- Email: [email protected]
Management of acute myocardial infarction
CORRESPONDENCE
Commentator’s reply Sir—I agree that the reader has a right to expect disclosure of conflicts of interest. As Andrew Galazka says, my roles in clinical trials of multiple sclerosis are “public knowledge”. Although my roles were not printed with my primary academic affiliation, the same criticism is true for other recent commentaries by Rice and Ebers,1 and Herndon and Jacobs.2 Not all share Galazka’s view that interferon b-1a (Rebif) shows a clearcut dose effect. Although the higher dose option may ultimately gain approval in Europe, the European Agency’s Committee for Proprietary Medicinal Products on May 4, 1998, issued a marketing authorisation valid throughout the European Union for the lower dose. I believe that there may be patients who, failing to respond to the low-dose option, may respond to the high-dose option. This hypothesis needs to be tested. Although a post-hoc explanatory analysis of the PRISMS data suggests the possibility of a dose effect in a small subgroup of patients with EDSS scores higher than 3·5, this interesting observation should be interpreted cautiously. With respect to Galazka's statement about publication of the full MRI data from the PRISMS study: my commentary was based on the published data. I look forward to clarification of the relation between detailed MRI measures, treatment assignment, baseline EDSS, and titre of neutralising antibodies. Patients in the North American SP trial (NASPT) are randomly assigned to treatment with placebo, interferon b1b fixed dose (8 MIU), or variable dose (5 MIU/m2 body surface area) on alternate days. On average, variabledose recipients (n=16) at our centre receive 12·5% more interferon b-1b than fixed-dose recipients (n=15). Variable-dose recipients in the NASPT all receive the same dose by body surface area. By comparison, the range of doses by body surface area across fixed-dose recipients raises the possibility that patients with greater body surface area may be suboptimally treated. If treatment effects are more convincing in the variable-dose recipients, individualised dosing by body surface area should be considered in clinical practice. Douglas Goodin’s table provides direct comparisons of interferon b that are inappropriate. The PRISMS study and phase III trial of Avonex differ significantly with respect to inclusion criteria and frequency of clinical followup that render direct comparisons of
498
efficacy difficult.3 The comparison of clinical attack rates is potentially misleading because exacerbation rates decline spontaneously over time. The time on-study is, on average, significantly longer for patients in the PRISMS study. Despite comments by Kenneth Johnson, data from published studies of glatiramer acetate in relapsing/ remitting and chronic progressive multiple sclerosis provide no convincing evidence that this drug delays onset on sustained progression of disability.4,5 This conclusion, shared by the US Food and Drug Administration, was written in August, 1998, as a warning to Teva Marion Partners: “In reference to the claim that glatiramer acetate is effective in slowing, preventing, or reversing the long term . . . disability . . . Teva Marion Partners is disseminating promotional materials that promote Copaxone (glatiramer acetate) for unapproved uses, and . . . contain statements of suggestions that are false, lacking in fair balance, or otherwise misleading . . .”. Johnson and Panitch believe my comment that interferon b-1b should immediately be made available for patients with secondary progressive disease, including those who have not had superimposed relapses, is premature and does not take into account the need for regulatory approval. I disagree. Off-label treatments for multiple sclerosis are common practice. After reviewing the European SP Trial, I predict that most will agree interferon b-1a should be approved expeditiously as a treatment option for patients with secondary progressive multiple sclerosis. D E Goodkin UCSF MT Zion Multiple Sclerosis Center, San Francisco, CA 94123, USA 1
2
3
4
5
Rice G, Ebers G. Interferons in the treatment of multiple sclerosis: do they prevent the progression of the disease? Arch Neurol 1998; 55: 1578–80. Herndon RM, Jacobs L. Interferons should be used to treat most patients with MS. Arch Neurol 1998; 55: 1581–83. Jacobs LD, Cookfair DL, Rudick RA, et al. Intermuscular interferon b-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285–94. Johnson KP, Brooks BF, Cohen JA, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology 1998; 50: 701–08. Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase II multicenter, double-blind,placebocontrolled trial. Neurology 1995; 45: 1268–76.
