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Thrombolytic therapy for eligible elderly patients with acute myocardial infarction
Letter to the Editors
Thrombolytic therapy for eligible elderly patients with acute myocardial infarction Avezum A and colleagues1 have shown that many eligible elderly patients with myocardial infarction (MI) are not treated with thrombolytics. Almost 58% of their patients were older than 65 years with about 26% of patients N75 years of age. The striking feature of their study was that evidence based therapy for acute syndrome (ACS), including thrombolytics were less often prescribed to the elderly patients, a group at higher risks and hence more likely to benefit from such therapy. Various reasons like atypical presentation, higher prevalence of ST depression on electrocardiogram (ECG), presence of co-morbid conditions and contraindications, have in the past been cited as possible reason for low thrombolytic use in the elderly population. However we have found that even in those elderly patients with MI who are eligible for thrombolytics and have no contraindications, age alone is an independent factor in decision making regarding the use of thrombolytic therapy. The study population consisted of all the patients with a discharge diagnosis of MI who were admitted to the Department of Medicine for the Elderly at the Derbyshire Royal Infirmary between Jan 1991 and Nov 1993. A diagnosis of MI in these patients was made on the presence of two of the following criteria. (1) chest pain, (2) characteristic electrocardiogram (ECG) changes of acute MI, (3) characteristic rise in cardiac enzymes. Patients were identified from the hospital database and all case notes including drug cards were reviewed. Data on age, sex, past and present medical histories, contraindication to thrombolysis, examination findings, investigations, arrhythmias, management and outcome were extracted onto data collection sheets by a single reviewer (SWY). Patients were considered eligible for thrombolysis if they had presented with chest pain, within 12 hours of onset of symptoms and had a 12 lead ECG which showed ST elevation of at least 1mm in limb leads or 2 mm in the chest leads or new left bundle branch block in the absence of contraindication to thrombolysis. Contraindication to thrombolysis were as published in the GISSI study.2 All ECGTS were read blind by one of us (KAM). Statistical analysis was carried out using the chi-square with Yates correction for the categorical variables. Smoking and hypertension was commoner in younger patients whereas atrial fibrillation was more prevalent in elderly patients. Otherwise both group had similar baseline characteristics. (Table I). More elderly patients had ST depression on their presenting ECG (P b .01). Almost equal number of patients had Q wave infarcts with no difference in the site of the infarct. We
found that of all patients (n = 645) with MI only 184 (28.4%) of patients were eligible for thrombolysis, of which only 60 (33%) were given thrombolytics. A further 14 patients who were not eligible, by our criteria were given thrombolytics making a total of 74 out of 645 (11.5%) who received thrombolytics. There was no incidence of major complication i.e. major bleeding or intracranial hemorrhage amongst 74 patients given thrombolytics. Mortality was higher in patients not given thrombolytics and aspirin (Thrombolytics + Aspirin vs Neither : P b .001 , Aspirin vs Neither : P b . 001). Equal number of patients were discharged on Aspirin. However less elderly patients were discharged on Betablockers ( P b .01). Increasing age was associated with less likelihood of receiving thrombolysis and betablockers (Table 1). Reason for not giving thrombolytics to patients who satisfied the eligibility criteria was mentioned in only 34 cases (age = 8, time since onset of symptoms = 9: all of which had presented within 12 hours, contraindication = 14: none of which was a true contraindication , refused = 1, inconclusive ECG = 1, multiple pathology = 1). Careful review of other 90 cases failed to reveal any contraindication or other obvious reason for withholding thrombolytics. Review of cases who were not eligible for thrombolysis showed that the majority of these patients (47 %) had non- specific ECG changes with contraindication present in only 9% of patients. Patients with prolonged chest pain were more likely to receive thrombolytics. No association was seen with sex or presence of risk factors. However patients older than 75 years were less likely to receive thrombolytics and beta blockers, which is in keeping with other reports in the literature.3 Information collected from our hospital data base for the same time period showed that the thrombolysis rate for patients less than 65 years of age was 63.5%. Our data do not allow evaluation of exactly why the pattern of practice were as observed. We looked at only patients who were eligible