Study suggests need for early implantable defibrillators in high-risk heart failure patients

12th September 2023

Percutaneous coronary intervention (PCI) combined with implantable defibrillators and optimal medical therapy (OMT) may benefit high-risk heart failure patients with low left ventricular ejection fractions, according to a recent study.

Patients with ischaemic left ventricular dysfunction normally undergo either coronary artery bypass graft or PCI before the insertion of implantable defibrillators. This is based on the assumption that PCI lowers the incidence of potentially fatal ventricular arrhythmias, avoiding the need to insert such defibrillators.

However, a randomised trial by researchers at King’s College London and funded by the British Heart Foundation (BHF) has revealed that PCI does not reliably improve the heart’s ability to pump or reduce the risk of these life-threatening ventricular arrhythmias. As a result, the team has suggested high-risk patients should no longer have to wait the standard 90 days following PCI before assessing the need for insertion of an implantable defibrillator.

Implantable defibrillators combined with PCI

Patients with heart failure and a low ejection fraction benefit from a cocktail of drug therapy which includes ACE inhibitors, beta-blockers and amiodarone. Consequently, the study protocol dictated that all patients should receive OMT as part of the standard treatment.

Some 700 patients with ischaemic left ventricular systolic dysfunction were randomised to receive either PCI with OMT or OMT alone. Although the use of an implantable defibrillator was considered to be an integral component of OMT for all patients, the decision to implant such a device was at the discretion of heart teams at recruiting centres.

The researchers set a composite primary outcome of all-cause death or aborted sudden death, which was defined as an appropriate implantable defibrillator therapy or a resuscitated cardiac arrest, at a minimum of 24 months.

The median left ventricular ejection fraction was low at 28%, and 53.1% of patients had an implantable defibrillator inserted before randomisation or during the study follow-up.

All-cause death or aborted sudden death occurred in a similar proportion of patients in each group (hazard ratio, HR = 1.03, 95% CI 0.82 – 1.30, p = 0.80). There was also no between-group difference in the occurrence of any of the secondary outcomes.

Commenting on these findings, one of the research team, Dr Holly Morgan, BHF clinical research fellow at the King’s College London BHF Centre of Research Excellence, said: ‘Our findings have revealed that many patients with a high-risk of heart failure could benefit from receiving an ICD [implantable cardioverter defibrillator device] straight away, rather than facing a 90-day wait.‘

She continued: ‘We hope our findings will influence existing guidance, so patients can be spared unnecessary waits to receive a potentially lifesaving defibrillator.‘

Dr Sonya Babu-Narayan, associate medical director at the BHF, added: ‘The results from this large UK-wide trial could lead to re-evaluation of how best to treat people living with severe heart failure due to coronary heart disease. The findings suggest that the current “wait and see“ approach to find out whether a patients’ heart function improves with medication and stents isn’t always best, and that an unnecessary wait could even be the difference between life and death.‘

Cardiac dysfunction reduced by atorvastatin in anthracycline-based chemotherapy

11th August 2023

The use of atorvastatin prior to anthracycline-based chemotherapy in lymphoma patients reduces the subsequent development of cardiac dysfunction, according to the findings of a randomised trial.

Provision of the cholesterol lowering drug atorvastatin before starting anthracycline-based chemotherapy for the treatment of lymphoma, lowered the risk of developing a reduction in left ventricular ejection fraction.

Published in the journal JAMA, the study was designed to test whether atorvastatin was associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.

The Statins to Prevent the Cardiotoxicity of Anthracyclines, STOP-CA trial, was a multicentre, double-blind, randomised, placebo-controlled trial of 40 mg daily of atorvastatin administered to patients receiving anthracyclines for lymphoma. It enrolled lymphoma patients who were scheduled to receive anthracycline-based chemotherapy, but it excluded those already treated with a statin or who had clinical indication for a statin.

Prior to chemotherapy, all participants underwent a baseline assessment of heart rate, blood pressure, weight, blood tests and left ventricular ejection fraction (LVEF). Individuals were then randomised in a 1:1 ratio to receive oral atorvastatin or placebo, commencing prior to the first scheduled anthracycline infusion and then continued for 12 months. Echocardiographic measures of LVEF were performed on anonymised images in a core laboratory at the University of Pennsylvania.

The primary endpoint was the proportion of participants in each group with an absolute decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55% over the 12-month study period.

A secondary endpoint was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.

Atorvastatin and decline in LVEF

Of the 300 participants, 286 completed the trial. Among the entire cohort, the baseline mean LVEF was 63% and the follow-up LVEF was 58%.

At the 12-month follow-up, the incidence of the primary endpoint was 9% in the atorvastatin group and 22% in the placebo group (p = 0.002). The researchers calculated that the odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost three times greater for participants randomised to placebo (odds ratio, OR = 2.9 95% C 1.4 – 6.4).

In addition, compared with placebo, atorvastatin also reduced the incidence of the secondary endpoint (13% vs 29%; p = 0.001). The number of serious related adverse events was low and similar between groups.

Based on the results, the authors wrote that these finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.