User login
Dual vs Triple Therapy Following ACS or PCI in Patients with Atrial Fibrillation
Study Overview
Objective. To compare the benefit of apixaban with a vitamin K antagonist and compare aspirin with placebo in patients with atrial fibrillation who had acute coronary syndrome or underwent percutaneous coronary intervention (PCI) and were planning to take a P2Y12 inhibitor.
Design. Multicenter, international, open-label, prospective randomized controlled trial with a 2-by-2 factorial design.
Setting and participants. 4614 patients who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor.
Intervention. Patients were assigned by means of an interactive voice-response system to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months.
Main outcome measures. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.
Main results. At 6 months, major or clinically relevant nonmajor bleeding had occurred in 10.5% of the patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.58-0.81, P < 0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (HR 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR 0.83; 95% CI, 0.74-0.93; P = 0.002) and similar incidence of ischemic events.
Conclusion. Among patients with atrial fibrillation and recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban without aspirin resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than the regimens that included a vitamin K antagonist, aspirin, or both.
Commentary
PCI is performed in about 20% of patients with atrial fibrillation. These patients require dual antiplatelet therapy to prevent ischemic events, combined with long-term anticoagulation to prevent stroke due to atrial fibrillation. Because the combination of anticoagulation and antiplatelet therapy is associated with a higher risk of bleeding, balancing the risk and benefit of dual antiplatelet therapy and anticoagulation in this population is crucial.
Previous studies have assessed the risk and benefit associated with anticoagulation and antiplatelet therapy. When warfarin plus clopidogrel (double therapy) was compared with warfarin, aspirin, and clopidogrel (triple therapy) in patients with acute coronary syndromes and stable ischemic coronary disease undergoing PCI, use of clopidogrel without aspirin (double therapy) was associated with a significant reduction in bleeding complications (19.4% versus 44.4%, HR, 0.36; 95% CI, 0.26-0.20; P < 0.0001) without increasing thrombotic events.1 Recent studies have compared triple therapy with warfarin to double therapy using direct oral anticoagulants (DOAC). The PIONEER AF-PCI study, which compared low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor to vitamin K antagonist plus dual antiplatelet therapy, found that the rates of clinically significant bleeding were lower in the low-dose rivaroxaban group compared to the triple-therapy group with a vitamin K antagonist (16.8% versus 26.7%; HR, 0.59; 95% CI, 0.47-0.76; P < 0.001).2 Similarly, the RE-DUAL PCI studied dabigatran and showed that the dual therapy group with dabigatran had a lower incidence of major or clinically relevant nonmajor bleeding events during follow-up compared to triple therapy including a vitamin K antagonist (15.4% versus 26.9%; HR, 0.52; 95% CI, 0.42-0.63; P < 0.001).3
In this context, Lopes at al investigated the clinical question of dual therapy versus triple therapy by performing a well-designed randomized clinical trial. In this trial with a 2-by-2 factorial design, the authors studied the effect of apixaban compared to vitamin K antagonist and the effect of aspirin compared to placebo. Major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (HR 0.69; 95% CI, 0.58-0.81; P < 0.001). The incidence of major or clinically relevant nonmajor bleeding was higher in patients receiving aspirin than in those receiving placebo (16.1% versus 9.0%; HR, 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR, 0.83; 95% CI, 0.74-0.93; P = 0.002). The incidence of ischemic events was similar between the apixaban group and vitamin K antagonist group and between the aspirin group and placebo group.
The strengths of this current study include the large number of patients it enrolled. Taking the results from the PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trials, it is clear that DOAC reduces the risk of bleeding compared to vitamin K antagonist. In addition, the AUGUSTUS trial was the first that evaluated the effect of aspirin in patients treated with DOAC and antiplatelet therapy. Aspirin was associated with increased risk of bleeding, with a similar rate of ischemic events compared to placebo.
The AUGUSTUS trial has several limitations. Although the incidence of ischemic events was similar between the apixaban group and the vitamin K antagonist group, the study was not powered to evaluate for individual ischemic outcomes. However, there was no clear evidence of an increase in harm. Since more than 90% of P2Y12 inhibitors used were clopidogrel, the safety and efficacy of combining apixaban with ticagrelor or prasugrel will require further study.
