Dr. Boden said at a press briefing preceding his formal presentation. “What was remarkable was how well optimal medical therapy did in this trial.”

At the press briefing, Dr. Boden said, “Historically, there has been an unproven assumption that if you have significant angiographic coronary disease or if you have inducible ischemia that you must proceed to revascularization. … Lost in the shuffle in all this has been medical therapy. It has gotten a bad rap over the years. It sort of seems old-fashioned.”

But he said the COURAGE trial clearly shows that physicians who help patients meet targets for cholesterol, blood pressure, diabetes control, and lifestyle modification can have a strong and favorable impact on prognosis.

The findings fly in the face of what has become standard practice in the United States. As many as 85% of more than a million PCI procedures performed each year are done electively in patients with stable CAD, according to Dr. Boden and colleagues in an article published online at the time of the press briefing (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa070829]).

COURAGE assessed 2,287 patients enrolled during 1999–2004 at 50 U.S. and Canadian medical centers and followed for a mean of 4.6 years. The subjects showed stenosis of at least 70% in at least one proximal coronary artery, plus either objective evidence of myocardial ischemia or classic angina.

A total of 1,138 patients were randomly assigned to receive optimal medical therapy alone and 1,149 were randomized to optimal medical therapy plus PCI. The entire study population showed high rates of adherence to medications and a regimen of diet, regular exercise, and smoking cessation. Seventy percent achieved target cholesterol levels, 65% reached target systolic blood pressure, 94% reached target diastolic blood pressure, and 45% of those with diabetes achieved target glycolated hemoglobin levels.

The estimated cumulative event rate, a composite outcome of death from any cause and nonfatal MI, was 19.0% in the PCI group and 18.5% in the medical therapy group, a nonsignificant difference. Similarly, there were no significant differences in rates of stroke, hospitalization for acute coronary syndromes, MI alone, death alone, or coronary artery bypass surgery, reported Dr. Boden of the Veterans Affairs Western New York Healthcare System, Buffalo.

Both study groups showed a substantial reduction in the prevalence of angina, and there was a significant difference in favor of PCI for the first few years of follow-up. But by 5 years, that difference had dwindled to the point that 74% of subjects in the PCI group and 72% of those in the medical therapy group were free of angina.

“Our findings reinforce existing clinical practice guidelines, which state that PCI can be safely deferred in patients with stable CAD, even in those with extensive, multivessel involvement and inducible ischemia, provided that intensive, multifaceted medical therapy is instituted and maintained,” the researchers noted.

But those guidelines have not been followed, according to Dr. Salim Yusuf, a panelist at the late-breaking trials session where the study was presented. For too long, the belief has persisted that stenosis is directly related to MI risk, or that PCI would prevent MIs and save lives if only its imperfections could be remedied by better stents, he said.

“We would all have liked to see PCI prevent MIs, prevent death, because surely spreading somebody's chest open is not a nice thing to do,” he said. “Unfortunately, the truth doesn't go that way.”

“The time has come to confront ourselves about why these myths have persisted,” he said. Sometimes, PCI is performed because “the referring doctor wants it,” maintained Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

Dr. Gregory J. Dehmer, president of the Society for Cardiovascular Angiography and Interventions (SCAI), said that the proportion of PCI procedures in patients with stable CAD is far lower than the COURAGE researchers' estimate. Most PCI procedures are performed in patients having severe acute MIs, those with unstable angina, and those with high-risk disease characteristics that would have made them ineligible for inclusion for the COURAGE trial, he said in an interview.

Also at the press briefing, Dr. William S. Weintraub of Christiana Hospital in Wilmington, Del., released lifestyle and economic findings of the study. Both optimal medical therapy and PCI quickly and markedly improved patients' angina frequency and quality of life.

Over most of the course of the study, PCI held a slight edge over medication in terms of reducing angina symptoms, leading to a significant but “very slight trend” to improved quality-of-life-years, he said.

The incremental cost-effectiveness ratio at 3 years favored PCI by $217,000, meaning that the cost of the procedure was beneficial in terms of quality of life gained.

The COURAGE study was funded by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institute of Health, and unrestricted grants from Merck & Co., Pfizer, Bristol-Myers Squibb, Fujisawa Healthcare Inc., Kos Pharmaceuticals Inc., Datascope Corp., Astra-Zeneca Pharmaceuticals, Key Pharmaceuticals, Sanofi-Aventis, First Horizon Pharmaceutical Corp, and GE Healthcare.

RENO, NEV. — Women taking hormone therapy had no increase in cardiovascular events and a lower overall death rate, compared with age-matched controls, in a retrospective study that used a primary care database and that was designed to mimic the patient population enrolled in the Women's Health Initiative.

The findings stand in sharp contrast to results of the WHI, although the investigators set out to match the cohort to the WHI study population in terms of inclusion criteria, study time frame, treatment, and outcome variables.

Dr. Kurt T. Barnhart and his associates at the University of Pennsylvania, Philadelphia, examined the records of women in the United Kingdom General Practice Research Database (GPRD), including 13,658 women aged 55–79 years who were taking combination estrogen/progestin hormone therapy (HT), 37,730 matched controls, and a separate group of younger subjects: 20,654 women on HT and 30,102 controls aged 50–55 years.

The results were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

“We found, in contrast to WHI, that there was no cardioadverse association with hormone replacement therapy. We didn't find it cardioprotective, either. In other words, if this had been the WHI, it wouldn't have been stopped,” explained Dr. Barnhart, who is with the department of obstetrics and gynecology at the university.

Women were selected for the retrospective study if their demographics matched those of the WHI cohort. They either took 0.625 mg daily of conjugated estrogen and 150 mcg of norgestrel on days 17–28 per cycle, or they served as controls.

In the GPRD, the adjusted hazard ratio for myocardial infarction was 0.95 (0.78–1.16) for older women and 0.91 (0.69–1.20) for younger women.

By contrast, in the WHI, the hazard ratio for nonfatal MI was 1.28 (0.96–1.70); for coronary heart disease deaths (including fatal MI), it was 1.10 (0.65–1.89) (N. Engl. J. Med. 2003;349:523–34).

Death from all causes was significantly lower in the older GPRD subjects taking HT than in control subjects, with a hazard ratio of 0.75 (0.65–0.86). It also was lower among the younger women taking hormones vs. younger controls (hazard ratio 0.76 [0.63–0.91]). In the WHI, overall mortality was not affected by HT.

In an interview at the meeting, Dr. Barnhart called the reduced mortality finding “mildly surprising.”

“Part of me wants to say that death is really the only thing that matters,” he said.

“You could have a stroke or have breast cancer or you could be protected from colorectal cancer, but really it matters what happened to you, and it looked like there was a lower death rate. I don't know why.”

Analyses are underway to determine whether missing data may help to account for the mortality findings that differed from the WHI results.

