ED ACS Adult Guideline revision 2020 - Revision history

AndyS: /* Co-author[s] */

2022-01-13T16:15:36Z

Co-author[s]

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	=== Co-author[s] ===		=== Co-author[s] ===
	: Megan Young, MD		: Megan Young, DO
	:		:

	=== Reviewer[s] ===		=== Reviewer[s] ===
	: Ann Marie Garritano, MD		: Ann Marie Garritano, MD

AndyS at 02:36, 19 November 2020

2020-11-19T02:36:05Z

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	* Develop a similar guideline for suspected ACS in a village clinic.		* Develop a similar guideline for suspected ACS in a village clinic.
	::- It differs enough to warrant being a standalone guideline; incorporating it into the ED guideline risks making the ED guideline too unwieldy to be quickly usable.		::- It differs enough to warrant being a standalone guideline; incorporating it into the ED guideline risks making the ED guideline too unwieldy to be quickly usable.
			::- This seems an ideal use of the [https://www.mdcalc.com/history-electrocardiogram-manchester-acute-coronary-syndromes-macs HE-MACS] score.
			* Deep dive into who the relative contraindications for fibrinolytics are most appropriately applied to: only patients at low risk of cardiac death?
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	== Primary Information Sources for Guideline Revision ==		== Primary Information Sources for Guideline Revision ==

