STAREE
Atorvastatin for primary prevention in older patients
As presented by Professor Sophia Zoungas (Monash School of Public Health and Preventive Medicine - Melbourne, Australia), STAREE is the first large randomised controlled trial to examine whether statins can be used for primary prevention in older patients.
This Australian double-blind trial was conducted in 9,971 people aged ≥70 years with no history of clinical cardiovascular disease, diabetes or dementia who were randomised to atorvastatin 40 mg daily or placebo. Over a median follow-up of 5.9 years, the researchers demonstrated that the risk of major cardiovascular events was reduced by 30% in the atorvastatin group compared with the placebo group (6.0% vs. 8.3%; hazard ratio [HR] 0.70; 95% CI 0.61 to 0.82; p<0.001). However, the risk of death, dementia or persistent physical disability did not substantively differ between the two groups (12.8% vs. 13.6%; HR 0.94; 95% CI 0.84 to 1.05; p=0.25). Muscle, liver and diabetes-related adverse events were more frequent in the atorvastatin group; however, serious adverse events were uncommon.
“Now that we have provided such strong evidence, we hope to see updated guidelines to help clinicians make use of this new finding,” concluded Prof. Zoungas.
AMUNDSEN
Evolocumab before PCI for acute MI
Professor Gilles Montalescot (Hôpital Pitié-Salpêtrière, Sorbonne University - Paris, France) explained that the majority of patients do not reach appropriate LDL-C levels after an acute MI despite ESC Guideline recommendations: “Patients are often discharged from hospital on a high-dose statin, then ezetimibe and possibly bempedoic acid may be added, but it can take months before treatment is intensified with a PCSK9 inhibitor, if it ever occurs,” he said. The AMUNDSEN trial investigated whether evolocumab, administered prior to PCI, could improve target LDL-C achievement and provide early clinical benefit.
This international trial randomised 2,161 acute MI patients to immediate evolocumab prior to PCI alongside standard care or standard care alone. Patients in the control group were treated with available therapeutic options, including a PCSK9 inhibitor, according to the 2019 ESC Guidelines. All patients had clinic visits at 6 weeks and 6, 9 and 12 months including LDL-C assessments.
In total, 82% of patients in the evolocumab group and 40% of patients in the standard-care group met the primary biological endpoint of an LDL-C reduction of ≥50% from baseline and LDL-C <55 mg/dL at 12 months. The primary clinical outcome, all-cause death or unplanned cardiovascular hospitalisations occurred in 14.6% of patients with evolocumab and 15.4% with standard care in the primary intent-to-treat analysis (not significant). In a pre-specified per-protocol analysis, event rates were 10.2% with evolocumab and 14.3% with standard care (p=0.037); a hypothesis-generating finding. “The lack of a clear effect on cardiovascular outcomes in the primary analysis suggests evolocumab may not have early clinically meaningful pleiotropic effects and the benefit of lipid lowering may require more time,” commented Prof. Montalescot.
TRANQUILITY
Phase II trial of the anti-IL-6 antibody, pacibekitug
Describing the rationale for the TRANQUILITY trial, Professor Deepak Bhatt (Icahn School of Medicine at Mount Sinai - New York City, USA) explained: “A growing body of genetic, epidemiological and clinical evidence suggests that IL-6 mediates a key inflammatory pathway linked to cardiovascular risk. We evaluated the long-acting monoclonal antibody against IL-6, pacibekitug, in patients at high inflammatory risk.”
This phase II study, conducted in the US, included 143 patients with CKD (stage 3–4) and elevated hs-CRP (2 to <15 mg/L). Participants were randomised to receive subcutaneous pacibekitug 25 mg or 50 mg every 90 days, 15 mg every 30 days or placebo for 6 months.
Median time-averaged change in hs-CRP at day 180 was +7% with placebo, −76% with pacibekitug 25 mg every 90 days, −85% with pacibekitug 50 mg every 90 days and −89% with pacibekitug 15 mg every 30 days (all p<0.0001 vs. placebo). Pacibekitug was well tolerated with no clear dose-related safety signals.
