STREAM-2 Study Presented at ACC.23/WCC

A pharmaco-invasive strategy that halved the dose of tenecteplase in older ST-elevation myocardial infarction (STEMI) patients resulted in better reperfusion than primary percutaneous coronary intervention (PCI). Reperfusion was measured by electrocardiographic data in the ECG core laboratory at the Canadian VIGOUR Centre (CVC), University of Alberta (U of A), and is a key component of the results of the STREAM-2 study presented on March 5th at ACC.23/WCC.

In this study, a total of 604 patients that were ≥60 years with ≥2 mm ST-elevation in 2 contiguous leads, and unable to undergo PCI within 1 hour, were randomized (2:1) to either a pharmaco-invasive treatment of half-dose tenecteplase followed by coronary angiography and PCI (if indicated) within 24 hours after randomization, or to timely primary PCI. The median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. Efficacy endpoints were resolution of ST-deviations and the 30-day composite of death, shock, heart failure, or reinfarction.

After last angiography, more pharmaco-invasive patients than primary PCI patients had ≥50% resolution of ST-elevation (85 vs 78%, medians, p=0.05), more resolution of ST-deviation (71 vs 62%, medians, p=0.03) and less residual ST-deviation (4.5 vs 5.5 mm, medians, p=0.02). The composite clinical endpoint occurred in 12.8% (51/400) of pharmaco-invasive and 13.3% (27/203) of primary PCI patients (relative risk: 0.96; 95% CI, 0.62 to 1.48). The incidence of major non-intracranial bleeding was low in both groups.

However, the researchers also found that the risk of intracranial hemorrhage was higher than expected with half-dose tenecteplase than primary PCI and attributed this in part to protocol violations. Specifically, it has been previously shown that excessive anticoagulation with heparins and treatment of patients with contraindications increase the risk of bleeding events. They conclude that if timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided contraindications to fibrinolysis are observed and excess anticoagulation avoided. “Our study provides new data supporting a reasonable alternative treatment strategy relevant to the large population of older STEMI patients world-wide who have high morbidity and mortality especially if they are unable to undergo primary PCI facility in a timely fashion,” says study Co-Chair Dr. Paul Armstrong (Distinguished Professor, Department of Medicine, U of A).

The STREAM-2 trial was co-ordinated by the University of Leuven in Belgium, with Canadian contributions led by the CVC. Dr. Paul Armstrong served along with Dr. Frans Van de Werf (University of Leuven) as Co-Chair for the STREAM-2 Study. In addition to being a member of the Executive Committee and a Co-Principal Investigator for the study, Dr. Robert Welsh (Professor, Department of Medicine, U of A) and his team of interventional cardiologists – ably supported by an excellent paramedical emergency and cardiac catheterization laboratory personnel – were the highest enrolling site in this international trial. Furthermore, The CVC ECG core laboratory, led by Dr. Kevin Bainey (Associate Professor, Department of Medicine, U of A), played a pivotal role through their careful analysis of the key trial endpoint.

The Vital Heart Response Program (VHR), established in 2006 by Dr. Welsh in the Alberta Health Services Edmonton Zone, is a cutting-edge initiative that has significantly impacted patient outcomes in Alberta and also played an important role in the initial STREAM-I study that transformed STEMI care. The VHR program introduced an innovative approach for delivering life-saving treatment to heart attack patients faster. The program works closely with a team of remote cardiologists to recommend a course of treatment based on ECG results, and highly-trained Emergency Medical Response (EMS) paramedics to administer specialized clot-busting drugs for STEMI heart attack patients before they arrive at the hospital. “Our model of STEMI care has substantially improved outcomes in this high-risk patient population and has now been applied in our regions nationally and internationally,” says Welsh.

The Canadian VIGOUR Centre’s established history providing leadership for clinical trials of cardiovascular therapies (like STREAM-2), along with the vast knowledge generated from numerous registries and population outcome studies, has contributed to remarkably lower mortality in the Edmonton and Northern Alberta region. “The STREAM-2 trial stands as another key signal of the CVC’s commitment to innovative thought leadership of international clinical trials and contributes to a learning health care system,” says Armstrong.