Difficult decisions on ACS pharmacotherapy in the elderly

Risk scores

Treatment strategies evolve around the patient’s ischemic risk (with the GRACE score being the most utilized, recommended by the ESC guidelines) and bleeding risk (CRUSADE score, also recommended by the ESC guidelines). However this is not always helpful because most of the ischemic risk factors are also risk factors for bleeding, and the elderly are often high risk for both. In an ACS setting, the GRACE risk scorehas been extensively validated in the elderly, however, the CRUSADE bleeding score has only a moderate correlation with outcomes in this group. In spite of the overlap between these risk scores, they can be used to guide our approach and course of action, for example for the timing of PCI (percutaneous coronary intervention) (the GRACE score: timing of PCI and management of low ischemic versus moderate to high ischemic risk), and the management of antithrombotic drugs (CRUSADE score: low bleeding versus high bleeding risk). 

Drugs

With regard to medical treatment, identification of those drugs that have the least adverse effects while maintaining optimal efficacy for the elderly is crucial. 

For antiplatelet treatment in elderly patients at low to moderate risk of bleeding (CRUSADE score <41)

The use of lowest-dose aspirin (150-300 mg oral or 75-150 mg i.v. for loading and 75 mg/day maintenance) in association with a P2Y12-i (P2Y12-inhibitor), such as prasugrel (30 mg load and 5 mg maintenance) or ticagrelor (180 mg load and 90 mg twice daily maintenance) is indicated; pre-treatment with P2Y12-i before PCI is controversial in the case of clopidogrel and ticagrelor, and pre-treatment with prasugrel is contraindicated. GPIIb/IIIa-i (glycoprotein IIb/IIIa inhibitors) are to be used if there are bailout/thrombotic complications and should be stopped as soon as possible. We are awaiting the results of the ELDERLY-ACS2 trial, which will compare prasugrel 5 mg vs. clopidogrel 75 mg in the elderly. In those having a CRUSADE score >41, low-dose clopidogrel (300 mg load/75 mg daily), low-dose aspirin (150-300 mg oral or 75-150 mg i.v. loading and 75 mg/day maintenance) should be used. Pre-treatment with P2Y12-i before PCI is not recommended (especially with prasugrel) and GPIIb/IIIa-i use is strictly limited to severe thrombotic complications (calculate drug dosage according to weight and stop as soon as possible if used). Independent of the CRUSADE score, we should add a proton pump inhibitor and avoid the use of non-steroid anti-inflammatory drugs.

The use of fondaparinux 2.5 mg/day (with additional unfractioned heparin (UFH) during PCI) is superior to enoxaparin, but enoxaparin low dose can be considered equally (no bolus followed by 0.75 mg/kg s.c. twice daily). Bivalirudin should be avoided due to discordant data, until further clarification. Drug dosage should be rigorously calculated according to patient’s weight. Anticoagulation can be stopped immediately after PCI (if there is a good angiographic result, no thrombus or thrombus-related complications during PCI), as soon as clinically indicated (symptom-free patient, no arrhythmias, acceptable ejection fraction) or maintained until discharge. If patients already on a vitamin K antagonist, do not administer UFH if international normalized ratio (INR)>2.5 and perform PCI without interruption of the vitamin K antagonist or novel oral anticoagulants; aspirin can be added at its lowest dose, but pre-treatment with P2Y12-i before PCI must be avoided. If the CRUSADE score is > 41, fondaparinux 2.5mg/day should be used (with additional UFH during PCI), bivalirudin should be avoided due to discordant data, rigorous drug dosage according to patient’s weight is mandatory. Anticoagulation should be discontinued immediately after PCI (if there is a good angiographic result, no thrombus or thrombus-related complications during PCI) or as soon as clinically indicated (symptom-free patient, no arrhythmias, acceptable ejection fraction). If patients already on a vitamin K antagonist, do not administer UFH if INR>2, perform PCI without interruption of the vitamin K antagonist or novel oral anticoagulant; aspirin can be added at its lowest dose and pre-treatment with P2Y12-i before PCI must be, again, avoided. Radial approach is the first choice in all patients and especially for those at high bleeding risk.

Conclusion

Treatment of ACS in the elderly remains controversial. In order to have the best outcome for our patients, there is a need for scores that integrate both ischemic and bleeding risk and which should measure the same outcomes: mortality, ischemic events and bleeding events, and at the same time intervals (for example 30 days, 6 months, 1 year, 3 years). In the elderly, these scores must integrate essential additional parameters for this subgroup, such as frailty, functional capacity, cognitive function and comorbidity, which are not included in the current risk scores and will certainly influence decision-making in clinical practice. Further guidance on the importance of frailty in acute cardiac care is soon to be issued by ACVC in a position paper. Medical treatment alone should be favored for those with high bleeding risk, frail and with survival expectancy less than 1 year.