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Statin absolute risk reduction benefit for cardiovascular outcomes only modest

Statin therapy produces only a modest absolute risk reduction in cardiovascular outcomes according to a meta-analysis of randomised trials

Statin treatment provides only a modest absolute risk reduction in adverse cardiovascular outcomes such as all-cause mortality, according to an analysis of randomised trials by researchers from the HRB Centre for Primary Care Research, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

It is increasingly recognised that the key initiating event in atherogenesis is the retention of low-density lipoprotein (LDL) cholesterol and other cholesterol-rich lipoproteins within the arterial wall. Consequently, much effort has been directed at reducing LDL cholesterol levels and treatment with a statin drug has become a well-recognised therapy for lowering LDL cholesterol. However, in many studies, authors report relative rather than absolute risk reductions. This approach represents an important weakness, since readers tend to overestimate the effect of an intervention when expressed in relative terms. In contrast, the absolute risk gives a better representation of the actual situation and also from the patient’s point of view, absolute risks often give more relevant information.

For the present analysis, the Irish team analysed both the relative and absolute risks associated with the use of statin therapy for outcomes such as all-cause mortality, myocardial infarction (MI) and stroke. They included trials which examined the efficacy of a statin on cardiovascular outcomes with a duration of at least 2 years, which enrolled more than 1,000 participants and where the comparator was either placebo or usual care.

Statin use and cardiovascular outcomes

A total of 21 trials including 1255 to 20,536 participants, of which 33% were for primary prevention, were included in the analysis. The average trial follow-up period was 4.4 years and ranged from 1.9 to 6.1 years.

From the meta-analysis, the overall absolute risk reduction (ARR) for all-cause mortality was 0.8%, 1.3% for MI and 0.4% for stroke for individuals randomised to receive a statin compared to either placebo or usual care. In contrast, the relative risk reductions (RRRs) were 9% (all-cause mortality), 29% (MI) and 14% (stroke). Using the ARR of 1.3% for MI, the authors calculated that 77 patients (i.e., 1/0.013) would need to be treated for an average of 4.4 years to prevent one myocardial infarction.

In subgroup analysis (primary vs secondary prevention), the ARR was 0.6%, 0.7% and 0.3% for all-cause mortality, MI and stroke respectively, in primary prevention trials. The corresponding RRRs were 13%, 38% and 24%.

For secondary prevention, the ARRs were 0.9% (all-cause mortality), 2.2% (MI) and 0.7% (stroke) with the corresponding RRRs of 14%, 27% and 13%.

The researchers also examined the the potential mediating effect of LDL cholesterol reduction with the absolute and relative treatment effects but these findings were inconclusive. In other words, it was not possible to either prove or disprove an association between the magnitude of LDL cholesterol reduction and the size of a treatment effect.

An important finding from the analysis was the high level of statistically heterogeneity in the studies, ranging from 27% to 82%, which suggested that pooling of results could make the findings unreliable.

The authors concluded that the absolute risk reductions associated with the use of a statin drug are modest in comparison to the often quoted relative risk reductions. However, they added that given the high level of heterogeneity, these results should be interpreted with caution. Despite this limitation, they suggested that clinicians should communicate both ARRs and RRRs to patients to enable informed decision-making about the benefits of statin treatment.

Byrne P et al. Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis Ann Intern Med 2022

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