Elderly, fibrinolytic therapy

Although the therapeutic benefit of coronary reperfusion—fibrinolytic therapy and primary percutaneous coronary intervention (PCI)—for the treatment of acute ST elevation myocardial infarction (STEMI) in younger patients is well established, there remains considerable debate over the appropriate choice of a reperfusion strategy for elderly patients. 

This chapter will first review the data on the efficacy of fibrinolytic therapy among elderly patients. We will define the risk of major hemorrhagic compfications associated with fibrinolytic therapy and explain how the available data can be used to help individualize the risk for a given elderly patient. We will also show how, even in eligible patients, there are considerable variations of care across ages, with the elderly receiving fibrinolytic therapy less frequently than younger patients. Finally, we will review the data on the use of primary PCI in elderly patients with STEMI. 

In 1994, the benefit of fibrinolytic therapy in the treatment of the elderly was brought into question by the Fibrinolytic Therapy Trialists (FTT) Collaborative Group (3). This meta-analysis included nine fibrinolytic trials incorporating over 58,600 patients. Of these patients, 17,000 were 65-74 years of age and 5754 were >75 years of age. This analysis revealed that the benefit of fibrinolytic therapy diminished with advancing age relative risk reduction (RRR) of death associated with fibrinolytic therapy was 22% in patients <55 years of age, 19% in patients 55-64 years of age, 16% in patients 65-74 years of age and only 4% in patients >75 years of age. However, while the relative effectiveness of fibrinolytic therapy diminished with advancing age, the 4% RRR translated into a 1% ARR, or NNT = 100, still a clinically important difference and similar to the 1.2% ARR in patients <55 years of age. Therefore, even small relative reductions in risk can be important when applied to groups with increased risk. 

Of the nine trials included in the FTT meta-analysis. Late Assessment of Thrombolytic Efficacy (LATE) and Estudio Multicentrico Estreptoquinasa Republicas de America del Sur (EMERAS) enrolled only patients who presented >6 hours after the onset of chest pain (8,9). Both of these studies demonstrated minimal benefit from fibrinolytic therapy as compared to the impressive reductions seen in GISSI and ISIS-2 (8.9% mortality in the t-PA group vs. 10.3% mortality in the control group in LATE and no benefit of streptokinase over control in patients presenting >12 hours after symptom onset in EMERAS). The inclusion of these two trials diluted the effects of fibrinolytic therapy in the FTT analysis. Furthermore, in the prematurely terminated APSAC Intervention Mortality Study (AIMS), only 3 of the total 502 patients were >70 years of age, raising concerns about the ability of the FTT to extrapolate these results to elderly patients (10). 

Since the original publication of the FTT, White reported unpublished data from the FTT that shows a more sustained benefit in the elderly (11). In contrast to the initial FTT analysis that included patients with factors associated with both reduced benefit and increased risk of fibrinolytic therapy (i.e., patients presenting >12 hours after the onset of symptoms as well as individuals showing ST depression or T wave... 

Numerous observational studies have confirmed the treatment benefit seen in the above RCTs of primary PCI as a reperfusion strategy in the elderly. In the previously mentioned analysis of the CCP, Berger et al. found primary PCI compared with no reperfusion was associated with significant reductions in both 30-day and 1-year mortality among patients without absolute contraindications for fibrinolytic therapy (13). Among the ideal patient subgroup, primary PCI yielded reductions in adjusted mortahty rates at 30 days and at 1 year compared with no therapy (OR 0.78,95% Cl 0.58-1.05 and OR 0.63,95% Cl 0.49-0.84). However, since this analysis used no reperfusion therapy as the comparison group, primary PCI and fibrinolytic therapy were not directly compared. 

Despite decades of study, uncertainty still remains about the optimal treatment strategy for the elderly patient with STEMI. There is mounting evidence that primary PCI is a safe and efficacious means of reperfusion and is superior to fibrinolytic therapy. Therefore, primary PCI, if available, should probably be the treatment of choice in the elderly patient with STEMI. However, primary PCI is not readily available as a reperfiision modahty at many of the institutions that admit patients with STEMI. Thus, fibrinolytic therapy may be the only reperfusion... 

In patients with ST-segment elevation (STE) ACS, in-hospital death rates are approximately 7% for patients who are treated with fibrinolytics and 16% for patients who do not receive reperfusion therapy. In patients with non-ST-segment elevation (NSTE) MI, in-hospital mortality is less than 5%. In-hospital and 1-year mortality rates are higher for women and elderly patients. In the first year following MI, 38% of women and 25% of men will die, most from recurrent infarction.1 At 1 year, rates of mortality and reinfarction are similar between STE and NSTE MI. 

There was a trend toward increased 30-day mortality among patients treated with TNK and abciximab compared with those treated with TNK and unfractionated heparin or TNK and LMWH. Given these findings, the ASSENT-3 authors concluded that caution should be exercised regarding the use of conjunctive therapy with abciximab in elderly patients with an AMI treated with a fibrinolytic agent. ... 

---