Statin use may be associated with a significantly lower risk of incident cancer and cancer-related mortality in heart failure, and this association is may be duration dependent, according to research results published in the European Heart Journal.

Currently, the literature lacks data that evaluate the relationship between statin use and cancer risk, as well as cancer-related mortality, in patients with heart failure. Researchers sought to address that deficiency in the current study, evaluating these relationships in a retrospective cohort study using data from the territory-wide Hong Kong Clinical Data Analysis Reporting System.

The primary study outcome was incident cancer subsequent to heart failure diagnosis. Patients were followed until a cancer diagnosis, death, or December 31, 2018.

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Investigators identified 87,102 patients with incident heart failure between 2003 and 2015. Of these, 64% were 75 years and older, 48% were men, and 51% had hypertension. Over one-third of patients (35%) had coronary artery disease.

In total, 36,176 patients used statins while 50,926 were statin nonusers.

Over a median follow-up period of 4.1 years (404,924 person-years), 12.7% of patients were diagnosed with cancer, and 4.4% of patients had cancer-related mortality. The most common types of cancers were colorectal, stomach, lung, and liver/biliary system.

Median age at cancer diagnosis was 79.7 years, with a median time to diagnosis from the heart failure index date of 3.8 years. Propensity-matched statin users had a lower risk of developing cancer, with a 5-year cumulative cancer incidence of 7.9% among those who used statins, and a 10.4% rate among nonusers. The 10-year cumulative incidence rates were 11.2% and 13.2% among statin users and nonusers, respectively.

The 10-year cancer mortality was 3.8% and 5.2% in statin users and nonusers. Statin use was significantly associated with a lower adjusted risk of cancer-related death compared with nonusers (subdistribution hazard ratio [SHR], 0.74; 95% CI, 0.67-0.81). The 10-year all-cause mortality was 60.5% and 78.8% among statin users and nonusers, and the use of statins was significantly associated with a lower adjusted all-cause mortality risk (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64).

Crude 10-year cumulative cancer incidence among statin users with atherosclerotic disease did not differ; absolute risk difference was 0.07%. Corresponding incidence among lipid control groups was 10.3%, 10.5%, and 10.8% in low-density lipoprotein (LDL) <1.8, 1.8 to 2.6, and >2.6 mmol/L. Following multivariable adjustment, cancer incidence in statin users was not related to statin indication or time-weighted LDL control.

The inverse relationship between statin use and cancer risk was duration dependent; risk of cancer was significantly lower with statin use of 4 to 6 years (adjusted SHR, 0.82) and was lowered further with long-term statin use of more than 6 years (adjusted SHR, 0.78).

Similar results demonstrating duration response were found in the association between statin use and cancer-related death. The risk of cancer-related death was significantly lower in statin use from 4 to 6 years and 6 or more years (adjusted SHR, 0.67 and 0.61) vs with short-term statin use.

Sensitivity analysis results were consistent after the exclusion of patients with a history of alcohol abuse or smoking. Cox regression HR for cancer risk was 0.83.

Study limitations include a lack of data on familial cancer history as a risk factor, no data on left ventricular ejection fraction, and potential residual confounders.

“We demonstrated that incident cancer was not uncommon [and] notably, statin use was associated with a reduced risk of cancer and cancer-related mortality,” the researchers concluded. “These findings have major clinical implications to reduce the associated burden in HF. The potential protective effect of statin on the development of cancer merits evaluation in future randomized studies.”


Ren QW, Yu SY, Teng TK, et al. Statin associated lower cancer risk and related mortality in patients with heart failure. Eur Heart J. Published online June 22, 2021. doi:10.1093/eurheartj.ehab325