Prof. Bhatt concluded: “The next step is to determine whether the effects observed will translate into improved cardiovascular outcomes for patients in a larger, longer-term phase III trial.”
REACT
Mapping the prevalence of silent atherosclerosis across adult life
Investigating the presence of silent atherosclerosis across the adult lifespan was the aim of the first part of the REACT Initiative presented by Professor Henning Bundgaard (Rigshospitalet - Copenhagen University Hospital - Copenhagen, Denmark). The study involved 16,808 adults aged 18–70 years without known ASCVD. Silent atherosclerosis was assessed by 3D ultrasound of carotid and femoral arteries and by coronary computed tomography angiography.
Silent atherosclerosis was detected in 57.1% of participants. It was already detectable in around 8% of participants aged 18–29 years and was found in more than 90% of participants aged 60–70 years, with multiterritorial involvement. Atherosclerosis prevalence increased earlier in men, whereas women showed a later and particularly steep midlife increase.
The researchers found that the SCORE2 risk tool classified only a small minority of participants with silent atherosclerosis as high risk, with a marked lack among younger participants. A major randomised trial is planned as part of the second phase of the REACT Initiative.
ENRICH-AF
Edoxaban in patients after ICH with AF
As explained by Professor Ashkan Shoamanesh (McMaster University - Hamilton, Canada), the ideal strategy to prevent ischaemic stroke is uncertain in patients with AF and a prior intracranial haemorrhage (ICH). He presented results from the ENRICH-AF trial, in which 948 patients with high-risk AF and prior ICH were randomised to edoxaban 60 mg (with dose adjustments according to the label) or no anticoagulation (no antithrombotic therapy or single antiplatelet therapy, as determined by the clinician).
Over an average of 28 months, edoxaban did not significantly reduce the primary endpoint of stroke (including ischaemic and haemorrhagic stroke) or systemic embolism compared with no anticoagulation (11.8% vs. 12.8%; HR 0.88; 95% CI 0.61 to 1.26; p=0.48). Ischaemic stroke and MI were significantly reduced with edoxaban vs. no anticoagulation; however, this benefit was offset by an almost three-fold excess in haemorrhagic stroke. The primary safety outcome of ISTH major bleeding occurred in 11.6% of patients with edoxaban and 5.2% with no anticoagulation (HR 2.23; 95% CI 1.39 to 3.59; p<0.001).
“Our findings do not support the use of standard-dose edoxaban in unselected patients with AF after ICH, but highlight the need for an individualised decision-making approach,” commented Prof. Shoamanesh. He noted ongoing trials, including the ASPIRE trial and the COCROACH meta-analysis, which will provide useful additional insights on optimal stroke prevention in this very vulnerable patient population.
DAN-RSV
RSVpreF vaccine for preventing cardiorespiratory hospitalisations
In the final presentation of the session, Professor Tor Biering-Sorensen (Gentofte University Hospital - Copenhagen, Denmark) presented an analysis of the ongoing, pragmatic DAN-RSV trial, evaluating the effectiveness of the bivalent RSV prefusion F protein–based (RSVpreF) vaccine across a broad adult population.
Among more than 500,000 adults aged ≥18 years, RSVpreF vaccination reduced the incidence of RSV-related respiratory tract disease hospitalisation during the first RSV season after vaccination compared with no vaccination (0.2 events per 1,000 person-years vs. 0.6 events per 1,000 person-years). The incidence of hospitalisation for any cardiorespiratory disease, a secondary endpoint, was 23.4 events per 1,000 person-years in the RSVpreF group and 24.9 events per 1,000 person-years in the no-vaccine group. It was concluded that these findings provide randomised evidence supporting RSVpreF vaccination for preventing severe RSV-related disease and suggest broader benefits for cardiorespiratory health in routine clinical practice.