In some respects, the GPRD study closely paralleled WHI conclusions. For example, elevated rates of stroke were seen in both studies, with hazard ratios of 1.23 in the GPRD and 1.41 in WHI results that were reported after the trial was discontinued early (JAMA 2002;288:321–33). Similarly, breast cancer was elevated among hormone users in both trials, with hazard ratios of 1.67 and 1.26 in the GPRD and WHI, respectively.

Venous thromboembolic events were elevated in hormone users in both trials, with hazard ratios of 1.55 in the GPRD and 2.22 in the WHI, while the risk of colorectal cancer was diminished (with a hazard ratio of 0.56 in the GPRD and 0.63 in the WHI).

The hazard ratios for hip fractures were similar in both studies, 0.82 in the GPRD and 0.66 in the WHI.

Dr. Barnhart said the sheer size and scope of the GPRD, plus the meticulous inclusion criteria, served to overcome bias often associated with observational studies as opposed to randomized trials such as the WHI.

“If you have a relatively small observational study, then you've got the possibility of selecting women that might be healthier. But when you look at a large number of women, a cross section of the population—this is close to 10% of the population—you're much more likely to see what's actually happening in real life.”

RENO, NEV. — Women taking hormone therapy had no increase in cardiovascular events and a lower overall death rate, compared with age-matched controls, in a retrospective study that used a primary care database and that was designed to mimic the patient population enrolled in the Women's Health Initiative.

The findings stand in sharp contrast to results of the WHI, although the investigators set out to match the cohort to the WHI study population in terms of inclusion criteria, study time frame, treatment, and outcome variables.

Dr. Kurt T. Barnhart and his associates at the University of Pennsylvania, Philadelphia, examined the records of women in the United Kingdom General Practice Research Database (GPRD), including 13,658 women aged 55–79 years who were taking combination estrogen/progestin hormone therapy (HT), 37,730 matched controls, and a separate group of younger subjects: 20,654 women on HT and 30,102 controls aged 50–55 years.

The results were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

“We found, in contrast to WHI, that there was no cardioadverse association with hormone replacement therapy. We didn't find it cardioprotective, either. In other words, if this had been the WHI, it wouldn't have been stopped,” explained Dr. Barnhart, who is with the department of obstetrics and gynecology at the university.

Women were selected for the retrospective study if their demographics matched those of the WHI cohort. They either took 0.625 mg daily of conjugated estrogen and 150 mcg of norgestrel on days 17–28 per cycle, or they served as controls.

In the GPRD, the adjusted hazard ratio for myocardial infarction was 0.95 (0.78–1.16) for older women and 0.91 (0.69–1.20) for younger women.

By contrast, in the WHI, the hazard ratio for nonfatal MI was 1.28 (0.96–1.70); for coronary heart disease deaths (including fatal MI), it was 1.10 (0.65–1.89) (N. Engl. J. Med. 2003;349:523–34).

Death from all causes was significantly lower in the older GPRD subjects taking HT than in control subjects, with a hazard ratio of 0.75 (0.65–0.86). It also was lower among the younger women taking hormones vs. younger controls (hazard ratio 0.76 [0.63–0.91]). In the WHI, overall mortality was not affected by HT.

In an interview at the meeting, Dr. Barnhart called the reduced mortality finding “mildly surprising.”

“Part of me wants to say that death is really the only thing that matters,” he said.

“You could have a stroke or have breast cancer or you could be protected from colorectal cancer, but really it matters what happened to you, and it looked like there was a lower death rate. I don't know why.”

Analyses are underway to determine whether missing data may help to account for the mortality findings that differed from the WHI results.

In some respects, the GPRD study closely paralleled WHI conclusions. For example, elevated rates of stroke were seen in both studies, with hazard ratios of 1.23 in the GPRD and 1.41 in WHI results that were reported after the trial was discontinued early (JAMA 2002;288:321–33). Similarly, breast cancer was elevated among hormone users in both trials, with hazard ratios of 1.67 and 1.26 in the GPRD and WHI, respectively.

Venous thromboembolic events were elevated in hormone users in both trials, with hazard ratios of 1.55 in the GPRD and 2.22 in the WHI, while the risk of colorectal cancer was diminished (with a hazard ratio of 0.56 in the GPRD and 0.63 in the WHI).

The hazard ratios for hip fractures were similar in both studies, 0.82 in the GPRD and 0.66 in the WHI.

Dr. Barnhart said the sheer size and scope of the GPRD, plus the meticulous inclusion criteria, served to overcome bias often associated with observational studies as opposed to randomized trials such as the WHI.

“If you have a relatively small observational study, then you've got the possibility of selecting women that might be healthier. But when you look at a large number of women, a cross section of the population—this is close to 10% of the population—you're much more likely to see what's actually happening in real life.”

RENO, NEV. — Women taking hormone therapy had no increase in cardiovascular events and a lower overall death rate, compared with age-matched controls, in a retrospective study that used a primary care database and that was designed to mimic the patient population enrolled in the Women's Health Initiative.

The findings stand in sharp contrast to results of the WHI, although the investigators set out to match the cohort to the WHI study population in terms of inclusion criteria, study time frame, treatment, and outcome variables.

Dr. Kurt T. Barnhart and his associates at the University of Pennsylvania, Philadelphia, examined the records of women in the United Kingdom General Practice Research Database (GPRD), including 13,658 women aged 55–79 years who were taking combination estrogen/progestin hormone therapy (HT), 37,730 matched controls, and a separate group of younger subjects: 20,654 women on HT and 30,102 controls aged 50–55 years.

The results were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

“We found, in contrast to WHI, that there was no cardioadverse association with hormone replacement therapy. We didn't find it cardioprotective, either. In other words, if this had been the WHI, it wouldn't have been stopped,” explained Dr. Barnhart, who is with the department of obstetrics and gynecology at the university.

Women were selected for the retrospective study if their demographics matched those of the WHI cohort. They either took 0.625 mg daily of conjugated estrogen and 150 mcg of norgestrel on days 17–28 per cycle, or they served as controls.

In the GPRD, the adjusted hazard ratio for myocardial infarction was 0.95 (0.78–1.16) for older women and 0.91 (0.69–1.20) for younger women.

By contrast, in the WHI, the hazard ratio for nonfatal MI was 1.28 (0.96–1.70); for coronary heart disease deaths (including fatal MI), it was 1.10 (0.65–1.89) (N. Engl. J. Med. 2003;349:523–34).

Death from all causes was significantly lower in the older GPRD subjects taking HT than in control subjects, with a hazard ratio of 0.75 (0.65–0.86). It also was lower among the younger women taking hormones vs. younger controls (hazard ratio 0.76 [0.63–0.91]). In the WHI, overall mortality was not affected by HT.

In an interview at the meeting, Dr. Barnhart called the reduced mortality finding “mildly surprising.”

“Part of me wants to say that death is really the only thing that matters,” he said.

“You could have a stroke or have breast cancer or you could be protected from colorectal cancer, but really it matters what happened to you, and it looked like there was a lower death rate. I don't know why.”

Analyses are underway to determine whether missing data may help to account for the mortality findings that differed from the WHI results.

