Trends in Management, Hospital and Long-Term Outcomes of Elderly Patients with Acute Myocardial Infarction

Article Outline

• Abstract
• Methods
  • Statistical Analysis
• Results
  • Clinical Characteristics
  • In-hospital Management
  • In-hospital Clinical Complications
  • Medications at Discharge
  • Mortality
• Discussion
  • Baseline Characteristics
  • Medications
  • Reperfusion Therapy
  • Clinical Complications
  • Mortality
  • New Definition of Acute Myocardial Infarction
  • Limitations
• Conclusion
• Acknowledgments
• References
• Copyright

Abstract 

Purpose

The number of elderly patients with acute myocardial infarction (AMI) is growing rapidly, and their early and postdischarge mortality is high. Several studies have reported a decline in mortality after myocardial infarction; however, the magnitude of the decline among the elderly has not been fully investigated.

Methods

We assessed trends in management, in-hospital, and long-term outcomes of 1475 elderly patients (aged ≥75 years, 42% women) hospitalized with AMI in all 25 operating coronary care units in Israel between 1992 and 2002, from our prospective nationwide biennial surveys.

Results

Between 1992 and 2002, a significant increase was observed in the use of acute reperfusion therapy (27%-48%), coronary angiography (6%-47%), percutaneous coronary intervention (3%-33%), coronary bypass (2%-8%), aspirin (53%-88%), beta-blockers (18%-65%), angiotensin-converting enzyme inhibitors (26%-63%), and lipid-lowering drugs (0%-43%). These changes were associated with a 42% reduction in 30-day mortality (27.6%-16.1%; adjusted odds ratio 0.57; 95% confidence interval [CI], 0.36-0.93). One-year cumulative mortality declined by 20% (37%-29%; adjusted odds ratio 0.74; 95% CI, 0.49-1.13).

Conclusions

The management of elderly patients with AMI changed substantially during the last decade. This change was associated with a significant reduction in early mortality, whereas cumulative 1-year mortality improved only slightly. Better adherence to in-hospital management guidelines and better implementation of postdischarge health policy may further decrease mortality and morbidity in the elderly after AMI.

Keywords: Elderly, Management, Myocardial infarction, Outcome, Reperfusion

Acute myocardial infarction (AMI) is highly prevalent among the elderly, and advanced age remains a strong determinant of management and prognosis in these patients.¹, ², ³, ⁴ Elderly patients account for 20% to 30% of patients with AMI and contribute to more than 50% of mortality rates. Their in-hospital and 1-year mortality remain high (20%-40%).³, ⁴, ⁵, ⁶

The diagnosis, management, and outcome of AMI have undergone major changes during the last decade, reflecting the implementation of various recommendations and guidelines. Although studies designed to guide the therapeutic management of this rapidly growing portion of our population should warrant high priority, many randomized clinical trials have excluded patients with AMI who are aged 75 years or more.⁷ Nonetheless, there is a growing body of evidence suggesting that various treatments may result in greater absolute gains in the elderly because of their higher comorbidity and mortality rates.⁷, ⁸

Data regarding secular trends in management and outcome in “real-world” practice are limited. Data on 1.5 million patients from the National Registry of Myocardial Infarction from 1990 to 1999 demonstrated that the use of intravenous thrombolytic therapy decreased, whereas the use of primary angioplasty and adjunctive therapies known to reduce mortality increased. These changes were associated with a decline in in-hospital mortality.⁹ Despite the reduction in early mortality after AMI, it is unclear whether a similar decline exists in the elderly and whether late mortality rates have been affected by the introduction of newer treatment strategies.

Previous studies in elderly Israeli patients with AMI have reported a decline in in-hospital complication rates, as well as a 30% decrease in 30-day and 1-year mortality rates from the early 1980s to the early 1990s.¹⁰, ¹¹

The purpose of the present study was to evaluate trends in management and their impact on early and late mortality rates of elderly patients (aged ≥75 years) who were admitted with AMI to all 25 operating coronary care units in Israel between 1992 and 2002.

