Mortality Unchanged by Enoxaparin Prophylaxis in Medical Inpatients

SAN FRANCISCO – Thromboprophylaxis with enoxaparin (Lovenox) did not reduce mortality among acutely ill, hospitalized medical patients in a trial funded by the maker of the low molecular weight heparin, Sanofi-Aventis.

Among 4,171 patients randomized to enoxaparin 40 mg subcutaneously for 10 days, plus or minus 4 days, all-cause 30-day mortality was 4.9%; among 4,136 randomized to placebo for the same amount of time, it was 4.8% (relative risk, 1.0; P = .83).

The major bleeding rate was below a half percent in both groups and not statistically different. Minor bleeding was seen in 1.8% in the enoxaparin group and 1.1% in the placebo group, a statistically significant difference, Dr. Samuel Goldhaber said at an international conference of the American Thoracic Society.

Commenting on the study, New England Journal of Medicine editor Dr. Jeffrey Drazen noted that, in the United States, the reflex has been to use prophylaxis on even low-risk patients for venous thromboembolism. "The reason we published these data was that maybe we should rethink this. Maybe we should be making decisions about who should be receiving pharmacologic prophylaxis based on factors other than the fact that they are in the hospital for an acute medical illness," he said.

Patients were hospitalized for acute decompensated heart failure, severe systemic infections, or active cancer. No mortality benefit was found for enoxaparin on subgroup analysis. Both groups wore knee-high elastic graduated compression stockings during the treatment phase of the trial (N. Engl. J. Med. 2011;365:2463-72).

The all-cause 1-90 day mortality curves for the two groups "were absolutely superimposable. We were quite surprised by the results," said Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, both in Boston.

They were surprised because enoxaparin has been proven to reduce venous thromboembolism in both surgical and medical patients, and to reduce the incidence of fatal pulmonary embolism and all-cause mortality in surgical patients.

There was a presumption it would save medical patients’ lives, too, although they have a lower pulmonary embolism rate. Current U.S. treatment guidelines recommend pharmacologic prophylaxis in both surgical and acutely-ill medical inpatients.

The study was conducted in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia because, in those places, enoxaparin prophylaxis for medical patients is "still considered an open question," Dr. Goldhaber said.

About 88% of the subjects were Asian, 63% were men. Their average age was 65 years and average body mass index about 23 kg/m². There were no statistically significant baseline differences between the placebo and enoxaparin groups.

Perhaps enoxaparin didn’t cut mortality in the trial because "the natural history of deep vein thrombosis differs between medical and surgical patients." It’s been assumed that "the natural history would be the same. This assumption may be incorrect," Dr. Goldhaber said.

It’s also possible that the elastic stockings used in the trial were enough to prevent fatal pulmonary embolisms in the mostly-Asian subjects, a group known historically to have a lower pulmonary embolism risk than Westerners. Just one patient in each group died from a pulmonary embolism in the study; infections were the main cause of death.

At this point, Dr. Goldhaber still tends to prophylaxis even low-risk medical inpatients. "In our world, the quality measures are in place, but I’d be thinking to myself that prophylaxis is not going, in all likelihood, to save [their lives] from a pulmonary embolism because [they’re] probably not going to develop that problem," he said.

Dr. Goldhaber disclosed that he is a paid consultant for Sanofi-Aventis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and several other companies. Dr. Drazen reported having no disclosures.

SAN FRANCISCO – Thromboprophylaxis with enoxaparin (Lovenox) did not reduce mortality among acutely ill, hospitalized medical patients in a trial funded by the maker of the low molecular weight heparin, Sanofi-Aventis.

Among 4,171 patients randomized to enoxaparin 40 mg subcutaneously for 10 days, plus or minus 4 days, all-cause 30-day mortality was 4.9%; among 4,136 randomized to placebo for the same amount of time, it was 4.8% (relative risk, 1.0; P = .83).

The major bleeding rate was below a half percent in both groups and not statistically different. Minor bleeding was seen in 1.8% in the enoxaparin group and 1.1% in the placebo group, a statistically significant difference, Dr. Samuel Goldhaber said at an international conference of the American Thoracic Society.

Commenting on the study, New England Journal of Medicine editor Dr. Jeffrey Drazen noted that, in the United States, the reflex has been to use prophylaxis on even low-risk patients for venous thromboembolism. "The reason we published these data was that maybe we should rethink this. Maybe we should be making decisions about who should be receiving pharmacologic prophylaxis based on factors other than the fact that they are in the hospital for an acute medical illness," he said.

Patients were hospitalized for acute decompensated heart failure, severe systemic infections, or active cancer. No mortality benefit was found for enoxaparin on subgroup analysis. Both groups wore knee-high elastic graduated compression stockings during the treatment phase of the trial (N. Engl. J. Med. 2011;365:2463-72).

The all-cause 1-90 day mortality curves for the two groups "were absolutely superimposable. We were quite surprised by the results," said Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, both in Boston.

