Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Editorial
Comorbidities in patients with acute coronary syndrome: rare and negligible in trials but common and crucial in the real world Micha T Maeder Treatment of a patient with acute myocardial infarction (MI) has become easy, at least in the case of the 55-year-old previously healthy 85 kg man with 4 mm ST-segment elevation in the precordial leads and typical chest pain since 1 h in whom the entire set of laboratory parameters is normal except for evidence of dyslipidaemia. In this patient, results from well-conducted randomised clinical trials precisely inform us which interventions to apply to optimise the clinical outcome.1 However, in an analysis from the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry published in Heart, Radovanovic et al2 show that in the real world it is not as simple as that. The AMIS Plus registry included nearly 30 000 patients admitted with acute coronary syndrome (ACS; acute MI as well as unstable angina) to 106 Swiss hospitals during a 10-year period. Nearly 50% of patients had one or more comorbidities, and comorbidities had an important impact on in-hospital outcomes as well as 1-year outcomes. There was a dose–effect relationship between the burden of comorbidities as quantified by the Charlson Comorbidity Index (CCI) and in-hospital mortality: the OR adjusted for other baseline characteristics and treatment for in-hospital mortality for patients with comorbidities weighted with one (CCI=1), two (CCI=2) or three or more (CCI≥3) points compared with those without any comorbidities (CCI=0) were 1.36, 1.65 and 2.20. When looking at single comorbidities, the strongest predictors of in-hospital mortality were heart failure, metastatic tumours, renal disease and diabetes. In a sizeable subgroup of 7066 patients with a median follow-up of 386 days after the event the age-adjusted OR for mortality was 1.44 per CCI point. This article is an important contribution to the literature for a number of reasons. First, this is the so far largest and Correspondence to Dr Micha T Maeder, Cardiology Division, Kantonsspital St. Gallen, Rorschacherstrasse 95, St. Gallen 9007, Switzerland; [email protected] 268
most comprehensive data set on the prognostic role of comorbidities in patients with ACS. The AMIS Plus registry is a well-conducted registry of all-comers with ACS, which has been going on for more than a decade in the majority of Swiss hospitals treating ACS patients. Strengths of this registry include the facts that (i) smaller hospitals without in-house lath cab as well as large hospitals with 7×24 h percutaneous coronary intervention (PCI) service are participating, that (ii) owing to the prospective acquisition of data by doctors or trained nurses the data quality is excellent and that (iii) very detailed data on patient characteristics and treatment are available. In the initial years of the registry, only in-hospital outcomes have been assessed. In the meantime, 1-year outcomes for a substantial number of patients are also available. The CCI was developed in a non-ACS population, and its role in the ACS setting has not been well known. Radovanovic et al2 demonstrated that there were some differences in the weight attributed to some single comorbidities according to the original CCI and the prognostic weight in the present population. Still overall the CCI was predictive of both in-hospital mortality and 1-year mortality suggesting that the CCI is a simple tool for risk assessment also in the ACS setting. In contrast to scores which estimate the risk of a coronary event (which are referred to when speaking of ‘high-risk ACS’), the CCI seems to be a good barometer of the noncoronary risk of the ACS patient. The study also represents an excellent opportunity to think about the nature of the association between comorbidities and outcomes in ACS patients and how to improve it. It is not surprising that a patient with two or three diseases has a higher chance to experience an adverse event compared with a patient with only one disease. It is not hard to understand that heart failure and diabetes predict outcome in ACS patients as these are surrogates for the severity of coronary artery disease. However, what is the role of treatment and non-treatment because of
