Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris

M.C.M Portegies*, R Schmitt, C.J Kraaij, S.H.J.G Braat, A Gassner, F Hagemeijer, H Pozenel, G Prager, J.W Viersma, E.E Van der Wall, C.H KLeinbloesem, K.I Lie

*Corresponding author for this work

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    Abstract

    We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to receive a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has anti-ischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.

    Original languageEnglish
    Pages (from-to)746-751
    Number of pages6
    JournalJournal of Cardiovascular Pharmacology
    Volume18
    Issue number5
    DOIs
    Publication statusPublished - Nov-1991

    Keywords

    • CALCIUM CHANNEL BLOCKERS
    • STABLE ANGINA PECTORIS
    • INOTROPIC EFFECTS
    • RO-40-5967
    • CHANNEL-BLOCKING-AGENTS
    • CORONARY-ARTERY DISEASE
    • DOUBLE-BLIND
    • VERAPAMIL
    • PROPRANOLOL
    • VASODILATOR
    • MECHANISM
    • EFFICACY
    • ISCHEMIA
    • PRESSURE

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