In-Hospital and long term results of primary angioplasty and medical therapy in nonagenarian patients with acute myocardial infarction

Introduction: Although percutaneous coronary intervention is an accepted "first-line" therapy in acute ST elevation myocardial infarction (STEMI) in general population, few data are available on the short- and long-term outcomes of very old patients (age >90 years). Our aim is to evaluate and compare the short and long-term outcomes after primary percutaneous coronary intervention (PPCI) or medical therapy in nonagenarian patients with STEMI. Methods: We retrospectively identified patients older than 90 years old in our clinic, with acute STEMI who presented within 12 hours after symptoms onset, either underwent PPCI or medically treated. In hospital events and long-term results analyzed subsequently. Results: From January 2005 to December 2014, 73 patients with STEMI either underwent PPCI (PPCI group n = 42) or had only medical treatment (Non-PPCI group n = 31). Mean age was 92.4 ± 3.1 (90-106). Patients were followed 26.5 ± 20.1 months. Recurrent myocardial infarction during hospitalization was not observed in both groups. In-hospital mortality, cerebrovascular events and acute renal failure rate were similar between two groups (respectively P = 0.797 and P = 1.000, P = 0.288), whereas arrhythmia was significantly higher in the PPCI group ( 0; 21.4%, P = 0.009). Results show re-infarction was similar in both groups (respectively 3.2%; 11.9%, P = 0.382) but mortality in long-term was significantly lower in the PPCI group (respectively 40.9%; 12.9%, P = 0.02). Conclusion: In nonagenarian patients, with STEMI mortality is very high. Although; in-hospital events were similar, the long-term mortality rate was significantly lower in patients treated with PPCI.

tients and patients' relatives. 42 patients accepted PPCI, 4 patients accepted thrombolytic therapy but 31 patients rejected any reperfusion therapy due to concern about the risk of intracerebral hemorrhage. Patients that received thrombolytic therapy were excluded from the study due to a small number of patients. In addition the patients experiencing more than 12 hours of pain, and patients with non-STEMI and allergy to any of the drugs used (aspirin, clopidogrel, GP IIb/IIIa inhibitors) were excluded from the study. Demographic measures, risk factors, and comorbidities are summarized in Table 1. The primary endpoints of this study are, in hospital and long-term outcomes. The patients were divided into two groups: PPCI group (n = 42) and non-PPCI group (medical group: with antiischemic, antiplatelet, anticoagulant therapy and clinical follow-up) (n = 31). All patients were given aspirin 300 mg and clopidogrel 300-600 mg on admission in the emergency department. PPCI was performed by femoral access using 6-7 F guiding catheter in all patients. Intravenous unfractioned heparin 100 IU/kg was administered to achieve an activated clotting time of >250 seconds. at the beginning of the procedure. Additional heparin, guided by activat ed clotting time, was administered dur ing percutaneous coronary intervention (PCI). Thrombus aspiration catheter and glycoprotein IIb/IIIa inhibitors were used accordingly to the physician's preference in each individual patient. Also either bare metal stent or drug eluting stent were implanted due to operator's discretion. A successful procedure was defined as infarcted artery stenosis <30% and Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 flow. PPCI was not performed in non-PPCI group. In the non-PPCI group, the patients were admitted to CCU and their electrocardiograms were continuously monitored for at least 72 hours. Hemodynamic monitoring by an arterial line and pulmonary artery balloon catheters was performed in patients with advanced heart failure. Patients of non-PPCI group not received any reperfusion therapy. Heparin was routinely administered to each patient in this group for 3-5 days unless there was contraindication. Patients received 75 mg/d clopidogrel and 300 mg/d aspirin in both groups. All other medications, including , β-blockers, angiotensin-converting enzyme inhibitors, statins, nitrates, vasopressor agents, digoxin, vasodilator agents, antiarrhythmic drugs, calcium channel blockers, analgesics (morphine and meperidine), antiemetic drugs and diuretics were used as needed in both groups. All participants underwent transthoracic echocardiography. Standard 2-dimensional echocardiographic examination was performed. Left ventricular ejection fraction (LVEF) was estimated by the modified Simpson rule. In hospital outcome evaluated by death, re-infarction, cerebrovascular accident (CVA), severe arrhythmia, severe bleeding and acute renal failure. After hospitalization, all surviving patients were contacted by clinical interview or telephone. The patients were followed 26.5 ± 20.1 months and death, CVA, re-infarction were assessed during the follow-up. Recurrent myocardial infarction was defined as ischemic type chest pain associated with an increase in creatine kinase and creatine kinase-MB more than twice the last value and/or new ST segment elevation or new pathological Q waves. CVA was defined as a permanent loss of neurological function caused by an ischemic or hemorrhagic vascular event. Severe arrhythmia was defined as patients with supraventricular /ventricular tachycardia, atrial fibrillation and mobitz type 2/3 AV block. Acute renal failure was defined as an increase of 0.5 mg/dL in creatinine. Major bleeding was defined as required transfusion of >2 units of blood and/or the occurrence of intracranial/retroperitoneal hemorrhage.

