CARDIOVASCULAR MEDICINE · EVIDENCE REVIEW
Cholesterol: A Valuable Ally
An English rendering of the Italian article’s discussion of a systematic review of statin trials.
Beyond relative risk reduction
In 2022, Paula Byrne and colleagues published a systematic review and meta-analysis in JAMA Internal Medicine investigating the association between statin-induced reductions in low-density lipoprotein cholesterol (LDL-C) and clinical outcomes, including all-cause mortality, myocardial infarction and stroke.
Statins can reduce cardiovascular events, but the way their benefits are communicated matters. Relative risk reduction (RRR), when presented without absolute risk reduction (ARR), may give patients an incomplete impression of the magnitude of benefit. Both measures are necessary for informed clinical decisions.
Methods and findings
The review followed Cochrane and PRISMA methodology, searched PubMed and EMBASE from January 1987 through June 2021, and considered large randomised trials involving at least 1,000 participants, planned follow-up of at least two years, and a statin-versus-placebo comparison. Twenty-one trials were included.
| Outcome | ARR (95% CI) | RRR (95% CI) |
|---|---|---|
| All-cause mortality | 0.8% (0.4–1.2) | 9% (5–14) |
| Myocardial infarction | 1.3% (0.9–1.7) | 29% (22–34) |
| Stroke | 0.4% (0.2–0.6) | 14% (5–22) |
Considerable heterogeneity was observed across trials. Meta-regression did not establish a consistent relationship between the magnitude of LDL-C lowering and relative or absolute clinical benefits.
Primary and secondary prevention
In subgroup analyses, primary prevention was associated with relative reductions of 13% in mortality, 38% in myocardial infarction and 24% in stroke. The corresponding reported relative reductions in secondary prevention were 14%, 27% and 13%, with somewhat larger absolute benefits than in primary prevention.
Clinical interpretation
The review suggests that statistically significant relative effects may correspond to relatively small absolute benefits, particularly in populations with lower baseline risk. The findings do not imply that statins are ineffective or that treatment should be withheld from high-risk patients. Instead, clinical decisions should take baseline cardiovascular risk, expected absolute benefit, adverse effects and patient preferences into account.
Important limitations include between-trial heterogeneity, reliance on published aggregate rather than individual participant data, and variation in treatment intensity, follow-up and outcome definitions. These factors complicate attempts to link the extent of LDL-C reduction directly to clinical effects.
Communicating ARR and RRR together can improve shared decision-making and support individualised treatment strategies.
Source discussed: 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. JAMA Internal Medicine. 2022.