SPICE: The Use of Hawthorn Extract in Congestive Heart Failure

Posted 04/26/2007

Luis Gruberg, MD, FACC Information from Industry Atrial Fibrillation Condition Site Explore the burden of AF and sinus rhythm as a treatment target.

These results may be a great source for future research; however, until then, the use of hawthorn extract remains only a homeopathic treatment with, as of yet, no proven beneficial effect in CHF patients

Presenter: Christian J.F. Holubarsch, MD (Median Kliniken Hospitals, Bad Krozingen, Germany) on Behalf of the SPICE Investigators

Hawthorn extracts have been used for centuries in traditional European medicine for the treatment of heart disease. Several medicinal products that contain hawthorn extract are sold over the counter (OTC) for the treatment of mild congestive heart failure (CHF), which are mainly based on popular beliefs. WS 1442 (Schwabe Pharmaceuticals, Karlsruhe, Germany) is a dry extract from hawthorn leaves and flowers (Crataegus oxyacantha L). It is believed to have a positive inotropic effect, vasodilating properties, anti-ischemic and antiarrhythmic effects, and antioxidant properties.

The Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in Congestive Heart Failure (SPICE) trial was designed to assess the safety of WS 1442 and its effects on morbidity and mortality in patients with New York Heart Association (NYHA) class II and III CHF in addition to optimal standard care.

Study Design

The randomized, multicenter, double-blind, placebo-controlled study was performed at 156 centers in 13 European countries. Patients with NYHA class II and III CHF and reduced left ventricular function (ejection fraction [EF] ≤ 35%) were randomized to either the study medication (450 mg twice daily) or placebo in addition to conventional treatment. Patients were treated and followed for 24 months.

Primary endpoint: Composite endpoint of cardiac mortality, nonfatal myocardial infarction, and hospitalization due to progression of heart failure.

Secondary endpoints:
* Cardiac mortality; and
* Sudden cardiac death.

Results

A total of 2681 patients were enrolled in the study and randomized to WS 1442 (n = 1338) or to placebo (n = 1343). Baseline clinical characteristics were well balanced between the 2 groups; the majority of patients were on optimal medical therapy ( Table 1 ).

The incidence of the trial's primary endpoint (composite endpoint of cardiac mortality, nonfatal myocardial infarction, and hospitalization due to progression of heart failure) was not significantly different between the active treatment and placebo groups (27.9% vs 28.9%, P = NS) ( Table 2 ), by 24-month follow-up, there was no difference in the rates of cardiac mortality or sudden cardiac death between the 2 groups ( Table 2 ). Subgroup analysis found that the rate of sudden cardiac death was lower in patients with EF ≥ 25% when treated with WS 1442.

Conclusions
1. Treatment with WS 1442 in mild CHF patients on optimal medical therapy is safe.
2. Patients treated with WS 1442 have a nonsignificantly lower incidence of adverse events compared with placebo.
3. Cardiac mortality is significantly reduced in the WS 1442 group at 18 months.
4. Sudden cardiac death is significantly reduced in the subgroup of patients with EF ≥ 25%.

Viewpoint

The results of SPICE suggest that hawthorn extract has no beneficial effect in patients with CHF treated with standard therapy. Unfortunately, the conclusions reached by the investigators were a little far-reaching and speculative on the basis of the data that they reported. In addition, it is difficult to draw any final conclusions on the basis of a subgroup analysis that was not a predetermined endpoint of the trial.

Nevertheless, these results may be a great source for future research; however, until then, hawthorn extract remains only a homeopathic treatment with, as of yet, no proven beneficial effect in CHF patients.