Beneficial Effects ofPimobendan on Exercise Tolerance andQualitofLifeinPatients WithHeartFailure

Background. Thismulticenter trial was conducted todetermine theefficacy andsafety ofpimobendan, an inotropic agentwithcalcium-sensitizing properties andactivity as a phosphodiesterase inhibitor, in patients withheartfailure. Methods andResults. Onehundredninety-eight ambulatory patients withsymptoms ofmoderate to severeheart failure despite therapy withdigitalis anddiuretics withorwithout a single vasodilator were randomly assigned toreceive either placebo (n=49)orpimobendan (n= 149)inadouble-blind fashion for 12weeks. A doserangeofpimobendan was usedincluding 2.5(n=49), 5 (n=51), or10mg/day(n=49). Onehundredfifty-eight (80%)patients were taking a converting enzymeinhibitor (CEI)and28(14%) patients were taking a non-CEIvasodilator. Atendpoint, the5-mgdoseofpimobendan significantly increased exercise duration compared withplacebo (121.6± 19.1seconds, p<0.001), whereas the10-mg doseproduced an increase ofborderline significance (81.1±19.5 seconds, p=0.05). PeakVo2 was significantly increased by2.23±0.58 ml/kg/min inthe5-mggroup(p<0.01 versusplacebo). Furthermore, quality oflife measured withtheMinnesota Living WithHeartFailure Questionnaire improved by8.5±2.3 units inthe5-mggroupcompared with1.3±2.2 units intheplacebo group(p<0.01). Therewere a total of23all-cause hospitalizations intheplacebo group,whichwas significantly greater compared with33in thethree groupstreated withpimobendan (p<0.01). Therewere no significant differences betweenthe placebo andpimobendan groupswithrespect tochanges inejection fraction andplasmanorepinephrine measured atbaseline andatthecompletion ofthe12-week study, proarrhythmic effect, orthenumberof patients witha significant adjustment inbackground therapy. Elevenpatients died, including three(6%) on placebo andeight (5%)on pimobendan (p=NS).Amongalladverse events, headache tendedtobe more common inthepimobendan groupscompared withplacebo, withtheincidence increasing withdose (p<0.05). Conclusions. Thesedatademonstrate thatpimobendan significantly increases exercise duration, peak Vo2, andquality oflife inpatients withheart failure. Pimobendan appearstobeuseful adjunctive therapy whenaddedtodigitalis, diuretics, andvasodilators. (Circulation 1992;85:942-949)