From the Guidelines
For elderly patients with Acute Coronary Syndrome (ACS), no specific dose adjustments are required for clopidogrel (Plavix) or ticagrelor (Brilinta) based on age alone, as per the most recent guidelines from 2025 1. The standard dosing regimens should be maintained: clopidogrel 300-600 mg loading dose followed by 75 mg daily maintenance, and ticagrelor 180 mg loading dose followed by 90 mg twice daily maintenance. However, clinical assessment is essential as elderly patients often have reduced renal function, lower body weight, and increased bleeding risk. For patients over 75 years with ACS undergoing PCI, some clinicians consider using a lower clopidogrel loading dose (e.g., 300 mg instead of 600 mg) to reduce bleeding risk, as suggested by the TRITON-TIMI 38 trial analysis 1. For ticagrelor, no dose adjustment is needed for elderly patients, but closer monitoring for bleeding complications is recommended. In patients with severe renal impairment (CrCl <30 mL/min), caution is advised with both medications. The benefit of dual antiplatelet therapy in preventing thrombotic events must be balanced against the increased bleeding risk in elderly patients, with regular assessment of this risk-benefit ratio throughout treatment, as emphasized in the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline 1. Concomitant use of proton pump inhibitors should be considered to reduce gastrointestinal bleeding risk in this vulnerable population. Key considerations include:
- Monitoring for signs of bleeding and adjusting the treatment plan as necessary
- Regular assessment of renal function and body weight
- Consideration of alternative antiplatelet therapies if necessary
- Patient education on the importance of adherence to the prescribed treatment regimen and recognition of potential side effects. It is also important to note that the 2025 guidelines 1 provide the most up-to-date recommendations for the management of patients with ACS, and should be consulted for detailed guidance on the use of antiplatelet therapies in this population.
From the Research
Dosing Adjustments for Clopidogrel and Ticagrelor in Elderly Patients with ACS
- The dosing adjustments for clopidogrel and ticagrelor in elderly patients with Acute Coronary Syndrome (ACS) are crucial to balance the risk of bleeding and ischemic events 2, 3, 4, 5, 6.
- Studies have shown that ticagrelor may be more effective than clopidogrel in reducing cardiovascular death and all-cause mortality in elderly patients with ACS, but it may also increase the risk of bleeding 2, 3, 4.
- The PLATO trial found that the clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years and those <75 years, with respect to the composite of cardiovascular death, myocardial infarction, or stroke 4.
- A meta-analysis found that ticagrelor reduced all-cause mortality and cardiovascular death in elderly patients with ACS, but increased the risk of bleeding 3.
- Another study found that in elderly patients carrying CYP2C19 loss-of-function variants, ticagrelor was associated with a higher risk of bleeding and similar ischemic events compared to clopidogrel 5.
- A real-world registry study found that clopidogrel and ticagrelor had comparable net clinical benefits in patients with ACS aged ≥65 years, with clopidogrel associated with a significantly lower risk of major bleeding 6.
Key Findings
- Ticagrelor may be more effective than clopidogrel in reducing cardiovascular death and all-cause mortality in elderly patients with ACS.
- Ticagrelor may increase the risk of bleeding in elderly patients with ACS.
- The clinical benefit of ticagrelor over clopidogrel is not significantly different between patients aged ≥75 years and those <75 years.
- Clopidogrel may be an effective alternative to ticagrelor in older patients with ACS, with a lower risk of major bleeding.
Considerations for Dosing Adjustments
- Elderly patients with ACS should be carefully evaluated for their risk of bleeding and ischemic events when considering dosing adjustments for clopidogrel and ticagrelor 2, 3, 4, 5, 6.
- The choice of P2Y12 inhibitor should be individualized based on the patient's clinical characteristics, including age, renal function, and bleeding risk 2, 3, 4, 5, 6.