Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Abstract

*These members of the Evidence Review Committee are listed alphabetically, and all participated equally in the process. Members reported no relationships with industry and other entities relevant to this report. Background:The optimal duration of dual antiplatelet therapy (DAPT) after implantation of newer-generation drug-eluting stents (DES) remains uncertain. Similarly, questions remain about the role of DAPT in long-term therapy of stable post-myocardial infarction (MI) patients. aim:Our objective was to compare the incidence of death, major hemorrhage, MI, stent thrombosis, and major adverse cardiac events in patients randomized to prolonged or short-course DAPT after implantation of newer-generation DES and in secondary prevention after MI. methods:We used traditional frequentist statistical and Bayesian approaches to address the following questions: Q1) What is the minimum duration of DAPT required after DES implantation? Q2) What is the clinical benefit of prolonging DAPT up to 18 to 48 months? Q3) What is the clinical effect of DAPT in stable patients who are >1 year past an MI? results: We reviewed evidence from 11 randomized controlled trials (RCTs) that enrolled 33 051 patients who received predominantly newer-generation DES to answer: A1) Use of DAPT for 12 months, as compared with use for 3 to 6 months, resulted in no significant differences in incidence of death (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.85 to 1.63), major hemorrhage (OR: 1.65; 95% CI: 0.97 to 2.82), MI (OR: 0.87; 95% CI: 0.65 to 1.18), or stent thrombosis (OR: 0.87; 95% CI: 0.49 to 1.55). Bayesian models confirmed the primary analysis. A2) 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 (OR: 1.14; 95% CI: 0.92 to 1.42) but was associated with increased major hemorrhage (OR: 1.58; 95% CI: 1.20 to 2.09), decreased MI (OR: 0.67; 95% CI: 0.47 to 0.95), and decreased stent thrombosis (OR: 0.45; 95% CI: 0.24 to 0.74). A risk-benefit analysis found 3 fewer stent thromboses (95% CI: 2 to 5) and 6 fewer MIs (95% CI: 2 to 11) but 5 more major bleeds (95% CI: 3 to 9) per 1000 patients treated with prolonged DAPT per year. Post hoc analyses provided weak evidence of increased mortality with prolonged DAPT. We reviewed evidence from 1 RCT of 21 162 patients and a post hoc analysis of 1 RCT of 15 603 patients to answer: A3): Use of DAPT >1 year after MI reduced the composite risk of cardiovascular death, MI, or stroke (hazard ratio: 0.84; 95% CI: 0.74 to 0.95) but increased major bleeding (hazard ratio: 2.32; 95% CI: 1.68 to 3.21). A meta-analysis and a post hoc analysis of an RCT in patients with stable cardiovascular disease produced similar findings. conclusions: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 ...

Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N‐oxide‐generating pathway, modulates platelet responsiveness and thrombosis risk

“…reviewed in ), and it is the acute thrombotic event that precipitates a myocardial infarction, stroke or often sudden cardiac death . Despite their many benefits, antiplatelet agents, including low‐dose aspirin, are limited by their tendency to foster unwanted bleeding events . Thus, there is a compelling need to optimize CVD event reduction without accompanying untoward bleeding complications.…”

Outcomes of ≤6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation

“…Moreover, a recently published meta-analysis which analyzed 12-month versus prolonged DAPT duration. [11] The authors reported that continuation of DAPT beyond 1 year was not associated with lower risk of ST, lower rates of major adverse CV, and cerebrovascular events, but did confer a higher bleeding risk. Our meta-regression analysis reflects the aforementioned findings, with a significant association between bleeding and non-CV mortality with 12-month DAPT, results also consistent with the findings of the DAPT trial [28] where bleeding events were related to trauma and cancer causes, in addition to the significant association between ST and MI, as well as mortality with short-term DAPT.…”

“…[8] Other previously published meta-analyses included fewer RCTs. [9–11] An updated meta-analysis evaluating the risks and benefits of DAPT for ≤6 months compared with the exact time point of 12 months is lacking. Our aim was to undertake a systematic review and meta-analysis of RCTs evaluating efficacy and safety of ≤6-month compared with 12-month DAPT after PCI with DES implantation.…”

Recommendations for the use of bioresorbable vascular scaffolds in percutaneous coronary interventions

“…The PEGASUS study concluded that ticagrelor significantly reduced the risk of MACE as compared with placebo. Recently, two meta-analyses [36, 37] showed that DAPT beyond 1 year among stabilised high-risk patients with prior MI decreased ischaemic events at the cost of an increase in major bleeding. Udell et al.…”