Deescalation From Ticagrelor to Clopidogrel for Myocardial Infarction With Chronic Kidney Disease: A Secondary
Sang Hyun Kim1,2, Kwan Yong Lee1,3, Jaeho Byeon4
1Division of Cardiology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Insights
De-escalating dual antiplatelet therapy from ticagrelor to clopidogrel in patients with chronic kidney disease (CKD) after acute myocardial infarction (AMI) significantly reduced bleeding events without increasing ischemic risks.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic kidney disease (CKD) increases risks of ischemic and bleeding complications after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).
- Optimizing dual antiplatelet therapy (DAPT) is crucial for managing these risks.
Purpose of the Study:
- To assess if an 11-month de-escalation strategy from ticagrelor to clopidogrel reduces bleeding without raising ischemic events in stabilized CKD patients post-AMI.
- This is a secondary analysis of the TALOS-AMI trial.
Main Methods:
- Post hoc analysis of the TALOS-AMI randomized clinical trial involving 305 patients with CKD.
- Patients received 1 month of ticagrelor-based DAPT post-PCI, then were randomized to continue ticagrelor or switch to clopidogrel for 11 months.
- Primary endpoint: composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding.
Main Results:
- Patients with CKD had higher ischemic event risk than those without.
- De-escalation to clopidogrel in CKD patients was associated with reduced primary endpoint events (6.2% vs 13.1%) and BARC 2, 3, or 5 bleeding (2.5% vs 8.3%).
- No significant increase in ischemic events was observed with de-escalation (4.4% vs 5.5%).
Conclusions:
- De-escalation from ticagrelor to clopidogrel at 1 month post-PCI for AMI is linked to decreased bleeding risk in CKD patients.
- This strategy did not elevate the risk of ischemic events.
- Further research with larger sample sizes is warranted to confirm these findings.
Importance:
Chronic kidney disease (CKD) is a significant risk factor for both ischemic and bleeding complications following percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Optimizing dual antiplatelet therapy (DAPT) is essential for improving clinical outcomes.
Objective:
To evaluate whether an 11-month, unguided deescalation strategy from ticagrelor to clopidogrel was associated with reduced bleeding without an increase in ischemic events in stabilized patients with CKD after AMI.
Design, Setting, And Participants:
This was a post hoc secondary analysis of the multicenter, open-label, Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) randomized clinical trial conducted at 32 major cardiac centers in South Korea. Patients with biomarker-positive AMI who tolerated 1 month of ticagrelor-based DAPT after PCI were included in the trial. Patient enrollment occurred from February 2014 to December 2018, with follow-up at 30 days and 3, 6, and 12 months after PCI. The present analysis focused on the subgroup of patients with CKD (estimated glomerular filtration rate [eGFR]<60 mL/min/1.73 m2). Data analyses were performed from July 2023 to October 2024.
Interventions:
In the TALOS-AMI trial, patients were randomized 1:1 to continue ticagrelor (active control group) or switch to clopidogrel (deescalation group) for 11 months after PCI.
Main Outcomes And Measures:
The primary end point was a composite of death from cardiovascular disease, myocardial infarction, stroke, and bleeding (Bleeding Academic Research Consortium [BARC] types 2, 3, or 5).
Results:
Of 2646 patients included in the trial, 305 had CKD (11.5%; mean [SD] age, 67.2 [11.4] years; 223 males [73.1%]; mean [SD] eGFR, 49.7 [9.5] mL/min/1.73 m2) and 2341 did not have CKD (1975 male [84.4%]; mean [SD] age, 59.0 [11.0] years). Patients with CKD had an increased risk of ischemic events compared with patients without CKD (hazard ratio [HR], 2.47; 95% CI, 1.38-4.42; P = .002), but there was no difference in bleeding risk (HR, 1.36; 95% CI, 0.80-2.31; P = .26). Among patients with CKD, deescalation (n = 160) vs active control (n = 145) was associated with reduced risks of the primary end point (10 patients [6.2%] vs 19 [13.1%]; HR, 0.45 [95% CI, 0.21-0.98]; P = .04) and BARC 2, 3, or 5 bleeding (4 patients [2.5%] vs 12 [8.3%]; HR, 0.29 [95% CI, 0.09-0.89]; P = .03). No increased risk of ischemic events was observed following deescalation (7 patients [4.4%] vs 8 [5.5%]; HR, 0.78 [95% CI, 0.28-2.16]; P = .64).
Conclusions And Relevance:
In this secondary analysis of a randomized clinical trial, deescalation from ticagrelor to clopidogrel at 1 month after PCI for AMI was associated with significant reduction in bleeding without increased risk of ischemic events among study-eligible patients with CKD. Further adequately powered studies are needed to validate these findings.
Related Concept Videos
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:33Hormonal Regulation
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...