A study conducted by the University of Bordeaux and the Bordeaux University Hospital (France) indicates that stopping statin treatment to lower cholesterol in people aged 75 or older is not inferior to continuing it in terms of overall mortality. However, no improvements in quality of life were observed, and the authors insist that any decision to discontinue medication should always be made after consulting with the responsible physician.
The work, published in the journal "The Lancet Healthy Longevity," aims to provide evidence to the debate on the usefulness of statins to prevent atherosclerotic cardiovascular disease in those over 75 years old without previous history.
To this end, individuals aged 75 or older who had been prescribed a statin for at least one year as primary prevention, without a history of atherosclerotic cardiovascular disease and with the capacity to give informed consent, were recruited.
In total, 639 participants remained in the group that continued with statins, while 521 were assigned to the group that interrupted treatment. The follow-up lasted for 36 months.
At the end of the observation period, 48 (7.9%) of the 604 participants who continued with statins had died, and 35 (7.2%) of the 484 who discontinued them. The absolute difference in mortality from any cause between the two groups, the primary endpoint of the trial, was -0.68 percent.
As the upper limit of that difference did not exceed the predetermined non-inferiority margin of five percent, the authors conclude that stopping the statin was not inferior to maintaining it regarding mortality from all causes at three years.
Regarding safety, adverse events were recorded in 461 (73.1%) of 631 people in the continuation group, and in 390 (74.0%) of 527 in the interruption group. Non-cardiovascular adverse events affected 456 (72.3%) of 631 participants who continued with statins and 383 (72.7%) of 527 who discontinued them.
Criticism from specialists on the design and scope of the study
The professor of Cardiology at the University of Sheffield (United Kingdom) Robert Storey has warned in statements to Science Media Centre (SMC) UK that this study "presents numerous limitations and should not be used to make decisions about most people treated with statins in this age group."
According to what has been pointed out, the trial is "too small" and the follow-up time is "too short" to clearly define the benefits of the treatment. Furthermore, it is noted that statins usually reduce the risk of myocardial infarction more than total mortality.
"In this study, a myocardial infarction occurred in 1.4 percent of those who continued with statins, compared to 2.1 percent of those who stopped taking them. Although the study was not large enough to get a very precise idea of the actual risk of myocardial infarction, these data should at least invoke some caution when it comes to discontinuing statins," it has been commented.
Storey has added that, although all participants were over 75 years old, more than half were over 80, so their probability of dying from non-cardiovascular causes was very high. Likewise, it has been emphasized, in line with the authors, that there were no indications that continuing treatment with statins was harmful.
He has also pointed out the difficulties in recruitment, which he attributes to the refusal of many people to interrupt a treatment perceived as beneficial solely because of their age. In his view, this could mean that the sample does not well represent the population over 75 years old that comes to consultation to assess whether to continue with statins or not.
Lack of statistical power and more robust prior evidence
In the same vein, the former president of the Spanish Society of Arteriosclerosis (SEA) and physician of the Internal Medicine Unit of the University Hospital Fundación Alcorcón, Carlos Guijarro, has questioned the solidity of the work in statements to SMC Spain, emphasizing that it does not provide sufficiently compelling data to assert that discontinuing treatment changes mortality, nor that it improves or deteriorates quality of life.
"In reality, the authors have not demonstrated that withdrawing statins is inferior, or superior, to maintaining them, because the power of the study is much lower than anticipated (half the patients have been recruited); and mortality was half of what was expected, so the power of the study must drop from 90 to less than 50 percent, such that the study's ability to detect the primary objective is in the range of flipping a coin, if it is not even lower," it has been asserted.
Guijarro also recalls that these results, in addition to being weak, contrast with the "very solid" evidence from previous intervention trials, such as a meta-analysis published also in "The Lancet" with 186,000 patients, of which about 14,000 were over 75 years old and were followed for 4.9 years, where consistent benefits were observed.
Likewise, he has pointed out that population studies have found that the suspension of statins is associated with an increase in cardiovascular morbidity and mortality. "It is true that they are observational studies, not intervention studies, and while their methodological quality is lower due to being subject to biases, they are studies with tens of thousands of patients," he has specified.
Guijarro insists that this trial should not be interpreted as proof that statins cease to be useful after the age of 80, and emphasizes that the findings reinforce the need for doctors to discuss individually with each older patient what to do in complex clinical situations, "as it should always be."