Benefit-Risk Assessment of Crataegus Extract WS 1442: An Evidence-Based Review

Abstract

Preparations from Crataegus (hawthorn) have a long history in the treatment of heart failure. WS 1442 is a dry extract from hawthorn leaves with flowers (4-6.6:1), extraction solvent of ethanol 45% (w/w), adjusted to 17.3-20.1% of oligomeric procyanidins. Nonclinical studies show that WS 1442 has positive inotropic and antiarrhythmic properties and protects the myocardium from ischemic damage, reperfusion injury, and hypertension-related hypertrophy, improves endothelial functions such as NO synthesis, and delays endothelial senescence. Randomized, controlled trials in patients with heart failure have demonstrated that the herbal medicinal product increases functional capacity, alleviates disabling symptoms, and improves health-related quality of life, all of which have become important targets of heart failure therapy according to current disease management guidelines. Clinical trials (including a 2-year mortality study with polypharmacy and > 1300 patients exposed) and post-marketing surveillance studies have shown that WS 1442 has a very favorable safety profile both as monotherapy and as add-on therapy, where no drug interactions have been observed. No specific adverse reactions to WS 1442 are known to date. WS 1442 may thus help to close the therapeutic gap between systolic and diastolic heart failure for which evidence of efficacy for other cardioactive drugs is sparse. Scientific evidence shows that WS 1442 is safe and has a beneficial effect in patients with heart failure corresponding to New York Heart Association classes II or III. The benefit-risk assessment for WS 1442 is therefore positive.

Fig. 1

Cumulative hazard for time to first cardiac event (from [40])

Fig. 2

Cumulative hazard for cardiac mortality (a, c) and sudden cardiac death (b, d): all patients (a, b) or patients with LVEF ≥ 25% (c, d) (from [40]). LVEF left ventricular ejection fraction

Fig. 3

Cardiac mortality and sudden cardiac death in total population and subgroup LVEF ≥ 25% (hazard ratios, 95% confidence intervals and two-sided log-rank test p values) (from [40]). LVEF left ventricular ejection fraction

Fig. 4

Maximum workload (W): meta-analysis of difference between Crataegus and placebo for change from baseline (means and 95% confidence intervals, random effects model) Data from [52], Fig. 1.1, based on studies reported by Bödigheimer and Chase [53] (LI 132), Hanak and Brückel [54], Tauchert [37] and Zapfe [55] (all WS 1442)

Fig. 5

Time for 2-km walking test (means and standard deviations; data from [45])

Fig. 6

Reduction in the total score of von Zerssen Complaints (means, standard deviations, and two-sided p values; from [37], Fig. 4, and [81])

Fig. 7

Average change in frequency and intensity of heart failure symptoms assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ) (from [45], Fig. 4)