for thrombolysis. Hence the question of late presentation, atypical history, contraindications and non-specific ECG changes do not arise. Thrombolytics in our hospital is usually administered in the coronary care unit which has no age related admission policy and same group of doctors were involved in the management of both younger and older patients. Also the data was analyzed in the intention to treat manner. It is possible that the physicians desire to avoid side effects may have contributed to the low administration of some drugs. Such perceptions may simply have been more prevalent in the management of elderly patients i.e. bias may have occurred, which shows our ineffectiveness to translate viable results from important clinical trials to everyday clinical practice. Another concerning issue in our study was the lack of documentation for withhold
American Heart Journal May 2005
e26 Yusuf et al
Table I. Clinical characteristics and treatment of the study sample (N = 645) Sex Male Female Clinical history Smoking Hypertension Angina Myocardial infarction Diabetes mellitus Symptoms Chest pain Dyspnoea Indigestion Confusion Collapse Examination Congestive cardiac failure Atrial fibrillation ECG changes ST elevation ST depression LBBB RBBB Normal Others Anterior location Treatment Eligible for thrombolysis Thrombolysis given Aspirin Beta-blocker Drugs on discharge Aspirin Beta-blockers Mortality
65-75 years (n = 154) (%) 68 (44) 86 (56)
N75 years (n = 491) (%) 173 (35) 318 (65)
34 (22)y 60 (39)y 19 (12) 33 (21) 17 (11)
51 119 92 110 60
(10) (24) (19) (22) (12)
117 (76) 62 (40) 0 (0) 1 (0.6) 17 (11)
328 213 8 29 88
(67) (43) (2) (6) (18)
49 (32) 19 (12)
190 (39) 107 (22)*
69 23 18 9 14 21 75
197 (40) 110 (25)* 50 (10) 26 (5) 40 (5) 68 (14) 236 (48)
(45) (15) (11) (6) (9) (13) (49)
51 (33) 32 (21)y 102 (66) 15 (10)y 87 (74) 16 (14)* 37 (24)
133 42 285 13
(27) (9) (58) (3)
236 (70) 17 (5) 157 (32)
*P b .01. yP b .001.
thrombolysis in eligible patients, as besides depriving these patients of potential benefit, the absence of documentation for failure to give treatment of proven medical benefit in appropriate cases may have medico legal implications. As suggested by and Avezum A and colleagues,1 intensive quality improvement initiatives directed at elderly population with MI is needed. Improving the utilization of thrombolytic therapy and other medications for MI may require targeted education about the net benefit of treating specific subgroups that are currently less likely to be treated. We showed this in our institution by educating the residents and staff involved in the care of patients with MI.
Review of 103 consecutive cases of MI in elderly patients (N65 years) admitted between 1st Jan 1995 and 30th Sep 1995 showed that 43 of 103 (42%) were eligible for thrombolysis of which 30 (70%) received thrombolytic therapy, which was spread evenly amongst patients of all age group. Study shows that patients with MI hospitalized during recent years are significantly older with 37% of them N75 years of age.4 Bias against elderly exists not only in treatment but also during enrollment as in studies of ACS the most common age cut off among trials with an age exclusion was 75 years,5 and more than half of the recently published trials failed to enroll patients aged 75 years or older.5 Disregarding age or sex as selection factors, thrombolytic treatment rates could be raised from 35% to 55% of all patients admitted with MI.6 Am Heart J 2005;149:e25- 6. 0002-8703/$ - see front matter doi:10.1016/j.ahj.2005.03.025
Syed Wamique Yusuf, MRCPI Kathy A. McLean, MRCP Radha A. Mishra, FRCPI Department of Medicine for the Elderly Derbyshire Royal Infirmary Derby, England
References 1. Avezum A, Makdisse M, Spencer F, Gore JM, et al. Impact of age on the management and outcome of acute coronary syndrome. Observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2005;149:67 - 73. 2. Gruppo Italiano Per Studio Della Streptochinasi NellT Infarcto Miarcardio (GISSI). Effectiveness of intravenous thrombolytic therapy in acute myocardial infarction. Lancet 1986;i:397 - 402. 3. Ketley D, Woods KL, for the European secondary prevention study group. Selection factors for the use of thrombolytic therapy in acute myocardial infarction. A population based study of current practice in the United Kingdom. Br Heart J 1995;74:224 - 8. 4. Goldberg RJ, Yarzebski J, Lessard D, Gore JM. A two-decades (1975 to 1995) long experience in the incidence, in-hospital and long-term case-fatality rates of acute myocardial infarction: a community-wide perspective. J Am Coll Cardiol 1999;33:1533 - 9. 5. Lee PY, Alexander KP, Hammill BG, Pasquali SK, Peterson ED. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA 2001;286: 708 - 13. 6. European Secondary Prevention Study Group. Translation of clinical trials into practice: a European based study of the use of thrombolysis for acute myocardial infarction. Lancet 1996;347:1203 - 7.
