Revascularization or Optimal Medical Therapy for Stable Ischemic Heart Disease: A Bayesian Meta-Analysis of Contemporary Trials

BackgroundThe role of revascularization in patients with stable ischemic heart disease (SIHD) has been controversial, more so in the present era of drug-eluting stents.AimsTo examine the absolute risk difference (ARD) between revascularization plus optimal medical therapy (OMT) versus OMT alone among patients with SIHD using Bayesian approach.MethodsPubMed/MEDLINE and Cochrane citation indices were utilized to identify randomized controlled trials (RCTs) through March 31, 2020. Among trials comparing initial revascularization plus OMT with initial OMT alone, revascularization arm must have comprised >50% of patients receiving either percutaneous or surgical revascularization, and >50% of patients must have received aspirin and statin as OMT in both arms.ResultsSeven RCTs (12,494) were included in the final analysis. The ARD of all-cause mortality for revascularization with respect to OMT was centred at −0.002 (95% CrI: −0.01; 0.01, Tau: 0.01, 67% probability of ARD of revascularization vs. OMT < 0). The ARD for cardiac mortality was centred at −0.0025 (95%CrI: −0.01; 0.01, Tau: 0.01, 77% probability of ARD of revascularization vs. OMT < 0). The ARD for MI was −0.02 (95% CrI: −0.06; 0.00, Tau: 0.02, 97% probability of ARD for revascularization vs. OMT < 0). There was 96% probability of ARD for unstable angina with revascularization vs. OMT < 0, 4.5% probability of ARD for freedom from angina with revascularization vs. OMT < 0, and 6% probability of ARD for stroke with revascularization vs. OMT < 0.ConclusionsBayesian analysis demonstrated minimal probability of difference in all-cause mortality and cardiac mortality in patients with SIHD who underwent revascularization compared with OMT alone. However, revascularization was associated with lower probability of MI, unstable angina, and increased freedom from angina, but a higher risk of stroke compared with OMT alone.PROSPEROThe protocol of this systematic review and meta-analysis was registered in PROSPERO [CRD42020160540].     

Medical and Revascularization Management of Stable Ischemic Heart Disease: An Overview

Stable ischemic heart disease (SIHD) affects approximately 10 million Americans with 500,000 new cases diagnosed each year. Patients with SIHD are primarily managed in the outpatient setting with aggressive cardiovascular risk factor modification via medical therapy and lifestyle changes. Currently, this approach is considered as the mainstay of treatment. The recently published ISCHEMIA trial has established the noninferiority of medical therapy in comparison to coronary revascularization in patients with moderate to severe ischemia. Percutaneous coronary intervention is currently recommended for patients with significant left main disease, large ischemic myocardial burden, and patients with severe refractory angina despite maximal medical therapy.     

Initial Strategy of Revascularization Versus Optimal Medical Therapy for Improving Outcomes in Ischemic Heart Disease: A Review of the Literature

Defining optimal management of patients with stable coronary artery disease continues to be a central area of debate. While it has been established that all patients with coronary artery disease should at least be managed with optimal medical therapy, many patients with stable coronary artery disease continue to be treated with revascularization, whether by percutaneous coronary intervention or coronary artery bypass grafting. What remains unclear is whether revascularization further improves outcomes when added to medical therapy. We start by reviewing trials that define optimal medical therapy. We then review results of randomized trials comparing both revascularization strategies with optimal medical therapy and assess the strengths and limitations of each. Next, we briefly describe the ongoing ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, which will seek to determine optimal management for patients with stable ischemic heart disease in a population of patients at a uniformly higher risk prior to diagnostic cardiac catheterization. We conclude that revascularization and medical therapy should be used as complementary strategies. Available data have shown some benefits of revascularization in addition to medical therapy, but further trials are needed to better define the optimal population and magnitude and cost effectiveness of adding revascularization to optimal medical therapy.     

Variation in Revascularization Practice and Outcomes in Asymptomatic Stable Ischemic Heart Disease

Objectives

The aims of this study were to assess variation in revascularization of asymptomatic patients with stable ischemic heart disease, identify the predictors of variation, and determine if it was associated with clinical outcomes.

