Early Surgery vs Drugs in Endocarditis Treatments
November 16, 2011 (Orlando, Florida) — EASE, the first randomized trial comparing early valve surgery with standard antimicrobial therapy in patients with severe infective endocarditis, shows early surgery reduces the risk of death and embolic events.
"Early surgery compared with conventional antibiotic therapy . . . can be done with significant improvements in outcomes by reducing the number of strokes (theoretically), reducing the number of recurrent infections, and showing no impact on the operative mortality, suggesting that this is a change in the paradigm for the management of this disease," surgeon Dr Robert Higgins (Ohio State University, Columbus) said, commenting on results of the EASE trial presented by Dr Duk Hyun Kang (Asan Medical Center, Seoul, Korea) here at theAmerican Heart Association 2011 Scientific Sessions.
Higgins pointed out that the existing guidance on the appropriate timing of surgery in patients with severe infective endocarditis is based only on case series and anecdotal data [1]. EASE is the first prospective trial to demonstrate that early surgery produces better outcomes than conventional therapy in these patients.
"We focused on the controversial issue of the embolic implications of surgery," Kang said. EASE randomized patients with severe left-sided native-valve infective endocarditis with at least 10 mm of vegetation to either conventional antimicrobial treatment according to the guidelines or surgery within 48 hours of randomization. Endocarditis was diagnosed with transesophageal echocardiography and computed tomography.
The trial enrolled 134 patients with confirmed endocarditis, but 26 underwent immediate surgery and 18 were given medical treatment without being randomized in the trial because they were not considered to be at risk for embolic events. Higgins said that the investigators' decision not to randomize those patients illustrates how it is "very hard to manage these things in real time." Another 14 patients dropped out for other reasons, so 76 were randomized to either surgery or conventional therapy based on the current guidelines.
Surgery outperformed conventional therapy for the primary end point of in-hospital death plus embolic events within six weeks of randomization (3% vs 23%; p=0.014). In the first six weeks, both groups had one death each, but there were eight embolic events in the conventional-therapy group and zero embolic events in the early-surgery group. Within the first six months, there was one additional death and one relapse of infective endocarditis in the standard-therapy group, but no more events in the surgery group.
Kang said that the event rates in the randomized trial almost exactly matched the rates from his center's experience over the past decade. "When we showed our protocol to the [internal review board] IRB in 2006, they commented that our study might not achieve statistical significance because of the low sample size and low event rate, but we insisted on a small sample size . . . because there was an ethical issue, and we believed that we could confirm our previous data in the randomized trial," Kang said.
"[Dr Kang's] group has done a remarkable job in a complicated group of patients. Yes, more robust data would be helpful, but I don't think it would change . . . the paradigm shift that is occurring. Earlier operation reduces stroke, reduces morbidity, and doesn't affect our ability to take care of those patients," Higgins said.
Kang and Higgins reported no conflicts of interest.
November 16, 2011 (Orlando, Florida) — EASE, the first randomized trial comparing early valve surgery with standard antimicrobial therapy in patients with severe infective endocarditis, shows early surgery reduces the risk of death and embolic events.
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| Dr Robert Higgins |
"Early surgery compared with conventional antibiotic therapy . . . can be done with significant improvements in outcomes by reducing the number of strokes (theoretically), reducing the number of recurrent infections, and showing no impact on the operative mortality, suggesting that this is a change in the paradigm for the management of this disease," surgeon Dr Robert Higgins (Ohio State University, Columbus) said, commenting on results of the EASE trial presented by Dr Duk Hyun Kang (Asan Medical Center, Seoul, Korea) here at theAmerican Heart Association 2011 Scientific Sessions.
Higgins pointed out that the existing guidance on the appropriate timing of surgery in patients with severe infective endocarditis is based only on case series and anecdotal data [1]. EASE is the first prospective trial to demonstrate that early surgery produces better outcomes than conventional therapy in these patients.
|
|
| Dr Duk Hyun Kang |
"We focused on the controversial issue of the embolic implications of surgery," Kang said. EASE randomized patients with severe left-sided native-valve infective endocarditis with at least 10 mm of vegetation to either conventional antimicrobial treatment according to the guidelines or surgery within 48 hours of randomization. Endocarditis was diagnosed with transesophageal echocardiography and computed tomography.
The trial enrolled 134 patients with confirmed endocarditis, but 26 underwent immediate surgery and 18 were given medical treatment without being randomized in the trial because they were not considered to be at risk for embolic events. Higgins said that the investigators' decision not to randomize those patients illustrates how it is "very hard to manage these things in real time." Another 14 patients dropped out for other reasons, so 76 were randomized to either surgery or conventional therapy based on the current guidelines.
Surgery outperformed conventional therapy for the primary end point of in-hospital death plus embolic events within six weeks of randomization (3% vs 23%; p=0.014). In the first six weeks, both groups had one death each, but there were eight embolic events in the conventional-therapy group and zero embolic events in the early-surgery group. Within the first six months, there was one additional death and one relapse of infective endocarditis in the standard-therapy group, but no more events in the surgery group.
Kang said that the event rates in the randomized trial almost exactly matched the rates from his center's experience over the past decade. "When we showed our protocol to the [internal review board] IRB in 2006, they commented that our study might not achieve statistical significance because of the low sample size and low event rate, but we insisted on a small sample size . . . because there was an ethical issue, and we believed that we could confirm our previous data in the randomized trial," Kang said.
"[Dr Kang's] group has done a remarkable job in a complicated group of patients. Yes, more robust data would be helpful, but I don't think it would change . . . the paradigm shift that is occurring. Earlier operation reduces stroke, reduces morbidity, and doesn't affect our ability to take care of those patients," Higgins said.
Kang and Higgins reported no conflicts of interest.