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ORIGINAL ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 1  |  Page : 14-18

A study on clinical profile and in-hospital outcome of elderly patients receiving thrombolytic therapy for ST elevation myocardial infarction


Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Science and Research, Bengaluru, Karnataka, India

Date of Submission05-Jan-2021
Date of Decision01-Feb-2021
Date of Acceptance16-Feb-2021
Date of Web Publication08-Feb-2022

Correspondence Address:
Dr. Darshan P Thakkar
Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Science and Research, Bengaluru - 560 078, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jicc.jicc_3_21

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  Abstract 


Objective: Ischemic heart disease is the leading cause of mortality in population above the age of 70 years. ST-elevation myocardial infarction (STEMI) constitutes important treatable cause of death in elderly population. However, many large, randomized trials have excluded this age group. The present study was planned to find out the benefits and complications related to thrombolytic therapy in elderly patients. Materials and Methods: The study was done between January 1, 2019, and December 31, 2019, in the Department of Cardiology, Sri Jayadeva Institute Of Cardiovascular Sciences and Research, Bengaluru, India, which included the study group comprising 106 elderly patients (age >70 years) with acute STEMI and underwent thrombolytic therapy. All patients were followed up till the index hospitalization and evaluated for in-hospital outcome. Results: Out of the 106 patients in the study group, 64 (60.38%) were male and 42 (39.62%) were female. Out of which, 88 (83%) patients were between 70 and 80 years whereas 18 (17%) patients were >80 years. Mortality was happened in 32 patients (30.2%). Coronary angiogram post thrombolysis was performed as pharmacoinvasive or rescue percutaneous coronary intervention (PCI) in 25 patients (23.6%), and cardiac arrhythmias were noted in 22 (20.6%) patients, acute kidney injury in 7 (6.6%) patients, ventricular septal rupture in 5.7%, ischemic stroke in 4.7%, free-wall rupture in 2.8%, and intracranial hemorrhage in 0.9% of patients. Conclusions: Primary PCI may offer clinical advantage over fibrinolytic therapy as manifested by the trends toward improvements in the combined endpoint of death, reinfarction, and stroke in the oldest patients. Despite the higher prevalence of comorbidities and high-risk features in elderly patients of acute STEMI, timely thrombolysis is also beneficial particularly who present early after symptom onset, absence of comorbid condition, and lower NYHA class on admission (NYHA I/II). In developing countries like India where primary PCI may not be feasible, timely thrombolysis should be given to the elderly patients also.

Keywords: Coronary artery disease, elderly, ST elevation myocardial infarction, thrombolysis


How to cite this article:
Thakkar DP, Ramalingam R, Palakshachar A, Patil SS, Subramanyam K, Moorthy N, Thacker MM, Arun B S, Manjunath C N. A study on clinical profile and in-hospital outcome of elderly patients receiving thrombolytic therapy for ST elevation myocardial infarction. J Indian coll cardiol 2022;12:14-8

How to cite this URL:
Thakkar DP, Ramalingam R, Palakshachar A, Patil SS, Subramanyam K, Moorthy N, Thacker MM, Arun B S, Manjunath C N. A study on clinical profile and in-hospital outcome of elderly patients receiving thrombolytic therapy for ST elevation myocardial infarction. J Indian coll cardiol [serial online] 2022 [cited 2022 May 27];12:14-8. Available from: https://www.joicc.org/text.asp?2022/12/1/14/337349




  Introduction Top


Ischemic heart disease (IHD) is the leading cause of mortality in population above the age of 70 years.[1],[2] Severity and the prevalence of coronary artery disease (CAD) increase with the increasing age. About 50% of the patients above 60 years of age have been found to be having severe CAD including triple-vessel disease (TVD) and/or left main disease, in various autopsy studies.[3] It is common to find peripheral artery disease in elderly patients who present with acute myocardial infarction (MI). Such abnormalities were detected in about 33% of men between 65 and 70 years and 45% of men above 85 years of age.[4],[5] Incidence of ST-elevation MI (STEMI) is high among the elderly population; however, many large randomized trials have excluded this age group.[6],[7],[8],[9],[10] The number of patients eligible for reperfusion strategy decreases with advancing age. Elderly patients with their delay recognition of symptoms and atypical presentation and associated comorbidities present challenges in treatment options. Elderly patients are still less likely to receive reperfusion even if eligible because of altered risk versus benefit ratios of revascularization strategies. Fibrinolytic therapy remains a sole mode of initial therapy in many parts of the world, especially in developing and underdeveloped nations. In India, PCI-capable centers are still unevenly distributed and poor transport facilities and low socioeconomic status will lead majority patients to receive fibrinolytic therapy as major revascularization strategy at first medical contact centers. Data regarding benefit and complications of fibrinolytic therapy in elderly patients are still lacking since most of the elderly patients are excluded from the randomized trials of STEMI.

