CAD Location May Influence Need for Prolonged DAPT Post-PCI

Extending dual antiplatelet therapy (DAPT) from 6 months to 2 years after PCI in patients with left main or proximal LAD (LM/pLAD) lumen narrowing provides additional protection against stent thrombosis, according to a subanalysis of the PRODIGY trial published online August 12, 2015, ahead of print in EuroIntervention. Patients without these angiographic characteristics did not derive such benefit from prolonged DAPT.

Thus, the presence of CAD in these coronary segments “may be a treatment modifier with respect to the duration of DAPT,” Marco Valgimigli, MD, PhD, of Erasmus Medical Center (Rotterdam, the Netherlands), and colleagues suggest.

In the main PRODIGY study, published in 2012, prolonged DAPT after stenting not only failed to reduce thrombotic events but doubled the risk of major bleeding.

For the retrospective analysis, researchers looked at a subset of 1,754 patients with (n = 953; 54.3%) and without (n = 801; 45.7%) LM/pLAD lumen narrowing, defined as ≥ 30% on angiography at baseline. Within each group, approximately half of patients had been randomized to 6 months of DAPT and half to 24 months.

LM/pLAD Narrowing Ups Ischemic Risk, Potential for Benefit

Patients in the narrowed LM/pLAD group tended to be older, more frequently have impaired kidney function or a history of PCI, and were less often smokers. They also had more extensive CAD and thus required more complex interventions. In addition, baseline characteristics were well matched between the DAPT duration groups, except for more NSTEMI in the narrowed LM/pLAD cohort allocated to longer antiplatelet therapy.

At 24 months, the combined rate of death, MI, or cerebrovascular accident (CVA) was higher in patients with than in those without LM/pLAD narrowing (11% vs 8.1%; P = .04), driven by a trend toward difference in MI (4.5% vs 2.7%; P = .053). This pattern remained when the 35.2% of LM/pLAD patients who received stents in these coronary segments were excluded from analysis.

However, adjustment for clinical and angiographic imbalances alleviated the difference between patients with vs without LM/pLAD narrowing and those with vs without LM/pLAD stenting (P = .21 and .07, respectively).

Prolonged clopidogrel did not affect the composite endpoint rate regardless of whether patients had LM/pLAD narrowing (P for interaction = .20), although there was a trend toward greater protection against cardiovascular death/MI in the narrowed LM/pLAD group (P for interaction = .056). Additionally, patients with narrowing had a lower cumulative rate of definite, probable, or possible stent thrombosis with 24 months compared with 6 months of DAPT, while patients who lacked LM/pLAD narrowing showed the opposite pattern (P for interaction = .002; table 1).

Bleeding (BARC 3 or 5 and 2, 3, or 5) was higher for patients receiving 24 months of DAPT, no matter the location of their CAD.

Mechanism Unclear

According to the authors, pLAD and LM arteries provide 45-55% and 84-100% of blood flow to the left ventricle, respectively. As such, “ischemic events occurring in these segments are more often fatal,” they say. “Coronary revascularization of significant LM/pLAD stenosis [has] demonstrated a longterm survival benefit compared with medical therapy alone, whereas the clinical implication of nonsignificant lesions in these segments, especially in stable [CAD] patients, is unclear.”

One explanation for the increased risk of recurrent ischemia—and greater effect of 24-month DAPT—seen for patients with LM/pLAD narrowing “could be the higher clinical and angiographic risk characteristics noted in these patients at baseline,” Dr. Valgimigli and colleagues propose. “This is consistent with previous studies which observed an additional benefit of a more potent antiplatelet therapy in patients at higher ischemic risk.

“As an alternative, not mutually exclusive, hypothesis, LM/pLAD location of the atherosclerotic plaques per se may be a driver for the greater ischemic risk,” they add, noting that imaging studies suggest these plaques are more prone to rupture.

Irrespective of the exact mechanism, CAD “in these segments carries a higher risk of ischemic events, and patients fulfilling these angiographic characteristics seem to benefit from a prolonged duration of [DAPT],” the researchers conclude.

Source: 
Costa F, Adamo M, Ariotti S, et al. Left main or proximal left anterior descending coronary artery disease location identifies high-risk patients deriving potentially greater benefit from prolonged dual antiplatelet therapy duration. EuroIntervention. 2015;Epub ahead of print.

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