the fear of complications, respectively? The authors nicely showed that on the one hand patients with higher CCI were in a more critical haemodynamic condition (higher Killip class, more multivessel disease), although they appeared to have smaller infarcts and less often had ST-segment elevation MI, and on the other hand, these patients received less medication, including dual antiplatelet therapy, β blockers and statins, and less often underwent reperfusion. At the first glance this sounds paradoxical, and we ask ourselves whether the treating physicians did a good job when they did not prescribe a dual antiplatelet therapy in 40% of patients with CCI ≥3, and in more than 50% of CCI ≥3 patients they decided against PCI. Are the bad outcomes of these patients with CCI ≥3 explained by the ‘underuse of evidencebased medication’ as discussed in other studies?3 4 The term ‘underuse’ implies that an intervention was not applied, although it was clear that this intervention would have been indicated. We have to critically ask ourselves how well we know risks and benefits of the various so-called ‘evidence-based therapies’ in the very comorbid patients. Table 1 summarises some key trials on which the contemporary treatment of patients with ACS is based.5–8 When looking at the eligibility criteria for these trials it becomes obvious that many patients with higher CCI score would not have qualified. When looking at the characteristics of the patients with different CCI it becomes also evident that there must be a rise in the risk of bleeding score across the CCI categories. This together with the lack of data on the benefit of various interventions in this setting and the reluctance of physicians to apply therapies meant to improve long-term cardiovascular outcomes in patients with advanced non-cardiac disease, in particular renal failure and cancer, may well explain why the high CCI patients less often received a number of the so-called evidence-based therapies. Thus, we must acknowledge that these physicians most likely did the right thing by following the principle of ‘primum nil nocere’ as the evidence on the usefulness of interventions for the treatment of ACS in the highly comorbid patients is much thinner than intuitively thought. As shown in figure 1, the interplay between comorbidities, treatment and outcomes in ACS patients is complex. It is probably not correct to assume that the application of a certain intervention (eg, PCI) may result in the same benefit in a patient with high CCI compared with a Maeder MT. Heart February 2014 Vol 100 No 4
Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Editorial Table 1
Main results and inclusion and exclusion criteria of landmark trials for the treatment of patients with acute coronary syndrome
Trial
Main result
N
Mean age (years)
Clopidogrel+ASA versus ASA alone in unstable angina/ NSTEMI5
Clopidogrel+ASA better 1° EP (composite of cardiovascular death, non-fatal MI and stroke): 9.3% versus 11.4%; p75 years Previous cardiac surgery LDL cholesterol >8 mmol/L (Poland, South Africa) or >7 mmol/L (other sites) Bypass surgery within 3 months PCI within 6 months Left bundle branch block or pacing Severe heart failure Severe anaemia Dialysis Insulin-dependent diabetes Hepatic dysfunction Therapy with drugs associated with rhabdomyolysis in combination with statins
ASA, acetylsalicylic acid; EP, endpoint; LDL cholesterol, low-density lipoprotein cholesterol; MI, myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
patient with low CCI. As shown in the figure, the patient with ACS and no comorbidities as described in the initial case vignette primarily has an elevated coronary risk, and he will tremendously benefit from emergency recanalisation and stenting of his totally occluded, noncollateralised proximal left anterior descending artery, dual antiplatelet therapy and high-dose statin treatment. This patient incurs a very small non-coronary risk (eg, bleeding, stroke or contrastinduced nephropathy) from the various interventions, but his risk of heart failure and death will be significantly reduced. The situation is different in the 82-year-old, 43 kg woman with previous coronary bypass surgery, estimated glomerular filtration rate of 18 mL/min/1.73 m2 and chronic warfarin treatment for paroxysmal atrial fibrillation and previous stroke presenting with a non-ST-segment elevation MI 72 h after the onset of symptoms. This highly comorbid ACS patient has not Maeder MT. Heart February 2014 Vol 100 No 4
only a high coronary risk but also a very high non-coronary risk (her risk is much higher than that of the ‘high-risk’ patients in the PCI trials), and the effects of the various interventions on these risks are not well known. In the best case, the coronary risk can be reduced by PCI of a culprit lesion without significant non-coronary adverse effects (figure 1, CCI ≥3, scenario A). It is, however, also possible that the reduction of the coronary risk is counterbalanced by a significant adverse event such as the need for dialysis or stroke as a consequence of cardiac catheterisation (figure 1, CCI ≥3, scenario B). In the worst case, the coronary risk is not reduced at all because PCI is technically not possible or even increased because of a procedure-related MI, and the patient also experiences serious non-coronary complication such as the need for dialysis or stroke, and the net effect of the intervention is significant hazard (figure 1, CCI ≥3, scenario C).