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Methods 

From 1992 to 2002, we performed biennial prospective nationwide AMI/acute coronary syndromes surveys, lasting 2 months each (usually January and February), collecting data prospectively from all patients hospitalized in each of the 25 operating coronary care units in Israel, as described elsewhere.⁵, ⁶, ¹⁰ In brief, demographic, historical, and clinical data, including in-hospital complications, medical management, and procedures performed, were recorded on prespecified forms for 6787 patients (1686 women, 25%) by dedicated study physicians. There was no age limit for inclusion in the survey. The study cohort included 1475 elderly persons (aged ≥75 years; 633 women, 42%) with AMI. The diagnosis of AMI was based on clinical, electrocardiography, and enzymatic findings (positive creatine kinase-MB and/or troponin). The diagnosis of AMI was based on troponin (in the presence of negative creatine kinase) in 4% and 20% of the cases in the 2000 and 2002 cohorts, respectively. Eligibility for inclusion in the study was validated before discharge from the coronary care unit. The organization, data acquisition, data management, and follow-up were performed in the same coordinating center in all surveys. There were no uniform guidelines for the use of medications, coronary angiography, or coronary intervention.

Early and 1-year mortality rates were assessed from hospital charts and by matching the identification numbers of the patients with the National Population Registry of the State of Israel. All patients were identified for follow-up.

Statistical Analysis 

All analyses were performed using SAS software, version 8.2 (SAS Institute Inc, Cary, NC). Continuous variables are expressed as mean ±1 standard deviation. Two-sided probability values are reported. The significance of changes over time in patients’ characteristics, management, and mortality were assessed by a P value for trend.

The association between age and the prescription of multiple evidence-based medications (three or more of the following: aspirin, beta-blockers, angiotensin-converting enzyme [ACE] inhibitors, or lipid-lowering drugs) at discharge was assessed by logistic regression analysis adjusting for potentially confounding variables including baseline characteristics, comorbidity, in-hospital complications, and the year the survey was performed (reference group: 1996 cohort).

One-year Kaplan-Meier survival curves were estimated and compared using the log-rank test (SAS Lifetest Procedure). Logistic regression analyses were used to assess covariate-adjusted mortality rates at 7 days, 30 days, and 1 year, and at 1 year in 7- and 30-day survivors (SAS Logistic Procedure) using pertinent covariates and the year the survey was performed (reference group: 1992 cohort).

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Results 

Clinical Characteristics 

The study cohort included 1475 elderly patients (aged ≥75 years) with AMI (842 males, 57%). During the study period, the proportion of elderly patients among the total study cohort increased from 18% in 1992 to 25% in 2002. The mean age and the proportion of octogenarians slightly increased, yet gender distribution remained unchanged. Other clinical characteristics are presented in Table 1.

Table 1. Changing Clinical Characteristics of Elderly Patients with Acute Myocardial Infarction

Year	1992	1994	1996	1998	2000	2002	P value for trend
No. of patients	174	192	175	249	313	372
Age (y), mean±SD	80.2±4.0	79.6±3.6	80.2±4.6	80.1±4.3	81.0±4.8	80.8±5.1	.05
Age>80 y	39.7	34.9	42.3	43.5	43.4	39.2	.09
Women (%)	39.7	42.7	44.0	45.0	41.9	39.2	.64
Medical history:
Diabetes (%)	24.7	27.6	23.4	23.7	29.7	31.7	.04
Hypertension (%)	50.6	46.9	54.9	57.8	58.5	64.2	<.001
Current smoking (%)	13.2	12.0	6.9	10.4	11.2	8.6	.19
Hyperlipidemia (%)	8.6	13.5	20.0	17.7	31.3	36.3	<.001
Angina (%)	40.8	32.8	49.7	24.1	41.2	35.5	.44
MI (%)	31.8	36.6	32.6	26.9	34.5	30.1	.43
CABG (%)	2.3	2.1	2.9	3.2	7.7	6.7	.003
PCI (%)	0	3.1	2.9	2.0	10.5	11.8	<.001
Stroke (%)	9.2	9.4	4.6	12.0	12.8	15.1	.002
Killip class≥2 (%)	53.9	55.0	40.6	44.8	37.7	42.3	<.001
ST-elevation (%)	NA	NA	NA	70.7	65.2	54.0	<.001
Q-wave MI (%)	86.2	63.5	62.9	54.2	65.2	55.1	<.001
Anterior MI (%)	42.8	54.2	52.7	50.9	55.9	50.7	.20

CABG=coronary artery bypass grafting; MI=myocardial infarction; PCI=percutaneous coronary intervention; SD=standard deviation; NA=not available.

