Wednesday, November 12, 2003
In response to Mr Alan Ho's article in the Commentary pages of the Straits Times, I have posted the following reply to the forum pages.
I fully expect this article to be discarded with a polite reply without publication, and am therefore posting it on my blog for public viewing.
*******
In response to Andy Ho's article claiming that thrombolysis is routine clinical practise for acute stroke, I would like to direct the public's attention to the following editorials and studies which fail to correlate the findings of the NINDs trial, which the ST reporter employs as the lynchpin with which to substantiate his arguments.
Thrombolysis for acute ischaemic stroke (Cochrane Review), Wardlaw JM, del Zoppo G, Yamaguchi T, Berge E , The Cochrane Library, Issue 4, 2003.
This meta-analysis of eighteen trials including 5727 patients did not support the widespread use of thrombolytic therapy in routine clinical practice at present moment, but suggested that further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which it may best be given.
Anticoagulants for acute ischaemic stroke (Cochrane Review), Gubitz G, Counsell C, Sandercock P, Signorini D, The Cochrane Library, Issue 4, 2003.
This meta-analysis of twenty-one trials including 23,427 patients concluded that "Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke."
Jerome R Hoffman, MA, MD, Professor of Medicine and Emergency Medicine at the School of Medicine UCLA writes in his article published in the MJA 2003; 179 (7): 333-334 that "Although advocates of the use of tissue plasminogen activator (tPA) in acute ischaemic stroke suggest that this “is one of the most important advances in stroke medicine” a recent Cochrane meta-analysis also supports “clinicians who choose . . . not to use the treatment at all” and all three major emergency medicine associations in North America have declined to endorse it as “standard of care”. Additionally, "the overall impact of tPA in acute ischaemic stroke is at most marginal, which makes it difficult to understand why “so much has been made of so little", and "There is a paucity of positive evidence; all but one small randomised controlled trial failed to find benefit in the primary outcome, or found substantial harm. Even in the NINDS trial, the benefit was primarily in patients treated less than 90 minutes after symptom onset (almost no such patients exist in actual community practice)". He then states that "Many of us believe that thrombolytic therapy in stroke remains far from proven, so that its use should be restricted to further randomised controlled trials... I f tPA use becomes more widespread, a very small number of patients may receive great personal benefit, while a very few others may be subjected to great personal harm. However, the broader implications of this debate are substantial. Modern health policy traditionally rests on the “precautionary principle”, which requires that no new practice be widely introduced until it is shown to be safe"
The Canadian Association of Emergency Physicians believes that "based on the available evidence, widespread use of thrombolytic therapy for acute stroke remains controversial and problematic." (Thrombolytic Therapy for Acute Ischemic Stroke, The CAEP Committee on Thrombolytic Therapy for Acute Ischemic Stroke)
In addition, they write that "Six grade-one multi-centre randomized controlled trials (RCTs) of thrombolytics for acute stroke demonstrated lack of benefit or worse outcomes with treatment. To date, the NINDS trial is the only published RCT (randomised controlled trial ) of intravenous thrombolytic therapy that has been positive... exuberance over the potential development of more effective stoke treatments has raised public expectations, causing anxiety, disappointment and confusion when treatments are not available, not indicated or not effective. Caution is warranted in public pronouncements of the value of thrombolytic therapy for stroke. Such pronouncements should detail the fact that this intervention is not appropriate for the majority of strokes... It is the position of the Canadian Association of Emergency Physicians that thrombolytic therapy for acute stroke should be restricted to use in the context of formal research protocols, or in closely monitored programs, until there is further evidence that the benefits of this therapy clearly outweigh the risks." They then argue that "Prior to NINDS, trials of thrombolytics for acute stroke provided very negative results....In an attempt to replicate the NINDS results, ECASS-II applied the same eligibility criteria and used the same 0.9 mg/kg t-PA dose, but enrolled patients within 6 hours of symptom onset. In this study, t-PA did not significantly increase the rate of favorable 90-day outcomes (40.3% vs. 36.6%, p=0.277), and was associated with a higher incidence of parenchymal hemorrhage (11.8% vs. 3.1%), symptomatic intracranial hemorrhage (8.8% vs. 3.4%), and early death due to intracranial hemorrhage (11 vs. 2 cases). Of note, there was no significant