In some respects, the GPRD study closely paralleled WHI conclusions. For example, elevated rates of stroke were seen in both studies, with hazard ratios of 1.23 in the GPRD and 1.41 in WHI results that were reported after the trial was discontinued early (JAMA 2002;288:321–33). Similarly, breast cancer was elevated among hormone users in both trials, with hazard ratios of 1.67 and 1.26 in the GPRD and WHI, respectively.

Venous thromboembolic events were elevated in hormone users in both trials, with hazard ratios of 1.55 in the GPRD and 2.22 in the WHI, while the risk of colorectal cancer was diminished (with a hazard ratio of 0.56 in the GPRD and 0.63 in the WHI).

The hazard ratios for hip fractures were similar in both studies, 0.82 in the GPRD and 0.66 in the WHI.

Dr. Barnhart said the sheer size and scope of the GPRD, plus the meticulous inclusion criteria, served to overcome bias often associated with observational studies as opposed to randomized trials such as the WHI.

“If you have a relatively small observational study, then you've got the possibility of selecting women that might be healthier. But when you look at a large number of women, a cross section of the population—this is close to 10% of the population—you're much more likely to see what's actually happening in real life.”

RENO, NEV. — There was no reduction in preterm birth but a higher cerclage rate and a doubling of hospital days when cervical scanning, rather than obstetric history, was used to determine necessity for the procedure.

Results of the randomized, controlled CIRCLE (Assessment of Cervical Cerclage for the Prevention of Preterm Labour) trial do not suggest any benefit in replacing historical indications for suture placement with ultrasound surveillance, Dr. Rachael Simcox said at the annual meeting of the Society for Gynecologic Investigation.

Dr. Simcox and associates recruited 247 women from nine centers in the United Kingdom carrying singleton pregnancies of less than 24 weeks' gestation and at high risk of preterm birth because of a history of a previous spontaneous delivery between 16 and 34 weeks.

They were stratified based on gestational age at previous preterm birth, then randomized to one of two groups. In the scanning arm, women were followed with trans- vaginal ultrasound every 2 weeks. If cervical length was 20 mm or less, the woman received a cerclage. In the traditional arm, cerclage placement was based on obstetric history and physician discretion. The groups were well matched for ethnicity, smoking status, and obstetric and surgical history.

Women in the scan group were 1.6 times more likely to receive a cerclage (39 of 122), compared with those in the history group (25 of 125). They also spent a total of 495 days in the hospital, compared with 240 days for the traditionally managed women, said Dr. Simcox of the division of reproductive health, endocrinology, and development at King's College London. The scan patients were significantly more likely to receive progesterone than those in the traditional arm (48 vs. 32, respectively), yet despite more intervention, they were not statistically more likely to deliver at term.

Late miscarriages were numerically more common in the traditionally managed group, but the numbers did not reach significance (12 of 125 vs. 4 of 122). Tommy's, the Baby Charity provided funding.

ELSEVIER GLOBAL MEDICAL NEWS

RENO, NEV. — There was no reduction in preterm birth but a higher cerclage rate and a doubling of hospital days when cervical scanning, rather than obstetric history, was used to determine necessity for the procedure.

Results of the randomized, controlled CIRCLE (Assessment of Cervical Cerclage for the Prevention of Preterm Labour) trial do not suggest any benefit in replacing historical indications for suture placement with ultrasound surveillance, Dr. Rachael Simcox said at the annual meeting of the Society for Gynecologic Investigation.

Dr. Simcox and associates recruited 247 women from nine centers in the United Kingdom carrying singleton pregnancies of less than 24 weeks' gestation and at high risk of preterm birth because of a history of a previous spontaneous delivery between 16 and 34 weeks.

They were stratified based on gestational age at previous preterm birth, then randomized to one of two groups. In the scanning arm, women were followed with trans- vaginal ultrasound every 2 weeks. If cervical length was 20 mm or less, the woman received a cerclage. In the traditional arm, cerclage placement was based on obstetric history and physician discretion. The groups were well matched for ethnicity, smoking status, and obstetric and surgical history.

Women in the scan group were 1.6 times more likely to receive a cerclage (39 of 122), compared with those in the history group (25 of 125). They also spent a total of 495 days in the hospital, compared with 240 days for the traditionally managed women, said Dr. Simcox of the division of reproductive health, endocrinology, and development at King's College London. The scan patients were significantly more likely to receive progesterone than those in the traditional arm (48 vs. 32, respectively), yet despite more intervention, they were not statistically more likely to deliver at term.

Late miscarriages were numerically more common in the traditionally managed group, but the numbers did not reach significance (12 of 125 vs. 4 of 122). Tommy's, the Baby Charity provided funding.

ELSEVIER GLOBAL MEDICAL NEWS

RENO, NEV. — There was no reduction in preterm birth but a higher cerclage rate and a doubling of hospital days when cervical scanning, rather than obstetric history, was used to determine necessity for the procedure.

Results of the randomized, controlled CIRCLE (Assessment of Cervical Cerclage for the Prevention of Preterm Labour) trial do not suggest any benefit in replacing historical indications for suture placement with ultrasound surveillance, Dr. Rachael Simcox said at the annual meeting of the Society for Gynecologic Investigation.

Dr. Simcox and associates recruited 247 women from nine centers in the United Kingdom carrying singleton pregnancies of less than 24 weeks' gestation and at high risk of preterm birth because of a history of a previous spontaneous delivery between 16 and 34 weeks.

They were stratified based on gestational age at previous preterm birth, then randomized to one of two groups. In the scanning arm, women were followed with trans- vaginal ultrasound every 2 weeks. If cervical length was 20 mm or less, the woman received a cerclage. In the traditional arm, cerclage placement was based on obstetric history and physician discretion. The groups were well matched for ethnicity, smoking status, and obstetric and surgical history.

Women in the scan group were 1.6 times more likely to receive a cerclage (39 of 122), compared with those in the history group (25 of 125). They also spent a total of 495 days in the hospital, compared with 240 days for the traditionally managed women, said Dr. Simcox of the division of reproductive health, endocrinology, and development at King's College London. The scan patients were significantly more likely to receive progesterone than those in the traditional arm (48 vs. 32, respectively), yet despite more intervention, they were not statistically more likely to deliver at term.

Late miscarriages were numerically more common in the traditionally managed group, but the numbers did not reach significance (12 of 125 vs. 4 of 122). Tommy's, the Baby Charity provided funding.

ELSEVIER GLOBAL MEDICAL NEWS

RENO, NEV. — Cervical dilatation at presentation and over the 6 hours following admission was highly predictive of preterm birth in women admitted with preterm labor, but obstetric history also contributed important information about which mothers were likely to deliver before 34 or 37 weeks' gestation, according to study findings presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

Dr. Jamie A. Bastek and associates in the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, reviewed the records of 400 women with singleton pregnancies who were admitted in preterm labor before 34 weeks' gestation.

They sought to determine whether the risk of preterm birth could be stratified based on a number of easily identifiable variables, including cervical dilatation and obstetric history.