Thrombolytic therapy for eligible elderly patients with acute myocardial infarction Avezum A and colleagues1 have shown that many eligible elderly patients with myocardial infarction (MI) are not treated with thrombolytics. Almost 58% of their patients were older than 65 years with about 26% of patients N75 years of age. The striking feature of their study was that evidence based therapy for acute syndrome (ACS), including thrombolytics were less often prescribed to the elderly patients, a group at higher risks and hence more likely to benefit from such therapy. Various reasons like atypical presentation, higher prevalence of ST depression on electrocardiogram (ECG), presence of co-morbid conditions and contraindications, have in the past been cited as possible reason for low thrombolytic use in the elderly population. However we have found that even in those elderly patients with MI who are eligible for thrombolytics and have no contraindications, age alone is an independent factor in decision making regarding the use of thrombolytic therapy. The study population consisted of all the patients with a discharge diagnosis of MI who were admitted to the Department of Medicine for the Elderly at the Derbyshire Royal Infirmary between Jan 1991 and Nov 1993. A diagnosis of MI in these patients was made on the presence of two of the following criteria. (1) chest pain, (2) characteristic electrocardiogram (ECG) changes of acute MI, (3) characteristic rise in cardiac enzymes. Patients were identified from the hospital database and all case notes including drug cards were reviewed. Data on age, sex, past and present medical histories, contraindication to thrombolysis, examination findings, investigations, arrhythmias, management and outcome were extracted onto data collection sheets by a single reviewer (SWY). Patients were considered eligible for thrombolysis if they had presented with chest pain, within 12 hours of onset of symptoms and had a 12 lead ECG which showed ST elevation of at least 1mm in limb leads or 2 mm in the chest leads or new left bundle branch block in the absence of contraindication to thrombolysis. Contraindication to thrombolysis were as published in the GISSI study.2 All ECGTS were read blind by one of us (KAM). Statistical analysis was carried out using the chi-square with Yates correction for the categorical variables. Smoking and hypertension was commoner in younger patients whereas atrial fibrillation was more prevalent in elderly patients. Otherwise both group had similar baseline characteristics. (Table I). More elderly patients had ST depression on their presenting ECG (P b .01). Almost equal number of patients had Q wave infarcts with no difference in the site of the infarct. We
found that of all patients (n = 645) with MI only 184 (28.4%) of patients were eligible for thrombolysis, of which only 60 (33%) were given thrombolytics. A further 14 patients who were not eligible, by our criteria were given thrombolytics making a total of 74 out of 645 (11.5%) who received thrombolytics. There was no incidence of major complication i.e. major bleeding or intracranial hemorrhage amongst 74 patients given thrombolytics. Mortality was higher in patients not given thrombolytics and aspirin (Thrombolytics + Aspirin vs Neither : P b .001 , Aspirin vs Neither : P b . 001). Equal number of patients were discharged on Aspirin. However less elderly patients were discharged on Betablockers ( P b .01). Increasing age was associated with less likelihood of receiving thrombolysis and betablockers (Table 1). Reason for not giving thrombolytics to patients who satisfied the eligibility criteria was mentioned in only 34 cases (age = 8, time since onset of symptoms = 9: all of which had presented within 12 hours, contraindication = 14: none of which was a true contraindication , refused = 1, inconclusive ECG = 1, multiple pathology = 1). Careful review of other 90 cases failed to reveal any contraindication or other obvious reason for withholding thrombolytics. Review of cases who were not eligible for thrombolysis showed that the majority of these patients (47 %) had non- specific ECG changes with contraindication present in only 9% of patients. Patients with prolonged chest pain were more likely to receive thrombolytics. No association was seen with sex or presence of risk factors. However patients older than 75 years were less likely to receive thrombolytics and beta blockers, which is in keeping with other reports in the literature.3 Information collected from our hospital data base for the same time period showed that the thrombolysis rate for patients less than 65 years of age was 63.5%. Our data do not allow evaluation of exactly why the pattern of practice were as observed. We looked at only patients who were eligible for thrombolysis. Hence the question of late presentation, atypical