Thiemann et al. evaluated the risk of intracranial bleed following thrombolysis in STEMI in elderly.[11] In their study, among patients aged 65–75 years, the 30-day crude mortality rates were 6.8% for patients treated with fibrinolytic therapy compared to 9.8% in the control group. However, among patients >75 years of age, the 30-day crude mortality rate was 18.0% with fibrinolytic treatment versus 15.4% without treatment, resulting in a mortality hazard ratio of 1.38. They concluded that fibrinolytic treatment for patients >75 years of age is unlikely to confer survival benefit and may have a significant survival disadvantage. Subsequent fibrinolytic therapy trialists' (FTT) meta-analysis of nine randomized placebo-controlled trials, including a total of 5754 patients >75 years of age, revealed that while the relative risk reduction was less for patients >75 years of age, the absolute risk reduction was 10 lives saved per 1000 patients treated (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.84–1.07). Complications such as ventricular septal rupture and free-wall rupture have also been reported in elderly.[12] Guidelines were further updated to include thrombolytic therapy in patients of more than 75 years also.[13],[14] In view of the above review of literature, it is clear that the recommendation of use of thrombolytic therapy in the elderly patients, which is a high-risk group, has caveats related to morbidity and mortality, especially in our Indian medical infrastructure. The present study was planned to find out the benefits and complications related to thrombolytic therapy in elderly patients.


  Materials and Methods Top


The present observational study was done between January 2019 and December 2019 in the Department of Cardiology, Sri Jayadeva Institute of Cardioascular Sciences and Research, Bengaluru, India, which included consecutive elderly patients who were admitted with acute STEMI and underwent thrombolytic therapy. All patients received loading doses of aspirin 325 mg, clopidogrel 300 mg if age was <75 years and 75 mg if age >75 years, and age-adjusted doses of low-molecular-weight heparin. All patients received other guideline-directed medical therapy. All were evaluated for outcome (in-hospital mortality) and complications. The patients were followed up till the index hospitalization. Various parameters including age, sex, window period, Killip's class on admission, presence of cardiogenic shock, blood investigations, CAD, complications, and arrhythmias related to mortality have been analyzed in this study.

Inclusion criteria

Between January 1, 2019, and December 31, 2019, a total of 106 consecutive patients of age more than 70 years, who presented with acute STEMI and underwent thrombolysis, were included in the study.

Exclusion criteria

  1. Age <70 years
  2. Patients were excluded from the thrombolytic therapy group if they had absolute contraindications to thrombolytic therapy.


  • Any previous intracranial hemorrhage
  • Known structural cerebral vascular lesion (e.g., arteriovenous malformation)
  • Known malignant intracranial neoplasm (primary or metastatic)
  • Ischemic stroke within 3 months except acute ischemic stroke within 4.5 h
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis (excluding menses)
  • Significant closed-head or facial trauma within 3 months
  • Intracranial or intraspinal surgery within 2 months
  • Severe uncontrolled hypertension (unresponsive to emergency therapy)
  • For streptokinase, previous treatment within the previous 6 months.


Statistical analysis

Categorical data were expressed as frequency and percentage and were analyzed using Chi-square test/Fisher's exact test as applicable. Statistical significance was considered at P <0.05. The statistical analysis was performed using Epi info version 7.2.1.0, developed by CDC, Atlanta, Georgia, USA.