Thus, the present study by Radovanovic and colleagues provides us with a very up-to-date snapshot of the real world of ACS patients and thereby highlights that comorbidities are not an exception but the rule in 50% of patients. Provocatively spoken we have now a wealth of information on how to reduce the relatively low risk of patients with no or little comorbidities, whereas we do not know how to treat patients with a substantial number of comorbidities and a high coronary and noncoronary risk. Thus, we need trials specifically evaluating the usefulness of interventions such as dual antiplatelet therapy and PCI which already belong to the armamentarium of ‘evidence-based therapies’ for the relatively low-risk patients also in ACS patients with comorbidities such as renal failure, heart failure or previous stroke. Otherwise we will continue to speculate about the ‘underuse’ of therapies in these patients. 269
Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Editorial 4
5
6
7
8
Balzi D, Barchielli A, Buiatti E, et al. Effect of comorbidity on coronary reperfusion strategy and long-term mortality after acute myocardial infarction. Am Heart J 2006;151:1094–100. The clopidogrel in unstable angina to prevent recurrent events trial investigators. Effect of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502. Anderesen HR, Nielsen TT, Rasmussen K, et al.; fort he DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 2003;349:733–42. FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:708–15. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effect of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study: a randomized trial. JAMA 2001;285:1711–18.
Figure 1 Schematic presentation of the effect of an intervention (eg, percutaneous coronary intervention) on outcomes in a patient without comorbidities (Charlson Comorbidity Index (CCI) =0) and a patient with a significant burden of comorbidities (CCI≥3). CCI=0: comorbidities weighted with zero points according to CCI. CCI≥3: comorbidities weighted with three or more points according to CCI. For additional explanation, see text.
Competing interests None.
REFERENCES
Provenance and peer review Commissioned; externally peer reviewed.
1
To cite Maeder MT. Heart 2014;100:268–270. Published Online First 22 November 2013
2
▸ http://dx.doi.org/10.1136/heartjnl-2013-304588
Heart 2014;100:268–270. doi:10.1136/heartjnl-2013-305104
270
3
Steg PG, James SK, Atar D, et al. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC guidelines form the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569–619. Radovanovic D, Seifert B, Urban P, et al.; on behalf of the AMIS Plus Investigators. Validity of Charlson Comorbidity Index in patients hospitalized with acute coronary syndrome. Insights from the nationwide AMIS Plus Registry 2002–2012. Heart 2014;100:288–94. Lee TC, Goodman SG, Yan RT, et al. Disparities in management patterns and outcomes of patients with non-ST elevation acute coronary syndrome with an without a history of cerebrovascular disease. Am J Cardiol 2010;105:1083–9.
