- Email: [email protected]
Safety of aprotinin (again)
Correspondence
identified as a significant risk factor (p<0·001) and was included in the model used to calculate the baseline renal risk score. Third, the need for an IABP postoperatively was considered, alongside the propensity score and other covariates for inclusion in the propensity-adjusted renal risk models (top panel table 2). Postoperative IABP was identified as a significant risk factor for renal dysfunction in five of the eight subgroup analyses; all four models comparing tranexamic acid and control and the analysis comparing aprotinin and control in off-pump patients not given ACE inhibitors. The need for an IABP postoperatively was not included in the baseline risk treatment effect models (bottom panel table 2). These analyses were adjusted for renal risk score and numbers of units of red cells only. We are unable to respond to the concerns of Sebastian Schneeweiss and colleagues at this time. We will provide a response at a later date. We declare that we have no conflict of interest.
*Kai Zacharowski, Chris Rogers, Ian Davies [email protected] Department of Anaesthesia, Bristol Royal Infirmary, Upper Maudlin Road, Bristol BS2 8HW, UK
Safety of aprotinin (again) Ronelle Mouton and co-workers (Feb 9, p 475)1 describe renal complications due to aprotinin plus angiotensin-converting-enzyme inhibitors in patients undergoing off-pump cardiac surgery. This finding surprisingly induced Derek Hausenloy and colleagues, in their companion Comment (p 449),2 to suggest that the interim analysis of the prospective, triple blind, triple dummy BART study, and the consequent withdrawal of aprotinin from the market, might have “the consequence www.thelancet.com Vol 372 July 5, 2008
All patients (n=2250)
High-risk patients* Low-risk patients Off-pump surgery (n=750) (n=1297) (n=203)
Number needing transfusion
673 (29·9%)
320 (42·6%)
313 (24·1%)
Median (IQR) volume of postoperative bleeding (mL)
355 (250–550)
435 (262–615)
300 (210–500)
Number needing reoperation for bleeding
120 (5·3%)
54 (7·2%)
60 (4·6%)
6 (2·9%)
77 (3·4%)
43 (5·7%)
29 (2·2%)
5 (2·4%)
Mortality
40 (19·7%) 310 (220–472)
*Combined surgery, resternotomy, surgery on thoracic aorta.
Table: Outcomes for cardiosurgical patients treated with tranexamic acid at Policlinico de Monza between between January, 2002, and June, 2007
that some high-risk patients…may not receive optimum therapy”. They justify their statement because aprotinin seemed slightly, but not significantly, more effective in reducing bleeding and its complications than did other antifibrinolytic drugs.3 In Italy, aprotinin (a derivative from bovine lung) was withdrawn in 1997 after the emergence of bovine spongiform encephalopathy. According to the Comment,2 would this translate into Italian cardiosurgical patients having been denied the goldstandard blood-sparing treatment for 10 years? We reviewed data on bleeding, transfusions, re-exploration for bleeding, and mortality in cardiosurgical patients operated on at our institution over the past 5 years, all of whom were treated with tranexamic acid (table). The results are comparable with those reported for aprotinin,3 and confirm our published data.4,5 Tranexamic acid seems as effective as aprotinin in limiting postoperative bleeding, allogeneic transfusion, and the need for re-exploration both in on-pump and off-pump cardiosurgical patients, and particularly in those at higher risk of bleeding. Perhaps some Italian cardiosurgical patients had a better postoperative course simply because they were treated with tranexamic acid instead of aprotinin. Will the BART study put an end to the eternal controversy about aprotinin? We declare that we have no conflict of interest.
*Valter Casati, Angelo Romano, Armando D’Angelo
[email protected] Division of Cardiovascular Anaesthesia and Intensive Care, Clinica S Gaudenzio, Via Bottini 3, 28100 Novara, Italy (VC, AR); and Coagulation Service and Thrombosis Research Unit, Scientific Institute H S Raffaele, Milan, Italy (AD’A) 1
2
3
4
5
Mouton R, Finch D, Davies I, Bincks A, Zacharowski K. Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study. Lancet 2008; 371: 474–82. Hausenloy D, Pagano D, Keogh B. Aprotinin— still courting controversy. Lancet 2008; 371: 449–50. Henry DA, Moxley AJ, Carless PA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic transfusion. Cochrane Database Syst Rev 2007; 4: CD001886. Casati V, Guzzon D, Oppizzi M, et al. Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effect on perioperative bleeding and allogeneic transfusions. J Thorac Cardiovasc Surg 2000; 120: 520-27. Casati V, Benussi S, Sandrelli L, et al. Intraoperative moderate acute normovolemic hemodilution associated with a comprehensive blood-sparing protocol in off-pump coronary surgery. Anesth Analg 2004; 98: 1217–23.
