Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: Insights from the PLATelet inhibition and patient outcomes (PLATO) trial

doi:10.1016/j.ahj.2013.06.019

American Heart Journal

Volume 166, Issue 3, September 2013, Pages 474-480

https://doi.org/10.1016/j.ahj.2013.06.019 Get rights and content

Background

Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG.

Methods

Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression.

Results

Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P_interaction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P_interaction = .46) prior CABG.

Conclusions

Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Section snippets

Patients

The primary results of the PLATO trial have been published.11, 12 In the present post hoc analysis, we classified the patients according to prior CABG, which was one of the clinical variables collected at enrollment in the study and was available in 18,613 patients.

Statistical analysis

Continuous parameters were presented as medians with interquartile ranges. Categorical variables were reported as percentages. The baseline characteristics of patients with and without prior CABG were compared using the Wilcoxon rank

Patient characteristics

Of the 18,613 study patients in whom prior CABG history was known, 1,133 (6.1%) had prior CABG, of whom 352 (31%) underwent SVG intervention and 191 (17%) underwent native coronary artery intervention. The baseline characteristics of the study patients are shown in Table I. The median time from CABG was 9 (5, 13) years. Prior-CABG patients were older, more likely to be men, and more likely to present with non–ST-segment elevation ACS. They were more likely to be white; to have higher body mass

Discussion

Our analysis shows that patients with ACS and prior CABG surgery (a) had higher cardiovascular risk that was in part due to the higher baseline clinical characteristics, (b) had lower risk for major bleeding, and (c) derived similar benefit from ticagrelor.

Conclusions

Compared with patients without prior CABG, prior-CABG patients who present with an acute coronary syndrome have significantly higher risk for death and adverse cardiac events and derive similar benefit from ticagrelor versus clopidogrel administration.

Acknowledgements

Ulla Nässander Schikan, PhD, at Uppsala Clinical Research Center, Uppsala, Sweden, provided editorial assistance.

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Cited by (32)

