February 2023 | Issue 68
20 Coronary Interventions
BRIGHT-4 trial: Bivalirudin cuts 30-day mortality for STEMI patients undergoing PCI compared to heparin BIVALIRUDIN IS A SAFER AND MORE effective anticoagulant than heparin for treating patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI), and can lower the risk of death or major bleeding by 31%. These are key findings from a new study led by researchers from the Icahn School of Medicine at Mount Sinai (New York, USA). This is the first largescale clinical trial to compare the two anticoagulants most widely used after PCI, and shows bivalirudin given with a two- to four-hour high-dose infusion significantly reduces death, major bleeding, and thrombosis when compared with heparin, the researchers behind the study have said. The results were presented in a late-breaking clinical trial at the American Heart Association Scientific Sessions (AHA 2022; 5–7 November, Chicago, USA) and published in The Lancet. This work could have broad implications, changing the treatment course for hundreds of thousands of patients across the world who experience a STEMI, the researchers claim. “For the first time, this study identifies the best and safest treatment course for patients undergoing stenting to treat a STEMI heart attack,” said co-principal investigator Gregg W Stone (Mount Sinai Hospital, New York, USA). “Compared with heparin, bivalirudin plus a short infusion substantially improved the likelihood of surviving a STEMI and reduced the two most feared complications—major bleeding and stent thrombosis.” In the BRIGHT-4 trial, patients with STEMI underwent primary PCI,
which requires anticoagulant therapy. The most common anticoagulant used during primary PCI is heparin, but its use can lead to ischaemic and haemorrhagic complications. Heparin and bivalirudin have been compared in six prior large randomised trials in patients with STEMI, but in those studies, they were administered with varying regimens and background therapies. This new research evaluates the two most widely used regimens of heparin and bivalirudin, which have never been directly compared with each other in an adequately sized trial. Stone along with Yaling Han (Shenyang Northern Hospital, Shenyang, China) led a team of researchers to analyse 6,106 patients enrolled in the study across 87 sites in China between February 2019 and April 2022. All underwent primary PCI for STEMI treatment, nearly all with a procedure that used the radial artery in the wrist to target the blocked heart artery. Patients were randomised to receive the two most widely used regimens of heparin and bivalirudin, which prior studies have shown to be the safest and most effective. One group received heparin alone, administered intravenously. The other group received bivalirudin intravenously, followed by a high-dose infusion for two to four hours after the procedure. Investigators followed patients for 30 days after the procedure. The primary goal of the study was to compare the occurrence of allcause mortality or major bleeding. Researchers found that 4.4% of patients treated with heparin died or had a major bleed within 30 days, compared to 3.1% of patients Gregg W treated with bivalirudin. Stone Overall, the bivalirudin
Depression increases likelihood of non-adherence to medical therapy post-PCI
Patients with depression are 10–20% less likely to adhere to guideline-directed medical therapy after percutaneous coronary intervention (PCI), research published in JAMA Network Open has shown. ACCORDING TO MATTHEW E Lapa (University of Pittsburgh School of Medicine, Pittsburgh, USA) and colleagues, who conducted the research, the recognition of depression among patients undergoing PCI may facilitate targeted interventions to address medical adherence and improve secondary cardiovascular disease prevention. Lapa et al conducted a retrospective cohort study of patients undergoing PCI from January 2014 to December 2019, using data from the Optum Clinformatics DataMart database. The study team identified a diagnosis of depression as occurring during the 12 months of enrolment prior to PCI, or within six months after the procedure. Medication adherence was assessed with the proportion of days covered (PDC), calculated as the ratio of the number of days a medication is available
and the number of follow-up observation days. Twelve-month adherence was categorised as adequate (PDC ≥80% to <90%) or optimal (PDC ≥90%). A total of 124,443 patients were included in the assessment, with a mean age of 69.3 years, 41,430 of whom (33.3%) were female. Of this population, 20,711 patients (16.6%) had a diagnosis of depression. The researchers found that those with depression were significantly less likely to obtain adequate 12-month adherence to antiplatelets (odds ratio [OR], 0.80; 95% confidence interval [CI] 0.77–0.85), β-blockers (OR, 0.84; 95 CI, 0.80–0.88), and statins (OR, 0.88; 95% CI, 0.85–0.93) than those without depression. There was no association between depression and adherence to renin-angiotensin-aldosterone system inhibitors (OR, 0.93; 95% CI, 0.85–1).
group had a 31% reduction in the rate of death or major bleeding compared with patients in the heparin group—a highly statistically significant reduction. The researchers then looked at the specific incidence of death alone and major bleeding alone between the groups. They found that deaths were reduced from 3.9% in heparin-treated patients to 3% in bivalirudintreated patients. Severe bleeding was also reduced from 0.8% in the heparin group to 0.2% in the bivalirudin group. Both differences were statistically significant. They further analysed the rate of stent thrombosis, finding that this was also lower in the bivalirudin group at 0.4% compared with 1.1% in the heparin group. “These results are dramatic,” Stone said. “The simple decision to use bivalirudin during primary PCI in patients with heart attacks, which is now generic and thus inexpensive, can save hundreds of thousands of lives per year and prevent major bleeding and stent thrombosis compared with heparin.” The BRIGHT-4 trial was an investigator sponsored and organised trial, funded by the Chinese Society of Cardiology Foundation with a research grant from Jiangsu Hengrui Pharmaceuticals.
The simple decision to use bivalirudin during primary PCI in patients with heart attacks, which is now generic and thus inexpensive, can save hundreds of thousands of lives per year and prevent major bleeding and stent thrombosis compared with heparin”
Those with depression had similarly ensure frequent follow-ups, prescription decreased likelihood of optimal reminders, and counselling to target 12-month adherence to antiplatelets, challenges to medical adherence.” β-blockers, and statins as well as The study’s authors note that their renin-angiotensin-aldosterone system research has several limitations, inhibitors (OR, 0.87; 95% CI, 0.82– chiefly that it only included individuals 0.94), the researchers report. with insurance, the potential “These results indicate for misclassification of the critical importance depression status due to of strategies to reliance on claims data, address depression the use of records from as part of secondary prescription fills to cardiovascular disease determine adherence, prevention,” Lapa et al and finally the potential write. “The American for residual confounding Heart Association from unmeasured has advised depression variables that may be screening for all patients associated with depression with coronary disease given and adherence. Patients with the adverse contribution “This cohort study of depression of depression to cardiac healthcare claims found 10–20% less prognosis. However, an association between likely to adhere to guideline-directed depression commonly depression and likelihood medical therapy goes unrecognised of adequate or optimal after PCI and undertreated in 12-month adherence to clinical settings. essential guideline-directed “Either due to resistance from medical therapy agents following PCI,” patients to report their depressive the study concludes. “Further studies are symptoms or poor screening practices, needed to determine whether treatment our findings of depression negatively of depression may improve medication affecting medication adherence could adherence as well as how such treatment be underestimated. We advocate for improves secondary prevention of multidisciplinary interventions to cardiovascular disease.”