differences in 30- or 90-day mortality. An ECASS-II subgroup analysis showed a trend towards improved neurological outcomes in patients with <3 hours of symptoms, but the numbers were small and statistically insignificant. ECASS-II therefore failed to reproduce the positive results of NINDS... it is likely that the benefit seen with t-PA in the NINDS trial is applicable to only 2-3% of patients who present with acute stroke syndromes." Most damnably, "The problem of limited early diagnostic accuracy i ndicates the need to proceed with caution. Rushed decisions to administer t-PA within the 3-hour window will mean that a subset of patients will be exposed to a substantial risk of hemorrhage without any potential to benefit" The writers then quote Katzan et al (Cleveland) who wrote that "In-hospital mortality was higher among t-PA recipients than matched patients not treated with t-PA (15.7% vs. 7.2%; p<.01). Mortality was also higher in t-PA recipients than in the general population of stroke patients not receiving t-PA (15.7% vs. 5.1%; p< .001)" and conclude that "These demonstrate that eligible patients are rare and that protocol violations are common when this thrombolysis is provided outside of controlled research settings.The Cleveland experience suggests that stroke thrombolysis may be more dangerous and patient outcomes worse in community settings than they were in the NINDS stroke trial"
I invite Andy Ho to explain in the face of existing international evidence that routine thrombolysis for stroke remains controversial across the world why the UK health authorities (eg the National Institute for Clinical Excellence) should take "steps to make sure stroke patients get their scans and tPA within the first three hours".
In addition, I would like to ask if patients in Singapore routinely receive thrombolysis for ischaemic cerebrovascular accidents, and tPA for all myocardial infarctions as Andy Ho suggests in his article.
If this is indeed the case I must voice my grave concerns for the safety and well-being of patients within the Singapore Healthcare System, because according to conventional medical wisdom such measures would expose patients to unnecessary risks (including haemorrhagic stroke, lifelong disability and death) unbalanced by proposed benefits of early coronary reperfusion.
The mainstay of thrombolytic agents in the UK is streptokinase, which carries approximately half the risk of intracranial haemorrhage compared to tPA and its newer variants alteplase, retiplase and tenecteplase. The latter are employed in the UK in specific subgroups of patients (young males with anterior MIs) deemed at lower risk of cerebral haemorrhage.
This is also in line with current US guidelines for thrombolysis for Acute Myocardial Infarction published in 1999 by the American Heart Association, which state that "the cost-benefit ratio (of accelerated alteplase and reteplase with intravenous heparin) is greatest in patients presenting early after onset of chest pain or symptoms and in those with a large area of injury (eg. anterior infarction) and at low risk of ICH." "
I would also like to take this opportunity to wish Mr and Mrs Lee Kuan Yew good health in their time of need, and I sincerely hope Mrs Lee achieves as speedy and complete a recovery as is possible. God bless.
Dr (name)
MBBS (UK)
***********
Not mentioned in the article I submitted (for obvious reasons):
the local (Singaporean) guidelines updated in 2003 for stroke management published by the Singaporean Ministry of Health with regards to imaging, and tPA are as follows :
"All patients with acute stroke should undergo brain scanning (CT or MRI) as soon as possible*, preferably within 24 hours" (and not 3 hours as Andy Ho appears to claim)
Additionally, in the immediate management of stroke,
"The routine use of drugs to limit neural damage, including the administration of corticosteroids, neuroprotectants, plasma volume expanders, barbiturates and streptokinase, (which is a form of thrombolysis) is of no proven benefit and should be discouraged."
also,
"Patients receiving anticoagulants or recent thrombolytic therapy or those with bleeding diathesis require urgent correction of coagulation defects. Thrombolytics, anti-platelet therapy and anticoagulants should be discouraged".
tPA is indeed mentioned in the Ministry of Health guidelines as follows :
"A randomised study of intravenous r-TPA in cerebral infarction demonstrated significant improvement in functional outcome in selected patients treated in specialist units within 3 hours of the onset of stroke, as did an intra-arterial trial of prourokinase within 6 hours of stroke onset. The use of streptokinase is contraindicated in view of its lack of beneficial effect on mortality and morbidity. The management of patients with acute ischaemic stroke using thrombolytic therapy carries the risk of catastrophic intracerebral haemorrhage; there is difficulty in predicting who might benefit or be at most risk of haemorrhage. Thrombolysis should not yet be regarded as routine therapy."