Debulking strategies in revascularization of diseased saphenous vein bypass grafts
2022, Debulking in Cardiovascular Interventions and Revascularization Strategies: Between a Rock and the Heart
Coronary artery bypass graft surgery is the mainstay cardiac operation for the treatment of severe atherosclerotic coronary disease. The surgery is founded on harvesting vascular conduits from select anatomic sites in the arterial and venous circulation to serve as bypass grafts. Unfortunately, over time, venous grafts are prone to develop the very same disease for which they have been originally used for as a treatment. Degenerative bypass graft disease involves relentless pathologic processes causing failure of these vascular structures following coronary artery surgery. The failure rate reaches 10%–25% already during the first year postsurgery, then between the second to the fifth year additional 5%–10% closure rate occurs. This is followed by 20%–25% failure rate between the sixth to the tenth year. Once the 10-year postoperation marker is reached, the patency rate of the bypass grafts is only 40%–50%. Distinct pathologic processes effect graft survival whereby thrombosis is a leading cause of early graft failure while atherosclerotic plaques and neointimal hyperplasia are predominant in the midterm stage. Thrombus also plays a significant role in the pathogenesis of late venous graft disease especially in association with rupture of atherosclerotic plaques. Altogether, thrombus superimposition is found in as many as 80% of old vein grafts. In patients with evidence of graft disease who experience angina pectoris, ischemia, congestive heart failure, myocardial infarction, and/or arrhythmias, the preferred management strategy is percutaneous intervention since repeat cardiac surgery is fraught with high mortality rate and poor clinical outcomes. Standard revascularization with balloons and adjunct stents is limited to simple graft lesions. In complex grafts lesions, which are commonly encountered, standard revascularization technology can cause major adverse clinical events such as severe reduction of the antegrade flow (the “no-reflow” phenomenon), distal embolization of thrombotic, fibrotic, and calcified material leading to myocardial tissue injury. Accordingly, debulking of the graft disease in patients with complex plaque/thrombus morphology with dedicated plaque removal devices, mechanical thrombectomy, and thrombus capturing/displacing stents provides a safer and efficacious revascularization strategy. As stenting usually completes the intervention to ensure long-term patency, a growing evidence suggests that the drug-eluting stents achieve improved results when compared with bare-metal stents. Overall, percutaneous interventions in diseased vein grafts that incorporate debulking strategies constitute a useful revascularization treatment option.
Risk Factors and Outcomes in Redo Coronary Artery Bypass Grafting
2020, Heart Lung and Circulation
Citation Excerpt :
The adjusted survival was comparable after 1, 3 and 5 years and was 93.5%, 90%, 85% in redo-CABG patients and 95.5%, 94.5%, 93% in first-time CABG patients, respectively (p = 0.2) (Figure 3). Reoperative CABG surgery has progressively declined in frequency in the last years [14] as a result of improved medical therapy [15], strict glucose control, more frequent use of the internal mammary artery, and more complete revascularisation. Percutaneous coronary intervention is the first line treatment in patients with angina or ischaemic findings after prior CABG; however, PCI in the setting of chronic total occlusions (CTO) results in lower PCI success rates and CTO is more prevalent in patients with previous CABG [16,17].
Reoperative coronary artery bypass grafting (redo-CABG) has declined during the last decade, while use of percutaneous coronary intervention (PCI) has increased. The aim of this retrospective study was to evaluate risk factors, in-hospital mortality, and long-term survival between first-time CABG and redo-CABG.
From January 2009 to December 2015, 2,581 patients underwent first-time CABG procedures while 132 underwent isolated redo-CABG. Logistic regression was used to identify risk factors predictive of redo-CABG and after propensity matching the in-hospital morbidity and long-term all-cause mortality were compared.
Risk factors for redo-CABG were prior PCI, dyslipidaemia, diabetes and hypertension. After propensity matching there were no significant differences between the redo-CABG (n = 126) and first-time CABG groups (n = 232) in baseline characteristics. The adjusted in-hospital mortality was 3.1% for redo-CABG and 2.1% for first-time CABG (p = 0.55). Redo-CABG required significantly more intraoperative red blood cells (p = 0.03), platelets (p < 0.001), cryoprecipitate (p < 0.007) and fresh frozen plasma (p < 0.001) than first-time CABG. There was no significant difference in reoperation for bleeding (p = 0.72), prolonged ventilation (p = 0.98), postoperative stroke (p = 0.92) or dialysis (p = 0.44). The survival at 1, 3 and 5 years for redo-CABG was 93.5%, 90%, and 85% respectively, and 95.5%, 94.5%, 93% for first-time CABG, respectively (p = 0.2).
Prior PCI after first time CABG and the risk factors for atherosclerotic disease are predictive for redo-CABG. An increased use of blood products is required during redo-CABG. After propensity matching, in-hospital mortality and long-term survival for redo-CABG is comparable to first-time operation. Re-sternotomy does not impact the survival in redo-CABG.
Update on Cardiac Catheterization in Patients With Prior Coronary Artery Bypass Graft Surgery
2019, JACC: Cardiovascular Interventions
Citation Excerpt :
In another meta-analysis of 9 randomized controlled trials, patients who received ticagrelor or prasugrel in addition to aspirin had lower mortality compared with patients taking clopidogrel and aspirin (relative risk: 0.49; 95% confidence interval [CI]: 0.33 to 0.71; p = 0.0002), whereas there was no significant difference when clopidogrel plus aspirin was compared with aspirin monotherapy (104). In a subanalysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, the reduction of the primary endpoint of cardiovascular death, MI, and stroke was not statistically significant in post-CABG patients (19.6% vs. 21.4%; adjusted hazard ratio: 0.91 [interquartile range: 0.67 to 1.24]) (105). Large, randomized trials are needed in order to clarify the usefulness of DAPT in different clinical settings (acute coronary syndromes vs. stable coronary artery disease) and the optimal antiplatelet combination.
Patients who undergo coronary bypass graft surgery often require subsequent cardiac catheterization and repeat coronary revascularization. Saphenous vein graft lesions have high rates for distal embolization that can be reduced with use of embolic protection devices. They also have high restenosis rates, which are similar with drug-eluting and bare-metal stents. Percutaneous coronary interventions of native coronary arteries is generally preferred over saphenous vein graft interventions, but can often be complex, requiring expertise and specialized equipment. Prolonged dual-antiplatelet therapy and close monitoring can help optimize subsequent clinical outcomes.
Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery
2019, Journal of the American College of Cardiology
Citation Excerpt :
Although the relative benefit of alirocumab versus placebo is consistent regardless of prior CABG status, those with prior CABG achieve substantially greater absolute risk reduction and consequently lower NNT. The finding that patients with prior CABG, specifically those with CABG before ACS, are at high risk for recurrent cardiovascular events is consistent with previous randomized clinical trial main (14,15) and subgroup (5–8,10–12,16) results. This observation may be due in part to a clustering of multiple prognostic factors including older age, diabetes, hypertension, chronic kidney disease, advanced atherosclerosis (e.g., prior myocardial infarction, cerebrovascular disease, peripheral artery disease), and higher levels of atherogenic lipoproteins.
Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death.
This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab).
Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. The primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003).
In each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [−2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [−0.1% to 1.0%], 0.5% [−1.9% to 2.9%], and 3.6% [0.0% to 7.2%]).
Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)
Antiplatelet effects of ticagrelor versus clopidogrel after coronary artery bypass graft surgery: A single-center randomized controlled trial
2019, Journal of Thoracic and Cardiovascular Surgery
The study objective was to compare the onset of platelet inhibition (inhibition of platelet aggregation) between ticagrelor 90 mg twice per day and clopidogrel 75 mg once per day in patients receiving coronary artery bypass grafting.
In a single-center, randomized, open-label study, 140 patients receiving coronary artery bypass grafting were randomly assigned to the aspirin + ticagrelor group or the aspirin + clopidogrel group in a 1:1 ratio. Participants in the aspirin + ticagrelor group took aspirin 100 mg once per day and ticagrelor 90 mg twice per day. Participants in the aspirin + clopidogrel group took aspirin 100 mg once per day and clopidogrel 75 mg once per day. Platelet function was determined before study treatment (0 hours); at 2 hours, 8 hours, 24 hours, and 72 hours after medication; and during follow-up at 30 days after surgery.
Inhibition of platelet aggregation at 2 hours after the first drug administration was greater for the aspirin + ticagrelor group than for the aspirin + clopidogrel group (34.2% [interquartile range, 9.1-66.0] vs 5.3% [interquartile range, −14.3-22.0], P < .001) and at all times in the study period (P < .001). More patients reached inhibition of platelet aggregation maximum within 24 hours in the aspirin + ticagrelor group than in the aspirin + clopidogrel group (52.9% vs 27.5%, P = .006). The average inhibition of platelet aggregation maximum from 2 to 24 hours was still greater in the aspirin + ticagrelor group than in the aspirin + clopidogrel group (72.3% ± 15.4% vs 49.2% ± 46.8%, P < .001). There were no differences in terms of bleeding or major adverse cardiac events between the 2 groups.
In patients receiving coronary artery bypass grafting, the onset of action was faster and the peak inhibition of platelet aggregation was higher with ticagrelor than with clopidogrel.
The spectrum of clinical presentations and management options for the treatment of degenerative atherothrombotic disease of saphenous vein grafts
2018, Cardiovascular Thrombus: From Pathology and Clinical Presentations to Imaging, Pharmacotherapy and Interventions
Atherosclerosis and associated thrombosis are among the most critical elements that govern the formation of degenerative venous graft disease. This relentlessly progressive disease accounts for vein graft failure following coronary artery bypass surgery. Accordingly, the failure rate is 10%–25% at 1 year; an additional closure rate of 5%–10% occurs at 1–5 years; then another 20%–25% develops along the interval of 6–10 years. Consequently, by the 10th year mark postsurgery the patency rate of old vein grafts is only 40%–50%. Distinct pathologic processes develop in these vascular conduits at different time periods, whereby thrombosis is the leading cause of early graft failure, while atherosclerotic degeneration and neointimal hyperplasia are predominant in the midterm stage. Thrombus plays a significant role in the pathogenesis of late venous graft disease as well, especially in association with rupture of atherosclerotic plaque. Altogether, thrombus superimposition is found in as many as 80% of old vein grafts. For patients with degenerative vein grafts who experience angina pectoris, ischemia, and myocardial infarction, a treatment option of repeat cardiac surgery is fraught with high mortality rates and poor clinical outcomes. Consequently, percutaneous vein graft intervention is considered the preferred treatment strategy. Dedicated thrombus removal strategies include pharmacotherapy, aspiration catheters, power-based mechanical thrombectomy, and thrombus capturing/displacing stents. Bare metal and drug-eluting stents are the most common devices applied in the management of thrombotic vein grafts. Studies have demonstrated that the drug-eluting stents achieve improved results in vein graft disease in comparison with bare metal stents. Nevertheless, poststenting, a more potent and longer antiplatelet therapy may be required for the benefit of patients undergoing intervention in vein grafts compared with native coronary arteries. Overall, the performance of percutaneous intervention in vein grafts carries higher risk of distal embolization, “no-reflow” phenomenon, and myocardial tissue injury, as well as a considerably higher risk of 2-year major adverse ischemic events compared with native coronary arteries.

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: Clinical Trial Registration: http://www.clinicaltrials.gov; NCT00391872.

: Eric R. Bates, MD, FACC, served as guest editor for this article.

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Clinical InvestigationAcute Ischemic Heart DiseaseEffect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: Insights from the PLATelet inhibition and patient outcomes (PLATO) trial

Background

Methods

Results

Conclusions

Section snippets

Patients

Statistical analysis

Patient characteristics

Discussion

Conclusions

Acknowledgements

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am Heart J

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Int J Cardiol

Clinical Investigation
Acute Ischemic Heart Disease
Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: Insights from the PLATelet inhibition and patient outcomes (PLATO) trial