history, contraindications and non-specific ECG changes do not arise. Thrombolytics in our hospital is usually administered in the coronary care unit which has no age related admission policy and same group of doctors were involved in the management of both younger and older patients. Also the data was analyzed in the intention to treat manner. It is possible that the physicians desire to avoid side effects may have contributed to the low administration of some drugs. Such perceptions may simply have been more prevalent in the management of elderly patients i.e. bias may have occurred, which shows our ineffectiveness to translate viable results from important clinical trials to everyday clinical practice. Another concerning issue in our study was the lack of documentation for withhold
American Heart Journal May 2005
e26 Yusuf et al
Table I. Clinical characteristics and treatment of the study sample (N = 645) Sex Male Female Clinical history Smoking Hypertension Angina Myocardial infarction Diabetes mellitus Symptoms Chest pain Dyspnoea Indigestion Confusion Collapse Examination Congestive cardiac failure Atrial fibrillation ECG changes ST elevation ST depression LBBB RBBB Normal Others Anterior location Treatment Eligible for thrombolysis Thrombolysis given Aspirin Beta-blocker Drugs on discharge Aspirin Beta-blockers Mortality
65-75 years (n = 154) (%) 68 (44) 86 (56)
N75 years (n = 491) (%) 173 (35) 318 (65)
34 (22)y 60 (39)y 19 (12) 33 (21) 17 (11)
51 119 92 110 60
(10) (24) (19) (22) (12)
117 (76) 62 (40) 0 (0) 1 (0.6) 17 (11)
328 213 8 29 88
(67) (43) (2) (6) (18)
49 (32) 19 (12)
190 (39) 107 (22)*
69 23 18 9 14 21 75
197 (40) 110 (25)* 50 (10) 26 (5) 40 (5) 68 (14) 236 (48)
(45) (15) (11) (6) (9) (13) (49)
51 (33) 32 (21)y 102 (66) 15 (10)y 87 (74) 16 (14)* 37 (24)
133 42 285 13
(27) (9) (58) (3)
236 (70) 17 (5) 157 (32)
*P b .01. yP b .001.
thrombolysis in eligible patients, as besides depriving these patients of potential benefit, the absence of documentation for failure to give treatment of proven medical benefit in appropriate cases may have medico legal implications. As suggested by and Avezum A and colleagues,1 intensive quality improvement initiatives directed at elderly population with MI is needed. Improving the utilization of thrombolytic therapy and other medications for MI may require targeted education about the net benefit of treating specific subgroups that are currently less likely to be treated. We showed this in our institution by educating the residents and staff involved in the care of patients with MI.
Review of 103 consecutive cases of MI in elderly patients (N65 years) admitted between 1st Jan 1995 and 30th Sep 1995 showed that 43 of 103 (42%) were eligible for thrombolysis of which 30 (70%) received thrombolytic therapy, which was spread evenly amongst patients of all age group. Study shows that patients with MI hospitalized during recent years are significantly older with 37% of them N75 years of age.4 Bias against elderly exists not only in treatment but also during enrollment as in studies of ACS the most common age cut off among trials with an age exclusion was 75 years,5 and more than half of the recently published trials failed to enroll patients aged 75 years or older.5 Disregarding age or sex as selection factors, thrombolytic treatment rates could be raised from 35% to 55% of all patients admitted with MI.6 Am Heart J 2005;149:e25- 6. 0002-8703/$ - see front matter doi:10.1016/j.ahj.2005.03.025
Syed Wamique Yusuf, MRCPI Kathy A. McLean, MRCP Radha A. Mishra, FRCPI Department of Medicine for the Elderly Derbyshire Royal Infirmary Derby, England
References 1. Avezum A, Makdisse M, Spencer F, Gore JM, et al. Impact of age on the management and outcome of acute coronary syndrome. Observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2005;149:67 - 73. 2. Gruppo Italiano Per Studio Della Streptochinasi NellT Infarcto Miarcardio (GISSI). Effectiveness of intravenous thrombolytic therapy in acute myocardial infarction. Lancet 1986;i:397 - 402. 3. Ketley D, Woods KL, for the European secondary prevention study group. Selection factors for the use of thrombolytic therapy in acute myocardial infarction. A population based study of current practice in the United Kingdom. Br Heart J 1995;74:224 - 8. 4. Goldberg RJ, Yarzebski J, Lessard D, Gore JM. A two-decades (1975 to 1995) long experience in the incidence, in-hospital and long-term case-fatality rates of acute myocardial infarction: a community-wide perspective. J Am Coll Cardiol 1999;33:1533 - 9. 5. Lee PY, Alexander KP, Hammill BG, Pasquali SK, Peterson ED. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA 2001;286: 708 - 13. 6. European Secondary Prevention Study Group. Translation of clinical trials into practice: a European based study of the use of thrombolysis for acute myocardial infarction. Lancet 1996;347:1203 - 7.