It appears that when Andy Ho writes "What should be relevant to the British public is whether their health authorities are taking steps to make sure stroke patients get their scans and tPA within the first three hours", he omits to mention that stroke patients in Singapore are not getting their scans and tPA within the first three hours either, because the Singaporean Ministry of Health, having reviewed study data from around the world does not feel they are warranted either.
In addition, he also omits to mention that in the fierce and ongoing debate regarding thrombolysis for ischaemic stroke, conventional medical wisdom is not in favour for routine thrombolysis, and he has, in effect written an authoritatively-worded, but factually-challenged article that lays clear his stark medical ignorance and journalistic unprofessionalism, for all the world to see.
One wonders if all stroke patients in Singapore are now going to begin demanding immediate thrombolysis from the moment they step through the casualty doors. Worse still, one wonders what will happen if the doctors in Singapore, in dischord with their own guidelines, begin offering this service, thanks to pseudo-political pressure applied by an irresponsible press.
It is time that the Singaporean public awakens, and realises that the Press in Singapore, in its overwhelming drive to sycophantically pander to the incumbent People's Action Party, is not above misrepresenting "facts and realities" as half-truths. What you see in the news is not really what is really happening, around the world. Or, worse still, that the press is writing authoritatively, and ignorantly about things they know little about, and representing their personal opinions as undeniable truths.
Singapore, it seems, has become the Matrix. And if information be power, then the Singaporean public are firmly under the thumbscrews of a deceitful and politically controlled (by the PAP, although whether intentionally or not is debatable) press.
I personally believe that the PAP is not applying much pressure to the Straits Times. I feel that in fact, the ST is bending over backwards to do what it Thinks the PAP wants it to do - that it is trying to second guess the PAP and write the stuff that will get it the most pats on the back.
And therein lies the reason for the publication of this completely imprudent article, in the one major english language newspaper of the entire country.
It is also time that the Press in Singapore realises that anybody can write. Anybody can string the words together. What distinguishes a journalist from a layperson is not his ease or proficiency with the language - but his sense of responsibility, and professionalism.
With these, you are a reporter, bringing the news, and the truth to the people, and doing something worthwhile with your life.
Without these - you are nobody, jotting down your mundane personal opinions to an imaginary public audience - you might as well quit your day job and start a blog.
I fully expect this article to be discarded with a polite reply without publication, and am therefore posting it on my blog for public viewing.
*******
In response to Andy Ho's article claiming that thrombolysis is routine clinical practise for acute stroke, I would like to direct the public's attention to the following editorials and studies which fail to correlate the findings of the NINDs trial, which the ST reporter employs as the lynchpin with which to substantiate his arguments.
Thrombolysis for acute ischaemic stroke (Cochrane Review), Wardlaw JM, del Zoppo G, Yamaguchi T, Berge E , The Cochrane Library, Issue 4, 2003.
This meta-analysis of eighteen trials including 5727 patients did not support the widespread use of thrombolytic therapy in routine clinical practice at present moment, but suggested that further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which it may best be given.
Anticoagulants for acute ischaemic stroke (Cochrane Review), Gubitz G, Counsell C, Sandercock P, Signorini D, The Cochrane Library, Issue 4, 2003.
This meta-analysis of twenty-one trials including 23,427 patients concluded that "Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke."
