Disclosures: Qamar reports receiving institutional grant support from NorthShore Auxiliary Research Scholar Fund, NorthShore CardioDiabetes Pilot Grant and Novo Nordisk; and fees for educational activities from the American College of Cardiology, the Clinical Exercise Physiology Association, Janssen, Medscape, Pfizer, the Society for Cardiovascular Angiography and Interventions and the Society for Vascular Medicine. Please see the study for all other authors’ relevant financial disclosures.
March 30, 2022
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P2Y12 inhibitors may be superior to aspirin for secondary CVD prevention

Disclosures: Qamar reports receiving institutional grant support from NorthShore Auxiliary Research Scholar Fund, NorthShore CardioDiabetes Pilot Grant and Novo Nordisk; and fees for educational activities from the American College of Cardiology, the Clinical Exercise Physiology Association, Janssen, Medscape, Pfizer, the Society for Cardiovascular Angiography and Interventions and the Society for Vascular Medicine. Please see the study for all other authors’ relevant financial disclosures.
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In patients requiring secondary CVD prevention, P2Y12 inhibitor monotherapy conferred reduced risk for major adverse CV events compared with aspirin monotherapy without raising risk for bleeding, researchers reported.

The researchers conducted a meta-analysis of nine trials — five comparing clopidogrel with aspirin and four comparing ticagrelor (Brilinta, AstraZeneca) with aspirin — including 61,623 patients with atherosclerotic CVD.

Graphical depiction of source quote presented in the article
Arman Qamar, MD, MPH, interventional cardiologist and auxiliary research scholar at NorthShore Cardiovascular Institute, NorthShore Health System, Evanston, Illinois.

“Patients with established atherosclerotic cardiovascular disease remain at high risk of thrombotic events throughout their life. Our general practice has been to treat them with intensive antiplatelet therapy like dual antiplatelet therapy in the initial phase following a MI or stenting, for example 1 year, and then switch to aspirin monotherapy lifelong,” Arman Qamar, MD, MPH, interventional cardiologist and auxiliary research scholar at NorthShore Cardiovascular Institute, NorthShore Health System, Evanston, Illinois, told Healio. “Many believe that every patient with atherosclerotic cardiovascular disease should be on aspirin lifelong; however, the safety and benefits of a P2Y12 inhibitor like clopidogrel is less recognized. Aspirin is associated with increased risk of gastrointestinal bleeding from gastric erosions and ulcers. Our study aimed to examine if P2Y12 inhibitor monotherapy was safer and better than aspirin monotherapy.”

The patients ranged in mean age from 62 to 67 years, and the percentage of women in each trial varied from 15% to 42%.

Thrombotic risk reduced

Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy reduced risk for major adverse CV events — defined in most studies as stroke, MI or death — by 11% (RR = 0.89; 95% CI, 0.84-0.95; I2 = 0%; number needed to treat to prevent one event = 141), and the results did not vary by P2Y12 inhibitor agent (P for interaction = .83), Qamar and colleagues found.

P2Y12 inhibitor monotherapy also reduced risk for MI compared with aspirin monotherapy (RR = 0.81; 95% CI, 0.71-0.92; I2 = 0%; number needed to treat to prevent one event = 273), the researchers wrote.

There were no differences between the groups in risk for stroke, death, major bleeding and any bleeding, according to the researchers.

“Our analysis does suggest that P2Y12 inhibitor monotherapy with medications like clopidogrel are superior to aspirin monotherapy,” Qamar told Healio. “Based on this, clopidogrel should be a preferred agent for long-term secondary CVD prevention. A recent trial called the HOST-EXAM trial, which we have included in our analysis, does support this too.”

Optimal strategy may vary

The optimal strategy for each patient varies, depending on factors, including response to clopidogrel, which some patients are unable to metabolize, Qamar said in an interview.

“We use pharmacogenomics testing to assess for nonresponder status to clopidogrel,” he said. “While the TAILOR PCI trial did not support routine testing of responder status, pooled meta-analyses have suggested that personalized approaches of antiplatelet therapy are associated with lower thrombotic and bleeding risk. For patients who are nonresponders to clopidogrel and have high thrombotic risk, prasugrel (which is generic and cheap) or ticagrelor should be considered, and in those at low thrombotic risk, aspirin is reasonable.”

He also said, “Since no recent trials in the U.S. have examined this on our population, it would be helpful to design a pragmatic electronic health records-based open-label randomized clinical trial to study this in the U.S.”

For more information:

Arman Qamar, MD, MPH, can be reached at aqamar@northshore.org; Twitter: @aqamarmd.