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Take a look at a selection of our recent media coverage:

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.

Atorvastatin of no value for ICU COVID-19 patients

13th January 2022

Atorvastatin use among intensive care patients does not result in a significant reduction of adverse outcomes among patients with COVID-19.

Atorvastatin given to patients infected with COVID-19 and admitted to an intensive care unit (ICU) is not associated with a significant reduction in adverse outcomes according to research by a team from the Rajaie Cardiovascular Medical and Research Centre, Tehran, Iran.

Hydroxymethylglutaryl coenzyme A reductase inhibitors (or statins), are known to exert a direct antithrombotic effect in models of arterial and venous thrombosis via a mechanism unrelated to the cholesterol-lowering activity, as well as having anti-inflammatory properties .

Furthermore, a 2021 systematic review also identified additional identified additional pleiotropic effects including antiviral and immunomodulatory that might help treat COVID-19.

Given this potential beneficial role for statins, the Iranian team sought to examine the impact of atorvastatin on thromboembolic events or death, in patients with the COVID-19, admitted to ICU. Their study was part of the INSPIRATION trial which had two arms: one that explored the effect of prophylactic anticoagulation and the other focusing on the use of atorvastatin.

The team recruited adult patients (> 18 years of age) with a PCR confirmed COVID-19 infection, admitted to ICU and in whom there was no baseline therapeutic need for a statin. Enrolled patients were then randomised 1:1 to atorvastatin 20 mg daily or matching placebo and followed for 30 days after randomisation.

For patients requiring mechanical ventilation, the drug was delivered via a nasogastric or orogastric tube. The primary outcome of interest was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation or all-cause mortality within 30 days of randomisation.

Findings

A total of 587 patients with a median age of 57 years (44% female) were randomised to atorvastatin or placebo and treatment was used for a median of 21 days and slightly less, at 19 days for placebo. The median length of stay within ICU was 5 days in both groups.

After 30 days, the primary outcome had occurred in 95 (33%) of patients assigned to atorvastatin and 108 (36%) of those given placebo (odds ratio, OR = 0.84, 95% CI 0.58 – 1.21, p = 0.35).

The results for the primary outcome were largely driven by mortality, with 31% and 35% of deaths in the atorvastatin and placebo groups respectively although no patients required extracorporeal membrane oxygenation.

The use of imaging tests such as computed tomography pulmonary angiograms and doppler, revealed a similar level of venous thromboembolism diagnoses in the two groups (20% vs 20%, p = 0.64).

There was also no difference in the incidence of arterial thrombosis. In subgroup analysis, there were no sex-related differences, among patients older/younger than 65 years, smokers or in those with/without obesity or diabetes.

In trying to account for their findings, the authors speculated that atorvastatin may have had a small protective effect which was undetectable or that statins were only of benefit in the early stages of COVID-19 infection prior to the inflammatory response which led to irreversible damage.

Citation
INSPIRATION-S investigators. Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial. BMJ 2022.

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