They were surprised because enoxaparin has been proven to reduce venous thromboembolism in both surgical and medical patients, and to reduce the incidence of fatal pulmonary embolism and all-cause mortality in surgical patients.

There was a presumption it would save medical patients’ lives, too, although they have a lower pulmonary embolism rate. Current U.S. treatment guidelines recommend pharmacologic prophylaxis in both surgical and acutely-ill medical inpatients.

The study was conducted in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia because, in those places, enoxaparin prophylaxis for medical patients is "still considered an open question," Dr. Goldhaber said.

About 88% of the subjects were Asian, 63% were men. Their average age was 65 years and average body mass index about 23 kg/m². There were no statistically significant baseline differences between the placebo and enoxaparin groups.

Perhaps enoxaparin didn’t cut mortality in the trial because "the natural history of deep vein thrombosis differs between medical and surgical patients." It’s been assumed that "the natural history would be the same. This assumption may be incorrect," Dr. Goldhaber said.

It’s also possible that the elastic stockings used in the trial were enough to prevent fatal pulmonary embolisms in the mostly-Asian subjects, a group known historically to have a lower pulmonary embolism risk than Westerners. Just one patient in each group died from a pulmonary embolism in the study; infections were the main cause of death.

At this point, Dr. Goldhaber still tends to prophylaxis even low-risk medical inpatients. "In our world, the quality measures are in place, but I’d be thinking to myself that prophylaxis is not going, in all likelihood, to save [their lives] from a pulmonary embolism because [they’re] probably not going to develop that problem," he said.

Dr. Goldhaber disclosed that he is a paid consultant for Sanofi-Aventis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and several other companies. Dr. Drazen reported having no disclosures.

SAN FRANCISCO – Thromboprophylaxis with enoxaparin (Lovenox) did not reduce mortality among acutely ill, hospitalized medical patients in a trial funded by the maker of the low molecular weight heparin, Sanofi-Aventis.

Among 4,171 patients randomized to enoxaparin 40 mg subcutaneously for 10 days, plus or minus 4 days, all-cause 30-day mortality was 4.9%; among 4,136 randomized to placebo for the same amount of time, it was 4.8% (relative risk, 1.0; P = .83).

The major bleeding rate was below a half percent in both groups and not statistically different. Minor bleeding was seen in 1.8% in the enoxaparin group and 1.1% in the placebo group, a statistically significant difference, Dr. Samuel Goldhaber said at an international conference of the American Thoracic Society.

Commenting on the study, New England Journal of Medicine editor Dr. Jeffrey Drazen noted that, in the United States, the reflex has been to use prophylaxis on even low-risk patients for venous thromboembolism. "The reason we published these data was that maybe we should rethink this. Maybe we should be making decisions about who should be receiving pharmacologic prophylaxis based on factors other than the fact that they are in the hospital for an acute medical illness," he said.

Patients were hospitalized for acute decompensated heart failure, severe systemic infections, or active cancer. No mortality benefit was found for enoxaparin on subgroup analysis. Both groups wore knee-high elastic graduated compression stockings during the treatment phase of the trial (N. Engl. J. Med. 2011;365:2463-72).

The all-cause 1-90 day mortality curves for the two groups "were absolutely superimposable. We were quite surprised by the results," said Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, both in Boston.

They were surprised because enoxaparin has been proven to reduce venous thromboembolism in both surgical and medical patients, and to reduce the incidence of fatal pulmonary embolism and all-cause mortality in surgical patients.

There was a presumption it would save medical patients’ lives, too, although they have a lower pulmonary embolism rate. Current U.S. treatment guidelines recommend pharmacologic prophylaxis in both surgical and acutely-ill medical inpatients.

The study was conducted in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia because, in those places, enoxaparin prophylaxis for medical patients is "still considered an open question," Dr. Goldhaber said.

About 88% of the subjects were Asian, 63% were men. Their average age was 65 years and average body mass index about 23 kg/m². There were no statistically significant baseline differences between the placebo and enoxaparin groups.

Perhaps enoxaparin didn’t cut mortality in the trial because "the natural history of deep vein thrombosis differs between medical and surgical patients." It’s been assumed that "the natural history would be the same. This assumption may be incorrect," Dr. Goldhaber said.

It’s also possible that the elastic stockings used in the trial were enough to prevent fatal pulmonary embolisms in the mostly-Asian subjects, a group known historically to have a lower pulmonary embolism risk than Westerners. Just one patient in each group died from a pulmonary embolism in the study; infections were the main cause of death.

At this point, Dr. Goldhaber still tends to prophylaxis even low-risk medical inpatients. "In our world, the quality measures are in place, but I’d be thinking to myself that prophylaxis is not going, in all likelihood, to save [their lives] from a pulmonary embolism because [they’re] probably not going to develop that problem," he said.

Dr. Goldhaber disclosed that he is a paid consultant for Sanofi-Aventis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and several other companies. Dr. Drazen reported having no disclosures.