Applications for Clinical Practice
In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, dual therapy with a P2Y12 inhibitor and DOAC should be favored over a regimen that includes a vitamin K antagonist and/or aspirin.
—Taishi Hirai, MD, University of Missouri Medical Center, and John Blair, MD, University of Chicago Medical Center
1. Dewilde WJM, Oirbans T, Verheugt FWA, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107-1115.
2. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434.
3. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513-1524.
Study Overview
Objective. To compare the benefit of apixaban with a vitamin K antagonist and compare aspirin with placebo in patients with atrial fibrillation who had acute coronary syndrome or underwent percutaneous coronary intervention (PCI) and were planning to take a P2Y12 inhibitor.
Design. Multicenter, international, open-label, prospective randomized controlled trial with a 2-by-2 factorial design.
Setting and participants. 4614 patients who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor.
Intervention. Patients were assigned by means of an interactive voice-response system to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months.
Main outcome measures. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.
Main results. At 6 months, major or clinically relevant nonmajor bleeding had occurred in 10.5% of the patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.58-0.81, P < 0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (HR 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR 0.83; 95% CI, 0.74-0.93; P = 0.002) and similar incidence of ischemic events.
Conclusion. Among patients with atrial fibrillation and recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban without aspirin resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than the regimens that included a vitamin K antagonist, aspirin, or both.
Commentary
PCI is performed in about 20% of patients with atrial fibrillation. These patients require dual antiplatelet therapy to prevent ischemic events, combined with long-term anticoagulation to prevent stroke due to atrial fibrillation. Because the combination of anticoagulation and antiplatelet therapy is associated with a higher risk of bleeding, balancing the risk and benefit of dual antiplatelet therapy and anticoagulation in this population is crucial.
Previous studies have assessed the risk and benefit associated with anticoagulation and antiplatelet therapy. When warfarin plus clopidogrel (double therapy) was compared with warfarin, aspirin, and clopidogrel (triple therapy) in patients with acute coronary syndromes and stable ischemic coronary disease undergoing PCI, use of clopidogrel without aspirin (double therapy) was associated with a significant reduction in bleeding complications (19.4% versus 44.4%, HR, 0.36; 95% CI, 0.26-0.20; P < 0.0001) without increasing thrombotic events.1 Recent studies have compared triple therapy with warfarin to double therapy using direct oral anticoagulants (DOAC). The PIONEER AF-PCI study, which compared low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor to vitamin K antagonist plus dual antiplatelet therapy, found that the rates of clinically significant bleeding were lower in the low-dose rivaroxaban group compared to the triple-therapy group with a vitamin K antagonist (16.8% versus 26.7%; HR, 0.59; 95% CI, 0.47-0.76; P < 0.001).2 Similarly, the RE-DUAL PCI studied dabigatran and showed that the dual therapy group with dabigatran had a lower incidence of major or clinically relevant nonmajor bleeding events during follow-up compared to triple therapy including a vitamin K antagonist (15.4% versus 26.9%; HR, 0.52; 95% CI, 0.42-0.63; P < 0.001).3
In this context, Lopes at al investigated the clinical question of dual therapy versus triple therapy by performing a well-designed randomized clinical trial. In this trial with a 2-by-2 factorial design, the authors studied the effect of apixaban compared to vitamin K antagonist and the effect of aspirin compared to placebo. Major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (HR 0.69; 95% CI, 0.58-0.81; P < 0.001). The incidence of major or clinically relevant nonmajor bleeding was higher in patients receiving aspirin than in those receiving placebo (16.1% versus 9.0%; HR, 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR, 0.83; 95% CI, 0.74-0.93; P = 0.002). The incidence of ischemic events was similar between the apixaban group and vitamin K antagonist group and between the aspirin group and placebo group.
The strengths of this current study include the large number of patients it enrolled. Taking the results from the PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trials, it is clear that DOAC reduces the risk of bleeding compared to vitamin K antagonist. In addition, the AUGUSTUS trial was the first that evaluated the effect of aspirin in patients treated with DOAC and antiplatelet therapy. Aspirin was associated with increased risk of bleeding, with a similar rate of ischemic events compared to placebo.