AndyS at 16:18, 18 November 2020

2020-11-18T16:18:36Z

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	Indeed, there has been much debate over whether ANY benefit exists for patients age >= 75. There was no statistically significant benefit for age >= 75 in the FTT-1994 meta-analysis. Additionally, multiple subsequent large observational studies reported more harm than benefit in this age group. This prompted many to conclude that age >= 75 should be an absolute contraindication to fibrinolytic treatment of STEMI. However, an evidence-based argument eventually emerged which argued that RCT's were indicated to definitively answer the question but that in the interim there exists enough data to infer benefit in this age group. The evidence consists mainly of two findings: 1) a re-analysis of the FTT-1994 outcomes with modern inclusion criteria (mainly symptoms < 12 hours and only ST-elevation/LBBB for diagnostic criteria) showed a benefit in this age group (OR 0.84, 95% CI 0.72 to 0.98) and 2) the GUSTO-1 trial directly compared TPA to streptokinase and showed a mortality benefit in the age >=75 group. Considering that many of the FTT-1994 patients received streptokinase, this is reasonably strong indirect evidence to support tPA in the age >= 75 group.<ref>Estess JM, Topol EJ. Fibrinolytic treatment for elderly patients with acute myocardial infarction. Heart. 2002;87(4):308-311. PMID: [https://pubmed.ncbi.nlm.nih.gov/11906993 11906993]. doi:[[ https://doi.org/10.1136/heart.87.4.308\|10.1136/heart.87.4.308]]</ref> However, authors continue to emphasize that RCT's are indicated to definitively answer this question because a small amount of bias in this data could lead to embracing a treatment which produces substantial harm (i.e. with regards to death).<ref>Van de Werf F. Reperfusion treatment in acute myocardial infarction in elderly patients. Kardiol Pol. 2018;76(5):830-837. PMID: [https://pubmed.ncbi.nlm.nih.gov/29633231 29633231]. doi:[https://doi.org/10.5603/KP.a2018.0092 10.5603/KP.a2018.0092]</ref> In summary, fibrinolytics are probably beneficial for age >= 75, but clinicians should be extremely vigil for the presence of other relative contraindications and should not be surprised if new RCT's eventually reverse this conclusion.		Indeed, there has been much debate over whether ANY benefit exists for patients age >= 75. There was no statistically significant benefit for age >= 75 in the FTT-1994 meta-analysis. Additionally, multiple subsequent large observational studies reported more harm than benefit in this age group. This prompted many to conclude that age >= 75 should be an absolute contraindication to fibrinolytic treatment of STEMI. However, an evidence-based argument eventually emerged which argued that RCT's were indicated to definitively answer the question but that in the interim there exists enough data to infer benefit in this age group. The evidence consists mainly of two findings: 1) a re-analysis of the FTT-1994 outcomes with modern inclusion criteria (mainly symptoms < 12 hours and only ST-elevation/LBBB for diagnostic criteria) showed a benefit in this age group (OR 0.84, 95% CI 0.72 to 0.98) and 2) the GUSTO-1 trial directly compared TPA to streptokinase and showed a mortality benefit in the age >=75 group. Considering that many of the FTT-1994 patients received streptokinase, this is reasonably strong indirect evidence to support tPA in the age >= 75 group.<ref name="Estess2002">Estess JM, Topol EJ. Fibrinolytic treatment for elderly patients with acute myocardial infarction. Heart. 2002;87(4):308-311. PMID: [https://pubmed.ncbi.nlm.nih.gov/11906993 11906993]. doi:[[ https://doi.org/10.1136/heart.87.4.308\|10.1136/heart.87.4.308]]</ref> However, authors continue to emphasize that RCT's are indicated to definitively answer this question because a small amount of bias in this data could lead to embracing a treatment which produces substantial harm (i.e. with regards to death).<ref>Van de Werf F. Reperfusion treatment in acute myocardial infarction in elderly patients. Kardiol Pol. 2018;76(5):830-837. PMID: [https://pubmed.ncbi.nlm.nih.gov/29633231 29633231]. doi:[https://doi.org/10.5603/KP.a2018.0092 10.5603/KP.a2018.0092]</ref> In summary, fibrinolytics are probably beneficial for age >= 75, but clinicians should be extremely vigil for the presence of other relative contraindications and should not be surprised if new RCT's eventually reverse this conclusion.
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	: UpToDate.com: [https://www.uptodate.com/contents/image?imageKey=CARD%2F68784&topicKey=CARD%2F55&source=see_link ''Absolute and relative contraindications to the use of thrombolytic therapy in patients with acute ST-elevation myocardial infarction''] (Graphic 68784 Version 11.0)		: UpToDate.com: [https://www.uptodate.com/contents/image?imageKey=CARD%2F68784&topicKey=CARD%2F55&source=see_link ''Absolute and relative contraindications to the use of thrombolytic therapy in patients with acute ST-elevation myocardial infarction''] (Graphic 68784 Version 11.0)
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			: The relative risks specified for intracranial hemorrhage in the checklist are from Gurwitz-1998.<ref name="Gurwitz1998"/>
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	The ~~relative risks specified for intracranial hemorrhage~~ in the ~~checklist are from Gurwitz~~-~~1998~~.<ref name="~~Gurwitz1998~~"/>
			:BP > 180/110 as an ABSOLUTE contraindication in patients at LOW risk of cardiac death but a RELATIVE contraindication in patients at a HIGH risk of cardiac death.
			::: ''Patients with a lower risk of death from STEMI have a lower likelihood of benefit from fibrinolysis; conversely, patients at higher risk of death from STEMI have a higher likelihood of benefit from fibrinolysis. The increased risk of ICH with BP > 180/110 still yields a net benefit in those at high risk of death from STEMI but not in those at low risk of death from STEMI. Alyward et al.<ref name="Aylward1996">Aylward PE, Wilcox RG, Horgan JH, et al. Relation of increased arterial blood pressure to mortality and stroke in the context of contemporary thrombolytic therapy for acute myocardial infarction. A randomized trial. GUSTO-I Investigators. Ann Intern Med. 1996;125(11):891-900. doi:[https://doi.org/10.7326/0003-4819-125-11-199612010-00004 10.7326/0003-4819-125-11-199612010-00004]</ref> discusses the outcomes associated with elevated BP at presentation versus risk of cardiac death, and Estess et al.<ref name="Estess2002"/> discusses risk of death and likelihood of benefit based upon age in the context of modern inclusion criteria for fibrinolytic treatment of STEMI. But be warned: this rabbit-hole is deep, dark, and yields only soft conclusions and 20-year-old pleas for future research (which is unlikely to occur at this point because PCI has become the standard of care in the types of institutions which perform randomized trials).''
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	== Credits ==		== Credits ==
	=== Lead Author[s] ===		=== Lead Author[s] ===