“As tocolytics are not without harm, we felt it was important to see if we could identify women with a low likelihood of preterm birth who could be managed without admission and/or tocolytic agents” she said in an interview. Of the total cohort, nearly 45% delivered before 34 weeks, and 63% delivered before 37 weeks' gestation.

In trying to determine what distinguished the women who delivered after 37 weeks, Dr. Bastek and associates found a number of features conferring protection, including later gestational age at presentation, less cervical dilatation at presentation, smaller rates of change in cervical dilatation, and obstetric history.

Presentation at fewer than 25 weeks' gestation conferred more than a 15-fold increase in the odds of delivering before 34 weeks, compared with women who presented at 32 weeks' gestation. Presentation before 28 weeks was also a noteworthy risk, bestowing 3.5 times the risk of delivering before 34 weeks.

However, presenting at more than 30 weeks' gestation did not demonstrate elevated odds of delivering before 34 weeks or before 37 weeks, compared with presentation at 32 weeks' gestation.

Cervical dilatation, both on presentation and over the course of 6 hours following admission, was significantly predictive of preterm birth, even after controlling for multiple other variables such as maternal age, race, prenatal care, and gestational age on admission.

Each 1-cm increase in cervical dilatation on presentation more than doubled the odds of delivering before 37 weeks, a significant finding (P less than .0001). However, this risk was modified depending on obstetric history.

At a dilatation of 2 cm on admission, for example, the patients who were at highest risk of a preterm birth before 37 weeks were those with no previous births, followed by those with one or more prior preterm deliveries. Rates were lower for mothers who had a history of both preterm and full-term deliveries, and for those who previously had only had full-term deliveries.

The interaction between obstetric history and cervical dilatation was complex. Patients with a previous preterm birth had the highest baseline risk of another preterm delivery before 37 weeks if cervical dilatation was not a consideration.

Within each obstetric history cohort, advancing cervical dilatation was significantly associated with preterm birth before 34 and 37 weeks. Advancing cervical dilatation had the greatest impact on those with no prior preterm birth and the least impact on those with only a prior preterm birth.

Notably, more than 60% of women with a history of one or more full-term deliveries and no preterm deliveries carried their pregnancies beyond 34 weeks.

What happened after admission was also relevant to the risk of preterm delivery. Just 17.8% of the cohort (71 patients) delivered within 6 hours of admission.

In the remaining 329 women, a 1- to 2-cm change in cervical dilatation after admission conferred almost a threefold risk of delivery before 34 weeks and a twofold risk of delivering before 37 weeks.

A 3-cm or greater change in cervical dilatation was associated with a nearly 12-fold increase in risk of a preterm birth before 34 weeks and a sevenfold increase of delivering before 37 weeks.

All eight women with more than a 4-cm change in dilatation over the first 6 hours after admission delivered before 34 weeks.

The research pointed to a number of factors that should be considered in women with preterm labor, especially gestational age at presentation; cervical dilatation on presentation and cervical change over the 6 hours following admission; and obstetric history.

RENO, NEV. — Cervical dilatation at presentation and over the 6 hours following admission was highly predictive of preterm birth in women admitted with preterm labor, but obstetric history also contributed important information about which mothers were likely to deliver before 34 or 37 weeks' gestation, according to study findings presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

Dr. Jamie A. Bastek and associates in the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, reviewed the records of 400 women with singleton pregnancies who were admitted in preterm labor before 34 weeks' gestation.

They sought to determine whether the risk of preterm birth could be stratified based on a number of easily identifiable variables, including cervical dilatation and obstetric history.

“As tocolytics are not without harm, we felt it was important to see if we could identify women with a low likelihood of preterm birth who could be managed without admission and/or tocolytic agents” she said in an interview. Of the total cohort, nearly 45% delivered before 34 weeks, and 63% delivered before 37 weeks' gestation.

In trying to determine what distinguished the women who delivered after 37 weeks, Dr. Bastek and associates found a number of features conferring protection, including later gestational age at presentation, less cervical dilatation at presentation, smaller rates of change in cervical dilatation, and obstetric history.

Presentation at fewer than 25 weeks' gestation conferred more than a 15-fold increase in the odds of delivering before 34 weeks, compared with women who presented at 32 weeks' gestation. Presentation before 28 weeks was also a noteworthy risk, bestowing 3.5 times the risk of delivering before 34 weeks.

However, presenting at more than 30 weeks' gestation did not demonstrate elevated odds of delivering before 34 weeks or before 37 weeks, compared with presentation at 32 weeks' gestation.

Cervical dilatation, both on presentation and over the course of 6 hours following admission, was significantly predictive of preterm birth, even after controlling for multiple other variables such as maternal age, race, prenatal care, and gestational age on admission.

Each 1-cm increase in cervical dilatation on presentation more than doubled the odds of delivering before 37 weeks, a significant finding (P less than .0001). However, this risk was modified depending on obstetric history.

At a dilatation of 2 cm on admission, for example, the patients who were at highest risk of a preterm birth before 37 weeks were those with no previous births, followed by those with one or more prior preterm deliveries. Rates were lower for mothers who had a history of both preterm and full-term deliveries, and for those who previously had only had full-term deliveries.

The interaction between obstetric history and cervical dilatation was complex. Patients with a previous preterm birth had the highest baseline risk of another preterm delivery before 37 weeks if cervical dilatation was not a consideration.

Within each obstetric history cohort, advancing cervical dilatation was significantly associated with preterm birth before 34 and 37 weeks. Advancing cervical dilatation had the greatest impact on those with no prior preterm birth and the least impact on those with only a prior preterm birth.

Notably, more than 60% of women with a history of one or more full-term deliveries and no preterm deliveries carried their pregnancies beyond 34 weeks.

What happened after admission was also relevant to the risk of preterm delivery. Just 17.8% of the cohort (71 patients) delivered within 6 hours of admission.

In the remaining 329 women, a 1- to 2-cm change in cervical dilatation after admission conferred almost a threefold risk of delivery before 34 weeks and a twofold risk of delivering before 37 weeks.

A 3-cm or greater change in cervical dilatation was associated with a nearly 12-fold increase in risk of a preterm birth before 34 weeks and a sevenfold increase of delivering before 37 weeks.

All eight women with more than a 4-cm change in dilatation over the first 6 hours after admission delivered before 34 weeks.

The research pointed to a number of factors that should be considered in women with preterm labor, especially gestational age at presentation; cervical dilatation on presentation and cervical change over the 6 hours following admission; and obstetric history.

RENO, NEV. — Cervical dilatation at presentation and over the 6 hours following admission was highly predictive of preterm birth in women admitted with preterm labor, but obstetric history also contributed important information about which mothers were likely to deliver before 34 or 37 weeks' gestation, according to study findings presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

Dr. Jamie A. Bastek and associates in the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, reviewed the records of 400 women with singleton pregnancies who were admitted in preterm labor before 34 weeks' gestation.

They sought to determine whether the risk of preterm birth could be stratified based on a number of easily identifiable variables, including cervical dilatation and obstetric history.

