From the Guidelines
The DECLARE-TIMI 58 study is not directly referenced in the provided evidence, however, based on the available information, the optimal duration of dual antiplatelet therapy (DAPT) after implantation of newer-generation drug-eluting stents (DES) remains uncertain. The study referenced 1 provides evidence on the duration of DAPT, which can be applied to the analysis of the DECLARE-TIMI 58 study.
Key Findings
- The study 1 reviewed evidence from 11 randomized controlled trials (RCTs) that enrolled 33,051 patients who received predominantly newer-generation DES.
- The results showed that use of DAPT for 12 months, as compared with use for 3 to 6 months, resulted in no significant differences in incidence of death, major hemorrhage, MI, or stent thrombosis.
- Use of DAPT for 18 to 48 months, compared with use for 6 to 12 months, was associated with no difference in incidence of all-cause death but was associated with increased major hemorrhage, decreased MI, and decreased stent thrombosis.
Clinical Implications
- The primary analysis provides moderately strong evidence that prolonged DAPT after implantation of newer-generation DES entails a tradeoff between reductions in stent thrombosis and MI and increases in major hemorrhage.
- Secondary analyses provide weak evidence of increased mortality with prolonged DAPT after DES implantation.
- In patients whose coronary thrombotic risk was defined by a prior MI rather than by DES implantation, the primary analysis provides moderately strong evidence of reduced cardiovascular events at the expense of increased bleeding, as seen in the study 1.
Recommendation
Based on the available evidence, the decision to extend DAPT should be individualized, taking into account the patient's risk of ischemic and bleeding events, as suggested by the study 1. This approach allows for personalized treatment strategies that balance the benefits and risks of prolonged DAPT.
From the Research
Study Overview
- The DECLARE-TIMI 58 study is a randomized, double-blind, placebo-controlled trial that evaluated the cardiovascular safety and efficacy of dapagliflozin in patients with type 2 diabetes mellitus (T2DM) 2.
- The study included 17,160 patients with T2DM and a history of either established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD 2.
Primary Outcomes
- The primary safety outcome was the time to the first event of the composite of cardiovascular death, myocardial infarction, or ischemic stroke (major adverse cardiovascular events; MACEs) 2.
- The co-primary efficacy outcomes were the composite of cardiovascular death, myocardial infarction, or ischemic stroke and the composite of cardiovascular death or hospitalization for heart failure 2.
Key Findings
- Dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6% in patients with previous myocardial infarction (MI) 3.
- Dapagliflozin appeared to robustly reduce the risk of both composite outcomes in patients with T2DM and previous MI 3.
- The beneficial effects of dapagliflozin on hospitalization for heart failure and renal outcomes were consistent across all baseline systolic blood pressure categories 4.
Subgroup Analysis
- Patients with T2DM and previous MI are at high risk of MACE and cardiovascular death/hospitalization for heart failure, and dapagliflozin appears to reduce the risk of both composite outcomes in these patients 3.
- Dapagliflozin has a strong protective effect in patients with AMI of advanced age with concomitant diabetes or those who are not on angiotensin receptor enkephalinase inhibitors 5.
Safety and Tolerability
- No safety concerns were identified in the study, and the rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance 6.
- Events of volume depletion, amputation, and acute kidney injury did not differ with dapagliflozin overall or within any baseline systolic blood pressure group 4.