Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).

Personalized absolute benefit of statin treatment for primary or secondary prevention of vascular disease in individual elderly patients

Objective: To estimate the absolute treatment effect of statin therapy on major adverse cardiovascular events (MACE; myocardial infarction, stroke and vascular death) for the individual patient aged C70 years. Methods: Prediction models for MACE were derived in patients aged C70 years with (n = 2550) and without (n = 3253) vascular disease from the ‘‘PROspective Study of Pravastatin in Elderly at Risk’’ (PROSPER) trial and validated in the ‘‘Secondary Manifestations of ARTerial disease’’ (SMART) cohort study (n = 1442) and the ‘‘Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm’’ (ASCOT-LLA) trial (n = 1893), respectively, using competing risk analysis. Prespecified predictors were various clinical characteristics including statin treatment. Individual absolute risk reductions (ARRs) for MACE in 5 and 10 years were estimated by subtracting ontreatment from off-treatment risk. Results: Individual ARRs were higher in elderly patients with vascular disease [5-year ARRs: median 5.1 %, interquartile range (IQR) 4.0–6.2 %, 10-year ARRs: median 7.8 %, IQR 6.8–8.6 %] than in patients without vascular disease (5-year ARRs: median 1.7 %, IQR 1.3–2.1 %, 10-year ARRs: 2.9 %, IQR 2.3–3.6 %). Ninetyeight percent of patients with vascular disease had a 5-year ARR C2.0 %, compared to 31 % of patients without vascular disease. Conclusions: With a multivariable prediction model the absolute treatment effect of a statin on MACE for individual elderly patients with and without vascular disease can be quantified. Because of high ARRs, treating all patients is more beneficial than prediction-based treatment for secondary prevention of MACE. For primary prevention of MACE, the prediction model can be used to identify those patients who benefit meaningfully from statin therapy.