“As tocolytics are not without harm, we felt it was important to see if we could identify women with a low likelihood of preterm birth who could be managed without admission and/or tocolytic agents” she said in an interview. Of the total cohort, nearly 45% delivered before 34 weeks, and 63% delivered before 37 weeks' gestation.

In trying to determine what distinguished the women who delivered after 37 weeks, Dr. Bastek and associates found a number of features conferring protection, including later gestational age at presentation, less cervical dilatation at presentation, smaller rates of change in cervical dilatation, and obstetric history.

Presentation at fewer than 25 weeks' gestation conferred more than a 15-fold increase in the odds of delivering before 34 weeks, compared with women who presented at 32 weeks' gestation. Presentation before 28 weeks was also a noteworthy risk, bestowing 3.5 times the risk of delivering before 34 weeks.

However, presenting at more than 30 weeks' gestation did not demonstrate elevated odds of delivering before 34 weeks or before 37 weeks, compared with presentation at 32 weeks' gestation.

Cervical dilatation, both on presentation and over the course of 6 hours following admission, was significantly predictive of preterm birth, even after controlling for multiple other variables such as maternal age, race, prenatal care, and gestational age on admission.

Each 1-cm increase in cervical dilatation on presentation more than doubled the odds of delivering before 37 weeks, a significant finding (P less than .0001). However, this risk was modified depending on obstetric history.

At a dilatation of 2 cm on admission, for example, the patients who were at highest risk of a preterm birth before 37 weeks were those with no previous births, followed by those with one or more prior preterm deliveries. Rates were lower for mothers who had a history of both preterm and full-term deliveries, and for those who previously had only had full-term deliveries.

The interaction between obstetric history and cervical dilatation was complex. Patients with a previous preterm birth had the highest baseline risk of another preterm delivery before 37 weeks if cervical dilatation was not a consideration.

Within each obstetric history cohort, advancing cervical dilatation was significantly associated with preterm birth before 34 and 37 weeks. Advancing cervical dilatation had the greatest impact on those with no prior preterm birth and the least impact on those with only a prior preterm birth.

Notably, more than 60% of women with a history of one or more full-term deliveries and no preterm deliveries carried their pregnancies beyond 34 weeks.

What happened after admission was also relevant to the risk of preterm delivery. Just 17.8% of the cohort (71 patients) delivered within 6 hours of admission.

In the remaining 329 women, a 1- to 2-cm change in cervical dilatation after admission conferred almost a threefold risk of delivery before 34 weeks and a twofold risk of delivering before 37 weeks.

A 3-cm or greater change in cervical dilatation was associated with a nearly 12-fold increase in risk of a preterm birth before 34 weeks and a sevenfold increase of delivering before 37 weeks.

All eight women with more than a 4-cm change in dilatation over the first 6 hours after admission delivered before 34 weeks.

The research pointed to a number of factors that should be considered in women with preterm labor, especially gestational age at presentation; cervical dilatation on presentation and cervical change over the 6 hours following admission; and obstetric history.

ANAHEIM, CALIF. – An evolving paradigm for the palliative care of seriously ill children centers on “family-focused comfort care” from the time of diagnosis, not just when aggressive attempts at disease eradication have failed, specialists said a meeting sponsored by the Los Angeles Pediatric Society.

The new palliative care movement grew out of significant resistance to the hospice model of care, which, in reality, seemed to place children in one of two categories: those considered curable and receiving life-prolonging therapy, or those whose disease had progressed beyond curative options, sending them into the realm of “palliative care.”

That approach simply did not work in many cases, because physicians and families proved so reluctant to shift a child from one category to the other, the specialists said.

In pediatric oncology, where most models of palliative care evolved, the goal is a cure, said Dr. Gary A. Walco, director of the David Center for Children's Pain and Palliative Care at the Hackensack (N.J.) University Medical Center.

That's where federal resources have been focused; that's where research has been centered; and that's been the mind-set for many specialists who care for children with life-threatening conditions, for the most part, he said.

“If you're talking about helping children die, by definition that goes against a 'good outcome,'” he said.

Nonetheless, Dr. Walco is probing the question, “What does a good death look like in childhood?” in hopes that the new model of palliation can begin to incorporate elements of his findings early in the course of treatment.

In his multicenter studies on quality of life and spirituality in terminally ill children, his accrual is “sadly pathetic.”

One patient was referred to the study 2 hours before death.

Indeed, previous research has determined that many children end up “suffering greatly” in what proves to be their last months of life because no one wants to “give up” and summon resources focused on the child's comfort and end-of-life physical, emotional/psychosocial, and spiritual issues, said Dr. Lonnie Zeltzer, director of the pediatric pain program at the University of California, Los Angeles, Mattel Children's Hospital.

“What parent wants to say, 'I give up on my child'?

“The idea of not wanting to–quote–'give up' on children tends to push many more procedures and many more heroics,” said Dr. Zeltzer, professor of pediatrics and anesthesiology at the University of California, Los Angeles.

The new model abandons the “either/or” wall between curative and palliative care, she explained, with age-appropriate quality-of-life and family issues addressed from the time of diagnosis or recognition that a child has a life-threatening or potentially life-limiting condition.

“They may not die,” she said. “They may get a transplant and be fine.”

However, children do die: More than 53,000 a year, from all causes, in the United States. There are 500,000 children diagnosed with life-limiting conditions each year and 5,000 of these children are living in their last 6 months of life right now, said Dr. Zeltzer.

More intensive communication up front has the promise of making all of these children more comfortable and having their emotional and spiritual needs, and those of their families, be a more integral part of their care. For those who do not move on to cure, difficult decisions will not come as such a shock to families, she predicted.

“As curative treatments become less and less likely [to be effective], comfort care issues become greater and greater,” she said. “It's not just giving meds. This is where the pediatrician or primary care family physician comes in. It's communicating with the family.”

The principles also are intended to be applied to a wider circle of children: not just those with cancer but also critically ill preemies and newborns, children with neurodegenerative diseases, and those with genetic illnesses.

The new palliative care paradigm has no place for time limits, such as the requirement in many states that a pediatric patient is not eligible for hospice care unless a physician determines he or she has 6 months or less to live.

The perils of delaying palliative care until the end were made clear by examples from Dr. Zeltzer's experience and examples cited by audience members.

Physicians told of relinquishing all contact with patients to hematology/oncology or other specialty groups, only to have them referred back, abruptly, when they had just weeks to live.

Dr. Zeltzer told of adolescents and their families individually despairing over the idea of more treatment unlikely to confer benefit but reluctant to “give up” for the sake of one another.

In a system in which palliation represents the end of life, parents may not accurately convey the degree of their child's pain for fear that it could divert attention from cure or force all involved to acknowledge deterioration in the child's condition.

ANAHEIM, CALIF. – An evolving paradigm for the palliative care of seriously ill children centers on “family-focused comfort care” from the time of diagnosis, not just when aggressive attempts at disease eradication have failed, specialists said a meeting sponsored by the Los Angeles Pediatric Society.

