Kerri Wachter

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study's prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study's prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study's prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study’s prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study’s prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study’s prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study’s prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study’s prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Biologics appear to be associated with a significantly greater rate of total adverse events, withdrawals due to adverse events, and an increased risk of tuberculosis reactivation compared with control agents, based on a meta-analysis involving more than 60,000 patients.

However, there were no significant differences in the rates of serious adverse events, serious infections, lymphoma, and congestive heart failure between biologics and control agents.

"Our review included indirect comparisons of the safety of biologics and should provide some guidance to clinicians and patients until head-to-head comparisons become available," wrote Dr. Jasvinder A. Singh and his coauthors (Cochrane Database Syst. Rev. 2011 [doi: 10.1002/14651858.CD008794.pub2]).

The results come from a network meta-analysis and Cochrane overview of the adverse effects of biologic drugs that are approved for the treatment of rheumatoid arthritis and other conditions in Europe, the United Kingdom, the United States, Canada, and Australia.

The investigators included randomized controlled trials (RCTs), controlled clinical trials, and open-label extension studies that involved one of the nine biologics for use in any indication and that reported this study’s prespecified adverse outcomes. The researchers did not include studies on biologics for the treatment of HIV/AIDS. The nine biologics investigated were abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan/MabThera), and tocilizumab (Actemra).

They searched the Cochrane Library, Medline, and Embase (through January 2010). The investigators performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework for the network meta-analysis.

In all, included in the analysis were 163 RCTs with 50,010 adult participants and 46 extension studies with 11,954 adult participants. The median duration was 6 months for the RCTs and 13 months for the extension studies. Given the short duration of the RCTs, all the results should be interpreted as applying to a fairly short time frame.

After the analysis was adjusted for dose, biologics as a group were associated with a significantly greater rate of total adverse events (odds ratio 1.19) and withdrawals due to adverse events (OR 1.32), as well as an increased risk of TB reactivation (OR 4.68), compared with control agents.

Notably, certolizumab pegol was associated with a significantly greater risk of serious infections than was control treatment (OR 3.51). Infliximab was associated with a significantly greater risk of withdrawals due to adverse events compared with the control (OR 2.04).

Heart failure and cancer have been of particular concern with the use of biologic drugs. There appears to be little or no difference in the number of people who experienced heart failure or cancer taking any biologic compared with people who took placebo. However, there were not many cases of congestive heart failure or cancer, so confidence in these results is low.

The researchers also were able to indirectly compare individual biologic drugs. These analyses revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events than were most other biologics. In addition, certolizumab pegol was associated with significantly greater odds of serious infections than were etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab. Abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections; abatacept, adalimumab, etanercept, and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. However, the authors noted that the overall numbers were relatively small and that these comparisons should be interpreted with caution.

The lack of long-term studies of biologics is still a concern, they added. "There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics," they concluded.

Dr. Singh and several of his coauthors reported that they have significant financial relationships with several pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

Patients with high on-treatment platelet reactivity after percutaneous coronary intervention who received high-dose clopidogrel fared no better in terms of cardiovascular events than did high-reactivity patients on standard-dose clopidogrel in the GRAVITAS trial.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," Dr. Matthew J. Price and his coinvestigators wrote in the March 16 issue of JAMA. However, "alternative treatment strategies incorporating platelet function testing merit further investigation."

In the Gauging Responsiveness With a VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial, researchers measured platelet function with the VerifyNow P2Y¹² test (Accumetrics) 12-24 hours after PCI. A greater P2Y¹² reaction unit (PRU) result reflects greater P2Y¹² mediated reactivity. High on-treatment reactivity was defined as 230 PRU or greater. This cutoff was chosen because it was similar to the cutoff suggested by a prior observational study.

Patients were eligible for enrollment if they had undergone PCI with at least one drug-eluting stent for the treatment of stable coronary artery disease or acute coronary syndromes. Patients with high on-treatment platelet reactivity were randomly assigned to receive either high-dose or standard-dose clopidogrel. High-dose clopidogrel was given as a total first-day dose of 600 mg followed by 150 mg daily for 6 months. Standard-dose clopidogrel involved a loading dose of placebo followed by a dose of 75 mg and placebo tablet daily.