Intensity of Guideline-Directed Medical Therapy for Coronary Heart Disease and Ischemic Heart Failure Outcomes

PurposeThe impact of guideline-directed medical therapy for coronary heart disease in those hospitalized with acute heart failure is unknown.MethodsWe studied guideline-directed medical therapies for coronary disease: angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta-adrenoreceptor antagonists, antiplatelet agents or anticoagulants, and statins. Using inverse probability of treatment weighting the propensity score, we examined associations of guideline-directed medical therapy intensity (categorized as low [0-1], high [2-3], or very high [4] number of drugs) with mortality in 1873 patients with angina, troponin elevation, or prior myocardial infarction.ResultsAt discharge, 0-1, 2-3, and 4 medications were prescribed in 467 (25%), 705 (38%), and 701 (37%) patients, respectively. Relative to those prescribed 0-1 drugs (reference), all-cause mortality was lower with 2-3 (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.28-0.84, P = 0.009) or all 4 drug classes (HR 0.56, 95% CI 0.33-0.96, P = 0.034) over 181-365 days, with similar reductions present from 0-180 days. In those with heart failure with preserved ejection fraction, mortality trended lower with 2-3 drug classes (HR 0.43, 95% CI 0.18-1.02, P = 0.054) and was significantly reduced with 4 drugs (HR 0.32, 95%CI 0.12-0.84, P = 0.021) during 0-180 day follow-up. In heart failure with reduced ejection fraction, all-cause mortality was reduced during both 0-180 and 181-365 days when discharged on 2-3 (HR 0.30 for 181-365 days, 95%CI 0.14-0.64, P = 0.002) or all 4 drug classes (HR 0.43, 95%CI 0.19-0.95, P = 0.038).ConclusionsIncreasing guideline-directed medical therapy intensity for coronary heart disease resulted in lower mortality in patients with acute ischemic heart failure with both preserved and reduced ejection fractions.     

Stable Ischemic Heart Disease in Women

Purpose of the review

Paradoxically, although women have a lower burden of coronary atherosclerosis, they experience more symptoms, more frequent hospitalizations, and a worse prognosis compared to men. This is in part due to biological variations in pathophysiology between the two sexes, and in part related to inadequate understanding of these differences, subconscious referral bias, and suboptimal application of existing women-specific guidelines. We sought to review the contemporary literature and provide an update on risk assessment, diagnosis, and management of IHD in women.

Recent findings

IHD in women is often secondary to diffuse non-obstructive atherosclerosis, coronary spasm, inflammation, and endothelial and microvascular dysfunction, and less commonly due to the male pattern of flow-limiting epicardial stenosis. Both IHD patterns likely represent sex-specific manifestations of the same disease process. Additionally, there is a differential expression of risk factors and symptoms between men and women. Application of male-pattern IHD risk factors and presentation to women contributes to under-recognition, under-testing, and under-treatment of IHD in women compared to men. Traditional diagnostic evaluation has focused on detection of epicardial disease, amenable to revascularization. Our improved understanding of sex-specific pathophysiology of IHD has enabled us to also develop tools for detection of microvascular disease. Advances in stress MRI, flow quantification on stress PET, and provocative invasive angiography have filled this void and offer important diagnostic and prognostic information.

Summary

Despite our improved understanding of sex-specific differences in presentation, risk factors, pathophysiology, diagnostic testing, and management strategies of IHD, women with IHD continue to experience worse outcomes than men. This disparity underscores the need for improved research and understanding of biological sex differences, elimination of subconscious gender bias in referral patterns, and improved application of existing research into clinical practice.

     

Endovascular Versus Medical Therapy for Atherosclerotic Renovascular Disease

The diagnosis of renal artery stenosis (RAS) has become increasingly common in part due to greater awareness of ischemic renal disease and increased use of diagnostic techniques. Over 90 % of RAS cases are caused by atherosclerotic renovascular disease (ARVD). Patients with ARVD are at high risk for fatal and nonfatal cardiovascular and renal events. The mortality rate in patients with ARVD is high, especially with other cardiovascular or renal comorbidities. Recent clinical studies have provided substantial evidence concerning medical therapy and endovascular interventional therapeutic approaches for ARVD. Despite previous randomized clinical trials, the optimal therapy for ARVD remained uncertain until the results of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial were released recently. CORAL demonstrated that optimal medical therapy was equally effective to endovascular therapy in the treatment of ARVD. Clinicians can now practice with more evidence-based medicine to treat ARVD and potentially decrease mortality in patients with ARVD using optimal medical therapy.     

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.