Monotherapy with P2Y12 in Complex Interventions: Less and Less Risky

 Monotherapy in patients with complex angioplasty: meta-analysis of 5 randomized studies. 

Even though prolonged dual antiplatelet therapy (DAPT) might reduce the risk of important ischemic complications, this reduction will come at the expense of a significant increase of bleeding risk, which makes us reassess the cost benefit ratio of this decision. This is also why guidelines recommend choosing a strategy on a case by case basis. 

Monoterapia con P2Y12 en intervenciones complejas

When opting for a short DAPT period after stenting, with de-escalation followed by P2Y12 inhibitor monotherapy, might there be atherothrombotic effects? 

Gragnano et al, looked into individual patient data (IPD) from randomized studies included in the meta-analysis Sidney-2 Collaboration, aiming at comparing P2Y12 inhibitor monotherapy (after one or 3 month DAPT) vs the standard treatment, both in simple and complex PCI (3 vessels, ≥3 implanted stents, ≥3 treated lesions, stent length ≥60mm, bifurcations with 2 stents, and chronic total occlusions). 

Efficacy primary end point was a composite of all cause death, MI and stroke. Safety end point was BARC bleeding 3 or 5. Secondary end points included individual primary end points plus cardiovascular mortality, ischemic or bleeding stroke, stent thrombosis and net adverse events. (NACE).

Read also: Is Using Drug-Eluting Balloons and Single Antiplatlelet Therapy Safe for Patients at High Risk for Bleeding Who Undergo Percutaneous Coronary Intervention?

The total cohort included 22941 patients from 5 studies (GLASSY, SMART-CHOICE, STOPDAPT-2, TICO and TWILIGHT), 20.4% received a complex PCI. Mean age was 64.9, patients with complex intervention were mostly men, diabetic and more frequently presented non ST elevation MI.

Efficacy end point according to treatment and complexity, saw non-significant reduction of events with monotherapy in the complex group, with HR 0.87 (CI 95% 0.64-1.19; P=0.379), and HR 0.91 (CI 95%, 0.76-1.09; P=0.299) in non-complex group. 

When looking at safety events, we saw a significant difference in favor of monotherapy in the same group (HR 0.51, CI 95% 0.31-0.84; P=0.008), as well as in non-complex interventions (HR 0.49, CI 95% 0.37-0.64; P≤0.001). looking at events rate and NACE, we saw 0.73 HR (CI 95% 0.56-0.95; P=0.021) in favor of short DAPT, with similar impact in non-complex lesions. 

Read also: Uncomplicated Type B Aortic Dissection.

These benefits were consistent across pre-specified subgroups, such as the use of clopidogrel vs. Other antiaggregants as in stratification according to clinical presentation.


P2Y12 inhibitor monotherapy was associated with similar rates of ischemic events compared against standard DAPT regardless PCI complexity. It also reduced the risk of major bleeding compared and NACE similarly in complex and non-complex procedures. This allow us to consider the benefit of short P2Y12 inhibitor treatments event in complex scenarios that we did not used to consider. 

Dr. Omar Tupayachi

Dr. Omar Tupayachi.
Member of the editorial board of

Original Title: P2Y12 Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions.

Reference: Gragnano F, Mehran R, Branca M, et al. P2Y12 Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions. J Am Coll Cardiol. 2023 Feb, 81 (6) 537–552.

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