Jerome R Hoffman, MA, MD, Professor of Medicine and Emergency Medicine at the School of Medicine UCLA writes in his article published in the MJA 2003; 179 (7): 333-334 that "Although advocates of the use of tissue plasminogen activator (tPA) in acute ischaemic stroke suggest that this “is one of the most important advances in stroke medicine” a recent Cochrane meta-analysis also supports “clinicians who choose . . . not to use the treatment at all” and all three major emergency medicine associations in North America have declined to endorse it as “standard of care”. Additionally, "the overall impact of tPA in acute ischaemic stroke is at most marginal, which makes it difficult to understand why “so much has been made of so little", and "There is a paucity of positive evidence; all but one small randomised controlled trial failed to find benefit in the primary outcome, or found substantial harm. Even in the NINDS trial, the benefit was primarily in patients treated less than 90 minutes after symptom onset (almost no such patients exist in actual community practice)". He then states that "Many of us believe that thrombolytic therapy in stroke remains far from proven, so that its use should be restricted to further randomised controlled trials... I f tPA use becomes more widespread, a very small number of patients may receive great personal benefit, while a very few others may be subjected to great personal harm. However, the broader implications of this debate are substantial. Modern health policy traditionally rests on the “precautionary principle”, which requires that no new practice be widely introduced until it is shown to be safe"
The Canadian Association of Emergency Physicians believes that "based on the available evidence, widespread use of thrombolytic therapy for acute stroke remains controversial and problematic." (Thrombolytic Therapy for Acute Ischemic Stroke, The CAEP Committee on Thrombolytic Therapy for Acute Ischemic Stroke)
In addition, they write that "Six grade-one multi-centre randomized controlled trials (RCTs) of thrombolytics for acute stroke demonstrated lack of benefit or worse outcomes with treatment. To date, the NINDS trial is the only published RCT (randomised controlled trial ) of intravenous thrombolytic therapy that has been positive... exuberance over the potential development of more effective stoke treatments has raised public expectations, causing anxiety, disappointment and confusion when treatments are not available, not indicated or not effective. Caution is warranted in public pronouncements of the value of thrombolytic therapy for stroke. Such pronouncements should detail the fact that this intervention is not appropriate for the majority of strokes... It is the position of the Canadian Association of Emergency Physicians that thrombolytic therapy for acute stroke should be restricted to use in the context of formal research protocols, or in closely monitored programs, until there is further evidence that the benefits of this therapy clearly outweigh the risks." They then argue that "Prior to NINDS, trials of thrombolytics for acute stroke provided very negative results....In an attempt to replicate the NINDS results, ECASS-II applied the same eligibility criteria and used the same 0.9 mg/kg t-PA dose, but enrolled patients within 6 hours of symptom onset. In this study, t-PA did not significantly increase the rate of favorable 90-day outcomes (40.3% vs. 36.6%, p=0.277), and was associated with a higher incidence of parenchymal hemorrhage (11.8% vs. 3.1%), symptomatic intracranial hemorrhage (8.8% vs. 3.4%), and early death due to intracranial hemorrhage (11 vs. 2 cases). Of note, there was no significant differences in 30- or 90-day mortality. An ECASS-II subgroup analysis showed a trend towards improved neurological outcomes in patients with <3 hours of symptoms, but the numbers were small and statistically insignificant. ECASS-II therefore failed to reproduce the positive results of NINDS... it is likely that the benefit seen with t-PA in the NINDS trial is applicable to only 2-3% of patients who present with acute stroke syndromes." Most damnably, "The problem of limited early diagnostic accuracy i ndicates the need to proceed with caution. Rushed decisions to administer t-PA within the 3-hour window will mean that a subset of patients will be exposed to a substantial risk of hemorrhage without any potential to benefit" The writers then quote Katzan et al (Cleveland) who wrote that "In-hospital mortality was higher among t-PA recipients than matched patients not treated with t-PA (15.7% vs. 7.2%; p<.01). Mortality was also higher in t-PA recipients than in the general population of stroke patients not receiving t-PA (15.7% vs. 5.1%; p< .001)" and conclude that "These demonstrate that eligible patients are rare and that protocol violations are common when this thrombolysis is provided outside of controlled research settings.The Cleveland experience suggests that stroke thrombolysis may be more dangerous and patient outcomes worse in community settings than they were in the NINDS stroke trial"
I invite Andy Ho to explain in the face of existing international evidence that routine thrombolysis for stroke remains controversial across the world why the UK health authorities (eg the National Institute for Clinical Excellence) should take "steps to make sure stroke patients get their scans and tPA within the first three hours".
In addition, I would like to ask if patients in Singapore routinely receive thrombolysis for ischaemic cerebrovascular accidents, and tPA for all myocardial infarctions as Andy Ho suggests in his article.
If this is indeed the case I must voice my grave concerns for the safety and well-being of patients within the Singapore Healthcare System, because according to conventional medical wisdom such measures would expose patients to unnecessary risks (including haemorrhagic stroke, lifelong disability and death) unbalanced by proposed benefits of early coronary reperfusion.
The mainstay of thrombolytic agents in the UK is streptokinase, which carries approximately half the risk of intracranial haemorrhage compared to tPA and its newer variants alteplase, retiplase and tenecteplase. The latter are employed in the UK in specific subgroups of patients (young males with anterior MIs) deemed at lower risk of cerebral haemorrhage.
