You might be interested in…Cardiovascular Disease Update (Part 1)

There has been a number of important papers published in the last few months on the broad topic of cardiovascular disease (CVD) that have practical implications for the clinician. I will deal with them in two parts over the next fortnight.

Aspirin and antiplatelet treatment
Guidelines recommend against routine initiation of low-dose aspirin in older adults for primary prevention of atherosclerotic CVD events. This study1 aimed to estimate long-term and post-trial effects of aspirin on major adverse cardiovascular events (MACE) and major haemorrhage using extended follow-up of participants from the ASPREE trial. In-trial (2010–17) and post-trial (2017–22) data were analysed.

At enrolment, participants were aged ≥70 years (≥65 years for US minorities) without prior cardiovascular (CV) events, dementia, or independence-limiting physical disability. Randomization was to daily low-dose aspirin or matching placebo for the 4.7 years of the trial.

Dr Ray O’Connor

The results showed that of the 19,114 participants randomized (9,525 aspirin, 9,589 placebo), 15,668 without in-trial MACE consented to post-trial follow-up. No long-term benefit of randomization to aspirin was observed for MACE for the entire in-trial and post-trial period.

However, during the post-trial period (median 4.3 years), there was a higher rate of MACE (HR 1.17) in those randomized to aspirin compared with placebo. Over the entire period, a higher rate of major haemorrhage was also observed in the randomized aspirin group compared with placebo (HR 1.24).

Thus, the study provides novel evidence concerning increased risk of long-term MACE and haemorrhage following aspirin use in initially healthy older adults. The finding of no long-term MACE benefit needs to be considered in clinical decision-making if aspirin is being considered for use in this context.

What about use of aspirin in those with high atherothrombotic risk and currently receiving long-term oral anticoagulation? This is a scenario all too familiar to GPs where an elderly patient on anticoagulation for atrial fibrillation for example is found to have ischaemic heart disease.

The study2 was a multicentre, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrolment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation.

The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of CV death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding.

A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group.

A primary efficacy outcome event occurred in 73 patients (16.9 per cent) in the aspirin group and in 53 patients (12.1 per cent) in the placebo group (adjusted hazard ratio, 1.53). Death from any cause occurred in 58 patients (13.4 per cent) in the aspirin group and in 37 (8.4 per cent) in the placebo group (adjusted hazard ratio, 1.72). Major bleeding occurred in 44 patients (10.2 per cent) in the aspirin group and in 15 patients (3.4 per cent) in the placebo group.

The conclusion was that among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding.

Patients benefit from antiplatelet therapy after coronary-artery bypass grafting (CABG) for an acute coronary syndrome. Whether the addition of ticagrelor to aspirin, as compared with aspirin alone, further reduces the risk of adverse CV outcomes is unclear.

This was an open-label, registry-based, clinical trial conducted at 22 Nordic cardiothoracic surgery centres.3 The authors randomly assigned patients in a 1:1 ratio to receive either ticagrelor plus aspirin or aspirin alone for one year after CABG for an acute coronary syndrome. The primary outcome was a composite of death, myocardial infarction, stroke, or repeat revascularization, evaluated at one year.

A key secondary outcome was net adverse clinical events, defined as a primary-outcome event or major bleeding. A total of 2,201 patients were randomly assigned to receive ticagrelor plus aspirin (1,104 patients) or aspirin alone (1,097 patients). The mean age of the patients was 66 years, and 14.4 per cent were women. A primary-outcome event occurred in 53 patients (4.8 per cent) in the ticagrelor-plus-aspirin group and 50 (4.6 per cent) in the aspirin-alone group (hazard ratio, 1.06; P = 0.77).

Net adverse clinical events occurred in 9.1 per cent of patients in the ticagrelor-plus-aspirin group and 6.4 per cent in the aspirin-alone group (hazard ratio, 1.45). Major bleeding occurred in 4.9 per cent of patients in the ticagrelor-plus-aspirin group and 2.0 per cent in the aspirin-alone group (hazard ratio, 2.50).

The conclusion was that among patients who underwent CABG for an acute coronary syndrome, ticagrelor plus aspirin did not result in a lower incidence of death, myocardial infarction, stroke, or repeat coronary revascularization than aspirin alone at one year, but the risk of major bleeding was higher.

Colchicine post MI
Inflammation is associated with adverse cardiovascular events. Data from recent trials have suggested that colchicine reduces the risk of CV events. This was a multicentre trial with a 2-by-2 factorial design.4 The authors randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo.

The results of the colchicine trial are reported in this paper. The primary efficacy outcome was a composite of death from CV causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. A total of 7,062 patients at 104 centres in 14 countries underwent randomization.

A primary-outcome event occurred in 322 of 3,528 patients (9.1 per cent) in the colchicine group and 327 of 3,534 patients (9.3 per cent) in the placebo group over a median follow-up period of three years. The conclusion was that treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from CV causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization).

CVD risk prediction
Five risk factors account for approximately 50 per cent of the global burden of CV disease (CVD). How the presence or absence of classic risk factors affects lifetime estimates of CVD and death from any cause remains unclear.

The authors of this study5 harmonized individual-level data from 2,078,948 participants across 133 cohorts, 39 countries, and six continents. Lifetime risk of CVD and death from any cause was estimated up to 90 years of age according to the presence or absence of arterial hypertension, hyperlipidaemia, underweight and overweight or obesity, diabetes, and smoking at 50 years of age.

Differences in life span (in terms of additional life-years free of CVD or death from any cause) according to the presence or absence of these risk factors were also estimated. Risk-factor trajectories were analysed to predict lifetime differences according to risk-factor variation.

The results were that the lifetime risk of CVD was 24 per cent among women and 38% among men for whom all five risk factors were present. In the comparison between participants with none of the risk factors and those with all the risk factors, the estimated number of additional life-years free of CVD was 13.3 for women and 10.6 for men.

The conclusion was that the absence of five classic risk factors at 50 years of age was associated with more than a decade greater life expectancy than the presence of all five risk factors, in both sexes. Persons who modified hypertension and smoking in midlife had the most additional life-years free of CVD and death from any cause, respectively.

References:

1. Wolfe R et al. Aspirin, cardiovascular events, and major bleeding in older adults: extended follow-up of the ASPREE trial. European Heart Journal (2025) 00, 1–13 https://doi.org/10.1093/eurheartj/ehaf514
2. Lemesle G et al. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation. N Engl J Med 2025 Published August 30, 2025. https://doi.org/10.1056/NEJMoa2507532
3. Jeppsson J et al. Ticagrelor and Aspirin or Aspirin Alone after Coronary Surgery for Acute Coronary Syndrome. N Engl J Med 2025. Published on September 1, 2025, at NEJM.org. https://doi.org/10.1056/NEJMoa2508026
4. Jolly SS et al. Colchicine in Acute Myocardial Infarction. N Engl J Med 2025;392:633-642 https://doi.org/10.1056/NEJMoa2405922. VOL. 392 NO. 7
5. The Global Cardiovascular Risk Consortium. Global Effect of Cardiovascular Risk Factors on Lifetime Estimates. N Engl J Med 2025;393:125-38. https://doi.org/10.1056/NEJMoa2415879