Less Cancer Among HF Patients Taking Statins, Registry Shows

Patients with heart failure (HF) on statin therapy have a lower risk of developing cancer as well as a lower risk of cancer-related mortality when compared with those not taking statins, according to a new study. That benefit was tied to the duration of statin treatment, with the reductions evident only in those treated with statins for 4 years or more.

The results hint that statins might have a role to play for reducing the noncardiovascular disease burden of HF patients, but there is a need for further study, say investigators.    

“I believe that our study first highlights that noncardiovascular events, in our case incident cancer and related mortality, are not uncommon in patients with HF,” said senior investigator Kai-Hang Yiu, MD (University of Hong Kong/Shen Zhen Hospital, China), in an email. “The observed association with a reduced risk of cancer and related mortality by statin may have major clinical implications for reducing the associated burden in HF. However, as our study is observational, it cannot show that statins cause the reduction in cancer risk, only that they are associated with it.”

Given that, Yiu told TCTMD their findings warrant further evaluation by future randomized studies before adopting widespread statin use in the hopes of preventing cancer in HF patients. Previous studies have shown that HF patients are at a higher risk of cancer—anywhere from 27% to 68% higher—than patients without HF. While the exact mechanism is not known, he said it might be the result of HF and cancer sharing several risk factors, such as diabetes, smoking, and dyslipidemia.

“Further, it has been hypothesized that HF is an oncogenic condition, possibly related to links between neurohormonal activation to tumorigenesis, systemic pathological processes such as inflammation and oxidative stress, common genetic predisposition, and clonal hematopoiesis of cancer and HF,” he said.

Observational Data so Caution Warranted

The study, published today in the European Heart Journal, involved 87,102 patients with newly diagnosed HF included in a territory-wide database from the Hong Kong Hospital Authority. Of these, 36,176 were taking statins, including 60.5% for atherosclerotic cardiovascular disease (ASCVD) and 23.0% for high cholesterol levels. To account for bias in the allocation of statin treatment, variables considered prognostically significant and those that influenced treatment were adjusted using inverse probability of treatment weighting. During follow-up, 11,052 patients developed cancer, including 3,864 who died.    

The cumulative incidence of cancer at 5 years was 7.9% among propensity-matched statin users and 10.4% among nonusers. At 10 years, the incidence of cancer was 11.2% and 13.2% in statin users and nonusers, respectively. After adjustment, statin users had a lower risk of developing cancer (HR 0.84; 95% CI 0.80-0.89) and a lower risk of cancer-related mortality than nonusers (HR 0.74; 95% CI 0.67-0.81) at a median 4.1 years of follow-up. At 10 years, use of statins also was associated with a lower risk of all-cause mortality (HR 0.62; 95% CI 0.61-0.64).

Statins’ benefit was linked to the duration of use. For example, there was no difference in the risk of cancer or cancer-related mortality between statin users and nonusers if patients were taking the LDL-lowering drugs for less than 4 years. However, there was a significant 18% lower risk of cancer and a 33% lower risk of cancer-related mortality among those taking statins anywhere from 4 years to less than 6 years. Those taking statins for 6 years or longer had a 22% lower risk of cancer and 39% lower risk of cancer-mortality when compared with nonusers.

“Although a causal relationship is yet to be defined by a randomized study, current data nonetheless indicates that statins might have a chemoprotective role, due to their adjunctive effect other than their lipid-lowering effect,” said Yiu.

To TCTMD, Gregg Fonarow, MD (University of California, Los Angeles), also raised the point that many risk factors predisposing patients to HF are also risk factors for cancer. However, in this latest analysis, there were large differences in patient characteristics between those treated with statins and those who were not, and they may account for the differences in cancer risk as opposed to statin use. With observational studies, the difference in outcomes may reflect selection bias and confounding as opposed to the beneficial effects of the lipid-lowering drugs, he said. 

Moreover, rigorous studies testing the potential role for statins for cancer prevention have flamed out thus far, said Fonarow.

“A large number of observational studies have shown lower mortality risk in patients with heart failure who were treated with statin therapy,” he said. “However, randomized placebo-controlled clinical trials of statins in heart failure have not demonstrated benefit for mortality or heart failure, highlighting that the observational findings, even with propensity matching, often can be misleading.”

Even outside HF, observational studies have suggested that statins for primary and secondary ASCVD prevention might lower the risk of cancer, but randomized controlled trials—with follow-up ranging from 3 to 6 years—have not demonstrated lower cancer risks, said Fonarow.

As an aside, Yiu noted that there has been a significant improvement in outcomes among patients with HF due to cardiovascular medications and treatments. The decline in cardiovascular mortality, however, is being offset by a “considerable increase in noncardiovascular mortality, with cancer-related death being the most prevalent cause,” said Yiu. For that reason, clinicians need to remain vigilant to the risk of noncardiovascular events, including cancer, in patients with stable HF, he said.