Short-vs Long-Term DAPT After Drug-Eluting Stent Implantation
Background Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE).
Objectives This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis.
Methods Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis).
Results Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT.
Conclusions Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement.
The optimal duration of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor after drug-eluting stent(s) (DES) implantation remains a matter of debate. Despite demonstration of improved efficacy, first-generation sirolimus-eluting stents and paclitaxel-eluting stent(s) (PES) result in greater rates of very late stent thrombosis (ST) and adverse cardiac events compared with bare-metal stents. Based on pathological findings showing delayed arterial endothelialization after sirolimus-eluting stents and PES implantation, as well as clinical retrospective studies suggesting higher rates of ST with first-generation DES versus bare-metal stents at time of DAPT discontinuation, the American College of Cardiology/American Heart Association guidelines extended the duration of DAPT from 3 months after sirolimuseluting stents and 6 months after PES placement (per randomized clinical trials [RCT]) to at least 1 year. Thus, 1 year of DAPT has become the standard of care worldwide for patients receiving DES, irrespective of DES type and despite the absence of evidence-based RCT results.
Because prolonged DAPT is associated with increased bleeding and health care costs, establishing optimal DAPT duration is of paramount importance. Yet observational studies have been inconsistent; some reports suggest increased rates of adverse events in patients with premature DAPT discontinuation, whereas others refute this association. Recently, several RCTs failed to show any benefit of prolonging DAPT (≥1 year) versus a shorter course, challenging the notion that 1 year of DAPT is necessary after DES implantation. However, given the low frequency of adverse events after DAPT discontinuation, all of these studies were insufficiently powered to detect modest but clinically meaningful differences in ischemic outcomes. For this reason, we performed an individual patient data metaanalysis of RCTs investigating the safety and efficacy of shortening DAPT to <1 year post-DES implantation.
Abstract and Introduction
Abstract
Background Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE).
Objectives This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis.
Methods Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis).
Results Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT.
Conclusions Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement.
Introduction
The optimal duration of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor after drug-eluting stent(s) (DES) implantation remains a matter of debate. Despite demonstration of improved efficacy, first-generation sirolimus-eluting stents and paclitaxel-eluting stent(s) (PES) result in greater rates of very late stent thrombosis (ST) and adverse cardiac events compared with bare-metal stents. Based on pathological findings showing delayed arterial endothelialization after sirolimus-eluting stents and PES implantation, as well as clinical retrospective studies suggesting higher rates of ST with first-generation DES versus bare-metal stents at time of DAPT discontinuation, the American College of Cardiology/American Heart Association guidelines extended the duration of DAPT from 3 months after sirolimuseluting stents and 6 months after PES placement (per randomized clinical trials [RCT]) to at least 1 year. Thus, 1 year of DAPT has become the standard of care worldwide for patients receiving DES, irrespective of DES type and despite the absence of evidence-based RCT results.
Because prolonged DAPT is associated with increased bleeding and health care costs, establishing optimal DAPT duration is of paramount importance. Yet observational studies have been inconsistent; some reports suggest increased rates of adverse events in patients with premature DAPT discontinuation, whereas others refute this association. Recently, several RCTs failed to show any benefit of prolonging DAPT (≥1 year) versus a shorter course, challenging the notion that 1 year of DAPT is necessary after DES implantation. However, given the low frequency of adverse events after DAPT discontinuation, all of these studies were insufficiently powered to detect modest but clinically meaningful differences in ischemic outcomes. For this reason, we performed an individual patient data metaanalysis of RCTs investigating the safety and efficacy of shortening DAPT to <1 year post-DES implantation.