In all, 5,429 patients from 83 sites in the United States and Canada were screened with platelet function testing. Of these, 2,214 (41%) had high on-treatment reactivity and were randomly assigned to either high-dose or standard-dose clopidogrel. An additional 586 patients without high on-treatment reactivity were selected at random and assigned to treatment with standard-dose clopidogrel (JAMA 2011;305:1097-105).

The primary efficacy end point, a composite of death from cardiovascular causes, nonfatal MI, or stent thrombosis at 6 months, was identical in both groups with high reactivity, at 25 (2.3%).

The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. That occurred in 15 (1.4%) and 25 (2.3%) of patients in the high- and low-dose groups, respectively, a nonsignificant difference.

In a secondary, observational comparison of patients with and without high on-treatment reactivity treated with standard-dose clopidogrel, the rate of death from cardiovascular causes, nonfatal MI, or stent thrombosis was numerically greater in the patients with high on-treatment reactivity than in those without high on-treatment reactivity, at 25 and 8, respectively, but this difference did not reach statistical significance.

In terms of safety, intracranial hemorrhage occurred in none of the patients with high on-treatment reactivity who were randomly assigned to high-dose clopidogrel, in two patients (0.2%) with high on-treatment reactivity on standard-dose clopidogrel, and in one patient (0.2%) without high on-treatment reactivity treated with standard-dose clopidogrel. The rate of discontinuation of study drug due to severe or moderate bleeding was similar across all three groups.

The results of GRAVITAS are of particular interest because studies have shown wide interindividual variability in the platelet inhibitory response to clopidogrel and suggested a link between a poor pharmacodynamic response to cardiovascular events after PCI.

"We found that compared with the standard maintenance dose of 75 mg daily, prolonged high-dose clopidogrel therapy in a population of patients with high on-treatment reactivity after PCI provided a modest pharmacodynamic effect but did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis," wrote Dr. Price, director of the cardiac catheterization laboratory at the Scripps Clinic in La Jolla, Calif., and his coinvestigators.

The researchers suggested several potential mechanisms that may explain the lack of a beneficial treatment effect with high-dose clopidogrel. It may be that on-treatment platelet reactivity is simply not a modifiable risk factor for thrombosis after PCI, or that the solution is to use an agent such as prasugrel, which doesn’t require metabolic transformation to reach its active form.

But the timing of the test may also play a role. Platelet reactivity resolved in nearly 40% of patients on normal-dose clopidogrel within 30 days, suggesting that the poststenting platelet activation may be temporary in a subset of patients.

"The dynamic nature of platelet reactivity that was observed underscores the importance of understanding the effect of the timing of the measurement on the level of reactivity and its association with adverse outcomes," they observed.

The GRAVITAS trial was sponsored by Accumetrics. Dr. Price said that he serves as a consultant to the company as well as to Sanofi-Aventis and Bristol-Myers Squibb, which provided the clopidogrel used in the study. Several other authors reported significant financial relationships with a number of pharmaceutical companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The American Heart Association has issued its first scientific statement on bariatric surgery for severely obese individuals with regard to cardiovascular risk factors. The statement appeared online in the journal Circulation on March 14.

The group makes no specific recommendations on bariatric surgery in the statement. Instead, the authors review the latest data on the indications for bariatric surgery, the different types of surgery, possible complications, the potential improvement in cardiovascular risk factors associated with bariatric surgery, and the need for multidisciplinary postoperative management.

"The statement is not an across-the-board endorsement of bariatric surgery for the severely obese. It is a consensus document that provides expert perspective based on the results of recent scientific studies," Dr. Paul Poirier and his coauthors said in a press statement. Dr. Poirier chaired the group, which developed the statement on behalf the American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (Circulation 2011 March 14 [doi:10.1161/CIR.0b013e3182149099]).

