ARTE - Dual versus single antiplatelet therapy after TAVI

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Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following transcatheter aortic valve replacement with a balloon-expandable valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) randomized clinical trial. JACC: Cardiovascular Intervention 2017 [online]

Bottom line: In patients undergoing TAVI with no other indication for anticoagulation or DAPT, 3 months of DAPT increases the risk of major/life-threatening bleeding (number needed to harm 14) versus ASA alone without any apparent benefit.

 

Patients (n=222)

  • Included patients who underwent TAVI (aka TAVR) with Edwards SAPIEN XT or SAPIEN 3 valve (balloon-expandable valve)
  • Excluded patients requiring chronic anticoagulation or dual antiplatelet therapy (DAPT) for other indication, or those who had a major bleed within 3 months before TAVI or any history of intracranial hemorrhage
  • Baseline characteristics
    • Age 79 y
    • Male 58%
    • Indexed AVA 0.4 cm2/m2
    • LVEF 55%
    • Procedural characteristics
      • Femoral approach ~70%
      • SAPIEN XT ~92%, SAPIEN 3 8%
      • Post-TAVI indexed AVA 0.95-1.0 cm2/m2
      • New-onset AF 11%

Interventions

  • I: DAPT - clopidogrel (300 mg/d load <1 day before/after TAVI, then 75 mg/d) x90 days
  • C: ASA monotherapy
  • In both groups, ASA started >24h before TAVI & continued for 6+ months
  • PPI use not reported (though authors report that all patients with GI bleed were receiving a PPI prior to the event)

Results @ 90 days

  • Types of major/life-threatening bleeds in DAPT group (all occurred in first 30 days): GI bleed (5), peri-operative or access-site bleed (annular rupture, femoral hematoma; 7)

 

Generalizability

  • This trial represents elderly patients undergoing TAVI with moderate-high risk of peri-operative mortality
    • Although the results of this trial do not apply to those requiring anticoagulation, we would expect an even greater increase in serious bleeds when adding DAPT to an oral anticoagulant
  • These results with the SAPIEN valves are also likely generalizable to self-expanding valves (Medtronic's CoreValve line)

Internal validity

  • Unclear risk of allocation bias (allocation concealment not adequately described)
  • High risk of performance & detection bias (no blinding to treatment)
  • Stopped prematurely due to slow enrolment + loss of funding

 

Other studies

  • Results from our systematic review of 4 small studies (2 RCTs & 2 cohorts) were consistent with the ARTE trial; DAPT increased the risk of bleeding events without significantly reducing stroke or other ischemic events
  • Notably, none of the studies - alone or in combination - have sufficient power to evaluate the efficacy of DAPT in this setting, though it is likely that the severity and magnitude of harm from bleeds related to DAPT likely exceeds any possible benefit in this patient population
  • Therefore, the existing evidence does not support routine use of DAPT in patients undergoing TAVI