Faculty Bibliography

Aims/UNASSIGNED:The association between depression care adequacy and the risk of subsequent adverse cardiovascular disease (CVD) outcomes among patients with a previous diagnosis of myocardial infarction (MI) or stroke is not well defined. Methods and Results/UNASSIGNED:This retrospective cohort study used commercial claims data (2010-2015) and included adults with newly diagnosed and treated MDD following an initial MI or stroke diagnosis. Depression care adequacy was assessed during the 3-month period following the MDD diagnosis index date using two measures: antidepressant dosage adequacy and duration adequacy. Cox models adjusted for the propensity of receiving adequate depression care were used to compare the risk of a composite CVD outcome (MI, stroke, congestive heart failure [CHF], and angina) as well as each individual CVD event between patients receiving adequate versus inadequate depression care. 1568 patients were included in the final cohort. Of these, 937 (59.8%) were categorized as receiving inadequate depression care based on at least 1 of the 2 treatment adequacy criteria. Propensity score adjusted Cox models showed that depression care inadequacy was associated with a significantly higher risk of the composite CVD endpoint (HR, 1.20; 95% CI, 1.04-1.39), stroke (HR 1.20, 95% CI, 1.02-1.42) and angina (HR 1.95, 95% CI, 1.21-3.16) with no significant interaction based on cohort included (MI vs. stroke) or the definition of inadequate depression (dose vs. duration inadequacy) (Pinteraction>0.05). Conclusions/UNASSIGNED:Inadequate MDD care was associated with a higher risk of adverse CVD events. These findings reveal a significant unmet clinical need in patients with post-MI or post-stroke MDD that may impact CVD outcomes.

BACKGROUND:Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. METHODS:The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. CONCLUSIONS:ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.

Coronary artery disease in patients with diabetes mellitus (DM) is characterized by extensive atherosclerosis, longer lesions, and diffuse distal disease. Consequently, these patients have worse outcomes after coronary revascularization, regardless of the modality used. Traditionally, coronary artery bypass grafting (CABG) has been regarded as more effective than percutaneous coronary intervention (PCI) in patients with DM, likely because of more complete revascularization and protection against disease progression in the bypass segment. Revascularization with balloon angioplasty, bare-metal stents, and first-generation drug-eluting stents have all been shown to be inferior to CABG in patients with DM. Current professional society guidelines reflect these findings, strongly recommending CABG over PCI in this setting. Newer stent platforms, however, have challenged this notion. The use of thinner struts, biocompatible polymer coating, and newer antiproliferative agents have improved the rates of cardiovascular events in patients with DM revascularized percutaneously. Since the publication of current guidelines, new studies suggested acceptable outcomes in patients with DM revascularized with second-generation drug-eluting stents, even though these conclusions are drawn from small subgroup analyses or nonrandomized studies. Robust registry data suggest similar mortality with lower rates of stroke after PCI compared with surgery, at the expense of increased rates of repeat revascularization. If complete revascularization can be achieved, similar rates of myocardial infarction are also observed. Therefore, contemporary revascularization in patients with DM with multivessel coronary artery disease should involve a multidisciplinary approach, in which interventional cardiologists and cardiac surgeons involve their patients to individualize treatment choices, and balance the risks and effectiveness of each modality.

Aims/UNASSIGNED:Assessments of cardiac rehabilitation (CR) in coronary heart disease (CHD) cohorts usually examine mortality in aggregate. The current study examines the prognosis and characteristics of patients who enrolled and completed CR, stratified by their level of improvement in cardiorespiratory fitness (CRF) by examining the characteristics, outcomes and predictors of non-response in CRF (NonRes) compared to low-responders (LowRes) and high-Responders (HighRes) after CR. Methods And Results/UNASSIGNED:1171 CHD patients were referred for a phase II CR program after therapy for an acute coronary syndrome, coronary artery bypass graft procedure or a percutaneous coronary intervention between January 1, 2000 and June 30, 2013 underwent cardiopulmonary exercise testing before and after CR. This cohort was divided according to absolute improvements in CRF [i.e., change in peak oxygen consumption expressed in ml•kg-1•min-1]. Mortality was analyzed after 0.5 to 13.4 years of follow-up (mean 6.4 years). 266 (23%) of subjects were NonRes. After adjustment for body mass index, age, gender, left ventricular ejection fraction and baseline CRF, NonRes and LowRes had a statistically significant 3-fold and 2-fold higher mortality, respectively, when compared to HighRes (HighRes: 8% vs LowRes: 17% vs NonRes: 22%; p < 0.001). Age, female gender, baseline CRF, hostility and presence of diabetes were significant predictors of NonRes and LowRes. In addition, higher waist circumference was a predictor of NonRes. Conclusions/UNASSIGNED:Significant proportions of subjects referred to CR have no/low improvement in CRF and higher associated mortality risks. Greater attention is required to increase improvements in CRF following CR and avoid NonRes.

Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers (ARBs) are merely considered an alternative for ACE inhibitor-intolerant patients. The aim of this review was to compare outcomes and adverse events between ACE inhibitors and ARBs in patients. In patients with hypertension and hypertension with compelling indications, we found no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.