In-hospital Management 

From 1992 to 2002 a substantial increase was noted in the use of evidence-based medications, such as aspirin, beta-blockers, ACE inhibitors, lipid-lowering drugs (mainly statins), thienopyridines, glycoprotein IIb/IIIa antagonists, and heparin (Figure 1). This increase was paralleled by a significant decline in the use of digoxin (from 14% to 6%) and calcium-channel blockers (from 23% to 12%).

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• Figure 1. 

  Trends in in-hospital medical therapy among elderly patients (aged≥75 years) with acute myocardial infarction (AMI) between 1992 and 2002. P for trend <.001 for all medications presented.

A considerable increase occurred concurrently in the use of reperfusion therapy (Figure 2). The use of coronary angiography, percutaneous coronary interventions, and coronary bypass grafting steadily increased. The rate of acute reperfusion (lysis or primary percutaneous coronary intervention) among patients with Q-wave infarction between 1992 and 1996 (when myocardial infarction was not defined by electrocardiogram on admission), or ST-elevation on admission between 1998 and 2002 increased from 27% in 1992 to 59% in the mid-late 1990s and declined thereafter to 46% in 2002; the use of lytic therapy peaked in the mid-late 1990s to 54% and declined thereafter to 26% in 2002, paralleled by an increased use of primary percutaneous coronary intervention (from 2% in 1994 to 21% in 2002, Figure 2).

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• Figure 2. 

  Trends in reperfusion therapy among elderly patients (aged≥75 years) with AMI between 1992 and 2002. P for trend <.001 for all reperfusion and revascularization procedures.

In-hospital Clinical Complications 

From 1992 to 2002, a decline in the prevalence of high-grade atrioventricular block and cardiogenic shock was noted, whereas the prevalence of heart failure increased. No changes were observed in the prevalence of other complications, such as ventricular tachycardia or fibrillation, atrial fibrillation, recurrent infarction, or ischemia and stroke (Table 2).

Table 2. Trends in In-hospital Complications

AV=atrioventricular; TIA=transient ischemic attack.

Medications at Discharge 

Medications at discharge were recorded from 1996 to 2002. During this period a steady significant increase in the use of aspirin (from 61% to 87%, respectively), beta-blockers (28% to 70%), ACE inhibitors (43% to 68%), lipid-lowering drugs (4% to 50%), and thienopyridines (0% to 37%) was noted, whereas the use of nitrates declined (from 42% to 33%, respectively, P for trend<.01, for all comparisons). The proportion of patients treated with digoxin and calcium-channel antagonists has not changed over time (5% and 11%, respectively).

Prescription of three or more evidence-based medications (aspirin, beta-blockers, ACE inhibitors, or lipid-lowering drugs) at discharge increased substantially over time, from 14% in 1996 to 65% in 2002 (Figure 3) for the entire cohort of elderly persons, as well as in the following age subgroups: 75 to 79 years (from 15% in 1996 to 72% in 2002), 80 to 84 years (from 11% in 1996 to 61% in 2002), and among the eldest, more than 85 years (from 15% in 1996 to 56% in 2002). Multivariate logistic regression analysis revealed that a 1-year increase in age was associated with a 4% lower use of three or more evidence-based medications at hospital discharge (odds ratio [OR]=0.96; 0.92-0.99). Categoric age subgroup analysis revealed that this association was more evident among the eldest aged more than 85 years (OR=0.55; 0.36-0.82 vs age 75-79 years) than among patients aged 80 to 84 years (OR=0.85; 0.61-1.17, vs age 75-79 years). Being part of a recent cohort (2002 vs 1996) was associated with an 11-fold (OR=11.13; 6.56-19.66) increase in the prescription of multidrugs at hospital discharge.

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• Figure 3. 

  Trends in the use of combination medical therapy (aspirin, beta-blockers, ACE-inhibitors, and statins) at discharge after AMI between 1996 and 2002. P for trend = .01 for all combinations used.

In the 2002 cohort, the four aforementioned evidence-based medications were newly initiated in-hospital (among patients who were not receiving these medications before the index hospitalization) in 53%-62% of the cases. Clopidogrel was newly initiated in-hospital in 97% of the cases.

