Mortality Associated with the Number of Diseased Vessels and Therapeutic Strategies for Coronary Artery Disease: Long-Term Follow-Up

Research Article

J Cardiovasc Disord. 2023; 9(1): 1053.

Mortality Associated with the Number of Diseased Vessels and Therapeutic Strategies for Coronary Artery Disease: Long-Term Follow-Up

Guilherme Fernandes de Carvalho, MD; Whady Hueb, MD*, PhD; Paulo Cury Rezende, MD, PhD; Eduardo Gomes Lima, MD, PhD; Paulo Rogério Soares, MD, PhD; Thiago Luis Scudeler, MD, PhD; Edimar Alcides Bocchi, MD, PhD; José Antônio Franchini Ramires, MD, PhD; Roberto Kalil Filho, MD, PhD

Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil

*Corresponding author: Whady Hueb, Av. DrEneas de Carvalho Aguiar 44, AB, Sala 114, Cerqueira César, São, Paulo-SP/Brazil. Tel: 55 11 2661 5032; Fax: 55 11 2661 5188 Email: whady.hueb@incor.usp.br

Received: October 05, 2023 Accepted:October 28, 2023 Published: November 04, 2023

Abstract

Background: The number of coronary arteries affected by atherosclerosis is believed to impact the prognosis of coronary artery disease, resulting in a higher incidence of cardiac events. However, conclusive results on the relationship between the extent of coronary atherosclerosis and outcomes are lacking.

Methods: This retrospective, single-center, observational cohort study included patients with stable coronary artery disease and preserved ventricular function who had the option of any of the three therapeutic strategies (medicine, angioplasty, or surgery) included in the MASS-Trials database. Patients were stratified according to the number of diseased arteries forming single-vessel, double-vessel, and triple-vessel disease groups. The atherosclerotic burden was assessed using the SYNTAX Score. Each group was eligible for any of the three therapeutic strategies. The primary endpoint was overall mortality. Secondary endpoints included the combination of all-cause death, nonfatal myocardial infarction, and additional coronary interventions.

Results: Between May 1998 and June 2009, 2,000 patients who met the inclusion criteria in the MASS-Trial database were included. The study enrolled 1,855 patients. Of these, 224(12%) had single-vessel disease (SVD), 536(29%) had double-vessel disease (2VD), and 1,095(59%) had triple-vessel disease (3VD). The entire follow-up of our sample was 5 years. Overall mortality for SVD, 2VD, and 3VD was 9(4%), 33(6.3%), and 43(3.9%), respectively (P=0.054). Pairwise comparison of mortality at 5-year follow-up showed no significant differences between SVD x 2VD, SVD x 3VD, and 2VD x 3VD (hazard ratio [HR] 1.41, 95% CI: 0.81-2.44). The secondary endpoints (combination of overall mortality, nonfatal infarction, and additional revascularization) also revealed no significant differences (P=0.2).

Conclusions: Overall mortality was similar regardless of the number of diseased arteries and the degree of arterial involvement. These data suggest that optimized medical treatment as an initial strategy is safe and has a similar rate of events in any applied therapeutic option.

Keywords: Coronary artery disease; Stable angina; Number of diseased vessels; Therapeutic strategies

Introduction

The long-term prognosis of Coronary Artery Disease (CAD) historically attributes to the number of diseased arteries. This concept is derived from the myocardial area at risk and the degree of luminal stenosis [1]. When associated, these two conditions carry substantial weight in the prognosis of coronary disease and may result in higher rates of occurrence of events and premature death. Initial studies on mortality related to the number of diseased vessels identified increased mortality associated with the degree of arterial involvement [2]. Similarly, other studies individualized artery by artery and their respective sites and associated them with their prognosis [3-4]. Moreover, they compared the prognosis of the artery in isolation and association with other arteries. For instance, the effect of associating the anterior Descending Artery (DA) with the Circumflex artery (CX) is different from the association between CX and the Right Coronary artery (RC). Finally, patients with disease in one vessel were compared with those with two-vessel and three-vessel involvement. Refinements regarding the number of affected arteries, the degree of arterial impairment, and the location of luminal stenosis identified a strong relationship with prognosis. Disease severity, interpreted as the occurrence of events, was more strongly associated with proximal lesions than with distal lesions, stenosis severity, and the number of affected vessels [5]. However, these studies did not consider ventricular function as a predictor of prognosis. In fact, studies with the objective of identifying this condition found conflicting mortality results in patients with the same compromised artery but without assessing the degree of ventricular function [6]. Thus, patients with the same number of vessel disease with ventricular dysfunction experienced marked mortality compared to those with preserved ventricular function [7]. Coronary interventions, both percutaneous and surgical, were developed to change this situation. Several studies have shown real benefit, in the long term, of interventions in certain subgroups of patients, changing the prognosis in the short and long term [8]. The present study reports a long-term follow-up of patients enrolled in the database of The Medicine, Angioplasty, or Surgery Study (MASS-Trials) with stable angina, preserved ventricular function stratified by the number of diseased vessels.