The new palliative care movement grew out of significant resistance to the hospice model of care, which, in reality, seemed to place children in one of two categories: those considered curable and receiving life-prolonging therapy, or those whose disease had progressed beyond curative options, sending them into the realm of “palliative care.”

That approach simply did not work in many cases, because physicians and families proved so reluctant to shift a child from one category to the other, the specialists said.

In pediatric oncology, where most models of palliative care evolved, the goal is a cure, said Dr. Gary A. Walco, director of the David Center for Children's Pain and Palliative Care at the Hackensack (N.J.) University Medical Center.

That's where federal resources have been focused; that's where research has been centered; and that's been the mind-set for many specialists who care for children with life-threatening conditions, for the most part, he said.

“If you're talking about helping children die, by definition that goes against a 'good outcome,'” he said.

Nonetheless, Dr. Walco is probing the question, “What does a good death look like in childhood?” in hopes that the new model of palliation can begin to incorporate elements of his findings early in the course of treatment.

In his multicenter studies on quality of life and spirituality in terminally ill children, his accrual is “sadly pathetic.”

One patient was referred to the study 2 hours before death.

Indeed, previous research has determined that many children end up “suffering greatly” in what proves to be their last months of life because no one wants to “give up” and summon resources focused on the child's comfort and end-of-life physical, emotional/psychosocial, and spiritual issues, said Dr. Lonnie Zeltzer, director of the pediatric pain program at the University of California, Los Angeles, Mattel Children's Hospital.

“What parent wants to say, 'I give up on my child'?

“The idea of not wanting to–quote–'give up' on children tends to push many more procedures and many more heroics,” said Dr. Zeltzer, professor of pediatrics and anesthesiology at the University of California, Los Angeles.

The new model abandons the “either/or” wall between curative and palliative care, she explained, with age-appropriate quality-of-life and family issues addressed from the time of diagnosis or recognition that a child has a life-threatening or potentially life-limiting condition.

“They may not die,” she said. “They may get a transplant and be fine.”

However, children do die: More than 53,000 a year, from all causes, in the United States. There are 500,000 children diagnosed with life-limiting conditions each year and 5,000 of these children are living in their last 6 months of life right now, said Dr. Zeltzer.

More intensive communication up front has the promise of making all of these children more comfortable and having their emotional and spiritual needs, and those of their families, be a more integral part of their care. For those who do not move on to cure, difficult decisions will not come as such a shock to families, she predicted.

“As curative treatments become less and less likely [to be effective], comfort care issues become greater and greater,” she said. “It's not just giving meds. This is where the pediatrician or primary care family physician comes in. It's communicating with the family.”

The principles also are intended to be applied to a wider circle of children: not just those with cancer but also critically ill preemies and newborns, children with neurodegenerative diseases, and those with genetic illnesses.

The new palliative care paradigm has no place for time limits, such as the requirement in many states that a pediatric patient is not eligible for hospice care unless a physician determines he or she has 6 months or less to live.

The perils of delaying palliative care until the end were made clear by examples from Dr. Zeltzer's experience and examples cited by audience members.

Physicians told of relinquishing all contact with patients to hematology/oncology or other specialty groups, only to have them referred back, abruptly, when they had just weeks to live.

Dr. Zeltzer told of adolescents and their families individually despairing over the idea of more treatment unlikely to confer benefit but reluctant to “give up” for the sake of one another.

In a system in which palliation represents the end of life, parents may not accurately convey the degree of their child's pain for fear that it could divert attention from cure or force all involved to acknowledge deterioration in the child's condition.

ANAHEIM, CALIF. – An evolving paradigm for the palliative care of seriously ill children centers on “family-focused comfort care” from the time of diagnosis, not just when aggressive attempts at disease eradication have failed, specialists said a meeting sponsored by the Los Angeles Pediatric Society.

The new palliative care movement grew out of significant resistance to the hospice model of care, which, in reality, seemed to place children in one of two categories: those considered curable and receiving life-prolonging therapy, or those whose disease had progressed beyond curative options, sending them into the realm of “palliative care.”

That approach simply did not work in many cases, because physicians and families proved so reluctant to shift a child from one category to the other, the specialists said.

In pediatric oncology, where most models of palliative care evolved, the goal is a cure, said Dr. Gary A. Walco, director of the David Center for Children's Pain and Palliative Care at the Hackensack (N.J.) University Medical Center.

That's where federal resources have been focused; that's where research has been centered; and that's been the mind-set for many specialists who care for children with life-threatening conditions, for the most part, he said.

“If you're talking about helping children die, by definition that goes against a 'good outcome,'” he said.

Nonetheless, Dr. Walco is probing the question, “What does a good death look like in childhood?” in hopes that the new model of palliation can begin to incorporate elements of his findings early in the course of treatment.

In his multicenter studies on quality of life and spirituality in terminally ill children, his accrual is “sadly pathetic.”

One patient was referred to the study 2 hours before death.

Indeed, previous research has determined that many children end up “suffering greatly” in what proves to be their last months of life because no one wants to “give up” and summon resources focused on the child's comfort and end-of-life physical, emotional/psychosocial, and spiritual issues, said Dr. Lonnie Zeltzer, director of the pediatric pain program at the University of California, Los Angeles, Mattel Children's Hospital.

“What parent wants to say, 'I give up on my child'?

“The idea of not wanting to–quote–'give up' on children tends to push many more procedures and many more heroics,” said Dr. Zeltzer, professor of pediatrics and anesthesiology at the University of California, Los Angeles.

The new model abandons the “either/or” wall between curative and palliative care, she explained, with age-appropriate quality-of-life and family issues addressed from the time of diagnosis or recognition that a child has a life-threatening or potentially life-limiting condition.

“They may not die,” she said. “They may get a transplant and be fine.”

However, children do die: More than 53,000 a year, from all causes, in the United States. There are 500,000 children diagnosed with life-limiting conditions each year and 5,000 of these children are living in their last 6 months of life right now, said Dr. Zeltzer.

More intensive communication up front has the promise of making all of these children more comfortable and having their emotional and spiritual needs, and those of their families, be a more integral part of their care. For those who do not move on to cure, difficult decisions will not come as such a shock to families, she predicted.

“As curative treatments become less and less likely [to be effective], comfort care issues become greater and greater,” she said. “It's not just giving meds. This is where the pediatrician or primary care family physician comes in. It's communicating with the family.”

The principles also are intended to be applied to a wider circle of children: not just those with cancer but also critically ill preemies and newborns, children with neurodegenerative diseases, and those with genetic illnesses.

The new palliative care paradigm has no place for time limits, such as the requirement in many states that a pediatric patient is not eligible for hospice care unless a physician determines he or she has 6 months or less to live.

The perils of delaying palliative care until the end were made clear by examples from Dr. Zeltzer's experience and examples cited by audience members.

Physicians told of relinquishing all contact with patients to hematology/oncology or other specialty groups, only to have them referred back, abruptly, when they had just weeks to live.

