Inpharma 1461 - 30 Oct 2004

News from the 26th Annual Congress of the European Society ofCardiology

Munich, Germany August-September 2004

The following is a summary of studies recently Table 1. Effects of drug-eluting stents on restenosispresented at the 26th Annual Congress of the European and clinical events, according to therapySociety of Cardiology (ESC).PTCAa Paclitaxel- Sirolimus-

Sirolimus-eluting stent superior (n = 100) eluting stent eluting stent (n = 100) (n - 100)The ISAR-DESIRE* study showed that the Cypher

sirolimus-eluting stent was more effective than the Incidence of restenosis at 6 months (% of patients):Taxus paclitaxel-eluting stent and percutaneous Angiographic 45 22* 14*transluminal coronary angioplasty (PTCA) in reducing restenosisrecurrent restenosis.1 The study involved 300 patients Target vessel 33 19** 8†

revascularisationwho had in-stent restenosis of a native coronary artery.Patients were randomised to receive a sirolimus-eluting Incidence of clinical events at 9 months (% of patients):stent (n = 100), a paclitaxel-eluting stent (100) or PTCA. Death 2 1 2Patients were excluded from the study if they had a Myocardial 0 2 1

infarctionhistory of acute myocardial infarction, left main arterydisease, or an allergy to sirolimus, paclitaxel, heparin, Late lumen losses (mm):aspirin or clopidogrel. The primary endpoint was the In-segment – 0.66 0.45‡

incidence of restenosis at 6 months, defined as a In-stent – 0.48 0.21††

stenosis of ≥ 50% of the vessel diameter (in-segment a Percutaneous transluminal coronary angioplastyanalysis) on angiography. The secondary outcome * p ≤ 0.001 vs PTCAmeasures were the net lumen gains and the incidences ** p < 0.05 vs PTCAat 12 months of target vessel revascularisation, death † p < 0.001 vs PTCA; p < 0.05 vs paclitaxel-eluting stentand myocardial infarction. ‡ p < 0.05 vs paclitaxel-eluting stent

†† p < 0.01 vs paclitaxel-eluting stentReduced rate of restenosisAt 6 months, the incidences of restenosis were

The researchers concluded that, for patients with in-significantly lower among patients in the sirolimus-stent restenosis, "a strategy based on drug-eluting stentseluting stent and paclitaxel-eluting stent groups thanis superior to plain balloon angioplasty for the reductionamong those in the PTCA group [see table 1]. Theof recurrent restenosis." However, the results are "lessincidences of target vessel revascularisation wereremarkable than those for de novo lesions suggesting thesignificantly lower in the groups receiving stents than inneed for modified dose-regimen." The study had somethe group undergoing PTCA. Furthermore, patients inlimitations, including a limited follow-up of 6 months forthe sirolimus-eluting stent group had a significantlyangiography, a small sample size and a potential for biaslower occurrence of target vessel revascularisation thandue to the higher late loss seen in the paclitaxel-elutingpaclitaxel-eluting stent recipients. Late lumen losses,stent group.both in-segment and in-stent, were significantly lower

among sirolimus-eluting, compared with paclitaxel- Fasudil promising in angina pectoriseluting, stent recipients. The incidences of death and Fasudil, an oral Rho-kinase antagonist whichmyocardial infarction were similar among the three selectively inhibits vasoconstriction of the coronarytreatment groups at 9 months. arteries, showed promising activity in a randomised,

double-blind, multicentre, phase II study involving84 patients with stable angina pectoris.2 Patients wereeligible for inclusion if they had objective evidence ofcoronary artery disease, reproducible exercise test timesand exercise-induced ST segment depression of ≥ 1mm.Following a 3-week washout period, patients receivedfasudil 20mg or placebo, three times daily for 8 weeks;the dose of fasudil was increased by 20mg every2 weeks. Patients were permitted to receive a β-blockeror calcium channel antagonist as monotherapy, andnitroglycerin [glyceryl trinitrate] when required.Concurrent aspirin, statins and ACE-inhibitors wereallowed during the study.

