Periprocedural Stroke and Myocardial Infarction as Risks for Long-Term Mortality in CREST

Abstract

BACKGROUND: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) previously reported increased mortality in patients who sustained a periprocedural stroke or cardiac event (myocardial infarction or biomarker only) in follow-up to 4 years. We now extend these observations to 10 years. METHODS AND RESULTS: CREST is a randomized, controlled trial designed to compare the outcomes of carotid stenting (CAS) versus carotid endarterectomy (CEA). Proportional hazards models were used to assess the association between mortality and periprocedural stroke, myocardial infarction (MI), or biomarker only events. Over 10-year follow up, patients with periprocedural stroke were at 1.74-times the risk of death compared to those without stroke (adjusted HR=1.74; 95% CI 1.21–2.50; p˂0.003). This increased risk was driven by increased early (between 0 and 90 days) mortality (adjusted HR=14.41; 95% CI 5.33–38.94; p˂0.0001), with no significant increase in late (between 91 days and 10 years) mortality (adjusted HR=1.40; 95% CI 0.93–2.10; p=0.11). Patients with a protocol MI were at 3.61-times increased risk of death compared to those without MI (adjusted HR=3.61; 95% CI 2.28–5.73; p˂0.0001), with an increased hazard both early (adjusted HR=8.20; 95% CI 1.86–36.2; p=0.006) and late (adjusted HR=3.40; 95% CI 2.09–5.53; p˂0.0001). Patients with a biomarker only event were at 2.04-times increased risk overall (adjusted HR=2.04; 95% CI 1.09–3.84; p=0.03) than those without myocardial infarction, with an increased early hazard (adjusted HR = 8.44; 95% CI 1.09–65.5; p=0.04), and a suggestive but non-significant association toward higher 91-day to10-year risk (1.88; 95% CI 0.97–3.64; p=0.062) contributing to the increased risk. CONCLUSIONS: In the CREST trial, patients with periprocedural events demonstrate a substantial increase in future mortality to 10 years. For stroke, this risk is largely confined to an early time frame while periprocedural MI or biomarker only events confer a continuous increased mortality over 10 years. Strategies to reduce periprocedural events and to optimize the evaluation and management of patients with cardiac events should be considered in efforts to reduce not only early but long-term mortality. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00004732

Comorbidities and Health-Related Quality of Life Following Revascularization for Asymptomatic Critical Internal Carotid Artery Stenosis Treated with Carotid Endarterectomy or Angioplasty with Stenting

“…Technological developments have been made in the equipment used for carotid artery angioplasty (stents), including the introduction of a new generation of stents [55–57]. Also, there has been the development of new eligibility criteria for CEA and CAS [19,40,58–61]. New eligibility for CAS surgery include patients with multilevel and multifocal atherosclerotic disease [62–65], with symptomatic carotid artery stenosis [19,20] and with symptoms, because for CAS, it is possible to perform simultaneous coronary angiography or even coronary angioplasty or to reclassify the patient for coronary artery bypass graft (CABG) surgery [66–68], to reduce perioperative MI.…”

“…Previous studies that have analyzed the influence of individual coexisting diseases on the effectiveness of CEA compared with CAS as assessed by the SF-36 QoL index did not assess several important comorbidities [78], which were identified as relevant in the present study. In the CREST cohort study, which included about 50% of patients with asymptomatic carotid artery stenosis, the role of symptomatic status on QoL was not investigated [35,61]. The authors discussed only periprocedural stroke and MI as a risk for long-term mortality in CREST [35,61].…”

“…In the CREST cohort study, which included about 50% of patients with asymptomatic carotid artery stenosis, the role of symptomatic status on QoL was not investigated [35,61]. The authors discussed only periprocedural stroke and MI as a risk for long-term mortality in CREST [35,61]. Involvement of the contralateral carotid artery and the effectiveness of CEA compared with CAS for revascularization has not been previously demonstrated [79].…”

Stroke Prevention: Extra-Cranial Carotid Artery Therapy

“…The CREST 10-year follow-up demonstrated that patients with periprocedural stroke were at increased risk of death compared with those without stroke (adjusted hazard ratio [HR]=1.74; 95% CI, 1.21-2.50; p<0.003). 27,28 This increased risk was driven by increased early (≤90-days) mortality (adjusted HR=14.41; 95% CI, 5.33-38.94; p<0.0001), with no significant increase in late (>90-days and 10-years) mortality (adjusted HR=1.40; 95% CI, 0.93-2.10; p=0.11). Patients with a periprocedural MI were at 3.61 times the risk of death compared with those without MI (adjusted HR=3.61; 95% CI, 2.28-5.73; p<0.0001), with an increased hazard both early (adjusted HR=8.20; 95% CI, 1.86-36.2; p=0.006) and late (adjusted HR=3.40; 95% CI, 2.09-5.53; p<0.0001).…”

Health-related quality of life in ischaemic stroke survivors after carotid endarterectomy (CEA) and carotid artery stenting (CAS): confounder-controlled analysis

“…The CAS, however, was associated with a significantly lower risk of periprocedural MI (OR = 0.45; 95% CI: 0.27–0.75), cranial nerve palsy (OR = 0.07; 95% CI: 0.04–0.14) and the composite outcome of death, stroke, MI, or cranial nerve palsy during the periprocedural period (OR = 0.75; 95% CI: 0.60–0.93) [11]. Indeed, 10-year data from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST-1) have recently shown that patients with periprocedural stroke were at 1.74× the risk of death compared with those without stroke (adjusted hazard ratio = 1.74; 95% CI: 1.21–2.50; p < 0.003) while patients with MI were at 3.61× increased risk of death compared with those without MI (adjusted hazard ratio =3.61; 95% CI: 2.28–5.73; p < 0.0001) [12]. Stroke, however, has a higher negative impact on HR-QoL than MI or heart failure [1, 12–15].…”