Maeder MT. Heart February 2014 Vol 100 No 4
Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Comorbidities in patients with acute coronary syndrome: rare and negligible in trials but common and crucial in the real world Micha T Maeder Heart 2014 100: 268-270 originally published online November 22, 2013
doi: 10.1136/heartjnl-2013-305104 Updated information and services can be found at: http://heart.bmj.com/content/100/4/268
These include:
References Email alerting service
Topic Collections
This article cites 8 articles, 2 of which you can access for free at: http://heart.bmj.com/content/100/4/268#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Drugs: cardiovascular system (8361) Epidemiology (3477) Acute coronary syndromes (2599) Interventional cardiology (2798) Percutaneous intervention (918)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Editorial
Comorbidities in patients with acute coronary syndrome: rare and negligible in trials but common and crucial in the real world Micha T Maeder Treatment of a patient with acute myocardial infarction (MI) has become easy, at least in the case of the 55-year-old previously healthy 85 kg man with 4 mm ST-segment elevation in the precordial leads and typical chest pain since 1 h in whom the entire set of laboratory parameters is normal except for evidence of dyslipidaemia. In this patient, results from well-conducted randomised clinical trials precisely inform us which interventions to apply to optimise the clinical outcome.1 However, in an analysis from the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry published in Heart, Radovanovic et al2 show that in the real world it is not as simple as that. The AMIS Plus registry included nearly 30 000 patients admitted with acute coronary syndrome (ACS; acute MI as well as unstable angina) to 106 Swiss hospitals during a 10-year period. Nearly 50% of patients had one or more comorbidities, and comorbidities had an important impact on in-hospital outcomes as well as 1-year outcomes. There was a dose–effect relationship between the burden of comorbidities as quantified by the Charlson Comorbidity Index (CCI) and in-hospital mortality: the OR adjusted for other baseline characteristics and treatment for in-hospital mortality for patients with comorbidities weighted with one (CCI=1), two (CCI=2) or three or more (CCI≥3) points compared with those without any comorbidities (CCI=0) were 1.36, 1.65 and 2.20. When looking at single comorbidities, the strongest predictors of in-hospital mortality were heart failure, metastatic tumours, renal disease and diabetes. In a sizeable subgroup of 7066 patients with a median follow-up of 386 days after the event the age-adjusted OR for mortality was 1.44 per CCI point. This article is an important contribution to the literature for a number of reasons. First, this is the so far largest and Correspondence to Dr Micha T Maeder, Cardiology Division, Kantonsspital St. Gallen, Rorschacherstrasse 95, St. Gallen 9007, Switzerland; [email protected] 268
most comprehensive data set on the prognostic role of comorbidities in patients with ACS. The AMIS Plus registry is a well-conducted registry of all-comers with ACS, which has been going on for more than a decade in the majority of Swiss hospitals treating ACS patients. Strengths of this registry include the facts that (i) smaller hospitals without in-house lath cab as well as large hospitals with 7×24 h percutaneous coronary intervention (PCI) service are participating, that (ii) owing to the prospective acquisition of data by doctors or trained nurses the data quality is excellent and that (iii) very detailed data on patient characteristics and treatment are available. In the initial years of the registry, only in-hospital outcomes have been assessed. In the meantime, 1-year outcomes for a substantial number of patients are also available. The CCI was developed in a non-ACS population, and its role in the ACS setting has not been well known. Radovanovic et al2 demonstrated that there were some differences in the weight attributed to some single comorbidities according to the original CCI and the prognostic weight in the present population. Still overall the CCI was predictive of both in-hospital mortality and 1-year mortality suggesting that the CCI is a simple tool for risk assessment also in the ACS setting. In contrast to scores which estimate the risk of a coronary event (which are referred to when speaking of ‘high-risk ACS’), the CCI seems to be a good barometer of the noncoronary risk of the ACS patient. The study also represents an excellent opportunity to think about the nature of the association between comorbidities and outcomes in ACS patients and how to improve it. It is not surprising that a patient with two or three diseases has a higher chance to experience an adverse event compared with a patient with only one disease. It is not hard to understand that heart failure and diabetes predict outcome in ACS patients as these are surrogates for the severity of coronary artery disease. However, what is the role of treatment and non-treatment because of
