TWILIGHT sub-study: complex PCI patients

New data from a post-hoc analysis of the TWILIGHT trial showed that, in patients who underwent a complex percutaneous coronary intervention (PCI) , ticagrelor monotherapy after an initial 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin was associated with significantly lower clinically relevant bleeding without increasing the risk of ischaemic events compared with continuing the DAPT. The TWILIGHT-COMPLEX sub-study was presented by Prof. George Dangas (Icahn School of Medicine at Mount Sinai, USA) and published simultaneously [1,2].

The original randomised, double-blind, placebo-controlled TWILIGHT trial recently determined that dropping aspirin after 3 months of DAPT with ticagrelor following PCI is associated with lower rates of bleeding but no increased risk of death, myocardial infarction (MI), or stroke [3]. The aim of this sub-study was to evaluate the effect of ticagrelor monotherapy versus ticagrelor + aspirin in patients undergoing complex PCI, defined as a combination of high-risk angiographic and procedural features.

Of the original 9,006 participants in the original TWILIGHT trial, investigators considered 2,342 (33%) as requiring complex PCI. Complex PCI was defined as 3 or more lesions or vessels treated, total stent length greater than 60 mm, bifurcation with 2 stents implanted, atherectomy device use, left main PCI, surgical bypass graft, or chronic total occlusion as target lesions.

All participants underwent 1:1 randomisation to either ticagrelor + placebo or to ticagrelor + aspirin and had a 1-year follow-up. All patients received aspirin before randomisation for the first 3 months following PCI. Like the TWILIGHT trial, the primary endpoint of this post-hoc analysis was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding, and investigators also assessed for a composite ischaemic endpoint of all-cause death, MI, or stroke.

Of the 2,342 patients who had had complex PCI, 1,158 were randomised to ticagrelor + placebo and 1,184 were randomised to ticagrelor + aspirin. Ticagrelor + placebo resulted in significantly lower rates of BARC type 2, 3, or 5 bleeding than ticagrelor + aspirin: 4.2% versus 7.7%, respectively (HR 0.54; 95% CI 0.38-0.76; P<0.001). BARC type 3 or 5 bleeding was also significantly reduced with ticagrelor + placebo (1.1%) compared with ticagrelor + aspirin (2.6%; HR 0.41; 95% CI 0.21-0.80; P=0.009).

This subgroup was not powered to assess differences in ischaemic outcomes between the 2 groups with results of death, MI, or stroke (3.8% vs 4.9%; HR 0.77; 95% CI 0.52-1.15) as well as cardiovascular death, MI, or stroke (3.6% vs 4.8%; HR 0.75; 95% CI 0.50-1.12). There were also no significant differences in all-cause deaths between groups (0.9% vs 1.5%; HR 0.59; 95% CI 0.27-1.29; see Table). In conclusion, this subset analysis established that withdrawing aspirin after complex PCI reduced bleeding.

Table. Bleeding and ischaemic events 1 year after randomisation. Modified from [2]

BARC, Bleeding Academic Research Consortium; CI, confidence interval; GUSTO, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries; ISTH, International Society on Thrombosis and Haemostasis; MI, myocardial infarction; TIMI, Thrombolysis In Myocardial Infarction.

 

1. Dangas GD, et al. Abstract 410-10.ACC/WCC 28-30 March 2020.
2. Dangas G, et al. J Am Coll Cardiol. 2020. DOI:10.1016/j.jacc.2020.03.011.
3. Mehran R, et al. N Engl J Med. 2019;381(21):2032-2042.

 

Posted on 8 September, 20205 November, 2020