The AUGUSTUS trial has several limitations. Although the incidence of ischemic events was similar between the apixaban group and the vitamin K antagonist group, the study was not powered to evaluate for individual ischemic outcomes. However, there was no clear evidence of an increase in harm. Since more than 90% of P2Y12 inhibitors used were clopidogrel, the safety and efficacy of combining apixaban with ticagrelor or prasugrel will require further study.
Applications for Clinical Practice
In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, dual therapy with a P2Y12 inhibitor and DOAC should be favored over a regimen that includes a vitamin K antagonist and/or aspirin.
—Taishi Hirai, MD, University of Missouri Medical Center, and John Blair, MD, University of Chicago Medical Center
Study Overview
Objective. To compare the benefit of apixaban with a vitamin K antagonist and compare aspirin with placebo in patients with atrial fibrillation who had acute coronary syndrome or underwent percutaneous coronary intervention (PCI) and were planning to take a P2Y12 inhibitor.
Design. Multicenter, international, open-label, prospective randomized controlled trial with a 2-by-2 factorial design.
Setting and participants. 4614 patients who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor.
Intervention. Patients were assigned by means of an interactive voice-response system to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months.
Main outcome measures. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.
Main results. At 6 months, major or clinically relevant nonmajor bleeding had occurred in 10.5% of the patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.58-0.81, P < 0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (HR 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR 0.83; 95% CI, 0.74-0.93; P = 0.002) and similar incidence of ischemic events.
Conclusion. Among patients with atrial fibrillation and recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban without aspirin resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than the regimens that included a vitamin K antagonist, aspirin, or both.
Commentary
PCI is performed in about 20% of patients with atrial fibrillation. These patients require dual antiplatelet therapy to prevent ischemic events, combined with long-term anticoagulation to prevent stroke due to atrial fibrillation. Because the combination of anticoagulation and antiplatelet therapy is associated with a higher risk of bleeding, balancing the risk and benefit of dual antiplatelet therapy and anticoagulation in this population is crucial.
Previous studies have assessed the risk and benefit associated with anticoagulation and antiplatelet therapy. When warfarin plus clopidogrel (double therapy) was compared with warfarin, aspirin, and clopidogrel (triple therapy) in patients with acute coronary syndromes and stable ischemic coronary disease undergoing PCI, use of clopidogrel without aspirin (double therapy) was associated with a significant reduction in bleeding complications (19.4% versus 44.4%, HR, 0.36; 95% CI, 0.26-0.20; P < 0.0001) without increasing thrombotic events.1 Recent studies have compared triple therapy with warfarin to double therapy using direct oral anticoagulants (DOAC). The PIONEER AF-PCI study, which compared low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor to vitamin K antagonist plus dual antiplatelet therapy, found that the rates of clinically significant bleeding were lower in the low-dose rivaroxaban group compared to the triple-therapy group with a vitamin K antagonist (16.8% versus 26.7%; HR, 0.59; 95% CI, 0.47-0.76; P < 0.001).2 Similarly, the RE-DUAL PCI studied dabigatran and showed that the dual therapy group with dabigatran had a lower incidence of major or clinically relevant nonmajor bleeding events during follow-up compared to triple therapy including a vitamin K antagonist (15.4% versus 26.9%; HR, 0.52; 95% CI, 0.42-0.63; P < 0.001).3
In this context, Lopes at al investigated the clinical question of dual therapy versus triple therapy by performing a well-designed randomized clinical trial. In this trial with a 2-by-2 factorial design, the authors studied the effect of apixaban compared to vitamin K antagonist and the effect of aspirin compared to placebo. Major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (HR 0.69; 95% CI, 0.58-0.81; P < 0.001). The incidence of major or clinically relevant nonmajor bleeding was higher in patients receiving aspirin than in those receiving placebo (16.1% versus 9.0%; HR, 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR, 0.83; 95% CI, 0.74-0.93; P = 0.002). The incidence of ischemic events was similar between the apixaban group and vitamin K antagonist group and between the aspirin group and placebo group.
