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

Abstract

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).

Figure 1:. Effects of statin therapy on cancer incidence in each study.

In the left panel, unweighted rate ratios (RRs) are plotted for each trial of the comparison of first event rates between randomly allocated treatment groups, along with their 99% confidence intervals (CIs). Trials are ordered according to the absolute reduction in LDL cholesterol at 1 year within each type of trial comparison (statin versus control and more versus less statin). In the right panel, rate ratios are weighted per 1 mmol/L LDL cholesterol difference at 1 year. Totals and subtotals, together with their 95% CIs, are indicated by open diamonds.

Figure 2:. Effects of statin therapy on cancer mortality in each study.

Symbols and conventions as in Figure 1. Deaths from cancers known to have been first diagnosed prior to randomization are excluded.

Figure 3:. Effects of statin therapy on cancer incidence and mortality, by duration of treatment.

Symbols and conventions as in Figure 1.

Figure 4:. Effects of statin therapy on cancer incidence and mortality, by baseline LDL cholesterol.

Symbols and conventions as in Figure 1. To convert from mmol/L to mg/dL divide by 0.02586.

Figure 5:. Effects of statin therapy on cancer incidence and mortality, by age and sex.

Symbols and conventions as in Figure 1.