The Year in Cardiology 2014: Coronary Intervention
The Year in Cardiology 2014: Coronary Intervention
Clopidogrel remains the preferred P2Y12 inhibitor for patients undergoing PCI for stable angina. For non-ST-elevation ACS patients, prasugrel can be used for clopidogrel naive patients scheduled for PCI, whereas ticagrelor can be used for all patients regardless of the treatment strategy. For STEMI patients undergoing PCI, either prasugrel or ticagrelor can be used. The ATLANTIC trial has shown that pre-hospital compared with in-hospital (a median time of only 31 min later then pre-hospital) administration of ticagrelor in patients with STEMI does not improve pre-PCI coronary reperfusion, but it does appear safe and may reduce post-procedural definite acute stent thrombosis. Further data from real-world registries (with potentially longer time difference between pre-hospital and in-hospital administration) are needed to evaluate the merit of pre-hospital treatment strategy.
The duration of DAPT has also been further explored in randomized trials in 2014. The ARCTIC-Interruption study evaluated DAPT beyond 1 year after DES implantation and found no significant benefit in low-risk patients and increased risk of bleeding events. Unfortunately, no conclusions can be drawn about high-risk patients. SECURITY and ISAR-SAFE trials have shown that 6-month DAPT is non-inferior to 12-month DAPT for patients undergoing PCI with the newer-generation DES. The recently published DAPT (Dual Antiplatelet Therapy Beyond One Year After Drug-eluting Coronary Stent Procedures) trial randomized 9961 patients to receive thienopyridine or placebo along with aspirin for an additional 18 months after completing 1 year of dual-antiplatelet therapy for DES implantation. Patients assigned to continued thienopyridine had a significantly lower incidence of stent thrombosis (0.4 vs. 1.4%, P < 0.001) and MI (2.1 vs. 4.1%, P < 0.001), but higher rates of moderate/severe bleeding (2.5 vs. 1.6%, P = 0.001). There was no difference in cardiovascular mortality; however, all-cause mortality (2.0 vs. 1.5%, P = 0.05) was higher with continued DAPT. A potential concern about oncological deaths needs further exploration.
From these trials, it appears that patients with high risk of bleeding may safely stop DAPT at 6 months, whereas patients with higher ischaemic/thrombotic and lower bleeding risk should continue DAPT beyond 12 months; an individualized risk–benefit assessment is vital.
Adjunctive anticoagulation therapy for patients undergoing PCI has remained a hot topic in 2014. Earlier trials in STEMI patients have shown that bivalirudin may be preferred over combination of unfractionated heparin and glycoprotein inhibitors (GPIs). The recent EUROMAX study comparing bivalirudin (n = 1089) with heparin plus routine upstream GPI (n = 649) or heparin plus bailout GPI (n = 460) also suggested superiority of bivalirudin. The primary outcome of death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67, 95% CI 0.46–0.97, P = 0.034), and 9.8% with heparin plus bailout GPI (HR 0.52, 95% CI 0.35–0.75, P = 0.006). However, there was no mortality benefit and stent thrombosis rates were higher with bivalirudin. Further trials have even questioned the efficacy of bivalirudin.
BRAVE-4 (Bavarian Reperfusion Alternatives Evaluation) trial aimed to compare prasugrel plus bivalirudin (n = 271) against clopidogrel plus unfractionated heparin (n = 277) in STEMI patients undergoing primary PCI. The primary endpoint of death, MI, unplanned revascularization of the infarct-related artery, stent thrombosis, stroke, or major bleeding at 30 days was similar between the two groups (Figure 2); however, it is important to highlight that this trial was terminated early and was underpowered. HEAT-PPCI (How Effective Are Antithrombotic Therapies in Primary PCI), a single-centre, randomized, controlled trial compared with bivalirudin and bailout GPI with unfractionated heparin and bailout GPI among STEMI patients undergoing primary PCI. The primary efficacy outcome of all-cause mortality, stroke, reinfarction, or unplanned revascularization occurred in 8.7% of the bivalirudin group vs. 5.7% of the heparin group (P = 0.01). Stent thrombosis was also more common in the bivalirudin group (3.4 vs. 0.9%, P = 0.001). The primary safety outcome of major bleeding occurred in 3.5% of the bivalirudin group vs. 3.1% of the heparin group (P = 0.59). It is recommended that all patients undergoing primary PCI should receive anticoagulation along with antiplatelet therapy; however, the choice of anticoagulant can be tailored according to the ischaemic and bleeding risk of an individual patient.
(Enlarge Image)
Figure 2.
Kaplan–Meier curves for primary and secondary endpoints in BRAVE-4 trial. Kaplan–Meier curves of the primary endpoint (A, composite of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, stroke, or major bleeding) and secondary composite ischaemic endpoint (B, death, myocardial infarction, revascularization of the infarct-related artery, stent thrombosis, or stroke) in the prasugrel plus bivalirudin and the clopidogrel plus heparin group at 30 days. Reproduced from Schulz et al.