Statistical analysis
The data was analyzed using the SPSS software for Windows version 15 LVEF and presence of severe valve disease were similar in both groups (respectively, P = 0.789; P = 0.191). Medical treatment after admission was similar in both groups only except glycoprotein IIb/IIIa treatment (1 patient in non-PPCI group, 4 patients in the PPCI group). Eight patients needed blood transfusion (3 patients in non-PPCI group, 5 patients in the PPCI group), but life-threatening bleeding was not observed in both groups. In-hospital mortality, cerebrovascular event, recurrent MI and acute renal failure rates were similar between the groups (respectively P = 0.797 and P = 1.000, P = 0.288). The rate of in-hospital severe arrhythmia was significantly higher in the PPCI group (0; 21.4%, P = 0.009) . The rate of acute MI was non-significantly higher in the PPCI group during the follow-up (respectively 3.2%; 11.9%, P = 0.382). All-cause mortality rate was significantly lower in the PPCI group (respectively 40.9%; 12.9%, P = 0.02) ( Table 2). Kaplan-Meier analysis demonstrated that PPCI group patients had a higher cumulative survival rate than non-PP-CI group patients. But the difference was not statistically significant. (PPCI group, %64.3; Non-PPCI group, 41.9%; P = 0.085 by the log-rank test) (Figure 1).

Discussion
Although older patients constitute a fast growing portion of cardiovascular patients, few data are available on the outcome of patients with STEMI undergoing primary angioplasty. To our knowledge, our study is the first trial to compare the short-and long-outcomes of PPCI versus only medical therapy without intervention. Aortoiliac tortuosity is higher therefore coronary engagement may be difficult in older patients. Also frequency of complications is higher. Due to these reasons radial access or long sheath can be used in these patient cohort Instead of radial approach femoral approach was preferred in our study. Previous studies demonstrated that high mortality and morbidity rates are associated with advancing age. 3 The high mortality in this patient group linked to the presence of additional diseases. Shah et al suggested an in hospital mortality rate of 32% in nonagenarian patients with STEMI. 7 Salinas et al reported that in hospital mortality rate of 34.2% in 38 nonagenarian patient with STEMI treated with PPCI. 2 In another study in hospital mortality rate was 16%. 8 Our results are similar compared to previous studies where in hospital mortality was 26% in PPCI, 29% in non-PPCI group. In >80 years, although shown to improve mortality rates with reperfusion therapy, 9 there are limited data to guide STEMI therapy in nonagenarian patients. Costin et al suggested a survival benefit with PPCI compared to medical group in a small-populated study. 10 In our study, in-hospital mortality was similar between two groups but in long-term follow-up mortality rate was significantly lower in the PPCI group. Comorbid diseases are accompanied by more frequent in elderly patients. 1 In our study, the most common cardiac risk factors were hypertension, diabetes mellitus, chronic renal failure and valvular heart disease. Conservative approach (medical therapy) has been the main treatment since very elderly patients will be accompanied by more frequent comorbid disease and there are more likely to occur of additional complications after any intervention. 2 In elderly patients, previous studies showed that hemorrhage rates are higher in any form of reperfusion therapy. [11][12][13] The risk of contrast-induced nephropathy is also expected to be higher in this patient cohort. 14,15 In our study blood transfusion was needed in 8 patients, but life-threatening bleeding was not observed. Also femoral access path related complications did not occur. Our results suggested that dual anti-platelet therapy was safe in this patient population. Acute renal failure rate was high (27.3%), but it was similar in both groups. Based on these results, PPCI does not increase the risk of bleeding and acute renal failure development.

Limitations
Limitations of the data presented include the retrospective, single-center design of the analysis, inadequate number of patients to allow statistically significant differences to be detected between the two groups.

Conclusion
PPCI compared to conservative medical therapy reduces mortality in long-term follow-up in older patients (>90 years old) with STEMI.

Ethical approval
The study complies with the principles outlined in the Declaration of Helsinki. The study was approved by our hos pital Ethics Committee. Informed consent form is taken before all interventions in our institute and are being kept in the archives. Moreover all patients or patients' relatives were contacted and informed about our study via phone call.