AndyS at 09:07, 15 November 2020

2020-11-15T09:07:51Z

← Older revision		Revision as of 09:07, 15 November 2020
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	: UpToDate.com: [https://www.uptodate.com/contents/image?imageKey=CARD%2F68784&topicKey=CARD%2F55&source=see_link ''Absolute and relative contraindications to the use of thrombolytic therapy in patients with acute ST-elevation myocardial infarction''] (Graphic 68784 Version 11.0)		: UpToDate.com: [https://www.uptodate.com/contents/image?imageKey=CARD%2F68784&topicKey=CARD%2F55&source=see_link ''Absolute and relative contraindications to the use of thrombolytic therapy in patients with acute ST-elevation myocardial infarction''] (Graphic 68784 Version 11.0)
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			The relative risks specified for intracranial hemorrhage in the checklist are from Gurwitz-1998.<ref name="Gurwitz1998"/>
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AndyS at 07:20, 13 November 2020

2020-11-13T07:20:16Z

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	== Future Directions (i.e. for future revisions)==		== Future Directions (i.e. for future revisions)==
	* Review/update this guideline every two years. Given the importance of the topic and the vast amount of active research, frequent updates are indicated.		* Review/update this guideline every two years. Given the importance of the topic and the vast amount of active research, frequent updates are indicated.
			* Review the status/results of the STREAM-2 trial,<ref>STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction - ClinicalTrials.gov. Accessed November 12, 2020. https://clinicaltrials.gov/ct2/show/NCT02777580</ref><ref>Armstrong PW, Bogaerts K, Welsh R, et al. The Second Strategic Reperfusion Early After Myocardial Infarction (STREAM-2) study optimizing pharmacoinvasive reperfusion strategy in older ST-elevation myocardial infarction patients. Am Heart J. 2020;226:140-146. PMID:[https://pubmed.ncbi.nlm.nih.gov/32553932 32553932]. doi:[https://doi.org/10.1016/j.ahj.2020.04.029 10.1016/j.ahj.2020.04.029]</ref> which will provide <u>direct</u> evidence of fibrinolytic therapy benefit in the elderly population.
	* Evidence-based troponin algorithm/cutoffs.		* Evidence-based troponin algorithm/cutoffs.
	::- Based upon institutional data or published data?		::- Based upon institutional data or published data?

AndyS at 06:58, 13 November 2020

2020-11-13T06:58:19Z

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	The chart below illustrates the NNT's by age group (to prevent one deaths) of the original FTT (1994) estimates versus those of the Estess (2002) re-analysis of the same data. Of note, there are three reasons to believe that ~~these~~ are <u>under</u>-estimates of the mortality reduction of modern practice:		The chart below illustrates the NNT's by age group (to prevent one deaths) of the original FTT (1994) estimates versus those of the Estess (2002) re-analysis of the same data. Of note, there are three reasons to believe that even the Estess (2002) results are <u>under</u>-estimates of the benefit (all-cause mortality reduction) of modern practice:
	# Many of the patients in the FTT dataset received streptokinase (which has subsequently been shown to be less effective).		# Many of the patients in the FTT dataset received streptokinase (which has subsequently been shown to be less effective).
	# Fibrinolytics are now dosed by weight (which decreases the rate of intracranial hemorrhage in lower weight persons).		# Fibrinolytics are now dosed by weight (which decreases the rate of intracranial hemorrhage in lower weight persons).

