heart failure - phosphodiesterase III inhibitors - all type of patients clinical trials results meta-analysis

<h1> <a href="TM8-32-phosphodiesterase III inhibitors -heart failure" > <strong>heart failure</strong> - phosphodiesterase III inhibitors </a> - all type of patients trial results systematic overview and meta-analysis </h1> <h2>Main characteristics of the included studies</h2> <table> <tr> <th>Trial</th> <th>Treatments</th> <th>Patients</th> <th>Methods</th> </tr> <tr> <td> <a href="../TRC_t771.htm"> WESG, 1991 </a> <br> </td> <td> Enoximone 150, 300 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 3 months<br> n=108/56<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t772.htm"> PROMISE, 1991 </a> <br> </td> <td> Milrinone 40mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA III,IV </td> <td> follow-up 20 months<br> n=561/527<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t774.htm"> PRIME II, 1997 </a> <br> </td> <td> oral ibopamine 100 mg three times daily<br>  <i>versus</i> <br> placebo </td> <td> patients with heart failure NYHA III-IV </td> <td> follow-up mean 11.4 months<br> n=953/953<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4564.htm"> AMTG, 1985 </a> <br> </td> <td> Amrinone <600mg/day<br>  <i>versus</i> <br> placebo </td> <td> patients with heart failure NYHA III/IV </td> <td> follow-up 3 months<br> n=-9/-9<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4565.htm"> Bergler-Klein, 1992 </a> <br> </td> <td> Pimobendan 10mg/day<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 6 months<br> n=12/12<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4566.htm"> Cowley, 1993 </a> <br> </td> <td> Flosequinan 125mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 4 months<br> n=64/71<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4567.htm"> Dies, 1989 </a> <br> </td> <td> Indolidan dose NA<br>  <i>versus</i> <br> placebo </td> <td> NYHA II,III </td> <td> follow-up 3 months<br> n=38/36<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4568.htm"> EMTG, 1990 </a> <br> </td> <td> Enoximone <450 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 4 months<br> n=50/52<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4569.htm"> EPOCH, 2002 </a> <br> </td> <td> Pimobendan 2.5 to 5mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II,III </td> <td> follow-up 12 months<br> n=147/151<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4570.htm"> ESG, 2000 </a> <br> </td> <td> Enoximone 75-150 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 3 months<br> n=70/35<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4571.htm"> FACET, 1993 </a> <br> </td> <td> Flosequinan 100 and 150 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 4 months<br> n=212/110<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4572.htm"> IRG, 1991 </a> <br> </td> <td> Imazodan 4,10, 20 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA III,IV </td> <td> follow-up 3 months<br> n=103/44<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4573.htm"> Lardoux, 1987 </a> <br> </td> <td> Enoximone 150, 300mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA NA </td> <td> follow-up 3 months<br> n=30/13<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4574.htm"> MMTG, 1989 </a> <br> </td> <td> Milrinone <40mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II-IV </td> <td> follow-up 3 months<br> n=119/111<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4575.htm"> OPC-8212 MRG, 1990 </a> <br> </td> <td> Vesnarinone 60mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II-IV </td> <td> follow-up 3 months<br> n=45/48<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4576.htm"> PICO, 1996 </a> <br> </td> <td> Pimobendan 2.5, 5 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II, III </td> <td> follow-up 6 months<br> n=219/112<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4577.htm"> PMRG, 1992 </a> <br> </td> <td> Pimobendan 2.5, 5, 10 mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA III,IV </td> <td> follow-up 3 months<br> n=149/49<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4578.htm"> REFLECT, 1993 </a> <br> </td> <td> Flosequinan 100mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II,III </td> <td> follow-up 3 months<br> n=93/100<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4579.htm"> REFLECT II, 1991 </a> <br> </td> <td> Flosequinan 100, 150 mg/d<br>  <i>versus</i> <br> </td> <td> NYHA II-IV </td> <td> follow-up 3 months<br> n=207/104<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4580.htm"> VEST, 1998 </a> <br> </td> <td> Vesnarinone 30, 60mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA III,IV </td> <td> follow-up 9 months<br> n=2550/1283<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4581.htm"> VSG, 1993 </a> <br> </td> <td> Vesnarinone 60mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA II-IV </td> <td> follow-up 6 months<br> n=-9/-9<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t4583.htm"> ESSENTIAL (I and II), 2009 </a> <br> NCT00051285 </td> <td> enoximone titrated to 50 mg three times daily<br>  <i>versus</i> <br> placebo </td> <td> Patients with New York Heart Association class III–IV HF symptoms, left ventricular ejection fraction 30%, and one hospitalization or two ambulatory visits for worsening HF in the previous year </td> <td> follow-up 16.6 mo (median)<br> n=926/928<br> Parallel groups<br> double blind <br> Europe and North andSouth America </td> </tr> <tr> <td> <a href="../TRC_t4585.htm"> Cowley, 1994 </a> <br> </td> <td> Enoximone 300mg/d<br>  <i>versus</i> <br> placebo </td> <td> NYHA III,IV </td> <td> follow-up 12 months<br> n=75/76<br> Parallel groups<br> double blind <br> </td> </tr> <tr> <td> <a href="../TRC_t7870.htm"> EMOTE, 2007 </a> <br> </td> <td> enoximone<br>  <i>versus</i> <br> placebo </td> <td> patients with ultra-advanced heart failure requiring IV inotropic therapy </td> <td> follow-up 26 weeks<br> n=101/100<br> Parallel groups<br> double blind <br> US </td> </tr> <tr> <td> <a href="../TRC_t9494.htm"> EMPOWER, </a> <br> NCT00077948 </td> <td> enoximone<br>  <i>versus</i> <br> placebo </td> <td> Advanced CHF Subjects Previously Intolerant to Beta-Blocker Treatment </td> <td> follow-up <br> n=-9/-9<br> Parallel groups<br> double blind <br> </td> </tr> </table> <h2>References</h2> <p> <b>WESG, 1991 : </b> <i>NEJM 1991;121:1471-1479</i> [PMID 7078592] </p> <p> <b>WESG, 1991 : </b> Narahara KAOral enoximone therapy in chronic heart failure: a placebo-controlled randomized trial. The Western Enoximone Study Group. <i>Am Heart J 1991 May;121:1471-9</i> [PMID 1826806] </p> <p> <b>PROMISE, 1991 : </b> Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, Kukin MLEffect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. <i>N Engl J Med 1991;325:1468-75</i> [PMID 1944425] </p> <p> <b>PRIME II, 1997 : </b> Hampton JR, van Veldhuisen DJ, Kleber FX, Cowley AJ, Ardia A, Block P, Cortina A, Cserhalmi L, Follath F, Jensen G, Kayanakis J, Lie KI, Mancia G, Skene AMRandomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators. <i>Lancet 1997;349:971-7</i> [PMID 9100622] </p> <p> <b>AMTG, 1985 : </b> Massie B, Bourassa M, DiBianco R, Hess M, Konstam M, Likoff M, Packer MLong-term oral administration of amrinone for congestive heart failure: lack of efficacy in a multicenter controlled trial. <i>Circulation 1985 May;71:963-71</i> [PMID 3886191] </p> <p> <b>Bergler-Klein, 1992 : </b> Bergler-Klein J, Globits S, Stefenelli T, Mayr H, Porenta G, Sochor H, Glogar D[Pimobendan (UDCG 115 BS) in long-term therapy of chronic heart failure] <i>Z Kardiol 1992 Oct;81:546-52</i> [PMID 1441695] </p> <p> <b>Cowley, 1993 : </b> Cowley AJ, McEntegart DJPlacebo-controlled trial of flosequinan in moderate heart failure. The possible importance of aetiology and method of analysis in the interpretation of the results of heart failure trials. <i>Int J Cardiol 1993 Feb;38:167-75</i> [PMID 8454379] </p> <p> <b>Dies, 1989 : </b> Dies F,Mcnay JL, Andrejasich CM, Burke PJ, EnasNH.Indolidan (a new phosphodiesterase inhibitor) in chronic heart failure. <i>Circulation 1989;80(suppl II):II-175 (abstr 0698)</i> [PMID ] </p> <p> <b>EMTG, 1990 : </b> Uretsky BF, Jessup M, Konstam MA, Dec GW, Leier CV, Benotti J, Murali S, Herrmann HC, Sandberg JAMulticenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group. <i>Circulation 1990 Sep;82:774-80</i> [PMID 2144216] </p> <p> <b>EPOCH, 2002 : </b> Effects of pimobendan on adverse cardiac events and physical activities in patients with mild to moderate chronic heart failure: the effects of pimobendan on chronic heart failure study (EPOCH study). <i>Circ J 2002 Feb;66:149-57</i> [PMID 11999639] </p> <p> <b>ESG, 2000 : </b> Lowes BD, Higginbotham M, Petrovich L, DeWood MA, Greenberg MA, Rahko PS, Dec GW, LeJemtel TH, Roden RL, Schleman MM, Robertson AD, Gorczynski RJ, Bristow MRLow-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group. <i>J