This is also in line with current US guidelines for thrombolysis for Acute Myocardial Infarction published in 1999 by the American Heart Association, which state that "the cost-benefit ratio (of accelerated alteplase and reteplase with intravenous heparin) is greatest in patients presenting early after onset of chest pain or symptoms and in those with a large area of injury (eg. anterior infarction) and at low risk of ICH." "
I would also like to take this opportunity to wish Mr and Mrs Lee Kuan Yew good health in their time of need, and I sincerely hope Mrs Lee achieves as speedy and complete a recovery as is possible. God bless.
Dr (name)
MBBS (UK)
***********
Not mentioned in the article I submitted (for obvious reasons):
the local (Singaporean) guidelines updated in 2003 for stroke management published by the Singaporean Ministry of Health with regards to imaging, and tPA are as follows :
"All patients with acute stroke should undergo brain scanning (CT or MRI) as soon as possible*, preferably within 24 hours" (and not 3 hours as Andy Ho appears to claim)
Additionally, in the immediate management of stroke,
"The routine use of drugs to limit neural damage, including the administration of corticosteroids, neuroprotectants, plasma volume expanders, barbiturates and streptokinase, (which is a form of thrombolysis) is of no proven benefit and should be discouraged."
also,
"Patients receiving anticoagulants or recent thrombolytic therapy or those with bleeding diathesis require urgent correction of coagulation defects. Thrombolytics, anti-platelet therapy and anticoagulants should be discouraged".
tPA is indeed mentioned in the Ministry of Health guidelines as follows :
"A randomised study of intravenous r-TPA in cerebral infarction demonstrated significant improvement in functional outcome in selected patients treated in specialist units within 3 hours of the onset of stroke, as did an intra-arterial trial of prourokinase within 6 hours of stroke onset. The use of streptokinase is contraindicated in view of its lack of beneficial effect on mortality and morbidity. The management of patients with acute ischaemic stroke using thrombolytic therapy carries the risk of catastrophic intracerebral haemorrhage; there is difficulty in predicting who might benefit or be at most risk of haemorrhage. Thrombolysis should not yet be regarded as routine therapy."
It appears that when Andy Ho writes "What should be relevant to the British public is whether their health authorities are taking steps to make sure stroke patients get their scans and tPA within the first three hours", he omits to mention that stroke patients in Singapore are not getting their scans and tPA within the first three hours either, because the Singaporean Ministry of Health, having reviewed study data from around the world does not feel they are warranted either.
In addition, he also omits to mention that in the fierce and ongoing debate regarding thrombolysis for ischaemic stroke, conventional medical wisdom is not in favour for routine thrombolysis, and he has, in effect written an authoritatively-worded, but factually-challenged article that lays clear his stark medical ignorance and journalistic unprofessionalism, for all the world to see.
One wonders if all stroke patients in Singapore are now going to begin demanding immediate thrombolysis from the moment they step through the casualty doors. Worse still, one wonders what will happen if the doctors in Singapore, in dischord with their own guidelines, begin offering this service, thanks to pseudo-political pressure applied by an irresponsible press.
It is time that the Singaporean public awakens, and realises that the Press in Singapore, in its overwhelming drive to sycophantically pander to the incumbent People's Action Party, is not above misrepresenting "facts and realities" as half-truths. What you see in the news is not really what is really happening, around the world. Or, worse still, that the press is writing authoritatively, and ignorantly about things they know little about, and representing their personal opinions as undeniable truths.
Singapore, it seems, has become the Matrix. And if information be power, then the Singaporean public are firmly under the thumbscrews of a deceitful and politically controlled (by the PAP, although whether intentionally or not is debatable) press.
I personally believe that the PAP is not applying much pressure to the Straits Times. I feel that in fact, the ST is bending over backwards to do what it Thinks the PAP wants it to do - that it is trying to second guess the PAP and write the stuff that will get it the most pats on the back.
And therein lies the reason for the publication of this completely imprudent article, in the one major english language newspaper of the entire country.
It is also time that the Press in Singapore realises that anybody can write. Anybody can string the words together. What distinguishes a journalist from a layperson is not his ease or proficiency with the language - but his sense of responsibility, and professionalism.
With these, you are a reporter, bringing the news, and the truth to the people, and doing something worthwhile with your life.
Without these - you are nobody, jotting down your mundane personal opinions to an imaginary public audience - you might as well quit your day job and start a blog.
