Treatment and Outcomes of Nonagenarians with ST-Elevation Myocardial Infarction

ABSTRACT: There is no age limit for reperfusion therapy in the current guidelines for the treatment of patients with ST-elevation myocardial infarction (STEMI). Reperfusion therapy, although associated with better outcomes, is not always offered to the oldest patients. A retrospective analysis at our institution of all patients greater than or equal to 90 years of age with a diagnosis of acute coronary syndrome at discharge from 2004 to 2008 identified 24 patients with STEMI. The majority of patients were Caucasian, females, hypertensive, with a low incidence of dementia and diabetes. Only 29% of patients presented to the hospital in less than 6 hours. Thirteen patients were treated with percutaneous coronary intervention (PCI) and 11 patients were treated medically. The in-hospital mortality was 23% in the PCI group and 36% in the medical therapy group. Kaplan-Meier analysis demonstrated a survival benefit favoring PCI, which disappeared when only patients presenting after 6 hours to the hospital were analyzed. PCI-treated patients had no procedure-associated complications and had a good prognosis if they survived to hospital discharge. PCI should be offered to nonagenarians presenting with STEMI. J INVASIVE CARDIOL 2010;22:474–478 Key words: STEMI, nonagenarians, PCI ——————————————————————————————————————— The elderly represent the fastest-growing segment of the United States population and heart disease remains the leading cause of death for both men and women of all ages.¹ It is estimated that by 2020, there will be 2.6 million nonagenarians and 135,000 centenarians in the U.S.^2,3 However, there are limited data regarding the outcome, clinical course and management of acute coronary syndromes (ACS) in nonagenarians. Despite the general acceptance that patients with STEMI should undergo primary PCI if available, regardless of age, there are scarce data in the nonagenarian population. The purpose of this study was to evaluate the outcome of STEMI in nonagenarians.

Methods

From January 2004 through December 2008, the charts of all patients age greater than or equal to 90 years discharged with a diagnosis of ACS based on the ICD-9 code 410.x1 were reviewed. Twenty-four patients were diagnosed with STEMI based on the presence of ischemic chest pain, ST elevation of greater than or equal to 1mm (greater than or equal to 2 mm in V1, V2) in 2 or more contiguous leads and elevated cardiac biomarkers. Standard techniques for PCI were used. Significant coronary artery disease was defined as visual estimation of percent diameter stenosis greater than or equal to 50%. Antiplatelet and antithrombotic medications were used at the discretion of the operator. Angiographic success was defined as thrombolysis in myocardial infarction (TIMI) 3 flow at the end of the intervention and residual stenosis of

