The CDAC Study - Cerebral Dysfunction After Coronary Revascularization

The CDAC Study - Cerebral Dysfunction After Coronary Revascularization

Neurocognitive decline has long been suspected to be a potential long-term complication of coronary artery bypass grafting surgery (CABG), with reports of post-operative cognitive dysfunction by objective testing approaching 15-50% of patients in the year following surgery. To determine the true rate of long-term cognitive dysfunction following CABG compared to percutaneous coronary intervention (PCI or coronary stent placement), we propose a multi-center, two-group, non-randomized study using computer-based customized neurocognitive testing (Cogsate), prior to the procedure and then at 30 days, 1-year and 2-years after revascularization to evaluate cognitive function vital for the maintenance and advancement of professional and personal activities. It is anticipated that the study will document a higher rate of cognitive dysfunction in the CABG group, that the landmark study will provide both the patient and physician with the information necessary to make an informed decision regarding the cognitive risks of CABG versus PCI when faced with the need for coronary revascularization, and that these results will change the clinical practice of recommending CABG as a primary revascularization option for those wishing to preserve cognitive function.

Neurocognitive decline has long been acknowledged as a potential complication of coronary artery bypass grafting surgery (CABG). The incidence of post-operative cognitive dysfunction (POCD) as measured by objective testing has been reported in several small studies to approach 15-50%, with great variability noted in study size, testing methods, and length of clinical follow-up. However, much controversy exists regarding the prevalence and severity of post-operative cognitive changes following CABG, as well as the methods of assessment. Currently, pre-revascularization discussions between a treating physician and a patient (Informed Consent) are limited to topics of morbidity, mortality, and surgical result, and these discussions do not include the potential risk of POCD. In contrast to CABG, percutaneous coronary intervention (PCI), including stent placement, has the potential of providing similar revascularization results without the risk of POCD or a negative impact on personal and professional quality of life. Thus, to determine the true rate of cognitive dysfunction for patients in 2 years following CABG compared to patients undergoing PCI, we propose a multi-center, observational, two-group, non-randomized cohort study. The decision to undergo CABG or PCI will be made by a treating physician and a patient before study enrollment, and thus, the choice of a procedure is not part of the research protocol, and there is no increased risk due to study enrollment. Patients at 30 centers will undergo baseline computer-based customized neurocognitive testing (Cogstate), chosen for its sensitivity to detect cognitive changes in multiple domains. Initial testing will be >48 hours after the qualifying diagnostic coronary angiogram and <2 months before CABG or PCI. The test will be repeated 30 days after hospital discharge and again at 1- and 2-years after revascularization. Diagnostic angiographic images will later be evaluated by three physicians to determine if the patients could have received similar results from CABG or PCI. Due to ethical concerns, randomization to a treatment option is not appropriate. While inferring causality in the absence of a randomized clinical trial design may be challenging, propensity score matching will be employed to enhance the efficiency of measured clinical variables or characteristics. The primary study endpoint is a change of within-patient cumulative computer-based neurocognitive test performance at baseline, with comparison to 2-years after revascularization (in addition to between-group comparisons). Secondary endpoints include test results 30 days and 1-year after discharge compared to baseline, return to work or usual activities interval, and a change in professional status, job title, or personal activities. Thus, the present study for the first time will provide both patient and physician with the information necessary to make an informed treatment decision when faced with the need for coronary revascularization, and the desire to maintain cognitive function, professional productivity and personal quality of life, and may also change the method of cognitive testing and the clinical practice of recommending CABG as a primary revascularization option.

Inclusion Criteria:

• Criteria for enrollment are age 18 years or more.
• A candidate for either elective single or multi-vessel CABG or PCI without limits for lesion location, lesion characteristics or complexity, the number of vessels treated, or the number of stents or bypass grafts placed, or the type of bypass grafts.
• The decision to undergo either CABG or PCI will be made by the treating physician and patient before research study enrollment, and thus, the revascularization decision is not directed by this research protocol.

Exclusion Criteria:

Patients will not be enrolled due to:

• Concomitant valve therapy (surgical or transcatheter).
• Prior CABG or surgical valve repair/replacement surgery.
• PCI within 1 year of the study entry procedure.
• A hybrid revascularization procedure (PCI plus CABG), an untreated carotid artery stenosis of >70%, inability to provide informed consent.
• The inability to perform pre-procedure tablet-based neurocognitive testing.
• The lack of stated agreement to return for follow-up on-site neurocognitive testing at the prescribed time points.