the fear of complications, respectively? The authors nicely showed that on the one hand patients with higher CCI were in a more critical haemodynamic condition (higher Killip class, more multivessel disease), although they appeared to have smaller infarcts and less often had ST-segment elevation MI, and on the other hand, these patients received less medication, including dual antiplatelet therapy, β blockers and statins, and less often underwent reperfusion. At the first glance this sounds paradoxical, and we ask ourselves whether the treating physicians did a good job when they did not prescribe a dual antiplatelet therapy in 40% of patients with CCI ≥3, and in more than 50% of CCI ≥3 patients they decided against PCI. Are the bad outcomes of these patients with CCI ≥3 explained by the ‘underuse of evidencebased medication’ as discussed in other studies?3 4 The term ‘underuse’ implies that an intervention was not applied, although it was clear that this intervention would have been indicated. We have to critically ask ourselves how well we know risks and benefits of the various so-called ‘evidence-based therapies’ in the very comorbid patients. Table 1 summarises some key trials on which the contemporary treatment of patients with ACS is based.5–8 When looking at the eligibility criteria for these trials it becomes obvious that many patients with higher CCI score would not have qualified. When looking at the characteristics of the patients with different CCI it becomes also evident that there must be a rise in the risk of bleeding score across the CCI categories. This together with the lack of data on the benefit of various interventions in this setting and the reluctance of physicians to apply therapies meant to improve long-term cardiovascular outcomes in patients with advanced non-cardiac disease, in particular renal failure and cancer, may well explain why the high CCI patients less often received a number of the so-called evidence-based therapies. Thus, we must acknowledge that these physicians most likely did the right thing by following the principle of ‘primum nil nocere’ as the evidence on the usefulness of interventions for the treatment of ACS in the highly comorbid patients is much thinner than intuitively thought. As shown in figure 1, the interplay between comorbidities, treatment and outcomes in ACS patients is complex. It is probably not correct to assume that the application of a certain intervention (eg, PCI) may result in the same benefit in a patient with high CCI compared with a Maeder MT. Heart February 2014 Vol 100 No 4
Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Editorial Table 1
Main results and inclusion and exclusion criteria of landmark trials for the treatment of patients with acute coronary syndrome
Trial
Main result
N
Mean age (years)
Clopidogrel+ASA versus ASA alone in unstable angina/ NSTEMI5
Clopidogrel+ASA better 1° EP (composite of cardiovascular death, non-fatal MI and stroke): 9.3% versus 11.4%; p75 years Previous cardiac surgery LDL cholesterol >8 mmol/L (Poland, South Africa) or >7 mmol/L (other sites) Bypass surgery within 3 months PCI within 6 months Left bundle branch block or pacing Severe heart failure Severe anaemia Dialysis Insulin-dependent diabetes Hepatic dysfunction Therapy with drugs associated with rhabdomyolysis in combination with statins
ASA, acetylsalicylic acid; EP, endpoint; LDL cholesterol, low-density lipoprotein cholesterol; MI, myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
patient with low CCI. As shown in the figure, the patient with ACS and no comorbidities as described in the initial case vignette primarily has an elevated coronary risk, and he will tremendously benefit from emergency recanalisation and stenting of his totally occluded, noncollateralised proximal left anterior descending artery, dual antiplatelet therapy and high-dose statin treatment. This patient incurs a very small non-coronary risk (eg, bleeding, stroke or contrastinduced nephropathy) from the various interventions, but his risk of heart failure and death will be significantly reduced. The situation is different in the 82-year-old, 43 kg woman with previous coronary bypass surgery, estimated glomerular filtration rate of 18 mL/min/1.73 m2 and chronic warfarin treatment for paroxysmal atrial fibrillation and previous stroke presenting with a non-ST-segment elevation MI 72 h after the onset of symptoms. This highly comorbid ACS patient has not Maeder MT. Heart February 2014 Vol 100 No 4
only a high coronary risk but also a very high non-coronary risk (her risk is much higher than that of the ‘high-risk’ patients in the PCI trials), and the effects of the various interventions on these risks are not well known. In the best case, the coronary risk can be reduced by PCI of a culprit lesion without significant non-coronary adverse effects (figure 1, CCI ≥3, scenario A). It is, however, also possible that the reduction of the coronary risk is counterbalanced by a significant adverse event such as the need for dialysis or stroke as a consequence of cardiac catheterisation (figure 1, CCI ≥3, scenario B). In the worst case, the coronary risk is not reduced at all because PCI is technically not possible or even increased because of a procedure-related MI, and the patient also experiences serious non-coronary complication such as the need for dialysis or stroke, and the net effect of the intervention is significant hazard (figure 1, CCI ≥3, scenario C).