The strengths of this current study include the large number of patients it enrolled. Taking the results from the PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trials, it is clear that DOAC reduces the risk of bleeding compared to vitamin K antagonist. In addition, the AUGUSTUS trial was the first that evaluated the effect of aspirin in patients treated with DOAC and antiplatelet therapy. Aspirin was associated with increased risk of bleeding, with a similar rate of ischemic events compared to placebo.
The AUGUSTUS trial has several limitations. Although the incidence of ischemic events was similar between the apixaban group and the vitamin K antagonist group, the study was not powered to evaluate for individual ischemic outcomes. However, there was no clear evidence of an increase in harm. Since more than 90% of P2Y12 inhibitors used were clopidogrel, the safety and efficacy of combining apixaban with ticagrelor or prasugrel will require further study.
Applications for Clinical Practice
In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, dual therapy with a P2Y12 inhibitor and DOAC should be favored over a regimen that includes a vitamin K antagonist and/or aspirin.
—Taishi Hirai, MD, University of Missouri Medical Center, and John Blair, MD, University of Chicago Medical Center
1. Dewilde WJM, Oirbans T, Verheugt FWA, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107-1115.
2. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434.
3. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513-1524.
1. Dewilde WJM, Oirbans T, Verheugt FWA, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107-1115.
2. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434.
3. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513-1524.
Use of Hybrid Coronary Revascularization in Patients with Multivessel Coronary Artery Disease
Study Overview
Objective. To investigate the 5-year clinical outcome of patients undergoing hybrid revascularization for multivessel coronary artery disease (CAD).
Design. Multicenter, open-label, prospective randomized control trial.
Setting and participants. 200 patients with multivessel CAD referred for conventional surgical revascularization were randomly assigned to undergo hybrid coronary revascularization (HCR) or coronary artery bypass grafting (CABG).
Main outcome measures. The primary endpoint was all-cause mortality at 5 years.
Main results. After excluding 9 patients who were lost to follow-up before 5 years, 191 patients (94 in HCR group and 97 in CABG group) formed the basis of the study. All-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% versus 9.2%, P = 0.69). The rates of myocardial infarction (4.3% versus 7.2%, P = 0.30), repeat revascularization (37.2% versus 45.4%, P = 0.38), stroke (2.1% versus 4.1%, P = 0.35), and major adverse and cardiac and cerebrovascular events (45.2% versus 53.4%, P = 0.39) were similar in the 2 groups. These findings were consistent across all levels of risk for surgical complications (EuroScore) and for complexity of revascularization (SYNTAX score).
Conclusion. HCR has similar 5-year all-cause mortality when compared with conventional CABG.
Commentary
HCR has been proposed as a less invasive, effective alternative revascularization strategy to conventional CABG for patients with multivessel CAD. The hybrid approach typically combines the long-term durability of grafting of the left anterior descending artery (LAD) using the left internal mammary artery and the percutaneous coronary intervention (PCI) for non-LAD stenosis; this approach has been shown to have similar or perhaps even better long-term patency compared with saphenous vein grafts.1,2 Previous studies have demonstrated the feasibility of HCR by comparing HCR to conventional CABG at 1 year.2 However, the long-term outcome of HCR compared to conventional CABG has not been previously reported.
In this context, Tajstra et al reported the 5-year follow-up from their prospective randomized pilot study. They report that among the 200 patients with multivessel coronary disease randomly assigned to either HCR or CABG, all-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% versus 9.2%, P = 0.69). The rates of myocardial infarction, repeat revascularization, stroke, and major adverse and cardiac and cerebrovascular event (MACCE) were also similar in the 2 groups.
This is an important study because it is the first to compare the long-term outcome of HCR with conventional CABG; previous studies have been limited due to their short- to mid-term follow-up.2 However, because this study was not powered to assess the superiority of the HCR compared to conventional CABG, future randomized control trials with a larger number of patients are needed.