Results

PCI was offered to 14 patients. Twelve patients underwent successful emergent PCI of the culprit artery. One patient underwent emergent cardiac catheterization, which revealed total obstruction of the circumflex artery and significant obstruction of the left main, left anterior descending (LAD) and right coronary artery (RCA). The patient unfortunately expired shortly after emergent coronary artery bypass. These 13 patients were analyzed as Group 1. One patient refused cardiac catheterization and was not given thrombolytic therapy due to late presentation (> 12 hours). A total of 11 patients were treated medically and formed Group 2. The reasons for choosing medical therapy were advanced dementia in 2 patients and patient preference in 3 patients. The other 6 patients had one of the following: severe and active chronic obstructive pulmonary disease, ventricular septal defect and late presentation, comatose state after resuscitation from cardiac arrest, age and chronic kidney disease (CKD), age and late presentation, and non-critical coronary artery stenosis by cardiac catheterization. Baseline characteristics are presented in Tables 1 and 2. The mean age was 92 ± 2.2 years. All patients were Caucasian and 18 (75%) were female. Almost all patients in Group 1 were female (92%), but the difference with Group 2 did not reach statistical significance. Group 1 had a statistically significantly lower presenting heart rate (62 ± 16 vs. 79 ± 23; p = 0.03), higher peak CPK (1798 ± 1509 vs. 642 ± 569; p = 0.04) and were more likely to receive clopidogrel (69% vs. 9%; p = 0.005). There was no significant difference between the medical therapy and PCI groups in terms of prior chronic disease, initial laboratory and electrocardiographic (ECG) data, medical management in the hospital or upon discharge, or complications. There was no difference in anterior STEMI on the presenting ECG between the two groups. The majority of patients were hypertensive (75%), and all had at least stage III chronic kidney disease as calculated with the Cockcroft-Gault formula (glomerular filtration rate [GFR] less than or equal to 60 ml/kg). Cardiac catheterization revealed significant three-vessel disease in 31% of the patients. There was 100% correlation between ECG localization of the infarct and the stented coronary artery. Angiographic success was 100%. There were no differences in complications between the two groups in terms of bleeding, cerebrovascular accidents or acute renal insufficiency (Table 3). There was a trend toward a statistically significant difference between the two groups in intra-aortic balloon pump (IABP) utilization. Five patients in the PCI group and 4 patients in the medical therapy group presented in cardiogenic shock, and 2 patients from each group expired during hospitalization. The in-hospital mortality rate was 23% (3/13) in Group 1 and 36% (4/11) in Group 2. Two patients in Group 1 expired after they developed a malignant ventricular arrhythmia on day 2 and day 6, respectively of hospitalization after successful stenting of the LAD. Another patient expired shortly after emergent coronary artery bypass graft surgery (CABG). In Group 2, in-hospital death was due to cardiogenic shock in all 4 patients. One patient had a ventricular septal defect and another patient was resuscitated from cardiac arrest, but circulatory and ventilator support was withdrawn after 24 hours. The 3-month mortality rates were 23% (3/13) for Group 1 and 64% (7/11) for Group 2, with 3 subsequent deaths only in Group 2. Two patients died of progressive heart failure. One of the patients was discharged after the index hospitalization to hospice and died 56 days later. One patient presented after 11 days with heart failure and cardiogenic shock and expired 48 hours later. Another patient was hospitalized 3 times for heart failure and expired at home 56 days after the initial MI. After a follow up of 21 ± 17 months (range 2–1673 days), the total mortality rate in Group 1 was 46%, and was 91% in Group 2. Three patients in Group 1 were rehospitalized: 1 for presyncope and 2 for heart failure. In Group 2, 4 patients were rehospitalized: 1 for syncope and 3 for heart failure. There were no differences in secondary outcomes between the two groups (p = 0.59). Kaplan-Meier survival analysis showed a mortality benefit with PCI compared to medical therapy (hazard ratio [HR] 3.28, 95% confidence interval [CI] 1.09–9.92; p = 0.035) (Figure 1A). However, if the survival analysis was restricted to patients presenting > 6 hours after the onset of symptoms, there was no significant difference between the groups (HR = 2.39, 95% CI 0.72–7.88; p = 0.15) (Figure 1B).

