Statins Linked to Lower Cancer Rate in Heart Failure Patients

A new study provides more evidence supporting the idea that statins may have a role in the prevention of cancer.

This latest study ― conducted in 87,000 patients with heart failure ― showed that those patients who took statins had a significantly reduced risk of developing cancer or of dying from cancer.

“In this large-population study in heart failure patients, we found a 16% reduction in the incidence of cancer and a 36% reduction in cancer deaths in patients taking statins compared to those not taking statins,” senior author Kai-Hang Yiu, MD, University of Hong Kong, told Medscape Medical News.

“This is the largest study to look at the effects of statins in heart failure and the first major study to investigate cancer-related outcomes in heart failure,” Yiu added. “Our results are important, as we are seeing an increase in the incidence of cancer in heart failure patients.”

The study was published online in the European Heart Journal on June 23.

Yiu explained that patients with heart failure are having improved outcomes and are living longer because of better treatments. The reasons for mortality are shifting from cardiovascular events to noncardiovascular conditions.

“In particular, cancer deaths make up one of the most important noncardiovascular mortalities in heart failure patients. So, it is important to look for any strategies to reduce the burden of cancer in these patients,” he said.

He noted that statins have been proposed to have chemoprotective effects in other studies, and his group wanted to investigate this possibility more closely in the heart failure population.

For the study, Yiu and colleagues analyzed data from 87,102 patients in Hong Kong who were admitted to hospital with heart failure between 2003 and 2015. Patients were followed until they were diagnosed with cancer, died, or until the end of 2018, whichever came earlier.

Participants were excluded from the study if they had a history of cancer or were diagnosed with or died from cancer within 90 days of the first diagnosis of heart failure, if they had HIV, or if they had taken statins for fewer than 90 days. This left 36,176 statin users and 50,926 statin nonusers for analysis.

Results showed that during a median follow-up of 4.1 years, 11,052 patients (12.7%) were newly diagnosed with cancer, and 3863 patients (4.4%) died from cancer. The most common types of cancer were of the bowel, stomach, lung, liver, and biliary system.

Propensity-matched statin users had a lower risk of developing cancer than nonusers. The 5-year cumulative incidence of cancer was 7.9% among statin users and 10.4% among nonusers; the 10-year cumulative incidence of cancer was 11.2% among statin users and 13.2% among nonusers.

Overall, statin users had a 16% lower risk for cancer than nonusers after multivariable adjustment (hazard ratio [HR], 0.84; 95% CI, 0.80 – 0.89).

The study also showed that statin users had a significantly lower risk of dying from cancer over the same period. The 10-year cancer-related mortality was 3.8% among statin users and 5.2% among nonusers (HR, 0.74; 95% CI, 0.67 – 0.81).

The 10-year all-cause mortality was also lower among statin users compared with nonusers: 60.5% vs 78.8% (HR, 0.62; 95% CI, 0.61 – 0.64).

The protective effect of statins appeared to be greater with longer duration of use. Compared with taking statins for 3 months to 2 years and after adjusting for other factors, if patients took statins for 4 to 6 years, the risk was reduced by 18%, and if they took statins for 6 or more years, the risk was reduced by 22%.

Similarly, compared to patients who took statins for 3 months to 2 years, among patients took statins for 4 to 6 years, the risk of dying from cancer was reduced by 33%, for those who took statins for 6 or more years, the risk was reduced by 39%.

“Our results are in line with previous observational studies of patients taking statins, but our study is unique in that we looked specifically for this effect in heart failure patients,” Yiu commented.

“While a 16% reduction is not a huge numerical figure, it is a respectable reduction and would make a difference clinically,” he added.

Yiu noted that they conducted many different sensitivity analyses to further validate the results, and they evaluated subgroups based on gender, age, hypertension status, and diabetes. The results were consistent across these subgroups.

“Because this was an observational study, it is not possible to draw a definite conclusion that statins will protect against cancer in heart failure patients,” he said. “We would only know that for certain from a randomized study, but this very large population study is very encouraging.”

On the possible mechanism involved, the researchers suggest that the well-known anti-inflammatory effects of statins may be a factor. In addition, statins have been shown to have antiproliferative effects and thus may have the potential to halt the cell-cycle progression in cancer cells, they note.

Yiu points out that the chemoprevention effect seen in this study seemed to be independent of lipid control and low-density lipoprotein (LDL) levels, “so we don’t think this effect is driven by LDL lowering alone.”

He notes that although heart failure itself is not a current indication for treatment with statins, many heart failure patients have other conditions for which statins are indicated, such as ischemic heart disease, previous stroke, and diabetes.

“Our results show that we have to think about noncardiovascular as well as cardiovascular complications in heart failure patients,” Yiu concluded. “While we can’t recommend statins specifically for preventing cancer in heart failure patients based on this observational data, I think these results should encourage clinicians to make sure patients with heart failure who do have an indication for statins are on one of these drugs. And this data also provides support for a randomized trial to obtain firm evidence of this effect.”

Robust Observational Data

Commenting for Medscape Medical News, James Kirkpatrick, MD, professor of medicine at University of Washington Medical Center, Seattle, Washington, said: “This study provides some of the most robust observational data to date suggesting a protective effect of statins against cancer. But, like prior studies, it provides correlative, rather than causative, evidence, and we lack definitive evidence to undergird recommendations for the widespread use of statins solely for the prevention of cancer, even in heart failure populations.”

Although Kirkpatrick agrees with Yiu that a randomized trial would be needed for such recommendations, he says the current study may help some patients and clinicians who are weighing available evidence on benefits, burdens, and risks of statin therapy and sway them toward statin use.

“Some patients with heart failure and a family history (or, perhaps, personal history) of cancer and an appropriately elevated coronary artery disease risk may be more convinced to opt for statin therapy,” he suggests.

Kirkpatrick points out that there has been somewhat of a “trade-off” in cardiology ― cardiovascular deaths are being prevented, and more patients are living long enough to develop cancer and dementia.

“While many are happy to have a longer life, for some in the geriatric population who are faced with the question of what they want to die from, the calculus may be different. This study suggests that perhaps statins may partially ameliorate this dilemma,” he added.

The study was supported by Sanming Project of Medicine, Shenzhen, China, and the University of Hong Kong–Shen Zhen Hospital Fund for Shenzhen Key Medical Discipline. The researchers have disclosed no relevant financial relationships.

Eur Heart J. Published online June 23, 2021. Full text

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