While obesity is an increasing problem worldwide, the severely obese – those with a body mass index (BMI) of 40 kg/m² or greater – are the most rapidly growing segment of the obese population, the authors noted. "It is projected that in the near future, there will be at least 31 million U.S. adults who are severely obese and may qualify for bariatric surgery."

The National Institutes of Health has proposed that surgical therapy be offered to patients with a BMI greater than 40 or with a BMI greater than 35 with serious obesity-related comorbidities.

Appropriately indicated bariatric surgery can lead to significant weight loss, which in turn leads to improvements in a number of comorbidities, including diabetes, dyslipidemia, liver disease, systemic hypertension, obstructive sleep apnea, and cardiovascular dysfunction, the authors observed. In fact, data from prospective, nonrandomized, or case-control population studies have shown that bariatric surgery can prolong life in severely obese individuals.

While there are three categories of bariatric surgical procedures – restrictive, malabsorptive, and combination – there is currently no consensus about which procedure is the best overall option. There are also no established criteria or algorithms to guide surgeons in selecting the best procedure for a given patient.

"Despite the lack of consensus, it is clear that obesity surgery today offers the only effective long-term treatment option for the severely obese patient," the group wrote. However, "currently, bariatric surgery should be reserved for patients who have severe obesity in whom efforts at medical therapy have failed and an acceptable operative risk is present."

"Bariatric procedures are generally safe; however, this is not a benign surgery," said lead author Dr. Poirier, who is director of the prevention/rehabilitation program at Quebec Heart and Lung Institute at Laval University, Quebec City. While generally rare (less than 2%), early complications include thromboembolism, pulmonary or respiratory insufficiency, hemorrhage, peritonitis, and wound infection. Late complications can include gastrointestinal obstruction, ulcers, incisional hernias, hypoglycemia, steatorrhea, diarrhea, bacterial overgrowth, and nutritional deficiencies of micronutrients.

The group observed that perioperative management is best achieved by an interdisciplinary team that includes a surgeon, a medical specialist, and a registered dietician. "Mental health professionals should be available to patients who struggle postoperatively with psychosocial changes," the group noted.

While the value of psychological evaluations and profiles in bariatric surgery cases is uncertain, the authors suggest that psychological evaluations should assess the behavioral and environmental factors that may have contributed to obesity and may impact a patient’s ability to make the dietary and behavioral changes needed following bariatric surgery.

The group recommends additional research on different bariatric surgical procedures to evaluate the impact of the beneficial metabolic and cardiovascular changes associated with weight loss procedures. In addition, more research is needed to evaluate the benefits of bariatric surgery in the severely obese adolescent population.

Dr. Poirier reported having no financial disclosures. Several other authors reported significant financial relationships with a number of pharmaceutical and surgical equipment companies.

The number of cancer survivors in the United States rose from 3 million in 1971 and 9.8 million in 2001 to 11.5 million in 2007, according to a new report by the Centers for Disease Control and Prevention and the National Cancer Institute.

The numbers come from the study "Cancer Survivors in the United States, 2007," which is published in the CDC’s March 11th Morbidity and Mortality Weekly Report. The study authors defined a cancer survivor as "a person living with a history of cancer."

The new numbers highlight the need for more research on the unique physical, psychological, and social issues facing cancer survivors. There is now "a growing number of people who have faced a cancer diagnosis which affects them and their loved ones – from the time of diagnosis through the rest of their lives," the NCI’s Julia H. Rowland, Ph.D., said in a press release. "Unfortunately for many cancer survivors and those around them, the effect of cancer does not end with the last treatment. ... This report underscores the need for continued research, as well as for the development and implementation of best practices to provide optimal care and support for all cancer survivors." Dr. Rowland is the director of the NCI’s Office of Cancer Survivorship.

The study authors analyzed the number of new cancer cases (except in situ and nonmelanoma skin cancers) as well as follow-up data from the NCI’s SEER (Surveillance, Epidemiology and End Results) program in 1971-2006. They estimated the number of persons who were ever diagnosed with cancer and were alive on Jan. 1, 2007 (MMWR 2011;60:269-72).