Management of acute myocardial infarction Sir—Eugene Braunwald’s excellent review (Nov 28, p 1771)1 notes that closed chest cardiac resuscitation was one development that led to the idea of the coronary care unit (CCU). Cardiac arrests in the CCU were initially managed by nurses who were trained to maintain basic life support with cardiopulmonary resuscitation until physicians arrived to do tracheal intubation and electrical defibrillation. Paradoxically, it soon became apparent that this cumbersome sequence of resuscitation that had stimulated the development of the CCU was usually not necessary in the unit. One night in 1964 an enterprising nurse working in the second CCU started in the USA by Lawrence Meltzer at Presbyterian Hospital in Philadelphia noted a ventricular fibrillation alarm. She twice called the cardiac fellow who was sleeping across the hall, but he did not respond. Intuitively, she did not start cardiopulmonary resuscitation. Instead she calmly picked up the defibrillator paddles and shocked the patient back to normal rhythm and an alert state of consciousness, saving his life and initiating the era of cardiac nurse specialists. Mouth to mouth resuscitation, closed chest cardiac compression, and tracheal intubation take time and increase the risk of brain damage, rib fracture, aspiration, and myocardial stunning. These complications are all avoided by swift effective electrical treatment. Unfortunately, too many cardiac arrests in monitored units are not managed in this way because the present generation of CCU nurses has forgotten or has not been taught the technique of their unheralded predecessor. The first response to cardiac arrest in the CCU should always be swift and definitive electrical defibrillation or external pacing. Cardiopulmonary resuscitation measures should be reserved for those cardiac arrests that are refractory to these measures. Herbert E Cohen Department of Cardiology, Thomas Jefferson University School of Medicine, Philadelphia, PA 19107, USA 1
Braunwald E. Evolution of the management of acute myocardial infarction: a 20th century saga. Lancet 1998; 352: 1771–74.
Sir—Eugene Braunwald’s review 1 of the evolution of the management of myocardial infarction illustrates the
THE LANCET • Vol 353 • February 6, 1999
Commentator’s reply Sir—I agree that the reader has a right to expect disclosure of conflicts of interest. As Andrew Galazka says, my roles in clinical trials of multiple sclerosis are “public knowledge”. Although my roles were not printed with my primary academic affiliation, the same criticism is true for other recent commentaries by Rice and Ebers,1 and Herndon and Jacobs.2 Not all share Galazka’s view that interferon b-1a (Rebif) shows a clearcut dose effect. Although the higher dose option may ultimately gain approval in Europe, the European Agency’s Committee for Proprietary Medicinal Products on May 4, 1998, issued a marketing authorisation valid throughout the European Union for the lower dose. I believe that there may be patients who, failing to respond to the low-dose option, may respond to the high-dose option. This hypothesis needs to be tested. Although a post-hoc explanatory analysis of the PRISMS data suggests the possibility of a dose effect in a small subgroup of patients with EDSS scores higher than 3·5, this interesting observation should be interpreted cautiously. With respect to Galazka's statement about publication of the full MRI data from the PRISMS study: my commentary was based on the published data. I look forward to clarification of the relation between detailed MRI measures, treatment assignment, baseline EDSS, and titre of neutralising antibodies. Patients in the North American SP trial (NASPT) are randomly assigned to treatment with placebo, interferon b1b fixed dose (8 MIU), or variable dose (5 MIU/m2 body surface area) on alternate days. On average, variabledose recipients (n=16) at our centre receive 12·5% more interferon b-1b than fixed-dose recipients (n=15). Variable-dose recipients in the NASPT all receive the same dose by body surface area. By comparison, the range of doses by body surface area across fixed-dose recipients raises the possibility that patients with greater body surface area may be suboptimally treated. If treatment effects are more convincing in the variable-dose recipients, individualised dosing by body surface area should be considered in clinical practice. Douglas Goodin’s table provides direct comparisons of interferon b that are inappropriate. The PRISMS study and phase III trial of Avonex differ significantly with respect to inclusion criteria and frequency of clinical followup that render direct comparisons of