Discussion

This retrospective analysis provides further evidence that treatment of STEMI with PCI is both feasible and beneficial in nonagenarians. It also suggests that nonagenarian patients treated with PCI for STEMI have a good prognosis if they survive the initial index hospitalization. There were no major complications due to cardiac catheterization, which is similar to a recently published report.⁴ This finding is promising, given the presence of moderate CKD in all patients. There was no worsening in renal function after PCI in our catheterization patients. Although there were no contraindications for PCI, 11 patients were treated medically for a variety of reasons. In 2 patients (18%), age played a role when the treating physician chose medical therapy. Analysis of more than 5,000 patients from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) database demonstrated a clear difference in survival between the younger elderly (75–89 years of age) and the older elderly (greater than or equal to 90 years of age) presenting with non-ST elevation ACS.⁵ The high mortality associated with advanced aged has been reported in multiple series. Shah et al. reported an in-hospital mortality rate of 32% in 73 nonagenarians presenting with STEMI.⁶ In an analysis of 177 nonagenarians presenting with ACS, most of whom received guideline-recommended therapies, Hovanesyan and Rich found a 1-year mortality rate of 53%.⁷ Two series from Italy, one of 88 patients age greater than or equal to 85 years⁸ and another one of 55 octogenarians,⁹ reported an in-hospital mortality rate of 17% and a 30-day mortality of 16%, respectively. Our mortality rates are comparable to these reports. In contradistinction to these studies, the largest cohort of 138 nonagenarians undergoing PCI from the Mayo Clinic reported an in-hospital mortality rate of 9.4%, which further decreased to 6% when only the 106 patients admitted after the year 2000 were evaluated.¹⁰ The in-hospital mortality of 32 patients treated before 2000 was 22%. The mortality at 1, 3 and 5 years was 25%, 41% and 71%, respectively, which was similar to an age- and gender-matched population. The characteristics of these patients were not significantly different compared to the prior published studies, but the time from onset of symptoms to revascularization, which is critical for survival, was not reported. Overall, our patients were “healthy” nonagenarians, with a low incidence of dementia and diabetes. Hypertension and CKD were the main cardiac risk factors. The 1-year mortality rate was higher in the medical group due to cardiac-related death, with all deaths occurring in the first 2 months following hospitalization for ACS. As expected, Kaplan-Meier analysis would suggest that PCI is better than medical therapy. There were several issues that could be raised about the comparison of these two groups, with selection bias being the most important. Although the two groups were similar in many aspects, there were differences that were not apparent in Table 1. Three patients in the medical therapy group presented in near extremis to the hospital and died in the first 24 hours, and their outcome theoretically would not have been changed by PCI. The “frailty” of the patients was not assessed. Only 1 patient in the medical group presented to the hospital in 11 Comparing only patients with late presentation demonstrated no significant difference in mortality between the two groups. This could suggest that PCI might not influence mortality for nonagenarians presenting after 6 hours, consistent with prior data on the impact of time delay on mortality.^9,12 Several large multicenter trials have demonstrated that reperfusion therapy for STEMI, whether PCI or fibrinolysis, improved mortality for patients 13 For patients greater than or equal to 85 years of age, the first law of medicine, “First do no harm,” is often applied, at times limiting treatment options. There are limited data to guide STEMI therapy in elderly patients, especially those greater than or equal to 85 years, with most trials excluding this patient population.¹³ Even studies designed specifically to evaluate reperfusion therapies in elderly patients have excluded patients > 90 years of age.^14,15 In the oldest elderly STEMI patients, those 85–90 years had a better outcome when compared to those aged > 90 years.⁸ Elderly patients usually have complex coronary artery disease, with higher mortality and morbidity and higher rates of complication following PCI, such as bleeding and cerebrovascular accidents.¹³ Despite higher bleeding rates expected in nonagenarians, especially with dual antiplatelet therapy, a retrospective study suggested that drug-eluting stents were safe to use in this high-risk population,¹⁶ a conclusion also supported by the accompanying editorial.¹⁷ The decision between fibrinolytics and PCI favors the latter in the > 85 years of age population,¹³ with intracranial hemorrhage and fatal stroke being the most feared complications with fibrinolytics. The recent TRIANA trial showed a trend toward improved outcome for patients treated with PCI versus fibrinolysis with a combined endpoint of death, recurrent MI and disabling stroke at 30 days. PCI patients had marked improvement of recurrent ischemia.¹⁸ In the previous SENIOR-PAMI trial, similar results were obtained, but a subgroup analysis of patients > 80 years of age showed no benefit of PCI over fibrinolysis.¹⁹ In the current study, the PCI group had higher CPK peak levels, even though they had better outcomes. The higher CPK could represent a larger area of infarction, though a closer examination of biomarker kinetics revealed that the classic ACS curve of biomarkers was not present in 78% of the patients treated medically. The higher CPK has also been reported in studies of acute reperfusion representing faster washout kinetics. The smaller CPK peak could also indicate late presentation, and not a smaller infarct size. Our data revealed a discrepancy in the use of clopidogrel between the two groups. Beneficial data on dual antiplatelet therapy for patients with STEMI not undergoing reperfusion were not published until December 2007,²⁰ and all of our patients in the medical group were treated before 2008. The recommendation was based on a randomized, controlled trial which showed a relative risk reduction for all-cause mortality of 7% in the dual antiplatelet arm.²¹ Clopidogrel has been recommended in patients with STEMI undergoing cardiac catheterization since 2004,²² which was reflected in the higher number of patients (69%) receiving clopidogrel prior to their procedure. The 31% of the patients undergoing PCI who did not receive dual antiplatelet agents underlines the known lower compliance with guidelines in the treatment of older patients.²³ In conclusion, this study shows nonagenarians presenting with STEMI within the first 6 hours benefit from emergent PCI compared to medical therapy.

References

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—————————————————————————————————— From the Hospital of Saint Raphael, New Haven, Connecticut. The authors report no conflicts of interest regarding the content herein. Manuscript submitted May 25, 2010, provisional acceptance given June 23, 2010, final version accepted June 29, 2010. Address for correspondence: Costin N. Ionescu, MD, PhD, Hospital of Saint Raphael, Division of Cardiology, 1450 Chapel Street, New Haven, CT 06511. E-mail: cnionescu@yahoo.com