Notably, 65% of cancer survivors on Jan. 1, 2007, received their diagnosis at least 5 years earlier. Also, people aged 65 years or older accounted for 60%. The largest group of cancer survivors was breast cancer survivors (22%), followed by prostate cancer survivors (19%) and colorectal cancer survivors (10%). Women accounted for slightly more than half (54%) of all survivors.

Clinicians can find research tools, publications and other resources through the NCI’s Office of Cancer Survivorship.

The number of cancer survivors in the United States rose from 3 million in 1971 and 9.8 million in 2001 to 11.5 million in 2007, according to a new report by the Centers for Disease Control and Prevention and the National Cancer Institute.

The numbers come from the study "Cancer Survivors in the United States, 2007," which is published in the CDC’s March 11th Morbidity and Mortality Weekly Report. The study authors defined a cancer survivor as "a person living with a history of cancer."

The new numbers highlight the need for more research on the unique physical, psychological, and social issues facing cancer survivors. There is now "a growing number of people who have faced a cancer diagnosis which affects them and their loved ones – from the time of diagnosis through the rest of their lives," the NCI’s Julia H. Rowland, Ph.D., said in a press release. "Unfortunately for many cancer survivors and those around them, the effect of cancer does not end with the last treatment. ... This report underscores the need for continued research, as well as for the development and implementation of best practices to provide optimal care and support for all cancer survivors." Dr. Rowland is the director of the NCI’s Office of Cancer Survivorship.

The study authors analyzed the number of new cancer cases (except in situ and nonmelanoma skin cancers) as well as follow-up data from the NCI’s SEER (Surveillance, Epidemiology and End Results) program in 1971-2006. They estimated the number of persons who were ever diagnosed with cancer and were alive on Jan. 1, 2007 (MMWR 2011;60:269-72).

Notably, 65% of cancer survivors on Jan. 1, 2007, received their diagnosis at least 5 years earlier. Also, people aged 65 years or older accounted for 60%. The largest group of cancer survivors was breast cancer survivors (22%), followed by prostate cancer survivors (19%) and colorectal cancer survivors (10%). Women accounted for slightly more than half (54%) of all survivors.

Clinicians can find research tools, publications and other resources through the NCI’s Office of Cancer Survivorship.

The number of cancer survivors in the United States rose from 3 million in 1971 and 9.8 million in 2001 to 11.5 million in 2007, according to a new report by the Centers for Disease Control and Prevention and the National Cancer Institute.

The numbers come from the study "Cancer Survivors in the United States, 2007," which is published in the CDC’s March 11th Morbidity and Mortality Weekly Report. The study authors defined a cancer survivor as "a person living with a history of cancer."

The new numbers highlight the need for more research on the unique physical, psychological, and social issues facing cancer survivors. There is now "a growing number of people who have faced a cancer diagnosis which affects them and their loved ones – from the time of diagnosis through the rest of their lives," the NCI’s Julia H. Rowland, Ph.D., said in a press release. "Unfortunately for many cancer survivors and those around them, the effect of cancer does not end with the last treatment. ... This report underscores the need for continued research, as well as for the development and implementation of best practices to provide optimal care and support for all cancer survivors." Dr. Rowland is the director of the NCI’s Office of Cancer Survivorship.

The study authors analyzed the number of new cancer cases (except in situ and nonmelanoma skin cancers) as well as follow-up data from the NCI’s SEER (Surveillance, Epidemiology and End Results) program in 1971-2006. They estimated the number of persons who were ever diagnosed with cancer and were alive on Jan. 1, 2007 (MMWR 2011;60:269-72).

Notably, 65% of cancer survivors on Jan. 1, 2007, received their diagnosis at least 5 years earlier. Also, people aged 65 years or older accounted for 60%. The largest group of cancer survivors was breast cancer survivors (22%), followed by prostate cancer survivors (19%) and colorectal cancer survivors (10%). Women accounted for slightly more than half (54%) of all survivors.

Clinicians can find research tools, publications and other resources through the NCI’s Office of Cancer Survivorship.