Background and Aims: Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients. Methods: MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819). Results: Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63–1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44–0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18–0.95; P = .037). There was no significant difference in mortality. Conclusions: No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.

Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is a frequent cause of hospital admission in older people, but clinical trials targeting this population are scarce. The After Eighty Study assessed the effect of an invasive vs a conservative treatment strategy in a very old population with NSTE-ACS. Between 2010 and 2014, the investigators randomized 457 patients with NSTE-ACS aged ≥80 years (mean age 85 years) to an invasive strategy involving early coronary angiography with immediate evaluation for revascularization and optimal medical therapy or to a conservative strategy (ie, optimal medical therapy). The primary endpoint was a composite of myocardial infarction, need for urgent revascularization, stroke, and death. The long-term outcomes are presented. After a median follow up of 5.3 years, the invasive strategy was superior to the conservative strategy in the reduction of the primary endpoint (incidence rate ratio: 0.76; 95% CI: 0.63-0.93; P = 0.0057). The invasive strategy demonstrated a significant gain in event-free survival of 276 days (95% CI: 151-400 days; P = 0.0001) at 5 years and 337 days (95% CI: 123-550 days; P = 0.0001) at 10 years. These results were consistent across subgroups of patients with respect to major cardiovascular prognostic factors. In patients aged ≥80 years with NSTE-ACS, the invasive strategy was superior to the conservative strategy in the reduction of composite events and demonstrated a significant gain in event-free survival. (The After Eighty Study: a randomized controlled trial; NCT01255540).

In the After Eighty study (ClinicalTrials.gov.number, NCT01255540), patients aged 80 years or more, with non-ST-elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UAP), were randomised to either an invasive or conservative management approach. We sought to compare the effects of these management strategies on health related quality of life (HRQOL) after 1 year. the After Eighty study was a prospective randomised controlled multicenter trial. In total, 457 patients aged 80 or over, with NSTEMI or UAP, were randomised to either an invasive strategy (n = 229, mean age: 84.7 years), involving early coronary angiography, with immediate evaluation for percutaneous coronary intervention, coronary artery bypass graft, optimal medical therapy, or to a conservative strategy (n = 228, mean age: 84.9 years). The Short Form 36 health survey (SF-36) was used to assess HRQOL at baseline, and at the 1-year follow-up. baseline SF-36 completion was achieved for 208 and 216 patients in the invasive and conservative groups, respectively. A total of 137 in the invasive group and 136 patients in the conservative group completed the SF-36 form at follow-up. When comparing the changes from follow-up to baseline (delta) no significant changes in quality-of-life scores were observed between the two strategies in any of the domains, expect for a small but statistically significant difference in bodily pain. This difference in only one of the SF-36 subscales may not necessarily be clinically significant. from baseline to the 1 year follow-up, only minor differences in change of HRQOL as measured by SF-36 were seen by comparing an invasive and conservative strategy. NCT01255540.

Background. The Nod‐Like‐Receptor‐Protein‐3 (NLRP3) inflammasome and the Interleukin‐6 (IL‐6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross‐sectional study, we aimed to study presence, localization, and genetic expression of inflammasome‐ and IL‐6‐ signaling‐related proteins in coronary thrombi and circulating leukocytes from ST‐elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Methods. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll‐Like‐Receptor‐4 (TLR4), NLRP3, caspase 1, Interleukin‐1β (IL1‐β), Interleukin‐18 (IL‐18), IL‐6, IL‐6‐receptor (IL‐6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT‐PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Results. Genes encoding the 8 markers were present in 76‐100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T (r = 0.455, p = 0.013), as did NLRP3 (r = 0.468, p = 0.024). Troponin T correlated with expression in circulating leukocytes of TLR4 (r = 0.438, p = 0.011), NLRP3 (r = 0.420, p = 0.0149), and IL‐1β (r = 0.394, p = 0.023). IL‐6R expression in thrombi correlated significantly to troponin T (r = 0.434, p = 0.019), whereas gp130 was inversely correlated (r = −0.398, p = 0.050). IL‐6 in circulating leukocytes correlated inversely to troponin T (r = −0.421, p = 0.015). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. Conclusions. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti‐inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822.