In the Journals

Ticagrelor monotherapy similar to DAPT regimen 2 years after stenting

Confirming previously presented results, ticagrelor monotherapy after 1 month of dual antiplatelet therapy was similar to a standard DAPT regimen for the prevention of ischemic events without differences in bleeding following drug-eluting coronary stenting.

According to findings from the GLASSY study published in the Journal of the American College of Cardiology, which were presented at the American College of Cardiology Scientific Session in March, 7.14% of patients in the experimental group and 8.41% of patients in the conventional group reached the 2-year coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke or urgent target vessel revascularization (RR = 0.85; 95% CI, 0.72-0.99). GLASSY was a prespecified ancillary study from the GLOBAL LEADERS trial.

The experimental treatment was noninferior (P for noninferiority < .001), but not superior (P = .0465) to conventional treatment for the prevention of ischemic events after stenting.

Moreover, a time-dependent effect was observed with the experimental treatment conferring a lower risk for MI (RR = 0.54; 95% CI, 0.33-0.88; P for interaction = .062) and stent thrombosis (RR = 0.14; 95% CI, 0.03-0.63; P for interaction = .007) 1 year post-PCI.

New evidence

“Our results provide new evidence that discontinuation of aspirin after 30 days while continuing ticagrelor alone does not expose patients to a higher ischemic risk compared with a standard DAPT regimen for 1 year and may have a favorable impact on the rates of MI and stent thrombosis compared with aspirin alone,” Anna Franzone, MD, PhD, of the department of advanced biomedical sciences at the Federico II University of Naples, Italy, and colleagues wrote. “Importantly, these findings are unique to our current study and were not observed within the parent trial despite the larger sample size.”

In other findings, Bleeding Academic Research Consortium type 3 or 5 bleeding, the rates of Bleeding Academic Research Consortium type 3 or 5 bleeding did not differ between the experimental and conventional groups (RR = 1; 95% CI, 0.75-1.33).

“[BARC-defined major bleeding tended to occur more frequently as ascertained by a central adjudication process, yet event rates were similar in the 2 study arms,” the researchers wrote. “We also found, [that] bleeding events in the second year of follow-up, that did not fulfill major BARC criteria, were roughly twofold higher with ticagrelor compared with aspirin monotherapy. These observations highlight the trade-off between benefit and risk with antithrombotic agents and should be interpreted in the context of the comparative prognostic implications for mortality of nonfatal ischemic versus major or nonmajor bleeding episodes in the secondary prevention setting.”

Using data from GLOBAL LEADERS, which compared two forms of antiplatelet therapy after stent implantation, researchers compared patients (n = 7,585; mean age, 65 years; 24% women; mean BMI, 28 kg/m2; 24% with diabetes) who underwent ticagrelor monotherapy (Brilinta, AstraZeneca) after 1-month DAPT and those who received DAPT for 11 months followed by aspirin alone with the aim of assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment.

Intriguing therapeutic strategy

“At present, ticagrelor monotherapy after PCI remains an intriguing therapeutic strategy that requires confirmation in a large cohort of patients before widespread clinical adoption,” Roxana Mehran, MD, professor of medicine and director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Wiener Cardiovascular Institute at Icahn School of Medicine at Mount Sinai, and colleagues wrote in a related editorial. “Despite encouraging signals that certain subjects could benefit from such a regimen, the clinical implications of ticagrelor monotherapy are far from being settled, and the ‘glass’ remains half empty.” – by Scott Buzby

Disclosures: The GLOBAL LEADERS study was sponsored by the European Cardiovascular Research Institute with grants from AstraZeneca, Biosensors and The Medicines Company. Franzone reports no relevant financial disclosures. Mehran reports she has financial ties with multiple pharmaceutical and device companies, including AstraZeneca. Please see the study and editorial for the other authors’ relevant financial disclosures.

Confirming previously presented results, ticagrelor monotherapy after 1 month of dual antiplatelet therapy was similar to a standard DAPT regimen for the prevention of ischemic events without differences in bleeding following drug-eluting coronary stenting.

According to findings from the GLASSY study published in the Journal of the American College of Cardiology, which were presented at the American College of Cardiology Scientific Session in March, 7.14% of patients in the experimental group and 8.41% of patients in the conventional group reached the 2-year coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke or urgent target vessel revascularization (RR = 0.85; 95% CI, 0.72-0.99). GLASSY was a prespecified ancillary study from the GLOBAL LEADERS trial.

The experimental treatment was noninferior (P for noninferiority < .001), but not superior (P = .0465) to conventional treatment for the prevention of ischemic events after stenting.

Moreover, a time-dependent effect was observed with the experimental treatment conferring a lower risk for MI (RR = 0.54; 95% CI, 0.33-0.88; P for interaction = .062) and stent thrombosis (RR = 0.14; 95% CI, 0.03-0.63; P for interaction = .007) 1 year post-PCI.

New evidence

“Our results provide new evidence that discontinuation of aspirin after 30 days while continuing ticagrelor alone does not expose patients to a higher ischemic risk compared with a standard DAPT regimen for 1 year and may have a favorable impact on the rates of MI and stent thrombosis compared with aspirin alone,” Anna Franzone, MD, PhD, of the department of advanced biomedical sciences at the Federico II University of Naples, Italy, and colleagues wrote. “Importantly, these findings are unique to our current study and were not observed within the parent trial despite the larger sample size.”

In other findings, Bleeding Academic Research Consortium type 3 or 5 bleeding, the rates of Bleeding Academic Research Consortium type 3 or 5 bleeding did not differ between the experimental and conventional groups (RR = 1; 95% CI, 0.75-1.33).

“[BARC-defined major bleeding tended to occur more frequently as ascertained by a central adjudication process, yet event rates were similar in the 2 study arms,” the researchers wrote. “We also found, [that] bleeding events in the second year of follow-up, that did not fulfill major BARC criteria, were roughly twofold higher with ticagrelor compared with aspirin monotherapy. These observations highlight the trade-off between benefit and risk with antithrombotic agents and should be interpreted in the context of the comparative prognostic implications for mortality of nonfatal ischemic versus major or nonmajor bleeding episodes in the secondary prevention setting.”

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Using data from GLOBAL LEADERS, which compared two forms of antiplatelet therapy after stent implantation, researchers compared patients (n = 7,585; mean age, 65 years; 24% women; mean BMI, 28 kg/m2; 24% with diabetes) who underwent ticagrelor monotherapy (Brilinta, AstraZeneca) after 1-month DAPT and those who received DAPT for 11 months followed by aspirin alone with the aim of assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment.

Intriguing therapeutic strategy

“At present, ticagrelor monotherapy after PCI remains an intriguing therapeutic strategy that requires confirmation in a large cohort of patients before widespread clinical adoption,” Roxana Mehran, MD, professor of medicine and director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Wiener Cardiovascular Institute at Icahn School of Medicine at Mount Sinai, and colleagues wrote in a related editorial. “Despite encouraging signals that certain subjects could benefit from such a regimen, the clinical implications of ticagrelor monotherapy are far from being settled, and the ‘glass’ remains half empty.” – by Scott Buzby

Disclosures: The GLOBAL LEADERS study was sponsored by the European Cardiovascular Research Institute with grants from AstraZeneca, Biosensors and The Medicines Company. Franzone reports no relevant financial disclosures. Mehran reports she has financial ties with multiple pharmaceutical and device companies, including AstraZeneca. Please see the study and editorial for the other authors’ relevant financial disclosures.