Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - insights from the IAMI trial.

BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI. METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification. RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028). CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. METHODS: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. RESULTS: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52-0.99]; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; P=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; P=0.57) in the influenza vaccine and placebo groups, respectively. CONCLUSIONS: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

BACKGROUND: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. METHODS/DESIGN: The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. IMPLICATIONS: The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.

Guideline-Recommended Time Less Than 90 Minutes From ECG to Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Is Associated with Major Survival Benefits, Especially in Octogenarians: A Contemporary Report in 11 226 Patients from NORIC.

Background Using contemporary data from NORIC (Norwegian Registry of Invasive Cardiology) we investigated the predictive value of patient age and time from ECG diagnosis to sheath insertion (ECG-2-sheath) in primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI). Methods and Results Data from 11 226 patients collected from all centers offering 24/7/365 primary percutaneous coronary intervention service were explored. For patients aged <80 years the mortality rates were 5.6% and 7.6% at 30 days and 1 year, respectively. For octogenarians the corresponding rates were 15.0% and 24.2%. The Cox hazard ratio was 2.02 (1.93-2.11, P value <0.0001) per 10 years of patient age. Time from ECG-2-sheath was significantly associated with mortality with a 3.6% increase per 30 minutes of time. Using achievement of time goal <90 minutes in patients aged >80 years and mortality at 30 days, mortality was 10.5% and 17.7% for <90 or ≥90 minutes, respectively. The number needed to prevent 1 death was 39 in the whole population and 14 in the elderly. Restricted mean survival gains during median 938 days of follow-up in patients with ECG-2-sheath time <90 minutes were 24 and 76 days for patients aged <80 and ≥80 years, respectively. Conclusions Time from ECG-diagnosis to sheath insertion is strongly correlated with mortality. This applies especially to octogenarians who derive the most in terms of absolute mortality reduction. Registration URL: https://helsedata.no/en/forvaltere/norwegian-institute-of-public-health/norwegian-registry-of-invasive-cardiology/.

Long-term survival after coronary bypass surgery and percutaneous coronary intervention.

OBJECTIVES: To assess whether there exists a long-term difference in survival after treatment with coronary bypass surgery or percutaneous coronary intervention in patients with coronary disease as judged by all-cause mortality. METHODS: Retrospective study from the Feiring Heart Clinic database of survival in 22 880 patients-15 078 treated with percutaneous coronary intervention and 7802 with bypass surgery followed up to 16 years. RESULTS: Cox regression and propensity score analysis showed no difference in survival for one-vessel and two-vessel disease during the whole study period. In three-vessel disease, however, the analysis revealed a consistent and highly significant survival benefit in the first 8 years with an HR of 0.76 (95% CI 0.69 to 0.84, p<0.001) in favour of bypass surgery with similar survival rates in the two treatment strategies after that time period. CONCLUSIONS: Treatment strategy did not affect survival in one-vessel and two-vessel disease, but bypass surgery offered an improved survival in the first 8 years in patients with three-vessel disease. These results are consistent with most previous reports and the survival benefit should be taken into account when selecting a strategy for this patient group.

Variability of quantitative coronary angiography: an evaluation of on-site versus core laboratory analysis.

To assess the validity of locally performed off-line quantitative coronary angiography (QCA) measurement in clinical trials, we carried out a comparative study between on-site QCA analysis and analysis performed at an independent external core laboratory. One local operator analyzed the pre, post and follow-up angiograms of 116 patients participating in the Stenting in Small Coronary Arteries Study (SISCA) prior to final QCA analysis in the core laboratory. The mean values of the reference diameter (RD), minimal lumen diameter (MLD) and diameter stenosis (DS) showed acceptable agreement between study site and core laboratory. However, on the level of individuals the interobserver differences were large, affecting the outcome of restenosis rate significantly, and in a such way that the conclusions in the SISCA trial might have come out differently if a core laboratory had not been used. This emphasizes the importance of using independent core laboratories in coronary interventional trials.

Clinical benefit of small vessel stenting: one-year follow-up of the SISCA trial.

OBJECTIVE: To assess the long-term clinical benefit of elective stenting as compared with percutaneous transluminal coronary angioplasty (PTCA) in small coronary arteries. DESIGN: The Stenting in Small Coronary Arteries (SISCA) trial was a randomized trial comparing elective stenting with PTCA in coronary arteries with a reference diameter of 2.1-3.0 mm. The heparin-coated beStent was used. Control angiography was performed after 6 months, and the patients were followed clinically for 12 months. RESULTS: At 6 months the clinical outcome was significantly better in the stent group as compared with the PTCA group, with an event-free survival in 90.5 and 76.1% (p = 0.016), respectively. From 6 to 12 months, event-free survival was unchanged in both groups, demonstrating a sustained long-term clinical benefit of elective stenting. CONCLUSION: Angioplasty in small coronary arteries is associated with a favorable clinical outcome after 1 year. The clinical benefit of elective stenting using the Hepamed-coated beStent is maintained beyond 6 months, without any tendency towards late events. Thus, elective stenting should be considered as an option when treating small coronary arteries.