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Phosphodiesterase III inhibitors for heart failure

E Amsallem, C Kasparian, G Haddour

    The Cochrane Database of Systematic Reviews
    |January 28, 2005
    PubMed

    Insights

    Phosphodiesterase inhibitors (PDIs) increase mortality in chronic heart failure patients compared to placebo. The chronic use of PDIs should be avoided in heart failure management due to increased risks.

    Area of Science:

    • Cardiology
    • Pharmacology

    Background:

    • Established treatments for chronic heart failure include vasodilators, ACE inhibitors, and beta-blockers.
    • Phosphodiesterase inhibitors (PDIs) increase intracellular cyclic AMP, enhancing myocardial contractility.
    • PDIs increase intracellular calcium, leading to a positive inotropic effect.

    Purpose of the Study:

    • To review data from randomized controlled trials comparing PDIs to placebo in symptomatic chronic heart failure patients.
    • To assess the primary endpoint of total mortality and secondary endpoints including cause-specific mortality, heart failure worsening, myocardial infarction, arrhythmias, and vertigo.
    • To examine therapeutic effects across subgroups based on concomitant vasodilators, heart failure severity, and PDI type.

    Main Methods:

    • Searched MEDLINE, EMBASE, Cochrane CENTRAL, and McMaster CVD registries for randomized trials of PDIs versus placebo.
    • Included trials with a follow-up duration exceeding three months.
    • Considered 21 eligible trials involving 8408 patients, evaluating 4 PDI derivatives and 8 molecules.

    Main Results:

    • PDIs were associated with a significant 17% increase in mortality compared to placebo (RR 1.17, 95% CI 1.06-1.30).
    • PDIs significantly increased cardiac death, sudden death, arrhythmias, and vertigo.
    • The detrimental effect of PDIs on mortality was consistent across subgroups, regardless of concomitant treatments or PDI type.

    Conclusions:

    • PDIs significantly increase mortality rates in chronic heart failure patients compared to placebo.
    • The increased mortality is not attributable to additional vasodilator treatment.
    • Chronic use of PDIs is not supported and should be avoided in heart failure management.
    Abstract

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