Gender difference in response to sacubitril/valsartan is unexplained

A clinical trial investigating heart failure patients’ responses to sacubitril/valsartan found that women respond to the medication combination better than men do. It is not known why this is, according to Jonathan W. Cunningham, MD, of Brigham and Women’s Hospital, Boston.

“Unfortunately, I think we’re still looking for the underlying physiological explanation for [the difference],” Cunningham said.

The trial involved 4,822 patients with heart failure and ejection fraction of 45% or higher. One group was given a combination of sacubitril and valsartan and the other group was given just valsartan. The trial investigated how the medications affected the rate of total hospitalizations for heart failure and death from cardiovascular causes.

Men in the sacubitril/valsartan group experienced a 3% increased risk of hospitalization for heart failure or death from cardiovascular causes. Women in the sacubitril/valsartan group, however, experienced a 27% reduced risk of hospitalization for heart failure or death from cardiovascular causes.

The 27% risk reduction was statistically significant. However, the overall trial had to determine that the drug combination’s risk reduction was statistically insignificant because the overall result with men included was statistically insignificant.

The trial found that a higher baseline of N-terminal pro-B-type natriuretic peptide (NT-proBNP) meant a higher risk of hospitalization for heart failure or death from cardiovascular causes. However, confoundingly, the sacubitril/valsartan combination reduced NT-proBNP similarly in men and women: by 18 compared to valsartan in women and by 20% compared to valsartan in men.

Valsartan is a drug which treats diabetic kidney disease, heart failure and high blood pressure. Heart failure, hypertension and kidney failure are known side effects of valsartan.

Sacubitril is an antihypertensive medication which is used in combination with valsartan for the treatment of heart failure.

Numerous medications containing valsartan have been recalled due to contamination with NDEA and NDMA. NDEA is classified by the World Health Organization as a Group 2A carcinogen. Researchers use it to generate liver tumors they can study. NDMA is classified by the U.S. Environmental Protection Agency as a probable carcinogen. Rats are given NDMA by researchers so the rats develop cancer which the researchers can study.

It is hypothesized that the contamination was caused by changes in the methods of valsartan manufacturing. These changes probably caused valsartan’s manufacturing environment to become too acidic. NDEA and NDMA can be created when a valsartan-creating chemical reaction is done in too acidic of an environment.

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Nadrich & Cohen, LLP

Nadrich & Cohen, LLP is a California personal injury law firm with offices in Los Angeles, San Francisco, Modesto, Fresno, Tracy and Palm Desert. The firm has been representing victims of dangerous drugs since 1990 and has recovered over $350,000,000 on behalf of clients in that time.

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