Approaches to ischemic heart disease before, during and after hospitalization
Investigators in Monday’s Late-Breaking Science session revealed surprising findings in four trials for managing ischemic heart disease. They found:
- Ticagrelor failed to demonstrate noninferiority to prasugrel in patients with diabetes and coronary artery disease undergoing percutaneous coronary intervention.
- Investigational GPIIb/IIIa inhibitor shows significant risk reduction in primary outcomes in patients with ST-segment elevation myocardial infarction.
- Extending dual antiplatelet therapy (DAPT) an additional year after drug-eluting stent (DES) implantation reduced ischemic events in patients with stable multivessel coronary artery disease.
- Cardiovascular magnetic resonance imaging enhanced detection of chest pain causes in patients with nonobstructive coronary arteries on coronary angiograms.
Ticagrelor failed to meet noninferiority compared to prasugrel in patients with diabetes and multivessel coronary artery disease after percutaneous coronary intervention
Is a ticagrelor-based DAPT noninferior to a prasugrel-based DAPT after percutaneous coronary intervention in patients with diabetes and multivessel disease for the prevention of cardiovascular outcomes? That was the question researchers addressed in Ticagrelor vs. Prasugrel in Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Randomized Comparison From the TUXEDO-2 Trial.
The prospective multicenter open-label trial was conducted at 66 centers in India. It randomly assigned 1,800 patients with diabetes and multivessel coronary artery disease who underwent percutaneous coronary intervention 1:1 to ticagrelor or prasugrel, each in combination with aspirin. Of enrolled patients, 85% had triple vessel disease. The primary outcome was a composite of death, nonfatal myocardial infarction, stroke or major bleeding as defined by the Bleeding Academic Research Consortium at one year.
Ticagrelor was not noninferior to prasugrel, and most clinical endpoints favored prasugrel in patients with diabetes and multivessel coronary disease after percutaneous coronary intervention. At one year, the primary endpoint occurred in 16.57% of participants on ticagrelor and 14.23% participants on prasugrel (p=0.12). The risk difference failed to meet the pre-specified threshold for noninferiority (p noninferiority=0.8365).
There was a numerically higher but not statistically significant composite of death, nonfatal MI and stroke (10.43% vs. 8.63%; p=0.30) and that of major bleeding (8.41% vs. 7.14%; p= 0.19) with ticagrelor vs. prasugrel. There was excess primary outcome with ticagrelor when compared with prasugrel in those with diabetes duration less than five years (HR=1.63; 95% CI 0.99: 0.70 to 1:39) and in those with high bleeding risk (HR=1.61; 95% CI: 1.02 to 2.53).
Sripal Bangalore, MD, MHA
Prehospital treatment with zalunfiban improved outcomes in patients with STEMI
Roughly 40% of patients presenting with acute myocardial infarction have ST-segment elevation myocardial infarction (STEMI), the most severe clinical subtype, characterized by complete or near-complete occlusion of a coronary artery by thrombus, resulting in abrupt cessation of blood flow. Early reperfusion of the occluded coronary artery is critical to reduce mortality and minimize irreversible myocardial injury. Yet, a significant number of people experiencing STEMI die before they reach the hospital.
Researchers evaluated if treatment in the prehospital setting with zalunfiban, a next-generation investigational GPIIb/IIIa inhibitor, could improve patient outcomes and prevent severe cardiac damage in the CeleBrate trial.
The trial is a phase 3 prospective, double-blinded, placebo-controlled trial conducted at 45 sites in the United States, Canada, Mexico and Europe. It randomized 2,467 patients at home, in the ambulance or in a hospital emergency department from 2021 to 2025 to a single subcutaneous injection of zalunfiban in either dose 1 (0.11 mg/kg; 853 patients), dose 2 (0.13 mg/kg; 818 patients) or placebo (796 patients). The dose was administered before transferring patients to the cath lab for angiography and percutaneous coronary intervention.
Patients received phone follow-up at 30 days to report adverse events, bleeding events and injection site reactions, at 12 months to report mortality and hospitalizations for heart failure or atrial fibrillation, and, in the event of stroke, at 90 days to record stroke disability.
Zalunfiban is a fast-acting GPIIb/IIIa inhibitor with a high-grade inhibition of platelet aggregation shortly after subcutaneous administration.
Arnoud van ’t Hof, MD, PhD
The study showed a statistically significant (21%) relative risk reduction in the primary efficacy endpoint: a seven-point clinical scale that included death, stroke, recurrent myocardial infarction, stent thrombosis, congestive heart failure, large-sized myocardial infarction and no major adverse cardiac endpoint, and a statistically significant reduction in large myocardial infarction and acute stent thrombosis, compared with placebo.