At week 8, patients receiving fasudil experienced asignificant increase from baseline in exercise duration1 hour post-dose; however, the increase was notsignificantly greater than that observed in the placebogroup (118.4 vs 86.1 seconds). Moreover, the time tothe onset of exercise-induced myocardial ischaemia wassignificantly greater among fasudil, compared withplacebo, recipients (172.1 and 43 seconds,respectively). Improvements from baseline wereobserved in physical limitation scores, treatment

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Inpharma 30 Oct 2004 No. 14611173-8324/10/1461-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

Single Article

satisfaction scores and Canadian Cardiovascular Society Table 2. Restenosis, according to stent type(CCS) class in the fasudil group, but none wasControl stent Abciximab-coatedstatistically significant. The researchers concluded that

(n = 78) stent"fasudil is promising as a new therapy for myocardial (n = 77)ischaemia."

Outcomes at 6 months:Vitamins useful after MI? Diameter stenosis 34.3 16.4*

A pilot study of the antioxidants ascorbic acid (%)[vitamin C] and tocopherol [vitamin E] suggests they Late loss (mm) 0.88 0.33*may improve the clinical outcome of patients who have Restenosis (% of 29.4 14.6

patients)had an acute myocardial infarction.3 In additional toTarget vessel 14.7 9.2routine medications, 800 patients received oral ascorbicrevascularisationacid 1200mg plus oral tocopherol 600mg, or placebo,(% of patients)once daily for 30 days; the initial dose of ascorbic acid

* p < 0.01 vs control stentwas 1000mg by IV infusion over 12 hours. The mean ageof patients was 62 years, and 69% were men. Theprimary endpoint was the combined incidence of During hospitalisation, there was one report ofcardiac mortality, new myocardial infarction, asystole, myocardial infarction and one report ofshock and pulmonary oedema. revascularisation in the control stent group. A further

Patients in the ascorbic acid plus tocopherol group two myocardial infarctions were reported in the controlexperienced significantly fewer primary endpoint events stent group during the 6-month clinical follow-upthan patients receiving placebo (14% vs 19%). There period. There were no reports of myocardial infarctionwere no serious adverse events observed among and revascularisation among patients in the abciximab-patients receiving ascorbic acid plus tocopherol. coated stent group. A coronary angiogram was

The researchers concluded that "intensive treatment performed in 62% and 65% of patients in the abciximab-with antioxidant vitamins is safe and seems to positively coated stent and control stent groups, respectively. Theinfluence the clinical outcome of patients with [acute mean diameter stenosis and the mean late loss weremyocardial infarction]". However, they also remarked significantly lower among abciximab-coated stent,that "a large study is warranted to provide further compared with control stent, recipients [see table 2].evidence of this promising and inexpensive regimen." Furthermore, the incidences of restenosis and target

vessel revascularisation were lower in patients receivingAbciximab-coated stent prevents restenosisabciximab-coated stents than those given control stents.Coronary stents coated with the glycoprotein IIb/IIIa Abciximab-coated stents are "safe and may be effectiveantagonist abciximab [ReoPro] may be effective in in the prevention of coronary restenosis," concluded thepreventing restenosis and other coronary events, researchers.according to the results of a randomised trial.4 The study* Intracoronary Stenting and Angiographic Results: Drug-Elutinginvolved 155 patients who received an abciximab-Stents for In-Stent Restenosiscoated stent (n = 77) or control stent for the1. Kastrati A, et al. Intracoronary stenting and angiographic results: drug-elutingrevascularisation of a native coronary artery. At baseline,

stents for in-stent restenosis: ISAR-DESIRE. ESC Congress 2004: Annualthe mean diameter stenosis and minimal luminalCongress of the European Society of Cardiology: Late-Breaker Abstracts : [7

diameter were similar in the two treatment groups. The pages], Aug-Sep 2004. Available from: URL: http://www.escardio.org.2. Vicari RM, et al. A randomized, double-blind, placebo-controlled, phase 2primary efficacy endpoint was the number of combined

study: the efficacy of fasudil in patients with stable angina. European Heartmajor adverse coronary events, including cardiac death, Journal 25 (Abstr. Suppl.): 138, Aug-Sep 2004.acute myocardial infarction, target vessel 3. Chamiec T, et al. Antioxidant vitamins C and E in the treatment of patients with

acute myocardial infarction: randomized, double-blind, placebo controlled,revascularisation and restenosis at 6 months.multicentre pilot MIVIT trial. European Heart Journal 25 (Abstr. Suppl.): 598,Aug-Sep 2004.

4. Jeong M, et al. The long-term clinical outcomes of a platelet glycoprotein IIb/IIIa receptor blocker (abciximab: ReoPro Rm) coated stent in patients withcoronary artery disease. European Heart Journal 25 (Abstr. Suppl.): 525, Aug-Sep 2004.

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