Statin associated lower cancer risk and related mortality in patients with heart failure

Abstract

Aims: Patients with heart failure (HF) have an increased risk of incident cancer. Data relating to the association of statin use with cancer risk and cancer-related mortality among patients with HF are sparse.

Methods and results: Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (n = 87 102) from 2003 to 2015. Inverse probability of treatment weighting was used to balance baseline covariates between statin nonusers (n = 50 926) with statin users (n = 36 176). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of cancer and cancer-related mortality associated with statin use. Of all eligible subjects, the mean age was 76.5 ± 12.8 years, and 47.8% was male. Over a median follow-up of 4.1 years (interquartile range: 1.6-6.8), 11 052 (12.7%) were diagnosed with cancer. Statin use (vs. none) was associated with a 16% lower risk of cancer incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.84; 95% confidence interval (CI), 0.80-0.89]. This inverse association with risk of cancer was duration dependent; as compared with short-term statin use (3 months to <2 years), the adjusted SHR was 0.99 (95% CI, 0.87-1.13) for 2 to <4 years of use, 0.82 (95% CI, 0.70-0.97) for 4 to <6 years of use, and 0.78 (95% CI, 0.65-0.93) for ≥6 years of use. Ten-year cancer-related mortality was 3.8% among statin users and 5.2% among nonusers (absolute risk difference, -1.4 percentage points [95% CI, -1.6% to -1.2%]; adjusted SHR = 0.74; 95% CI, 0.67-0.81).

Conclusion: Our study suggests that statin use is associated with a significantly lower risk of incident cancer and cancer-related mortality in HF, an association that appears to be duration dependent.

Keywords: Cancer; Cardio-oncology; Heart failure; Prevention; Statin.

Statin use is associated with a significantly lower risk of incident cancer and cancer-related mortality in patients with heart failure and results were consistent across clinical subgroups and in sensitivity analyses. The potential protective effect of statin on development of cancer merits evaluation in future randomized studies.

Figure 1

Flow chart of the study cohort. HF, heart failure; HIV, human immunodeficiency virus. *Statin user was defined by filled prescription for at least 90 consecutive days use of statin after the index date; statin nonuser was defined as never use of statin or <90 consecutive days of statin use after the index date.

Figure 2

Cumulative incidence of cancer between statin user and nonuser. Statin user was defined by filled prescription for at least 90 consecutive days of statin use after the index date (the date on which a patient was diagnosed as incident heart failure). Statin nonuser was defined as never use of statin or <90 consecutive days of statin use after the index date. We calculated the P-value using Gray’s test for equality of the cumulative functions between each exposure group after inverse probability of treatment weighting, accounting for competing risks of all-cause mortality. The inset shows the same data on an expanded y-axis.

Figure 3

Cancer-related mortality between statin user and nonuser. Statin user was defined by filled prescription for at least 90 consecutive days of statin use after the index date (the date on which a patient was diagnosed as incident heart failure). Statin nonuser was defined as never use of statin or <90 consecutive days of statin use after the index date. We calculated the P-value using Gray’s test for equality of the cumulative functions between each exposure group after inverse probability of treatment weighting, accounting for competing risks of non-cancer-related mortality. The inset shows the same data on an expanded y-axis.

Figure 4

Multivariable stratified analysis of the association between statin use and risk of cancer. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; SHR, subdistribution hazard ratio. *Statin use was defined by filled prescription for at least 90 consecutive days of statin use after the index date (the date on which a patient was diagnosed as incident heart failure). We calculated the P-value using Gray’s test for equality of the cumulative functions between each exposure group after inverse probability of treatment weighting, accounting for competing risks of all-cause mortality.