AndyS at 06:56, 13 November 2020

2020-11-13T06:56:04Z

← Older revision		Revision as of 06:56, 13 November 2020
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	The NNT's by age group (to prevent one deaths) of the original FTT (1994) versus those of the Estess (2002) re-analysis ~~are illustrated in~~ the ~~chart below~~. Of note, these are ~~probably '''~~under~~'''~~estimates ~~considering that many~~ of the patients in ~~this~~ dataset received streptokinase (which has subsequently been shown to be less effective) ~~and fibrinolytics~~ are now dosed by weight (which decreases the rate of intracranial hemorrhage in lower weight persons).		The chart below illustrates the NNT's by age group (to prevent one deaths) of the original FTT (1994) estimates versus those of the Estess (2002) re-analysis of the same data. Of note, there are three reasons to believe that these are <u>under</u>-estimates of the mortality reduction of modern practice:
			# Many of the patients in the FTT dataset received streptokinase (which has subsequently been shown to be less effective).
			# Fibrinolytics are now dosed by weight (which decreases the rate of intracranial hemorrhage in lower weight persons).
			# Heparin/Lovenox and platelet inhibitor dosing is now adjusted for age and/or renal function (which also lowers the rate of intracranial hemorrhage).
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	[[File:Fibrinolytic benefit chart NNT.PNG~~\|750 × 454px~~\|center]]		[[File:Fibrinolytic benefit chart NNT.PNG\|center]]
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AndyS at 06:14, 13 November 2020

2020-11-13T06:14:41Z

← Older revision		Revision as of 06:14, 13 November 2020
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	Indeed, there has been much debate over whether ANY benefit exists for patients age >= 75. There was no statistically significant benefit for age >= 75 in the FTT-1994 meta-analysis. Additionally, multiple subsequent large observational studies reported more harm than benefit in this age group. This prompted many to conclude that age >= 75 should be an absolute contraindication to fibrinolytic treatment of STEMI. However, an evidence-based argument eventually emerged which argued that RCT's were indicated to definitively answer the question but that in the interim there exists enough data to infer benefit in this age group. The evidence consists mainly of two findings: 1) a re-analysis of the FTT-1994 outcomes with modern inclusion criteria (mainly symptoms < 12 hours and only ST-elevation/LBBB for diagnostic criteria) showed a benefit in this age group (OR 0.84, 95% CI 0.72 to 0.98) and 2) the GUSTO-1 trial directly compared TPA to streptokinase and showed a mortality benefit in the age >=75 group. Considering that many of the FTT-1994 patients received streptokinase, this is reasonably strong indirect evidence to support tPA in the age >= 75 group.<ref>Estess JM, Topol EJ. Fibrinolytic treatment for elderly patients with acute myocardial infarction. Heart. 2002;87(4):308-311. PMID: [https://pubmed.ncbi.nlm.nih.gov/11906993 11906993]. doi:[[ https://doi.org/10.1136/heart.87.4.308\|10.1136/heart.87.4.308]]</ref> However, authors continue to emphasize that RCT's are indicated to definitively answer this question because a small amount of bias in this data could lead to embracing a treatment which produces substantial harm (i.e. with regards to death).<ref>Van de Werf F. Reperfusion treatment in acute myocardial infarction in elderly patients. Kardiol Pol. 2018;76(5):830-837. PMID: [https://pubmed.ncbi.nlm.nih.gov/29633231 29633231]. doi:[https://doi.org/10.5603/KP.a2018.0092 10.5603/KP.a2018.0092]</ref> In summary, fibrinolytics are probably beneficial for age >= 75, but clinicians should be extremely vigil for the presence of other relative contraindications and should not be surprised if new RCT's eventually reverse this conclusion.		Indeed, there has been much debate over whether ANY benefit exists for patients age >= 75. There was no statistically significant benefit for age >= 75 in the FTT-1994 meta-analysis. Additionally, multiple subsequent large observational studies reported more harm than benefit in this age group. This prompted many to conclude that age >= 75 should be an absolute contraindication to fibrinolytic treatment of STEMI. However, an evidence-based argument eventually emerged which argued that RCT's were indicated to definitively answer the question but that in the interim there exists enough data to infer benefit in this age group. The evidence consists mainly of two findings: 1) a re-analysis of the FTT-1994 outcomes with modern inclusion criteria (mainly symptoms < 12 hours and only ST-elevation/LBBB for diagnostic criteria) showed a benefit in this age group (OR 0.84, 95% CI 0.72 to 0.98) and 2) the GUSTO-1 trial directly compared TPA to streptokinase and showed a mortality benefit in the age >=75 group. Considering that many of the FTT-1994 patients received streptokinase, this is reasonably strong indirect evidence to support tPA in the age >= 75 group.<ref>Estess JM, Topol EJ. Fibrinolytic treatment for elderly patients with acute myocardial infarction. Heart. 2002;87(4):308-311. PMID: [https://pubmed.ncbi.nlm.nih.gov/11906993 11906993]. doi:[[ https://doi.org/10.1136/heart.87.4.308\|10.1136/heart.87.4.308]]</ref> However, authors continue to emphasize that RCT's are indicated to definitively answer this question because a small amount of bias in this data could lead to embracing a treatment which produces substantial harm (i.e. with regards to death).<ref>Van de Werf F. Reperfusion treatment in acute myocardial infarction in elderly patients. Kardiol Pol. 2018;76(5):830-837. PMID: [https://pubmed.ncbi.nlm.nih.gov/29633231 29633231]. doi:[https://doi.org/10.5603/KP.a2018.0092 10.5603/KP.a2018.0092]</ref> In summary, fibrinolytics are probably beneficial for age >= 75, but clinicians should be extremely vigil for the presence of other relative contraindications and should not be surprised if new RCT's eventually reverse this conclusion.
			<br>
			<br>
			The NNT's by age group (to prevent one deaths) of the original FTT (1994) versus those of the Estess (2002) re-analysis are illustrated in the chart below. Of note, these are probably '''under'''estimates considering that many of the patients in this dataset received streptokinase (which has subsequently been shown to be less effective) and fibrinolytics are now dosed by weight (which decreases the rate of intracranial hemorrhage in lower weight persons).
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			[[File:Fibrinolytic benefit chart NNT.PNG\|750 × 454px\|center]]
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AndyS at 05:22, 13 November 2020

