1. This systematic review and meta-analysis found a modest absolute risk reduction of 0.8% in all-cause mortality from statin-induced therapy aimed at reducing low-density lipoprotein cholesterol (levels to improve cardiovascular outcomes.

2. Based on the results of this study, calculated absolute and relative risk reduction benefits should be interpreted with caution due to the presence of significant clinical and statistical heterogeneity among included trials.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Low-density lipoprotein cholesterol (LDL-C) has the ability to accumulate in vessel walls and is a causative factor for the development of atherosclerotic cardiovascular disease. The reduction of LDL-C has become a target for prevention, however the association between statin-induced reduction in LDL-C and the absolute risk reduction (ARR) of individual outcomes such as all-cause mortality, and acute cardiac events is unclear. This systematic review and meta-analysis investigated the association between statin-induced reductions in LDL-C and the ARRs in individual clinical outcomes. The primary outcome was all-cause mortality and secondary outcomes included myocardial infarction and stroke. A total of 21 large randomized clinical trials (RCTs) examining the effectiveness of statins in men and women older than 18 years were included. A meta-analysis was conducted on 19 of the 21 included studies. Meta-analyses showed the ARR to be 0.8% for all-cause mortality, 1.3% for myocardial infarction, and 0.4% for stroke. The relative risk reduction (RRR) for the same clinical outcomes was found to be 9%, 29%, and 14%, respectively. Overall, the ARR of statin-induced therapy was modest in comparison to the RRR in terms of individual clinical outcomes, and no evidence of a conclusive association was found. These findings highlight the importance of discussing ARRs during shared decision making between clinicians and patients. A major strength of this review was the evaluation of individual clinical outcomes, rather than composite outcomes which tend to be inconstantly defined and inadequately reported. A limitation to this study however, was the significant clinical and statistical heterogeneity of the included RCTs.

Click to read the study in JAMA Internal Medicine

Relevant Reading: Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions

In-Depth [systematic review and meta-analysis]: This systematic review and meta-analysis investigated the absolute and relative risk reduction in total mortality and cardiovascular events achieved with statin therapy. An initial database search of PubMed and Embase identified 275 studies, with an additional 31 studies identified from other sources. Of these, 36 studies were selected for full-text review of which, 21 studies were included in this review for quantitative synthesis. Included studies were RCTs that examined the efficacy of statin therapy on total mortality and cardiovascular outcomes within a population size greater than 1000 participants, and with a placebo comparator. Meta-analyses demonstrated reductions in the ARR of 0.8% (95% CI, 0.4%-1.2%, p=.11) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%, p= <.001) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%, p=.14) for stroke, across 21 trials with a study population randomized to receive treatment with statins. Using the same outcomes, the RRR was found to be 9% (95% CI, 5%-14%, p=.01), 29% (95% CI, 22%-34%, p=.07), and 14% (95%CI, 5%-22%, p=.01) respectively. The unadjusted meta-regression analyses demonstrated a weak association between the absolute LDL-C reductions and clinical outcomes. However, upon adjusting for study population and length of follow-up, evidence of an association was found for the relative effect on all-cause mortality, and stroke. The meta-regression was found to be inconclusive in terms of the association between statin-induced LDL-C reduction and all-cause mortality, myocardial infarction, and stroke.

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