Studies compare PCI and CABG in patients with left main CAD
Two recent industry-funded studies reported results of comparisons of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease (CAD).
The first, the NOBLE Trial, was a prospective, randomized, open-label, noninferiority trial in patients with left main CAD at 36 centers in Europe from Dec. 9, 2008, to Jan. 21, 2015. Patients were eligible for the study if they had stable or unstable angina pectoris or non-ST-elevation myocardial infarction (MI). Those who had ST-elevation MI within 24 hours, who were considered to be at too high risk for CABG or PCI, or who were expected to survive for less than a year were excluded. Patients were randomly assigned to receive PCI or CABG; those in the PCI group were required to receive drug-eluting stents, and biolimus-eluting stents were recommended beginning in March 2010. The study was funded in part by Biosensors, the stent manufacturer. The primary end point was major adverse cardiac or cerebrovascular events (MACCEs), defined as a composite of all-cause mortality, nonprocedural MI, any repeated coronary revascularization, and stroke. Results were published online Oct. 31, 2016, by The Lancet and appeared in the Dec. 3, 2016, issue.
Overall, 598 patients were assigned to PCI and 603 were assigned to CABG. Mean age was 66.2 years in each group, and 80% and 76% of those in each group, respectively, were men. Five hundred ninety-two patients in each group were included in the intention-to-treat analysis. The Kaplan-Meier five-year estimate of the primary end point was 29% in the PCI group and 19% in the CABG group (hazard ratio [HR], 1.48; 95% CI, 1.11 to 1.96; P<0.0066 in favor of CABG), while as-treated estimates were 28% vs. 19% (HR, 1.55; 95% CI, 1.18 to 2.04; P=0.0015). Rates of MACCE at one year were the same in each group. When each component of the primary end point was examined separately, five-year estimate rates for PCI and CABG were 12% and 9% for all-cause mortality (HR, 1.07; 95% CI, 0.67 to 1.72; P=0.77), 7% and 2% for nonprocedural MI (HR, 2.88; 95% CI, 1.40 to 5.90; P=0.0040), 16% and 10% for any revascularization (HR, 1.50; 95% CI, 1.04 to 2.17; P=0.032), and 5% and 2% for stroke (HR, 2.25; 95% CI, 0.93 to 5.48; P=0.073).
The authors pointed out that their original primary end point, noninferiority of PCI to CABG as assessed by MACCE at two years' follow-up, was changed due to lower than expected event rates and that this was a substantial limitation of their study. In addition, they noted that their results should be generalized with caution and may not apply to the acute care setting. However, they concluded that their trial indicated potentially better outcomes for left main CAD with CABG than with PCI.
In the second study, the EXCEL Trial, researchers randomly assigned 1,905 patients with left main CAD and low or intermediate anatomical complexity to PCI with everolimus-eluting stents or to CABG. Patients were eligible if they had at least 70% stenosis of the left main coronary artery estimated visually or 50% to below 70% if considered hemodynamically significant on invasive or noninvasive testing and if they had CAD of low to intermediate anatomical complexity. The study's primary end point was rate of a composite of death from any cause, stroke, or MI at three years, while secondary end points included rates of a composite of death from any cause, stroke, or MI at 30 days and a composite of death, stroke, MI, or ischemia-driving revascularization at three years. Abbot Vascular, the stent manufacturer, sponsored the study and participated in protocol design and site selection and management. The study results were published online Oct. 31, 2016, by the New England Journal of Medicine and appeared in the Dec. 8, 2016, issue.
Patients were recruited at 126 sites in 17 countries from Sept. 29, 2010, to March 6, 2014. A total of 1,905 patients were randomized, 948 to the PCI group and 957 to the CABG group. Mean age in each group was 66.0 years and 65.9 years, respectively. Most patients (76.2% and 77.5%) were men, and almost all (91.5% and 92.0%) were white. Almost all of the implanted stents (99.2%) were everolimus-eluting. At three years, 15.4% of patients in the PCI group and 14.7% in the CABG group had experienced a primary end point event (P=0.02 for noninferiority). Of the secondary end points, death, stroke, or MI at 30 days occurred in 4.9% of the PCI group and 7.9% of the CABG group (P<0.001 for noninferiority), and death, stroke, MI, or ischemia-driven revascularization at three years occurred in 23.1% of the PCI group and 19.1% of the CABG group (P=0.01 for noninferiority). Seventy-seven patients in the PCI group (8.1%) and 220 patients in the CABG group (23.0%) experienced major periprocedural adverse events within 30 days after group assignment (P<0.001), and 18 more people died after PCI than after CABG, mainly due to noncardiovascular causes. Rates of cardiovascular mortality were similar between groups.
The study authors noted that blinding of patients and investigators was not possible, that some patients were found to have a high anatomical complexity score after randomization, that long-term use of medications varied after PCI and CABG, and that a study with longer follow-up is required. However, they concluded that based on this analysis, PCI with everolimus-eluting stents is noninferior to CABG for a composite outcome of death, stroke, or MI at three years in patients with left main CAD and low or intermediate anatomical complexity.
CT may reduce need for coronary angiography in suspected CAD
Computed tomography (CT) may be preferred in patients referred for coronary angiography to evaluate intermediate-probability coronary artery disease (CAD), according to a recent study.