Future studies must address some important questions. First, the patients in the present study were younger (mean age, 62.1 ± 8.3 years) with less comorbidity and a relatively low SYNTAX score (23.6 ± 6.1 for the HCR arm). As CABG and PCI are associated with similar long- term outcomes in patients with low (< 22) to intermediate (22–32) SYNTAX score,3 comparisons between HCR and multivessel PCI using the current generation of drug-eluting stents are needed. The results from the ongoing Hybrid Coronary Revascularization Trial (NCT03089398) will shed light on this clinical question. Second, whether these findings can be extended to patients with a high baseline SYNTAX score needs further study. Nonetheless, outcomes were similar between the 2 strategies in the intermediate (n = 98) and high (n = 8) SYNTAX score groups. Interestingly, there is no clear benefit of HCR in the high surgical risk groups as measured by EuroScore. Third, in addition to the hard outcomes (death and MACCE), the quality of life of patients measured by an established metric, such as the Seattle Angina Questionnaire, need to be assessed. Last, the completeness of revascularization in each group needs to be further evaluated because incomplete revascularization is a known predictor of adverse outcomes.4,5
Applications for Clinical Practice
In patients with multivessel coronary disease with low SYNTAX score, the 5-year outcome for HCR was similar to that of conventional CABG. Further larger studies are needed to assess the superiority of this approach.
—Taishi Hirai, MD, University of Missouri Medical Center, Columbia, MO; Hiroto Kitahara, MD, University of Chicago Medical Center, Chicago, IL; and John Blair, MD, Medstar Washington Hospital Center, Washington, DC
1. Lee PH, Kwon O, Ahn JM, et al. Safety and effectiveness of second-generation drug-eluting stents in patients with left main coronary artery disease. J Am Coll Cardiol. 2018;71:832-841.
2. Gasior M, Zembala MO, Tajstra M, et al. Hybrid revascularization for multivessel coronary artery disease. JACC Cardiovasc Interv. 2014;7:1277-1283.
3. Serruys PW, Onuma Y, Garg S, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009;5:50-56.
4. Genereux P, Palmerini T, Caixeta A, et al. Quantification and impact of untreated coronary artery disease after percutaneous coronary intervention: the residual SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) score. J Am Coll Cardiol. 2012;59:2165-2174.
5. Choi KH, Lee JM, Koo BK, et al. Prognostic implication of functional incomplete revascularization and residual functional SYNTAX score in patients with coronary artery disease. JACC Cardiovasc Interv. 2018;11:237-245.
Study Overview
Objective. To investigate the 5-year clinical outcome of patients undergoing hybrid revascularization for multivessel coronary artery disease (CAD).
Design. Multicenter, open-label, prospective randomized control trial.
Setting and participants. 200 patients with multivessel CAD referred for conventional surgical revascularization were randomly assigned to undergo hybrid coronary revascularization (HCR) or coronary artery bypass grafting (CABG).
Main outcome measures. The primary endpoint was all-cause mortality at 5 years.
Main results. After excluding 9 patients who were lost to follow-up before 5 years, 191 patients (94 in HCR group and 97 in CABG group) formed the basis of the study. All-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% versus 9.2%, P = 0.69). The rates of myocardial infarction (4.3% versus 7.2%, P = 0.30), repeat revascularization (37.2% versus 45.4%, P = 0.38), stroke (2.1% versus 4.1%, P = 0.35), and major adverse and cardiac and cerebrovascular events (45.2% versus 53.4%, P = 0.39) were similar in the 2 groups. These findings were consistent across all levels of risk for surgical complications (EuroScore) and for complexity of revascularization (SYNTAX score).
Conclusion. HCR has similar 5-year all-cause mortality when compared with conventional CABG.
Commentary
HCR has been proposed as a less invasive, effective alternative revascularization strategy to conventional CABG for patients with multivessel CAD. The hybrid approach typically combines the long-term durability of grafting of the left anterior descending artery (LAD) using the left internal mammary artery and the percutaneous coronary intervention (PCI) for non-LAD stenosis; this approach has been shown to have similar or perhaps even better long-term patency compared with saphenous vein grafts.1,2 Previous studies have demonstrated the feasibility of HCR by comparing HCR to conventional CABG at 1 year.2 However, the long-term outcome of HCR compared to conventional CABG has not been previously reported.