Percutaneous Coronary Intervention Adjunctive Therapy
Antiplatelet Therapy
Clopidogrel remains the preferred P2Y12 inhibitor for patients undergoing PCI for stable angina. For non-ST-elevation ACS patients, prasugrel can be used for clopidogrel naive patients scheduled for PCI, whereas ticagrelor can be used for all patients regardless of the treatment strategy. For STEMI patients undergoing PCI, either prasugrel or ticagrelor can be used. The ATLANTIC trial has shown that pre-hospital compared with in-hospital (a median time of only 31 min later then pre-hospital) administration of ticagrelor in patients with STEMI does not improve pre-PCI coronary reperfusion, but it does appear safe and may reduce post-procedural definite acute stent thrombosis. Further data from real-world registries (with potentially longer time difference between pre-hospital and in-hospital administration) are needed to evaluate the merit of pre-hospital treatment strategy.
The duration of DAPT has also been further explored in randomized trials in 2014. The ARCTIC-Interruption study evaluated DAPT beyond 1 year after DES implantation and found no significant benefit in low-risk patients and increased risk of bleeding events. Unfortunately, no conclusions can be drawn about high-risk patients. SECURITY and ISAR-SAFE trials have shown that 6-month DAPT is non-inferior to 12-month DAPT for patients undergoing PCI with the newer-generation DES. The recently published DAPT (Dual Antiplatelet Therapy Beyond One Year After Drug-eluting Coronary Stent Procedures) trial randomized 9961 patients to receive thienopyridine or placebo along with aspirin for an additional 18 months after completing 1 year of dual-antiplatelet therapy for DES implantation. Patients assigned to continued thienopyridine had a significantly lower incidence of stent thrombosis (0.4 vs. 1.4%, P < 0.001) and MI (2.1 vs. 4.1%, P < 0.001), but higher rates of moderate/severe bleeding (2.5 vs. 1.6%, P = 0.001). There was no difference in cardiovascular mortality; however, all-cause mortality (2.0 vs. 1.5%, P = 0.05) was higher with continued DAPT. A potential concern about oncological deaths needs further exploration.
From these trials, it appears that patients with high risk of bleeding may safely stop DAPT at 6 months, whereas patients with higher ischaemic/thrombotic and lower bleeding risk should continue DAPT beyond 12 months; an individualized risk–benefit assessment is vital.
Anticoagulant Therapy
Adjunctive anticoagulation therapy for patients undergoing PCI has remained a hot topic in 2014. Earlier trials in STEMI patients have shown that bivalirudin may be preferred over combination of unfractionated heparin and glycoprotein inhibitors (GPIs). The recent EUROMAX study comparing bivalirudin (n = 1089) with heparin plus routine upstream GPI (n = 649) or heparin plus bailout GPI (n = 460) also suggested superiority of bivalirudin. The primary outcome of death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67, 95% CI 0.46–0.97, P = 0.034), and 9.8% with heparin plus bailout GPI (HR 0.52, 95% CI 0.35–0.75, P = 0.006). However, there was no mortality benefit and stent thrombosis rates were higher with bivalirudin. Further trials have even questioned the efficacy of bivalirudin.
BRAVE-4 (Bavarian Reperfusion Alternatives Evaluation) trial aimed to compare prasugrel plus bivalirudin (n = 271) against clopidogrel plus unfractionated heparin (n = 277) in STEMI patients undergoing primary PCI. The primary endpoint of death, MI, unplanned revascularization of the infarct-related artery, stent thrombosis, stroke, or major bleeding at 30 days was similar between the two groups (Figure 2); however, it is important to highlight that this trial was terminated early and was underpowered. HEAT-PPCI (How Effective Are Antithrombotic Therapies in Primary PCI), a single-centre, randomized, controlled trial compared with bivalirudin and bailout GPI with unfractionated heparin and bailout GPI among STEMI patients undergoing primary PCI. The primary efficacy outcome of all-cause mortality, stroke, reinfarction, or unplanned revascularization occurred in 8.7% of the bivalirudin group vs. 5.7% of the heparin group (P = 0.01). Stent thrombosis was also more common in the bivalirudin group (3.4 vs. 0.9%, P = 0.001). The primary safety outcome of major bleeding occurred in 3.5% of the bivalirudin group vs. 3.1% of the heparin group (P = 0.59). It is recommended that all patients undergoing primary PCI should receive anticoagulation along with antiplatelet therapy; however, the choice of anticoagulant can be tailored according to the ischaemic and bleeding risk of an individual patient.
(Enlarge Image)
Figure 2.
Kaplan–Meier curves for primary and secondary endpoints in BRAVE-4 trial. Kaplan–Meier curves of the primary endpoint (A, composite of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, stroke, or major bleeding) and secondary composite ischaemic endpoint (B, death, myocardial infarction, revascularization of the infarct-related artery, stent thrombosis, or stroke) in the prasugrel plus bivalirudin and the clopidogrel plus heparin group at 30 days. Reproduced from Schulz et al.
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