Researchers at a university hospital in Germany performed a randomized trial to determine whether invasive coronary angiography or cardiac CT should be done in patients with suspected CAD and atypical angina or chest pain. Three hundred forty patients were randomly assigned to receive CT (n=168), followed by coronary angiography if results were positive for obstructive CAD, or immediate coronary angiography (n=172).
Obstructive CAD was defined as at least one stenosis of 50% diameter in the left main coronary artery or at least one stenosis of 70% diameter in other coronary arteries. Major procedural complications related to CT or angiography within 48 hours of the last procedure was the primary outcome measure, and length of stay and radiation exposure were secondary outcomes. Allocation could not be blinded, but outcomes were assessed by blinded independent investigators. After randomization, one patient declined CT and 10 patients declined coronary angiography. As a result, 167 patients in the CT group (88 women, 79 men) and 162 patients in the coronary angiography group (78 women, 84 men) were available for analysis. Mean age was 60.4 years.
Results were published online by The BMJ on Oct. 24, 2016.
The need for coronary angiography decreased from 100% to 14% in the CT group (P<0.001), and CT was also associated with a higher diagnostic yield for coronary angiography, defined as rate of obstructive CAD (75% vs. 15%; P<0.001). Rates of major procedural complications were small and were similar in both groups, as was radiation exposure. The CT group was less likely to experience minor procedural complications than the coronary angiography group (3.6% vs. 10.5%; P=0.014). The CT group had a median length of stay of 30.0 hours, while the coronary angiography group had a median length of stay of 52.9 hours (P<0.001).
At a median of 3.3 years of follow-up, seven of 167 patients in the CT group (4.2%) and six of 162 patients in the coronary angiography group (3.7%) had experienced major cardiovascular events (adjusted hazard ratio, 0.90; P=0.86). Most patients (79%) reported that they would prefer CT over coronary angiography for future testing.
The researchers noted that their study was conducted at a single hospital and may not reflect routine clinical practice. In addition, they pointed out that the study was underpowered for the predefined primary outcome due to lower than expected prevalence of CAD and revascularization rates. However, they concluded that their study indicates a higher diagnostic yield with CT compared with coronary angiography for patients with suspected CAD, along with no increase in long-term cardiac events. Patients also preferred CT over coronary angiography, and CT resulted in a shorter hospital stay. The authors noted that CT could help reduce costs when used in appropriate patients and called for future cost-effectiveness analyses that would compare CT with invasive tests in various patient groups.
Tranexamic acid did not increase risk of death, thrombotic complications after coronary artery surgery
Compared to placebo, the use of tranexamic acid did not increase the risk of death or thrombotic complications after coronary artery surgery, according to a multicenter, double-blind study.
In addition, researchers found that the antifibrinolytic was associated with a lower risk of bleeding complications and a higher risk of postoperative seizures compared to placebo.
Between March 2006 and October 2015, the Aspirin and Tranexamic Acid for Coronary Artery Surgery trial randomized 4,662 patients who were undergoing coronary artery surgery and who were at increased risk for complications to receive tranexamic acid (n=2,329) or placebo (n=2,333). Patients intravenously received either tranexamic acid or 0.9% saline as placebo more than 30 minutes after the induction of anesthesia. After exclusions, 2,311 patients in the tranexamic acid group and 2,320 patients in the placebo group were included in the analysis.
The primary outcome was a composite of death and thrombotic events (nonfatal myocardial infarction [MI], stroke, pulmonary embolism, renal failure, or bowel infarction) 30 days postoperation. Secondary outcomes were death, nonfatal MI, stroke, pulmonary embolism, renal failure, bowel infarction, reoperation due to major hemorrhage or cardiac tamponade, and a requirement for transfusion. In light of research suggesting a link between tranexamic acid and seizures, researchers in 2012 added postoperative seizures as a safety outcome (they also halved the dose of tranexamic acid at this time).
Results were published online on Oct. 23, 2016, by the New England Journal of Medicine and appeared in the Jan. 12, 2017, issue.
In the tranexamic acid group, 386 patients (16.7%) died or experienced thrombotic complications, compared to 420 patients (18.1%) in the placebo group (relative risk [RR], 0.92; 95% CI, 0.81 to 1.05; P=0.22). Two hundred sixty-nine patients (11.6%) in the tranexamic acid group experienced MI, compared to 300 patients (12.9%) in the placebo group, making the RR 0.84 (95% CI, 0.70 to 1.00; P=0.045) when MI was defined only according to the third universal definition. Other thrombotic outcomes were similar between groups.
The tranexamic acid group had lower rates than the placebo group for several bleeding-related outcomes: the number of patients who had blood loss during surgery, the number of units of any blood products that were transfused, and the number of patients who underwent blood transfusion (P<0.001 for all). The tranexamic acid group also had lower rates of reoperation due to major hemorrhage or cardiac tamponade than the placebo group (1.4% vs. 2.8%; P=0.001).
Postoperative seizures occurred in 15 patients (0.7%) in the tranexamic acid group and in two patients (0.1%) in the placebo group (RR, 7.60; 95% CI, 1.80 to 68.70; P=0.002). The smaller dose did not reduce the risk of seizure.
The study authors noted limitations of their work, such as how the dose-effect analysis of tranexamic acid was underpowered and that the trial included few patients at the highest risk for bleeding or thrombosis. The attending anesthesiologists were sometimes aware of the treatment-group assignment, and the study included only a small proportion of patients undergoing off-pump surgery, they added.