Mortality 

Early and late mortality declined significantly from 1992 to 2002 (Table 3 and Figure 4). The most striking decline in mortality (by ≈40%) occurred in the early stage after AMI (at 7 and 30 days), whereas survival thereafter up to 1 year remained unchanged. One-year cumulative mortality declined by 20%.

Table 3. Mortality of Elderly Patients with Acute Myocardial Infarction Hospitalized in Critical Care Units Throughout Israel

CI=confidence interval; OR=odds ratio; RRR=relative risk reduction.

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• Figure 4. 

  One-year Kaplan-Meier survival curves among elderly patients (aged≥75 years) hospitalized with AMI between 1992 and 2002.

The covariate-adjusted ORs for decline in mortality are presented in Table 3. Age as a continuous variable was associated with an increase in cumulative 1-year mortality; the risk was estimated to increase exponentially by approximately 6% per 1 year of age (OR = 1.06; 1.03-1.09).

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Discussion 

The present nationwide survey of elderly patients with AMI represents “real-world” practice during the last decade. The study indicates that the medical and interventional management of elderly patients hospitalized with AMI in Israeli coronary care units has changed substantially during the last decade and was associated with a decline in cumulative 1-year mortality of 20%. The most striking decline in mortality (by ≈40%) occurred in the early stage after myocardial infarction, whereas survival thereafter up to 1 year remained unchanged. The study also indicates a consistent increase in the proportion of elderly patients aged 75 years or more who are hospitalized with AMI in the coronary care units (18%-25%).

Baseline Characteristics 

During the study period, changes in several common disease definitions occurred that lowered the threshold values for the diagnosis of hypertension,¹² diabetes mellitus,¹³ and hypercholesterolemia,¹⁴ resulting in an increase in the proportion of patients with disease in the cohort.

Medications 

Despite the steady increase in the use of evidence-based medications in our study, it remains relatively low compared with that in younger patients treated in the same coronary care units.⁵ Previous studies similarly suggested suboptimal use of evidence-based medications after AMI among older populations,³, ⁴, ¹⁵, ¹⁶, ¹⁷ with an inverse correlation between age and their use.³, ⁴, ⁵ The use of aspirin, beta-blockers, ACE inhibitors, and statins at discharge, or their combination (three to four of these drugs) increased substantially from 14% in 1996 to 65% in the 2002 cohort. This trend was observed also among the eldest patients. Nonetheless, with advancing age, the use of combined medical therapy declined. Our findings are in accordance with recent data from the Worcester Heart Attack Study showing underuse of combination therapy with advancing age¹⁵ and an increase in the use of three or more evidence-based medications from 7% in 1990 to 65% in 2001 among elderly persons aged 75 years or more. Thus, there is room for further improvement in the management of elderly patients with AMI.

Reperfusion Therapy 

Our survey shows a significant increase in the use of coronary angiography over time, followed by more percutaneous coronary interventions and bypass operations. However, coronary angiography was carried out in less than one half of our elderly patients. This probably reflects the fact that the proportion of elderly patients with AMI who are considered suitable for invasive procedures decreases with age, mainly because of their comorbidities and the uncertainty regarding the balance of benefit and risk.³, ⁴, ⁵, ¹⁷

Acute reperfusion by either lytic therapy or primary percutaneous coronary intervention was used in one half of the patients. This is in accordance with data from Medicare showing that the effect of age on guideline-indicated therapies in AMI was largest for acute reperfusion.¹⁷ During the period studied, the rate of acute reperfusion did not change and even slightly declined. This decline in recent years is probably the result of the aging of the study population, higher prevalence of comorbidities,³, ⁴, ⁵ and perhaps greater bed availability in coronary care units for elderly patients who in the past were hospitalized in medicine wards. Furthermore, elderly patients with AMI frequently present with vague symptoms such as fatigue, shortness of breath, and functional or cognitive decline, thus delaying diagnosis and depriving these patients of acute reperfusion therapy.⁵ Some older patients are excluded from acute reperfusion therapy, even when eligible, because clinicians are not yet completely prepared to efficiently manage frail elderly persons with AMI.¹⁸

The mode of acute reperfusion changed during the period studied. In the mid-late 1990s lytic therapy was the preferred mode of acute reperfusion, whereas primary percutaneous coronary intervention was seldom used and mainly reserved for more ill patients with large infarctions or hemodynamic compromise. In recent years, the use of primary percutaneous coronary intervention increased significantly. Nevertheless, its use still remained low in the elderly (21% in 2002). This change in practice most probably was influenced by the publications of recent randomized studies on reperfusion strategies for ST-elevation myocardial infarction,¹⁹, ²⁰ suggesting more favorable outcomes and lower complication rates with the use of primary percutaneous coronary intervention than with lytic therapy. However, these trials did not specifically evaluate the elderly. Data from observational studies are consistent with these results.²¹, ²² Thus, the optimal reperfusion strategy in this rapidly growing segment of the population remains to be established in large-scale randomized clinical trials.