In this context, Tajstra et al reported the 5-year follow-up from their prospective randomized pilot study. They report that among the 200 patients with multivessel coronary disease randomly assigned to either HCR or CABG, all-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% versus 9.2%, P = 0.69). The rates of myocardial infarction, repeat revascularization, stroke, and major adverse and cardiac and cerebrovascular event (MACCE) were also similar in the 2 groups.
This is an important study because it is the first to compare the long-term outcome of HCR with conventional CABG; previous studies have been limited due to their short- to mid-term follow-up.2 However, because this study was not powered to assess the superiority of the HCR compared to conventional CABG, future randomized control trials with a larger number of patients are needed.
Future studies must address some important questions. First, the patients in the present study were younger (mean age, 62.1 ± 8.3 years) with less comorbidity and a relatively low SYNTAX score (23.6 ± 6.1 for the HCR arm). As CABG and PCI are associated with similar long- term outcomes in patients with low (< 22) to intermediate (22–32) SYNTAX score,3 comparisons between HCR and multivessel PCI using the current generation of drug-eluting stents are needed. The results from the ongoing Hybrid Coronary Revascularization Trial (NCT03089398) will shed light on this clinical question. Second, whether these findings can be extended to patients with a high baseline SYNTAX score needs further study. Nonetheless, outcomes were similar between the 2 strategies in the intermediate (n = 98) and high (n = 8) SYNTAX score groups. Interestingly, there is no clear benefit of HCR in the high surgical risk groups as measured by EuroScore. Third, in addition to the hard outcomes (death and MACCE), the quality of life of patients measured by an established metric, such as the Seattle Angina Questionnaire, need to be assessed. Last, the completeness of revascularization in each group needs to be further evaluated because incomplete revascularization is a known predictor of adverse outcomes.4,5
Applications for Clinical Practice
In patients with multivessel coronary disease with low SYNTAX score, the 5-year outcome for HCR was similar to that of conventional CABG. Further larger studies are needed to assess the superiority of this approach.
—Taishi Hirai, MD, University of Missouri Medical Center, Columbia, MO; Hiroto Kitahara, MD, University of Chicago Medical Center, Chicago, IL; and John Blair, MD, Medstar Washington Hospital Center, Washington, DC
Study Overview
Objective. To investigate the 5-year clinical outcome of patients undergoing hybrid revascularization for multivessel coronary artery disease (CAD).
Design. Multicenter, open-label, prospective randomized control trial.
Setting and participants. 200 patients with multivessel CAD referred for conventional surgical revascularization were randomly assigned to undergo hybrid coronary revascularization (HCR) or coronary artery bypass grafting (CABG).
Main outcome measures. The primary endpoint was all-cause mortality at 5 years.
Main results. After excluding 9 patients who were lost to follow-up before 5 years, 191 patients (94 in HCR group and 97 in CABG group) formed the basis of the study. All-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% versus 9.2%, P = 0.69). The rates of myocardial infarction (4.3% versus 7.2%, P = 0.30), repeat revascularization (37.2% versus 45.4%, P = 0.38), stroke (2.1% versus 4.1%, P = 0.35), and major adverse and cardiac and cerebrovascular events (45.2% versus 53.4%, P = 0.39) were similar in the 2 groups. These findings were consistent across all levels of risk for surgical complications (EuroScore) and for complexity of revascularization (SYNTAX score).
Conclusion. HCR has similar 5-year all-cause mortality when compared with conventional CABG.
Commentary
HCR has been proposed as a less invasive, effective alternative revascularization strategy to conventional CABG for patients with multivessel CAD. The hybrid approach typically combines the long-term durability of grafting of the left anterior descending artery (LAD) using the left internal mammary artery and the percutaneous coronary intervention (PCI) for non-LAD stenosis; this approach has been shown to have similar or perhaps even better long-term patency compared with saphenous vein grafts.1,2 Previous studies have demonstrated the feasibility of HCR by comparing HCR to conventional CABG at 1 year.2 However, the long-term outcome of HCR compared to conventional CABG has not been previously reported.