“While in-hospital treatment for heart attacks has greatly improved over the years, aspirin is currently the only antiplatelet treatment routinely used in the U.S. for heart attacks before patients can get to the hospital,” van ‘t Hof said. “If zalunfiban secures regulatory approval, it would provide medical first responders with an important new tool to improve outcomes from STEMI heart attacks. Early and rapid care can lead to a cascade of benefits: opening the heart artery more quickly, reducing the risk of death and damage to the heart and improving patients’ long-term health, both here in the U.S. and around the world.”
The study was published simultaneously in New England Journal of Medicine Evidence.
Extended DAPT with clopidogrel and aspirin reduced the risk of ischemic events in patients with stable multivessel coronary artery disease
What is the best antiplatelet strategy for high-risk patients after they have safely completed their first year of treatment? That was the critical question researchers examined in Efficacy and Safety of Extended Dual Antiplatelet Therapy in Patients With Multivessel Coronary Artery Disease Undergoing Drug-Eluting Stent Implantation (DAPT-MVD).
The investigator-initiated multicenter, open-label superiority trial was conducted in 97 centers in China from 2020 to 2024. It enrolled 8,250 patients with multivessel coronary artery disease during the first 12 months after DES implantation. Patients were randomized 1:1 to extended DAPT: clopidogrel 75 mg + aspirin (75-150 mg/day) or aspirin (75-150 mg/day) monotherapy for an additional 12 months. All patients were stable after percutaneous coronary intervention without major ischemic or bleeding events. The primary efficacy endpoint was a composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. The primary safety outcome was clinically relevant bleeding, Bleeding Academic Research Consortium (BARC) types 2-5.
After a median follow-up of 34.3 months, researchers found the extended DAPT strategy was superior for efficacy and noninferior for safety. The primary efficacy outcome was significantly reduced in the extended DAPT group, occurring in 5.8% of patients vs. 6.8% of patients in the aspirin monotherapy group. This represents an 18% relative risk reduction (HR, 0.82; p=0.03). This benefit was primarily driven by a 30% relative risk reduction in myocardial infarction (HR, 0.68). The primary safety outcome was statistically identical between the groups: 1.4% in the DAPT group vs. 1.5% in the aspirin monotherapy group (HR, 0.89; p=0.54). Major bleeding (BARC 3-5) was also similar.
“These results solve a major clinical dilemma. Previous landmark trials of extended DAPT, such as the DAPT and PEGASUS-TIME 54 trials showed a trade-off. To reduce ischemic events, you had to accept a significant increase in major bleeding,” said principal investigator Jinwei Tian, MD, PhD, professor of cardiology at Harbin Medical University in Harbin, China. “But these results provide strong evidence to change clinical practice for a very specific and common patient population, he said.
“In patients with multivessel disease who are stable and event-free one year after stenting, extending DAPT with clopidogrel for another 12 months reduces the long-term risk of ischemic events without increasing the risk of bleeding. For this high-risk population, 12 months of DAPT is not enough. Extending it to 24 months appears to be the new optimal strategy.”
Myocardial blood flow imaging clarified the cause of chest pain, compared with angiography
Chest pain is one of the most common reasons patients seek primary and secondary care. Still, half or more of patients with suspected anginal symptoms who undergo clinically indicated CT coronary angiography or invasive coronary angiography do not have identified obstructive coronary artery disease. Findings from Noninvasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial help shed light on a diagnosis. The study found that compared with angiography-guided management, noninvasive cardiovascular magnetic resonance (CMR) imaging of myocardial blood flow by adenosine stress perfusion clarified the cause of chest pain and led to improvements in symptoms and health-related quality of life.
The prospective multicenter parallel group superiority trial, which builds on prior research, took place in Scotland from February 2021 to August 2023. It enrolled 272 outpatients diagnosed with noncardiac chest pain and unobstructed coronary arteries following invasive angiography to noninvasive imaging of myocardial blood flow by adenosine stress perfusion CMR imaging and randomization to CMR-guided management or standard angiography-guided management at a single reference center. All patients underwent stress CMR imaging.
In the CMR-guided group, the myocardial blood flow findings by CMR were used to inform the final diagnosis. in the control group, the myocardial blood flow results were not used to inform the final diagnosis until one year after enrollment. Patients, clinicians and research staff were blind to the results of the CMR imaging until the final follow-up visit was completed at one year. The study was coordinated by an independent clinical trial unit. The data were collected by a central data management system, and results were analyzed by a statistician who was blind to the intervention and control group allocation.
Patients received standard treatment associated with the final diagnosis post CMR scan. Of the 272 enrolled patients, 250 underwent CMR-guided imaging. Mean age of participants was 63 years; 51% were female and 17.2% had diabetes.
Approximately half of these patients had microvascular angina undiagnosed by coronary angiography, and the diagnosis was reclassified following randomized disclosure of the CMR imaging findings to the attending cardiologist. In these patients, angina burden and health-related quality of life were improved at six months and one year, compared with the control group.
Colin Berry, MBChB, PhD