Thus, the present study by Radovanovic and colleagues provides us with a very up-to-date snapshot of the real world of ACS patients and thereby highlights that comorbidities are not an exception but the rule in 50% of patients. Provocatively spoken we have now a wealth of information on how to reduce the relatively low risk of patients with no or little comorbidities, whereas we do not know how to treat patients with a substantial number of comorbidities and a high coronary and noncoronary risk. Thus, we need trials specifically evaluating the usefulness of interventions such as dual antiplatelet therapy and PCI which already belong to the armamentarium of ‘evidence-based therapies’ for the relatively low-risk patients also in ACS patients with comorbidities such as renal failure, heart failure or previous stroke. Otherwise we will continue to speculate about the ‘underuse’ of therapies in these patients. 269
Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Editorial 4
5
6
7
8
Balzi D, Barchielli A, Buiatti E, et al. Effect of comorbidity on coronary reperfusion strategy and long-term mortality after acute myocardial infarction. Am Heart J 2006;151:1094–100. The clopidogrel in unstable angina to prevent recurrent events trial investigators. Effect of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502. Anderesen HR, Nielsen TT, Rasmussen K, et al.; fort he DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 2003;349:733–42. FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:708–15. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effect of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study: a randomized trial. JAMA 2001;285:1711–18.
Figure 1 Schematic presentation of the effect of an intervention (eg, percutaneous coronary intervention) on outcomes in a patient without comorbidities (Charlson Comorbidity Index (CCI) =0) and a patient with a significant burden of comorbidities (CCI≥3). CCI=0: comorbidities weighted with zero points according to CCI. CCI≥3: comorbidities weighted with three or more points according to CCI. For additional explanation, see text.
Competing interests None.
REFERENCES
Provenance and peer review Commissioned; externally peer reviewed.
1
To cite Maeder MT. Heart 2014;100:268–270. Published Online First 22 November 2013
2
▸ http://dx.doi.org/10.1136/heartjnl-2013-304588
Heart 2014;100:268–270. doi:10.1136/heartjnl-2013-305104
270
3
Steg PG, James SK, Atar D, et al. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC guidelines form the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569–619. Radovanovic D, Seifert B, Urban P, et al.; on behalf of the AMIS Plus Investigators. Validity of Charlson Comorbidity Index in patients hospitalized with acute coronary syndrome. Insights from the nationwide AMIS Plus Registry 2002–2012. Heart 2014;100:288–94. Lee TC, Goodman SG, Yan RT, et al. Disparities in management patterns and outcomes of patients with non-ST elevation acute coronary syndrome with an without a history of cerebrovascular disease. Am J Cardiol 2010;105:1083–9.
Maeder MT. Heart February 2014 Vol 100 No 4
Downloaded from http://heart.bmj.com/ on June 8, 2015 - Published by group.bmj.com
Comorbidities in patients with acute coronary syndrome: rare and negligible in trials but common and crucial in the real world Micha T Maeder Heart 2014 100: 268-270 originally published online November 22, 2013
doi: 10.1136/heartjnl-2013-305104 Updated information and services can be found at: http://heart.bmj.com/content/100/4/268
These include:
References Email alerting service
Topic Collections
This article cites 8 articles, 2 of which you can access for free at: http://heart.bmj.com/content/100/4/268#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Drugs: cardiovascular system (8361) Epidemiology (3477) Acute coronary syndromes (2599) Interventional cardiology (2798) Percutaneous intervention (918)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