Dr. Zeltzer told of adolescents and their families individually despairing over the idea of more treatment unlikely to confer benefit but reluctant to “give up” for the sake of one another.

In a system in which palliation represents the end of life, parents may not accurately convey the degree of their child's pain for fear that it could divert attention from cure or force all involved to acknowledge deterioration in the child's condition.

LOS ANGELES — The number of Americans diagnosed with AIDS is now approaching the 1 million mark, with more than a half-million deaths since the epidemic began and 17,000 more people dying of the disease each year, Dr. Harold Jaffe said during a plenary session at the 14th Conference on Retroviruses and Opportunistic Infections.

That mortality—58 per million—is “twice as high as any country in the European Union and 10 times as high as in the United Kingdom,” said Dr. Jaffe, former director of HIV prevention for the Centers for Disease Control and Prevention and currently head of the department of public health at Oxford University, England.

A troubling jump in incidence in 2005, the latest year for which data are available, compounded by signs of risky behavioral trends in gay men, points to the critical need for community leadership, personal responsibility, and support of preventive efforts proven to work, he said.

“The need for treatment is critical, but I agree with my colleague Dr. Kevin de Kock [WHO director of HIV/AIDS] that we are not going to be able to treat our way out of this epidemic.

“I guess it seems obvious that we should be implementing what works, evaluating what might work, and stop trying to do what doesn't work,” added Dr. Jaffe, who singled out federal funding for abstinence-only education as an example of a strategy based on beliefs rather than science.

A “very comprehensive” study in press in the Cochrane Review, for example, reviewed eight published randomized controlled trials of abstinence-only programs, compared with standard sex education or safe-sex programs, involving 13,191 American youths.

With a median follow-up of 12 months, none of the abstinence-only programs demonstrated a significant decline in self-reported sexual activity or any biological outcome such as pregnancy or diagnosis with a sexually transmitted disease (STD), compared with the other approaches, said Dr. Jaffe at the conference, sponsored by the Foundation for Retrovirology and Human Health.

A recent University of Pennsylvania study of 662 African American children (median age, 12 years) did show significantly less sexual activity among those receiving abstinence-only education, compared with those exposed to other interventions; even so, nearly a third of the virgins in the abstinence-only group became sexually active over the course of the 2-year study.

Dr. Jaffe said it cannot be entirely ruled out that abstinence-only education could benefit “very specific groups,” but the preponderance of evidence suggests it is not efficacious.

By contrast, he pointed to condom promotion, shown to be “highly efficacious” in preventing HIV transmission, and needle- and syringe-exchange programs, which demonstrate at least modest evidence of reducing intermediate-level activities with the capacity to spread HIV, as more effective approaches.

Condom distribution campaigns are currently being opposed by individuals who believe availability will undermine abstinence-only programs.

President Bush's proposed 2007 budget includes $204 million in support of abstinence-only education, while “no administration, Democrat or Republican, has ever put any [federal] money whatsoever into needle-exchange programs in this country, in contrast to many other countries, including the U.K.,” Dr. Jaffe said.

Purely behavioral interventions, primarily skill-building sessions aimed at reducing risky activities among high-risk individuals, are highly significantly efficacious in reducing unprotected sex and acquiring STDs, he said.

Finally, HIV testing by itself is a profound risk-reducing strategy, because individuals who learn they have been exposed to the virus sharply reduce behaviors that could lead to transmission to others, he noted.

Public health prevention strategies can go only so far in curbing the epidemic, emphasized Dr. Jaffe, particularly when it comes to sexual behavior change.

However, some indicators suggest that resources must be quickly marshaled to stem a rising tide of cases, especially among men who have sex with men and among African Americans and other ethnic minorities.

“We are seeing behavior trends in gay men in the United States and Western Europe that are similar to trends in the late ′70s, years just before tens of thousands of young men were about to lose their lives,” he said.

He urged activists and community leaders to “step forward” and policy makers “to use science rather than moral judgment, religious beliefs, or wishful thinking to guide our strategies.”

LOS ANGELES — The number of Americans diagnosed with AIDS is now approaching the 1 million mark, with more than a half-million deaths since the epidemic began and 17,000 more people dying of the disease each year, Dr. Harold Jaffe said during a plenary session at the 14th Conference on Retroviruses and Opportunistic Infections.

That mortality—58 per million—is “twice as high as any country in the European Union and 10 times as high as in the United Kingdom,” said Dr. Jaffe, former director of HIV prevention for the Centers for Disease Control and Prevention and currently head of the department of public health at Oxford University, England.

A troubling jump in incidence in 2005, the latest year for which data are available, compounded by signs of risky behavioral trends in gay men, points to the critical need for community leadership, personal responsibility, and support of preventive efforts proven to work, he said.

“The need for treatment is critical, but I agree with my colleague Dr. Kevin de Kock [WHO director of HIV/AIDS] that we are not going to be able to treat our way out of this epidemic.

“I guess it seems obvious that we should be implementing what works, evaluating what might work, and stop trying to do what doesn't work,” added Dr. Jaffe, who singled out federal funding for abstinence-only education as an example of a strategy based on beliefs rather than science.

A “very comprehensive” study in press in the Cochrane Review, for example, reviewed eight published randomized controlled trials of abstinence-only programs, compared with standard sex education or safe-sex programs, involving 13,191 American youths.

With a median follow-up of 12 months, none of the abstinence-only programs demonstrated a significant decline in self-reported sexual activity or any biological outcome such as pregnancy or diagnosis with a sexually transmitted disease (STD), compared with the other approaches, said Dr. Jaffe at the conference, sponsored by the Foundation for Retrovirology and Human Health.

A recent University of Pennsylvania study of 662 African American children (median age, 12 years) did show significantly less sexual activity among those receiving abstinence-only education, compared with those exposed to other interventions; even so, nearly a third of the virgins in the abstinence-only group became sexually active over the course of the 2-year study.

Dr. Jaffe said it cannot be entirely ruled out that abstinence-only education could benefit “very specific groups,” but the preponderance of evidence suggests it is not efficacious.

By contrast, he pointed to condom promotion, shown to be “highly efficacious” in preventing HIV transmission, and needle- and syringe-exchange programs, which demonstrate at least modest evidence of reducing intermediate-level activities with the capacity to spread HIV, as more effective approaches.

Condom distribution campaigns are currently being opposed by individuals who believe availability will undermine abstinence-only programs.

President Bush's proposed 2007 budget includes $204 million in support of abstinence-only education, while “no administration, Democrat or Republican, has ever put any [federal] money whatsoever into needle-exchange programs in this country, in contrast to many other countries, including the U.K.,” Dr. Jaffe said.

Purely behavioral interventions, primarily skill-building sessions aimed at reducing risky activities among high-risk individuals, are highly significantly efficacious in reducing unprotected sex and acquiring STDs, he said.

Finally, HIV testing by itself is a profound risk-reducing strategy, because individuals who learn they have been exposed to the virus sharply reduce behaviors that could lead to transmission to others, he noted.