Clinical Complications 

During the period studied, a significant decrease in the proportion of elderly patients developing cardiogenic shock was noted, yet the overall rates remained high (11%). Elderly patients developing shock are traditionally considered to have a poorer prognosis.²³ Although the SHOCK trial found that an aggressive revascularization approach was associated with improved survival only for patients aged less than 75 years,²⁴ the SHOCK registry²⁵ and the National Registry of Myocardial Infarction registry²⁶ reported that revascularization was associated with a marked survival benefit. Thus, it seems that an aggressive approach in elderly patients with shock is appropriate and likely to result in substantial clinical benefit.

Although the prevalence of cardiogenic shock decreased during the period studied, the proportion of elderly persons developing heart failure in-hospital increased. This may reflect better management during the acute phase with more frequent use of acute reperfusion therapy, better hemodynamic monitoring, and other beneficial evidence-based medications, thus preventing shock and early mortality, but resulting in higher rates of heart failure in survivors. Moreover, older patients presenting with AMI typically have more comorbid conditions,³, ⁴, ⁵ such as hypertension and diabetes, that are associated with diastolic heart failure.²⁷, ²⁸

Mortality 

A main concern emerging from this study is the difference in the rates of decline in early and late mortality. Although the decline in early mortality over the past decade was in the magnitude of 40%, a decline in 1-year mortality in 7- and 30-day survivors was not evident. This finding emphasizes the need for a better postdischarge health policy with closer observation that will improve adherence to medications and the management of associated comorbidities in the elderly.

New Definition of Acute Myocardial Infarction 

The new definition of AMI issued in 2000 by the American College of Cardiology/European Society of Cardiology, based largely on troponin levels,²⁹ labels patients who were previously diagnosed with unstable angina as having non-ST-elevation AMI. Given the higher sensitivity of the newer biomarkers for myocardial necrosis, it has been reported that 20% to 30% of patients previously diagnosed with unstable angina are now diagnosed with AMI.³⁰ In our study, a diagnosis of AMI based on troponin (in the presence of negative creatine kinase) increased from 4% of the cases in 2000 cohort to 20% of the cases in 2002. This change in diagnosis results in the inclusion of patients with smaller myocardial infarctions in the cohort. Although the early outcome of these latter patients is better than that of patients diagnosed with myocardial infarction according to the old definition, their long-term outcome after discharge is similar or even worse.³¹, ³², ³³ This fact partially explains our observation that the most striking decline in mortality during the decade studies occurred at the early stage after AMI, but vanished at 1 year.

Limitations 

Although each biennial survey was planned prospectively, the present study is retrospective in nature. The study sampled only patients treated in the coronary care units during a 2-month period. There are no data on out-of-hospital mortality trends. In addition, as is true for any nonrandomized observational study, it is difficult to establish any cause–effect relationship between management and outcomes, particularly when confounding by treatment indications may play an important role in any observed associations. The study was also of a cross-sectional nature of a whole country, making it difficult to know whether preexisting differences in management between the sites affected our findings.

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Conclusion 

During the past decade, the extent of both the medical and the interventional management of elderly persons with AMI changed substantially but still remained relatively low. There was a significant reduction in early mortality but a less striking decline in late mortality rates. Better adherence to in-hospital management guidelines and better implementation of postdischarge health policy may further decrease mortality and morbidity in elderly patients with AMI.

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Acknowledgments 

We are indebted to all the physicians and nurses who participated in the AMI surveys from 1992 to 2002, The Israel Society for the Prevention of Heart Attacks for the data management and analysis, The Working Group on Intensive Cardiac Care of the Israel Heart Society, The Israel Center for Disease Control, and Lori Mandelzweig, PhD, for editorial assistance.

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