2020-11-13T05:22:42Z

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	Understanding this data is critically important when considering likelihood of benefit versus harm. Age 65-74 appears to be the group which benefits most, but this age factor can combine with other relative contraindications to markedly increase the risk of ICH and thus nullify (or even reverse) the likelihood of benefit. Therefore age 65-74 is listed as a relative contraindication, and when combined with other relative contraindications (especially two or more) should equate to an absolute contraindication. But if there are no other relative contraindications, the age 65-74 has the greatest benefit (NNT = 38 to prevent death from any cause). This effect is even more important for patients age >= 75.		Understanding this data is critically important when considering likelihood of benefit versus harm. Age 65-74 appears to be the group which benefits most, but this age factor can combine with other relative contraindications to markedly increase the risk of ICH and thus nullify (or even reverse) the likelihood of benefit. Therefore age 65-74 is listed as a relative contraindication, and when combined with other relative contraindications (especially two or more) should equate to an absolute contraindication. But if there are no other relative contraindications, the age 65-74 has the greatest benefit (NNT = 38 to prevent death from any cause). This effect is even more important for patients age >= 75.
			<br>
			<br>
			Indeed, there has been much debate over whether ANY benefit exists for patients age >= 75. There was no statistically significant benefit for age >= 75 in the FTT-1994 meta-analysis. Additionally, multiple subsequent large observational studies reported more harm than benefit in this age group. This prompted many to conclude that age >= 75 should be an absolute contraindication to fibrinolytic treatment of STEMI. However, an evidence-based argument eventually emerged which argued that RCT's were indicated to definitively answer the question but that in the interim there exists enough data to infer benefit in this age group. The evidence consists mainly of two findings: 1) a re-analysis of the FTT-1994 outcomes with modern inclusion criteria (mainly symptoms < 12 hours and only ST-elevation/LBBB for diagnostic criteria) showed a benefit in this age group (OR 0.84, 95% CI 0.72 to 0.98) and 2) the GUSTO-1 trial directly compared TPA to streptokinase and showed a mortality benefit in the age >=75 group. Considering that many of the FTT-1994 patients received streptokinase, this is reasonably strong indirect evidence to support tPA in the age >= 75 group.<ref>Estess JM, Topol EJ. Fibrinolytic treatment for elderly patients with acute myocardial infarction. Heart. 2002;87(4):308-311. PMID: [https://pubmed.ncbi.nlm.nih.gov/11906993 11906993]. doi:[[ https://doi.org/10.1136/heart.87.4.308\|10.1136/heart.87.4.308]]</ref> However, authors continue to emphasize that RCT's are indicated to definitively answer this question because a small amount of bias in this data could lead to embracing a treatment which produces substantial harm (i.e. with regards to death).<ref>Van de Werf F. Reperfusion treatment in acute myocardial infarction in elderly patients. Kardiol Pol. 2018;76(5):830-837. PMID: [https://pubmed.ncbi.nlm.nih.gov/29633231 29633231]. doi:[https://doi.org/10.5603/KP.a2018.0092 10.5603/KP.a2018.0092]</ref> In summary, fibrinolytics are probably beneficial for age >= 75, but clinicians should be extremely vigil for the presence of other relative contraindications and should not be surprised if new RCT's eventually reverse this conclusion.
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AndyS at 06:06, 12 November 2020