Public health prevention strategies can go only so far in curbing the epidemic, emphasized Dr. Jaffe, particularly when it comes to sexual behavior change.

However, some indicators suggest that resources must be quickly marshaled to stem a rising tide of cases, especially among men who have sex with men and among African Americans and other ethnic minorities.

“We are seeing behavior trends in gay men in the United States and Western Europe that are similar to trends in the late ′70s, years just before tens of thousands of young men were about to lose their lives,” he said.

He urged activists and community leaders to “step forward” and policy makers “to use science rather than moral judgment, religious beliefs, or wishful thinking to guide our strategies.”

LOS ANGELES — The number of Americans diagnosed with AIDS is now approaching the 1 million mark, with more than a half-million deaths since the epidemic began and 17,000 more people dying of the disease each year, Dr. Harold Jaffe said during a plenary session at the 14th Conference on Retroviruses and Opportunistic Infections.

That mortality—58 per million—is “twice as high as any country in the European Union and 10 times as high as in the United Kingdom,” said Dr. Jaffe, former director of HIV prevention for the Centers for Disease Control and Prevention and currently head of the department of public health at Oxford University, England.

A troubling jump in incidence in 2005, the latest year for which data are available, compounded by signs of risky behavioral trends in gay men, points to the critical need for community leadership, personal responsibility, and support of preventive efforts proven to work, he said.

“The need for treatment is critical, but I agree with my colleague Dr. Kevin de Kock [WHO director of HIV/AIDS] that we are not going to be able to treat our way out of this epidemic.

“I guess it seems obvious that we should be implementing what works, evaluating what might work, and stop trying to do what doesn't work,” added Dr. Jaffe, who singled out federal funding for abstinence-only education as an example of a strategy based on beliefs rather than science.

A “very comprehensive” study in press in the Cochrane Review, for example, reviewed eight published randomized controlled trials of abstinence-only programs, compared with standard sex education or safe-sex programs, involving 13,191 American youths.

With a median follow-up of 12 months, none of the abstinence-only programs demonstrated a significant decline in self-reported sexual activity or any biological outcome such as pregnancy or diagnosis with a sexually transmitted disease (STD), compared with the other approaches, said Dr. Jaffe at the conference, sponsored by the Foundation for Retrovirology and Human Health.

A recent University of Pennsylvania study of 662 African American children (median age, 12 years) did show significantly less sexual activity among those receiving abstinence-only education, compared with those exposed to other interventions; even so, nearly a third of the virgins in the abstinence-only group became sexually active over the course of the 2-year study.

Dr. Jaffe said it cannot be entirely ruled out that abstinence-only education could benefit “very specific groups,” but the preponderance of evidence suggests it is not efficacious.

By contrast, he pointed to condom promotion, shown to be “highly efficacious” in preventing HIV transmission, and needle- and syringe-exchange programs, which demonstrate at least modest evidence of reducing intermediate-level activities with the capacity to spread HIV, as more effective approaches.

Condom distribution campaigns are currently being opposed by individuals who believe availability will undermine abstinence-only programs.

President Bush's proposed 2007 budget includes $204 million in support of abstinence-only education, while “no administration, Democrat or Republican, has ever put any [federal] money whatsoever into needle-exchange programs in this country, in contrast to many other countries, including the U.K.,” Dr. Jaffe said.

Purely behavioral interventions, primarily skill-building sessions aimed at reducing risky activities among high-risk individuals, are highly significantly efficacious in reducing unprotected sex and acquiring STDs, he said.

Finally, HIV testing by itself is a profound risk-reducing strategy, because individuals who learn they have been exposed to the virus sharply reduce behaviors that could lead to transmission to others, he noted.

Public health prevention strategies can go only so far in curbing the epidemic, emphasized Dr. Jaffe, particularly when it comes to sexual behavior change.

However, some indicators suggest that resources must be quickly marshaled to stem a rising tide of cases, especially among men who have sex with men and among African Americans and other ethnic minorities.

“We are seeing behavior trends in gay men in the United States and Western Europe that are similar to trends in the late ′70s, years just before tens of thousands of young men were about to lose their lives,” he said.

He urged activists and community leaders to “step forward” and policy makers “to use science rather than moral judgment, religious beliefs, or wishful thinking to guide our strategies.”

LAS VEGAS — Look no further than your own office staff in deciding which cosmetic products to offer for sale in your practice, Dr. Kathy Fields suggested at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

The best product lines are simple, efficacious, relatively affordable, and beyond all else, safe, said Dr. Fields, a dermatologist in private practice in San Francisco.

But how do you know?

She suggests conducting mini-trials in-house, using your office staff.

"Leverage your team. Grab your staff and do your own before-and-afters," she said.

It will quickly become clear if a product line is popular. An added bonus is that staff members serve as in-house examples of how well a product works.

In one mini-trial in her office, 7 out of 12 staff members had skin reactions to a product line she was testing.

Obviously, that one never made it to the consumer shelf.

"Test it and make sure," she said.

Certain products are sure to sell if they work, especially if they're "elegant, simple products."

For example, many consumers love eye creams, night "boosters," and products containing Retin-A, Dr. Fields said.

LAS VEGAS — Look no further than your own office staff in deciding which cosmetic products to offer for sale in your practice, Dr. Kathy Fields suggested at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

The best product lines are simple, efficacious, relatively affordable, and beyond all else, safe, said Dr. Fields, a dermatologist in private practice in San Francisco.

But how do you know?

She suggests conducting mini-trials in-house, using your office staff.

"Leverage your team. Grab your staff and do your own before-and-afters," she said.

It will quickly become clear if a product line is popular. An added bonus is that staff members serve as in-house examples of how well a product works.

In one mini-trial in her office, 7 out of 12 staff members had skin reactions to a product line she was testing.

Obviously, that one never made it to the consumer shelf.

"Test it and make sure," she said.

Certain products are sure to sell if they work, especially if they're "elegant, simple products."

For example, many consumers love eye creams, night "boosters," and products containing Retin-A, Dr. Fields said.

LAS VEGAS — Look no further than your own office staff in deciding which cosmetic products to offer for sale in your practice, Dr. Kathy Fields suggested at the annual meeting of the American Society of Cosmetic Dermatology and Aesthetic Surgery.

The best product lines are simple, efficacious, relatively affordable, and beyond all else, safe, said Dr. Fields, a dermatologist in private practice in San Francisco.

But how do you know?

She suggests conducting mini-trials in-house, using your office staff.

"Leverage your team. Grab your staff and do your own before-and-afters," she said.

It will quickly become clear if a product line is popular. An added bonus is that staff members serve as in-house examples of how well a product works.

In one mini-trial in her office, 7 out of 12 staff members had skin reactions to a product line she was testing.

Obviously, that one never made it to the consumer shelf.

"Test it and make sure," she said.

Certain products are sure to sell if they work, especially if they're "elegant, simple products."

For example, many consumers love eye creams, night "boosters," and products containing Retin-A, Dr. Fields said.