Am Coll Cardiol 2000;36:501-8</i> [PMID 10933364] </p> <p> <b>FACET, 1993 : </b> Massie BM, Berk MR, Brozena SC, Elkayam U, Plehn JF, Kukin ML, Packer M, Murphy BE, Neuberg GW, Steingart RMCan further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET). <i>Circulation 1993 Aug;88:492-501</i> [PMID 8339411] </p> <p> <b>IRG, 1991 : </b> Goldberg AD, Nicklas J, Goldstein SEffectiveness of imazodan for treatment of chronic congestive heart failure. The Imazodan Research Group. <i>Am J Cardiol 1991 Sep 1;68:631-6</i> [PMID 1715125] </p> <p> <b>Lardoux, 1987 : </b> Lardoux H, Trimarco B, Granier G,Marcadet O, Dubois-Rande JL,Multicentric, double blind and controlled study of oral enoximone (MDL 17043) in chronic heart failure. <i>Circulation 1987;76(suppl IV):IV-179(abstr 0711).2</i> [PMID ] </p> <p> <b>MMTG, 1989 : </b> DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright RA comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. <i>N Engl J Med 1989 Mar 16;320:677-83</i> [PMID 2646536] </p> <p> <b>OPC-8212 MRG, 1990 : </b> A placebo-controlled, randomized, double-blind study of OPC-8212 in patients with mild chronic heart failure. OPC-8212 Multicenter Research Group. <i>Cardiovasc Drugs Ther 1990 Apr;4:419-25</i> [PMID 2285626] </p> <p> <b>PICO, 1996 : </b> Lubsen J, Just H, Hjalmarsson AC, La Framboise D, Remme WJ, Heinrich-Nols J, Dumont JM, Seed PEffect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. <i>Heart 1996 Sep;76:223-31</i> [PMID 8868980] </p> <p> <b>PMRG, 1992 : </b> Kubo SH, Gollub S, Bourge R, Rahko P, Cobb F, Jessup M, Brozena S, Brodsky M, Kirlin P, Shanes JBeneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group. <i>Circulation 1992 Mar;85:942-9</i> [PMID 1537130] </p> <p> <b>PMRG, 1992 : </b> Rector TS, Cohn JNAssessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group. <i>Am Heart J 1992 Oct;124:1017-25</i> [PMID 1529875] </p> <p> <b>REFLECT, 1993 : </b> Packer M, Narahara KA, Elkayam U, Sullivan JM, Pearle DL, Massie BM, Creager MADouble-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. Principal Investigators of the REFLECT Study. <i>J Am Coll Cardiol 1993 Jul;22:65-72</i> [PMID 8509565] </p> <p> <b>REFLECT, 1993 : </b> Packer M, Narahara KA, Elkayam U, Sullivan JM, Pearle DL, Massie BM, Creager MADouble-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. Principal Investigators of the REFLECT Study. <i>J Am Coll Cardiol 1993 Jul;22:65-72</i> [PMID 8509565] </p> <p> <b>REFLECT II, 1991 : </b> Pitt B, on behalf of the REFLECT II Study Group.A randomized, multicenter, double-blind placebo controlled study of the efcacy of Flosequinan in patients with chronic heart failure. <i>Circulation 1991;84(suppl II):II-311 abstr 1238)ge/pj</i> [PMID ] </p> <p> <b>VEST, 1998 : </b> Cohn JN, Goldstein SO, Greenberg BH, Lorell BH, Bourge RC, Jaski BE, Gottlieb SO, McGrew F 3rd, DeMets DL, White BGA dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. <i>N Engl J Med 1998 Dec 17;339:1810-6</i> [PMID 9854116] </p> <p> <b>VSG, 1993 : </b> Feldman AM, Bristow MR, Parmley WW, Carson PE, Pepine CJ, Gilbert EM, Strobeck JE, Hendrix GH, Powers ER, Bain RPEffects of vesnarinone on morbidity and mortality in patients with heart failure. Vesnarinone Study Group. <i>N Engl J Med 1993 Jul 15;329:149-55</i> [PMID 8515787] </p> <p> <b>ESSENTIAL (I and II), 2009 : </b> Metra M, Eichhorn E, Abraham WT, Linseman J, Böhm M, Corbalan R, DeMets D, De Marco T, Elkayam U, Gerber M, Komajda M, Liu P, Mareev V, Perrone SV, Poole-Wilson P, Roecker E, Stewart J, Swedberg K, Tendera M, Wiens B, Bristow MREffects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials. <i>Eur Heart J 2009 Dec;30:3015-26</i> [PMID 19700774] </p> <p> <b>Cowley, 1994 : </b> Cowley AJ, Skene AMTreatment of severe heart failure: quantity or quality of life? A trial of enoximone. Enoximone Investigators. <i>Br Heart J 1994 Sep;72:226-30</i> [PMID 7946771] </p> <p> <b>EMOTE, 2007 : </b> Feldman AM, Oren RM, Abraham WT, Boehmer JP, Carson PE, Eichhorn E, Gilbert EM, Kao A, Leier CV, Lowes BD, Mathier MA, McGrew FA, Metra M, Zisman LS, Shakar SF, Krueger SK, Robertson AD, White BG, Gerber MJ, Wold GE, Bristow MRLow-dose oral enoximone enhances the ability to wean patients with ultra-advanced heart failure from intravenous inotropic support: results of the oral enoximone in intravenous inotrope-dependent subjects trial. <i>Am Heart J 2007 Nov;154:861-9</i> [PMID 17967591] </p>