  Results Top


A total of 106 patients of acute STEMI, who received thrombolytic therapy, were observed during the study period at our institution. Out of the 106 patients in the study group, 64 (60.38%) were male and 42 (39.62%) were female. 88 (83%) patients were between 70 and 80 years of age whereas 18 (17%) patients were >80 years. The traditional risk factors and comorbid conditions such as the prevalence of diabetes mellitus (29.2%), hypertension (42.5%), IHD (14.2%), cerebrovascular accident (CVA) (1.9%), obesity (9.4%), smoker 30.2%), alcoholic (3.8%), chronic obstructive pulmonary disease (COPD) (9.4%), and malignancy (2.8%) were present. [Table 1] shows average window period for patients admitted as STEMI.
Table 1: Window period distribution of patients studied

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On admission, Killip's class is also one of the important parameters having impact on outcome of the patients; those patients came with Killip's class III/IV had higher mortality.

[Graph 1] shows relation of Killip's class to mortality. In our study, patients who were in Killip's class I during admission had mortality 13% in the group. Mortality was higher in Killip's class II-IV. Patients with Killip's class II, III, and IV having mortality were 36%, 37.5%, and 86%, respectively, which suggest elderly patients with cardiogenic shock have extremely poor outcome. Majority of patients who had Killip's class III and IV had long window period of 10–12 h and severe left ventricular dysfunction.



Thrombolytic agents were selected depending on age (<75 years or >75 years) and risk of bleeding to the patient. Injection streptokinase in standard dose (1.5 million units) was given to 61 patients (57.5%), half dose of injection streptokinase (0.75 million units) was given to 43 patients (40.6%), injection reteplase was given to 1 (0.9%), and injection urokinase was given to 1 (0.9%) of patients. No benefit was observed with half dose of injection streptokinase, instead mortality was higher in half-dose group probably due to more severe left ventricular dysfunction and development of cardiogenic shock. Rescue PTCA was performed in 4 out of 61 patients in the full-dose group whereas 2 patients out of 43 in the half-dose group.

Mortality occurred in 32 patients (30.2%), while various complications were observed in 22 (20.6%) patients. Coronary angiogram post thrombolysis was performed as pharmacoinvasive or rescue PCI in 25 patients (23.6%), and cardiac arrhythmias were noted in 22 (20.6%) patients. [Table 2] compares the various parameters of the study populations between those patients who survived and discharged versus those patients who expired during hospitalization. [Table 2] classically shows those patients having low left ventricular ejection fraction (LVEF), low systolic and diastolic blood pressure (SBP and DBP), anemia, renal dysfunction, higher potassium, low high-density lipoprotein, and high low-density lipoprotein LDL values having significant higher mortality. The study showed various classic parameters for morbidity and mortality also having significant impact on elderly population.
Table 2: Comparison of clinical variables according to discharge/death of patients studied

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Various comorbidities and their outcome on mortality were also analyzed in elderly population. [Graph 2] and [Table 3] show comparison of comorbidities and associated outcome of the patients. The prevalence of diabetes, hypertension, CVA, history of IHD, and history of smoking was significantly higher in those patients who were expired. When comparing sex, female patients were having higher mortality (44%) compared with male patients (22%).

Table 3: Comorbidities distribution in relation to death of patients studied

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Mortality was observed in a total of 32 (30.2%) patients out of 106 patients with cardiogenic shock as the most common cause of death (78.1%); various other causes of death were VT/VF in 3 patients (9.4%), free-wall rupture in 3 patients (9.4%), and ICH in 1 patient (3.1%). [Table 4]
Table 4: Cause of death

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Various complications have been noted in the study group patient such as acute kidney injury in 6.6%, ischemic stroke in 4.7%, intracranial hemorrhage in 0.9%, ventricular septal rupture in 5.7%, free-wall rupture in 2.8% as a complication of thrombolytic therapy 22 (20.8%) patients had developed arrhythmia during hospitalisation. Complete heart block was the most common rhythm abnormality noted in 10 (9.4%) out of total 106 patients.

Out of 106 patients, coronary angiogram was performed in 25 patients (23.6%) as a pharmacoinvasive approach, and distribution of CAD has been studied. Out of which, 5 patients had TVD, 9 had double-vessel disease, and 11 patients had single-vessel disease. Patients who underwent invasive revascularization had less mortality compared to patients kept on medical management.


  Discussion Top


Fibrinolytic treatment is the standard of care for eligible patients presenting early with acute ST segment elevation MI to hospitals where rapid triage to primary angioplasty is unavailable.[15] First trials of fibrinolytic therapy by GISSI, ISIS-2, and GUSTO group of investigators showed undoubted mortality benefit of using fibrinolytics over placebo. Although fibrinolytic treatment of elderly patients is generally accepted, there are questions about its safety and efficacy. Few large-scale, randomized controlled trials have included patients over 75 years of age. The numbers of elderly patients included in these studies are generally considered to be small and placebo versus fibrinolytic comparisons are limited; thus, firm conclusions must be interpreted in that context. In our study, we found that 30.2% of patients died in the index hospitalization and the remaining patients were discharged home in clinically stable condition.