498
efficacy difficult.3 The comparison of clinical attack rates is potentially misleading because exacerbation rates decline spontaneously over time. The time on-study is, on average, significantly longer for patients in the PRISMS study. Despite comments by Kenneth Johnson, data from published studies of glatiramer acetate in relapsing/ remitting and chronic progressive multiple sclerosis provide no convincing evidence that this drug delays onset on sustained progression of disability.4,5 This conclusion, shared by the US Food and Drug Administration, was written in August, 1998, as a warning to Teva Marion Partners: “In reference to the claim that glatiramer acetate is effective in slowing, preventing, or reversing the long term . . . disability . . . Teva Marion Partners is disseminating promotional materials that promote Copaxone (glatiramer acetate) for unapproved uses, and . . . contain statements of suggestions that are false, lacking in fair balance, or otherwise misleading . . .”. Johnson and Panitch believe my comment that interferon b-1b should immediately be made available for patients with secondary progressive disease, including those who have not had superimposed relapses, is premature and does not take into account the need for regulatory approval. I disagree. Off-label treatments for multiple sclerosis are common practice. After reviewing the European SP Trial, I predict that most will agree interferon b-1a should be approved expeditiously as a treatment option for patients with secondary progressive multiple sclerosis. D E Goodkin UCSF MT Zion Multiple Sclerosis Center, San Francisco, CA 94123, USA 1
2
3
4
5
Rice G, Ebers G. Interferons in the treatment of multiple sclerosis: do they prevent the progression of the disease? Arch Neurol 1998; 55: 1578–80. Herndon RM, Jacobs L. Interferons should be used to treat most patients with MS. Arch Neurol 1998; 55: 1581–83. Jacobs LD, Cookfair DL, Rudick RA, et al. Intermuscular interferon b-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285–94. Johnson KP, Brooks BF, Cohen JA, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology 1998; 50: 701–08. Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase II multicenter, double-blind,placebocontrolled trial. Neurology 1995; 45: 1268–76.
Management of acute myocardial infarction Sir—Eugene Braunwald’s excellent review (Nov 28, p 1771)1 notes that closed chest cardiac resuscitation was one development that led to the idea of the coronary care unit (CCU). Cardiac arrests in the CCU were initially managed by nurses who were trained to maintain basic life support with cardiopulmonary resuscitation until physicians arrived to do tracheal intubation and electrical defibrillation. Paradoxically, it soon became apparent that this cumbersome sequence of resuscitation that had stimulated the development of the CCU was usually not necessary in the unit. One night in 1964 an enterprising nurse working in the second CCU started in the USA by Lawrence Meltzer at Presbyterian Hospital in Philadelphia noted a ventricular fibrillation alarm. She twice called the cardiac fellow who was sleeping across the hall, but he did not respond. Intuitively, she did not start cardiopulmonary resuscitation. Instead she calmly picked up the defibrillator paddles and shocked the patient back to normal rhythm and an alert state of consciousness, saving his life and initiating the era of cardiac nurse specialists. Mouth to mouth resuscitation, closed chest cardiac compression, and tracheal intubation take time and increase the risk of brain damage, rib fracture, aspiration, and myocardial stunning. These complications are all avoided by swift effective electrical treatment. Unfortunately, too many cardiac arrests in monitored units are not managed in this way because the present generation of CCU nurses has forgotten or has not been taught the technique of their unheralded predecessor. The first response to cardiac arrest in the CCU should always be swift and definitive electrical defibrillation or external pacing. Cardiopulmonary resuscitation measures should be reserved for those cardiac arrests that are refractory to these measures. Herbert E Cohen Department of Cardiology, Thomas Jefferson University School of Medicine, Philadelphia, PA 19107, USA 1
Braunwald E. Evolution of the management of acute myocardial infarction: a 20th century saga. Lancet 1998; 352: 1771–74.
Sir—Eugene Braunwald’s review 1 of the evolution of the management of myocardial infarction illustrates the
THE LANCET • Vol 353 • February 6, 1999