2020-11-12T06:06:42Z

← Older revision		Revision as of 06:06, 12 November 2020
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	Understanding this data is critically important when considering likelihood of benefit versus harm. Age 65-74 appears to be the group which benefits most, but this age factor can combine with other relative contraindications to markedly increase the risk of ICH and thus nullify (or even reverse) the likelihood of benefit. Therefore age 65-74 is listed as a relative contraindication, and when combined with other relative contraindications (especially two or more) should equate to an absolute contraindication. But if there are no other relative contraindications, the age 65-74 has the greatest benefit (NNT = 38 to prevent death from any cause).		Understanding this data is critically important when considering likelihood of benefit versus harm. Age 65-74 appears to be the group which benefits most, but this age factor can combine with other relative contraindications to markedly increase the risk of ICH and thus nullify (or even reverse) the likelihood of benefit. Therefore age 65-74 is listed as a relative contraindication, and when combined with other relative contraindications (especially two or more) should equate to an absolute contraindication. But if there are no other relative contraindications, the age 65-74 has the greatest benefit (NNT = 38 to prevent death from any cause). This effect is even more important for patients age >= 75.

	A point of controversy is whether age >= 75 should be an absolute contraindication, or to be more consistent with the data, if age < 74 should be a required indication. In the 1994 meta-analysis by FTT, seven of the nine RCT's studies included patients >= 75, with N = 5,754. The meta-analysis of this age group showed no statistically significant effect for death. Administering a treatment with this much evidence indicating no benefit is not something routinely done in other settings (i.e. surgical interventions, antibiotics, etc). Additionally, The FTT-1994 meta-analysis shows identical outcomes for giving fibrinolytic > 12h after symptom onset (figure 3) and with age >= 75 (figure 2), and we do not give the fibrinolytic at greater than 12 hours; thus it seems difficult to rationalize withholding the fibrinolytic after 12 hours but giving it for those with age >= 75. One must also consider the prevalence of comorbidities in this age group, and the fact that the presence of ANY risk factors for bleeding will yield a greater likelihood of causing a death than of preventing one. Intelligent and well-informed persons may reasonably differ in their interpretation of data, and therefore clinicians may reasonably differ in deciding whether fibrinolytics should be offered to patients age >= 75.
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	== Fibrinolytic Consent Data-Sources ==		== Fibrinolytic Consent Data-Sources ==
	: ''When administered within 6 hours of pain onset, about 1 in 40 persons will have their life saved.''		: ''When administered within 6 hours of pain onset, about 1 in 40 persons will have their life saved.''