In this context, Tajstra et al reported the 5-year follow-up from their prospective randomized pilot study. They report that among the 200 patients with multivessel coronary disease randomly assigned to either HCR or CABG, all-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% versus 9.2%, P = 0.69). The rates of myocardial infarction, repeat revascularization, stroke, and major adverse and cardiac and cerebrovascular event (MACCE) were also similar in the 2 groups.
This is an important study because it is the first to compare the long-term outcome of HCR with conventional CABG; previous studies have been limited due to their short- to mid-term follow-up.2 However, because this study was not powered to assess the superiority of the HCR compared to conventional CABG, future randomized control trials with a larger number of patients are needed.
Future studies must address some important questions. First, the patients in the present study were younger (mean age, 62.1 ± 8.3 years) with less comorbidity and a relatively low SYNTAX score (23.6 ± 6.1 for the HCR arm). As CABG and PCI are associated with similar long- term outcomes in patients with low (< 22) to intermediate (22–32) SYNTAX score,3 comparisons between HCR and multivessel PCI using the current generation of drug-eluting stents are needed. The results from the ongoing Hybrid Coronary Revascularization Trial (NCT03089398) will shed light on this clinical question. Second, whether these findings can be extended to patients with a high baseline SYNTAX score needs further study. Nonetheless, outcomes were similar between the 2 strategies in the intermediate (n = 98) and high (n = 8) SYNTAX score groups. Interestingly, there is no clear benefit of HCR in the high surgical risk groups as measured by EuroScore. Third, in addition to the hard outcomes (death and MACCE), the quality of life of patients measured by an established metric, such as the Seattle Angina Questionnaire, need to be assessed. Last, the completeness of revascularization in each group needs to be further evaluated because incomplete revascularization is a known predictor of adverse outcomes.4,5
Applications for Clinical Practice
In patients with multivessel coronary disease with low SYNTAX score, the 5-year outcome for HCR was similar to that of conventional CABG. Further larger studies are needed to assess the superiority of this approach.
—Taishi Hirai, MD, University of Missouri Medical Center, Columbia, MO; Hiroto Kitahara, MD, University of Chicago Medical Center, Chicago, IL; and John Blair, MD, Medstar Washington Hospital Center, Washington, DC
1. Lee PH, Kwon O, Ahn JM, et al. Safety and effectiveness of second-generation drug-eluting stents in patients with left main coronary artery disease. J Am Coll Cardiol. 2018;71:832-841.
2. Gasior M, Zembala MO, Tajstra M, et al. Hybrid revascularization for multivessel coronary artery disease. JACC Cardiovasc Interv. 2014;7:1277-1283.
3. Serruys PW, Onuma Y, Garg S, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009;5:50-56.
4. Genereux P, Palmerini T, Caixeta A, et al. Quantification and impact of untreated coronary artery disease after percutaneous coronary intervention: the residual SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) score. J Am Coll Cardiol. 2012;59:2165-2174.
5. Choi KH, Lee JM, Koo BK, et al. Prognostic implication of functional incomplete revascularization and residual functional SYNTAX score in patients with coronary artery disease. JACC Cardiovasc Interv. 2018;11:237-245.
1. Lee PH, Kwon O, Ahn JM, et al. Safety and effectiveness of second-generation drug-eluting stents in patients with left main coronary artery disease. J Am Coll Cardiol. 2018;71:832-841.
2. Gasior M, Zembala MO, Tajstra M, et al. Hybrid revascularization for multivessel coronary artery disease. JACC Cardiovasc Interv. 2014;7:1277-1283.
3. Serruys PW, Onuma Y, Garg S, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009;5:50-56.
4. Genereux P, Palmerini T, Caixeta A, et al. Quantification and impact of untreated coronary artery disease after percutaneous coronary intervention: the residual SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) score. J Am Coll Cardiol. 2012;59:2165-2174.
5. Choi KH, Lee JM, Koo BK, et al. Prognostic implication of functional incomplete revascularization and residual functional SYNTAX score in patients with coronary artery disease. JACC Cardiovasc Interv. 2018;11:237-245.