β-cell transplantation for diabetes therapy Piero Ruggenenti and colleagues (March 15, p 883)1 highlight their failure to establish a clinical islet transplantation programme. Results of islet transplantation are similar to those of the early days of organ transplantation, where initial success rarely met with long-term function.2 The Edmonton protocol achieved reproducible insulin independence after islet transplantation,3 with more than 80% of recipients still insulinfree at 1 year. Differences in outcome among centres3 illustrate the complexity of the procedure and its immunological challenges.2 27
identified as a significant risk factor (p<0·001) and was included in the model used to calculate the baseline renal risk score. Third, the need for an IABP postoperatively was considered, alongside the propensity score and other covariates for inclusion in the propensity-adjusted renal risk models (top panel table 2). Postoperative IABP was identified as a significant risk factor for renal dysfunction in five of the eight subgroup analyses; all four models comparing tranexamic acid and control and the analysis comparing aprotinin and control in off-pump patients not given ACE inhibitors. The need for an IABP postoperatively was not included in the baseline risk treatment effect models (bottom panel table 2). These analyses were adjusted for renal risk score and numbers of units of red cells only. We are unable to respond to the concerns of Sebastian Schneeweiss and colleagues at this time. We will provide a response at a later date. We declare that we have no conflict of interest.
*Kai Zacharowski, Chris Rogers, Ian Davies [email protected] Department of Anaesthesia, Bristol Royal Infirmary, Upper Maudlin Road, Bristol BS2 8HW, UK
Safety of aprotinin (again) Ronelle Mouton and co-workers (Feb 9, p 475)1 describe renal complications due to aprotinin plus angiotensin-converting-enzyme inhibitors in patients undergoing off-pump cardiac surgery. This finding surprisingly induced Derek Hausenloy and colleagues, in their companion Comment (p 449),2 to suggest that the interim analysis of the prospective, triple blind, triple dummy BART study, and the consequent withdrawal of aprotinin from the market, might have “the consequence www.thelancet.com Vol 372 July 5, 2008
All patients (n=2250)
High-risk patients* Low-risk patients Off-pump surgery (n=750) (n=1297) (n=203)
Number needing transfusion
673 (29·9%)
320 (42·6%)
313 (24·1%)
Median (IQR) volume of postoperative bleeding (mL)
355 (250–550)
435 (262–615)
300 (210–500)
Number needing reoperation for bleeding
120 (5·3%)
54 (7·2%)
60 (4·6%)
6 (2·9%)
77 (3·4%)
43 (5·7%)
29 (2·2%)
5 (2·4%)
Mortality
40 (19·7%) 310 (220–472)
*Combined surgery, resternotomy, surgery on thoracic aorta.
Table: Outcomes for cardiosurgical patients treated with tranexamic acid at Policlinico de Monza between between January, 2002, and June, 2007
that some high-risk patients…may not receive optimum therapy”. They justify their statement because aprotinin seemed slightly, but not significantly, more effective in reducing bleeding and its complications than did other antifibrinolytic drugs.3 In Italy, aprotinin (a derivative from bovine lung) was withdrawn in 1997 after the emergence of bovine spongiform encephalopathy. According to the Comment,2 would this translate into Italian cardiosurgical patients having been denied the goldstandard blood-sparing treatment for 10 years? We reviewed data on bleeding, transfusions, re-exploration for bleeding, and mortality in cardiosurgical patients operated on at our institution over the past 5 years, all of whom were treated with tranexamic acid (table). The results are comparable with those reported for aprotinin,3 and confirm our published data.4,5 Tranexamic acid seems as effective as aprotinin in limiting postoperative bleeding, allogeneic transfusion, and the need for re-exploration both in on-pump and off-pump cardiosurgical patients, and particularly in those at higher risk of bleeding. Perhaps some Italian cardiosurgical patients had a better postoperative course simply because they were treated with tranexamic acid instead of aprotinin. Will the BART study put an end to the eternal controversy about aprotinin? We declare that we have no conflict of interest.
*Valter Casati, Angelo Romano, Armando D’Angelo
[email protected] Division of Cardiovascular Anaesthesia and Intensive Care, Clinica S Gaudenzio, Via Bottini 3, 28100 Novara, Italy (VC, AR); and Coagulation Service and Thrombosis Research Unit, Scientific Institute H S Raffaele, Milan, Italy (AD’A) 1
2
3
4
5
Mouton R, Finch D, Davies I, Bincks A, Zacharowski K. Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study. Lancet 2008; 371: 474–82. Hausenloy D, Pagano D, Keogh B. Aprotinin— still courting controversy. Lancet 2008; 371: 449–50. Henry DA, Moxley AJ, Carless PA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic transfusion. Cochrane Database Syst Rev 2007; 4: CD001886. Casati V, Guzzon D, Oppizzi M, et al. Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effect on perioperative bleeding and allogeneic transfusions. J Thorac Cardiovasc Surg 2000; 120: 520-27. Casati V, Benussi S, Sandrelli L, et al. Intraoperative moderate acute normovolemic hemodilution associated with a comprehensive blood-sparing protocol in off-pump coronary surgery. Anesth Analg 2004; 98: 1217–23.
β-cell transplantation for diabetes therapy Piero Ruggenenti and colleagues (March 15, p 883)1 highlight their failure to establish a clinical islet transplantation programme. Results of islet transplantation are similar to those of the early days of organ transplantation, where initial success rarely met with long-term function.2 The Edmonton protocol achieved reproducible insulin independence after islet transplantation,3 with more than 80% of recipients still insulinfree at 1 year. Differences in outcome among centres3 illustrate the complexity of the procedure and its immunological challenges.2 27