An early study among elderly patients conducted by Thiemann et al.[11] used tissue plasminogen activator (t-PA) as the fibrinolytic agent. They concluded that fibrinolytic treatment for patients >75 years of age is unlikely to confer survival benefit and may have a significant survival disadvantage. Sub-analysis of elderly patients in early trials of fibrinolytic efficacy GISSI-1, ISIS-2, and GUSTO trials[16],[17] has consistently showed mortality benefit compared to placebo but with slight increasing in the hemorrhagic stroke rates as age advances more than 85 years. Using a conventional thrombolytic criterion, the FTT data show that among patients >75 years of age, the absolute risk reduction was 34/1000 patients treated (OR: 0.84, 95% CI: 0.72–0.98). A significant proportion of the patients from this earlier meta-analysis received streptokinase rather than t-PA, and some of the trials did not include a routine aspirin and heparin strategy. Their mortality rate was 24.3% at 35 days. In our study, 57% used full dose of 1.5 million streptokinase and 40% used only half dose of streptokinase due to expected increasing in bleeding risk. Half dose of streptokinase might be responsible for failure of thrombolysis and a greater number of deaths. A major cause of death is cardiogenic shock related to pump failure accounting for 78%. Half dose of fibrinolytic strategy in patients aged >75 years as studied in the Strategic Reperfusion Early After Myocardial infarction study (STREAM) showed that half dose of tenecteplase is noninferior to full dose of tenecteplase and with a smaller number of bleeding events. Similarly, alteplase has also been studied and showed to be beneficial with half dose. Randomized controlled trial data regarding half dose of streptokinase are lacking, needs future studies.

Time to presentation is a critical factor. When given within the 1st h, mortality reduction has been reported to be up to 50% with progressive loss of benefit and an increase in the rate of myocardial rupture with delay of treatment. In our study, only 6 patients came within 3 h and majority of the patients are between 3 and 6 h. Time delays in the presentation of elderly patients can be due to atypical symptoms and social factors in Indian setup, which adds to success of reperfusion strategy and outcomes. Common indicators such as low LVEF, low blood pressure, renal dysfunction, anemia and presence conventional risk factor such as diabetes, hypertension, previous history of IHD, smoking and COPD were more common in elderly patients who suffered mortality compared to who survived.

The risk of stroke has been shown to increase with both t-PA and SK as age increases. Independent risk factors for intracranial hemorrhage were identified as age >75 years, female sex, black race, prior stroke, systolic blood pressure >160 mm Hg, t-PA versus SK, excessive anticoagulation (international normalized ratio >4), and below median weight (<65 kg for women, and <80 kg for men). Age in itself should not be considered a contraindication for fibrinolysis. In our study, one patient suffered intracranial hemorrage (ICH). Judicious use of heparin is also quite important ,at least 12-h delay after thrombolysis might prevent hemorrhagic complications particularly in elderly patients. Mechanical complications such as ventricular septal rupture and free-wall rupture are also common in elderly. In our study, these complications were seen in 5.7% and 2.8%, respectively.

Limitations of the study

The study is an observational single-center study and the sample size was small.


  Conclusions Top


Primary PCI may offer clinical advantage over fibrinolytic therapy as manifested by the trends toward improvements in the combined endpoint of death, reinfarction, and stroke in the older patients. Despite the higher prevalence of comorbidities and high-risk features in elderly patients of acute STEMI, timely thrombolysis is also beneficial. However, in the present study, in-hospital mortality was less in thrombolytic therapy who presented early after symptom onset (window period <6 years, absence of comorbid condition, and lower NYHA class on admission (NYHA I/II); however, patients with long window period, comorbid condition, NYHA III/IV on admission, presence of severe LV dysfunction, low SBP and DBP on admission, and higher LDL and low LDL level had significant higher mortality. In developing countries like India where primary PCI may not be feasible, timely thrombolysis should be given to the elderly patients also to improve clinical outcomes and prevent in-hospital mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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