Methods

Study Design and Patient Population

Patients with obstructive coronary artery disease with proximal stenosis of more than 70%, confirmed ischemia, and considered equally treatable with the three strategies were enrolled between May 1998 and June 2009 in the MASS Trial database. The MASS registry, which includes details on recruitment, inclusion and exclusion criteria, objectives, data collection, patient management, procedural guidelines, and event definitions, has been previously published [9]. Briefly, the MASS-Registry includes randomized and non-randomized prospective unicentric patients, comparing surgical, percutaneous, or medical therapy strategies in those with stable coronary disease and preserved ventricular function. Patients who were clinically eligible for any therapeutic strategy and who consented to enter the study were prospectively followed up for over 5 years. Myocardial ischemia was documented by a stress test or in the occurrence of angina pectoris assessment of the Canadian Cardiovascular Society (CCS) (Class II or III). Thus, all patients included were approved based on interventional cardiology and the surgeon, who indicated that revascularization could be performed using any strategy. In the present study, patients were grouped according to the number of diseased arteries. So, the study population included patients with Single-Vessel Disease (SVD), patients with Two-Vessel Disease (2VD), and patients with Three-Vessel Disease (3VD). The ethics committee of the Heart Institute approved the protocol, and all procedures were performed following the Declaration of Helsinki. Written informed consent was obtained from every patient.

Treatment Protocol

The medications administered to the patients were similar in the three study groups. All patients received aspirin and/or clopidogrel, and optimal medical therapy, consisting of a stepped-approach using nitrates, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or a combination of these drugs, unless contraindicated, was used to keep the patient free of angina. Statins were also prescribed along with a low-fat, low-carbohydrate diet on an individual basis. Insulin and oral hypoglycemic agents were also used in patients with diabetes. As it was a public hospital, medications were provided free of charge. Finally, patients were assigned to continue aggressive medical therapy alone or to undergo Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG) concurrently with Medical Therapy (MT).

For patients referred for PCI, the procedure was available shortly after assignment. Devices used for catheter-based therapeutic strategies, including stents, lasers, directional atherectomy, and balloon angioplasty, were at the discretion of the operator. Angioplasty was performed according to a standard protocol. The interventional cardiologist was encouraged to treat all arteries that were likely to contribute to ischemia and/or had >70% diameter stenosis. Successful revascularization in the PCI group was defined as a residual stenosis of <50% reduction in luminal diameters with grade 3 Myocardial Infarction (TIMI) flow thrombolysis. Patients treated with coronary stents were maintained on clopidogrel 75mg for 12 months, plus lifetime aspirin.

Patients assigned to the CABG group required the operation shortly after assignment. Complete revascularization was accomplished, if technically feasible, with saphenous vein grafts, internal mammary arteries, and other conduits such as radial or gastroepiploic arteries. The use of the left internal mammary artery to graft the left anterior descending coronary artery was strongly advised for all cases.

Equivalent revascularization was encouraged but not mandatory. Standard surgical techniques were used under hypothermic arrest with blood cardioplegia. No off-pump CABG was performed.

Study Endpoints

Patients were evaluated every three months during the first year of inclusion and every six months until the 5th year of follow-up. The primary endpoint was predefined as death from any cause, while the secondary endpoint was defined as a composite of death from any cause, nonfatal myocardial infarction, and angina requiring revascularization. Myocardial Infarction (MI) was defined as the presence of significant new Q-waves in at least two ECG leads or symptoms compatible with MI associated with troponin concentrations that were more than five times the upper limit of the reference range. The primary endpoint of the study aimed to compare the mortality rates of patients with CAD according to the number of diseased vessels, stable angina, and preserved left ventricular function at a five-year follow-up. In addition, we stratified the results based on the number of diseased vessels and the treatment option (surgical, percutaneous, or medical).

Statistical Analysis

Statistical analysis was conducted using the SPSS software. Differences in clinical and demographic baseline characteristics among groups were assessed using chi-square or Fisher's exact test for dichotomous variables and t-tests or Wilcoxon tests for continuous variables. Event rates were estimated using the Kaplan-Meier method, and differences among groups were compared using the log-rank test. The Cox proportional hazards method was utilized to develop a multivariate model of 5-year mortality rates, including variables such as age, hypertension, gender, hyperlipidemia, number of coronary diseases, and treatment allocation. All data were analyzed according to the intention-to-treat principle rather than the treatment received. All tests were two-tailed, and a P-value of <0.05 was considered statistically significant.

Results

Between May 1998 and June 2009, 2,000 patients who met the inclusion criteria were included in the MASS-Trial database. The study consisted of 1,855 patients, of whom 224(12%) had Single-Vessel Disease (SVD), 536 (29%) had double-vessel disease (2VD), and 1,095(59%) had Triple-Vessel Disease (3VD). The follow-up period for the entire sample was 5 years. The cohort flow diagram is presented in Figure 1.