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SUITA CITY, Japan, Sept. 25 -- Heart failure patients who added 30 mg of Pepcid (famotidine) to standard therapy significantly improved NYHA functional class and reduced plasma B-type natriuretic peptide levels compared with patients given 150 mg of teprenone.

In a prospective open-label study, the 25 patients assigned to Pepcid for 24 weeks also had significant improvement in blood pressure, left ventricular end diastolic volume, and left ventricular end systolic volume compared with patients in the teprenone group, wrote Masfumi Kitakaze, M.D., Ph.D., and colleagues form National Cardiovascular Center.

The results of the prospective study appeared to confirm results of a retrospective study, and both findings were published together in a single paper in the Oct. 3 issue of the Journal of the American College of Cardiology.

The retrospective analysis compared heart failure parameters in 159 congestive heart failure patients who were also taking 20 to 40 mg of Pepcid for treatment of reflux symptoms with 159 controls matched for age, gender and cause of congestive heart failure. Patients in the control were taking teprenone, an antiulcer drug that does not block histamine.

They found that patients using Pepcid had significantly lower systolic and diastolic blood pressure, lower heart rate, and lower plasma B-type natriuretic peptide levels (P<0.05 for all).

In the prospective study, five patients who were NYHA class III at baseline improved to class II and three class III patients improve to class I, while seven class III patients had no change in functional class. Two patients who were NYHA class II at baseline improve to class I, four remained unchanged and four had a worsening of function after Pepcid treatment (P<0.05 for functional improvement).

Other findings form the prospective study:

• In the Pepcid group diastolic blood pressure decreased from an average of 67 mm Hg to 60 mm Hg (P<0.05) and systolic from an average of 112 mmHg to 107 mmHg (P<0.01).

• Plasma B-type natriuretic peptide decreased to an average of 183 pg/ml, down from an average of 285 pg/ml (P<0.05).

• The frequency of hospital admission for worsening heart failure was lower in the Pepcid group than in the control group (4% versus 24% P<0.05).

The researchers conclude that the findings demonstrate that blockade of histamine H₂ receptors favors improvement of the pathophysiology of congestive heart failure.

"These conclusions propose the novel findings that histamine stimulated histamine H₂ receptors is one of the neurohumoral factors for worsening of [congestive heart failure], and that the blockade of histamine H₂ receptors becomes the novel strategy for treatment," they wrote.

In a JACC editorial, Gary S. Francis, M.D., of the Cleveland Clinic, wrote that the researchers first identified the heart failure treatment potential of the popular over-the-counter heart burn drug using data mining, a technique rarely used in clinical trials, but one which may provide a useful shortcut to identify potentially beneficial drugs.

They "mined" medical and pharmacy records from 1,100 heart failure patients and discovered that beta-blockers, angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists -- the standard treatments for congestive heart failure -- all were independently associated with better B-type natriuretic peptide levels and improved functioning.

But that same mining expedition, also found that statins and alpha-glucosidase inhibitors as well as histamine receptor blockers such as Pepcid also attenuated the severity of congestive heart failure.

Histamine, the authors wrote, "plays an important role in the regulation and malregulation of cardiac and coronary function."

Dr. Kitakaze acknowledged that the results from the prospective study, while promising, are preliminary. He said his group now wants to conduct a larger-prospective study to confirm these results.

The editorial, which Dr. Francis co-authored with W.H. Wilson Tang, M.D., also of the Cleveland Clinic, pointed out the need to "find out more about the interactions between histamine, mast calls, and heart failure syndrome."

And while adding several cautions about the preliminary nature of the findings, the Drs. Francis and Tang concede the need for "some new and imaginative thinking in this arena, and perhaps this article will serve to provide that."

The study was funded by the Japan Cardiovascular Research Foundation.

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