Correspondence Address:
Jassim Al-Suwaidi
,

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Long-term treatment with aspirin and clopidogrel post PCI reduce complications

The Clopidogrel for the Reduction of Events During Observation (CREDO) trial investigators evaluated the benefit of long-term (12-month) treatment with clopidogrel after PCI and the benefit of initiating clopidogrel with a pre-procedure loading dose, both in addition to aspirin therapy.

The study, double-blind and placebo-controlled, randomized 2116 patients who were to undergo elective percutaneous coronary revascularization (PCI) or were deemed at high likelihood of undergoing PCI. The study participants were enrolled in 99 centers in North America from June 1999 to April 2001.

Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke. Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days. However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% for this end point compared with no reduction with treatment less than 6 hours before PCI.

Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P=0.07).

The study concluded that following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.

The findings from this trial (CREDO) and the previously published PCI-CURE trial suggest that dual antiplatelet therapy with clopidogrel and aspirin in patients undergoing PCI for at least one year instead of the current standard of 2-4 weeks leads to significant reduction in clinical complications. The study also suggests that when clopidogrel loading of 300 mg is administered more than 6 hours before PCI it may well offer substantial benefit.

Glycoprotein IIb/IIIa inhibitors of no value as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts

A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed to evaluate the utility of using platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts. Outcomes of graft interventions were assessed at 30 days and 6 months.

Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P=0.006) and 6 months (4.7% versus 2.0%, PIs it time to use genetic risk profile for myocardial infarction in primary prevention?

The investigators examined the associations between genetic variants and myocardial infarction. A fluorescence- or colorimetry-based allele-specific DNA-primer-probe assay system was used to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction (2003 men and 816 women) and 2242 unrelated Japanese controls (1306 men and 936 women).

112 polymorphisms were crosschecked in 909 patients with myocardial infarction (MI). After adjustment for age, body-mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia, 19 polymorphisms were selected in men and 18 in women by means of logistic-regression analysis.

In a large-scale study involving the selected polymorphisms and the remaining 4152 subjects, similar logistic-regression analysis revealed that the risk of myocardial infarction was significantly associated with the C1019T polymorphism in the connexin 37 gene (PRhythm control or rate control in atrial fibrillation



The AFFIRM TRIALTHE RACE TRIALEditorial to AFFIRM & RACE The Affirm Trial

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial compared the two approaches to the treatment of atrial fibrillation: (1) cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and (2) the use of rate-controlling drugs, allowing atrial fibrillation to persist. The study was a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death.

The primary end point was overall mortality. In both approaches, the use of anticoagulant drugs is recommended. A total of 4060 patients (mean [�SD] age, 69.7�9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent.

There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; P=0.08).

More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio (INR) was subtherapeutic.

The study concluded that management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy. A potential advantage in the rate-control strategy was lower risk of adverse drug effects. Anticoagulation should be continued in high-risk patients.

The Race Trial

The purpose of the trial was similar to the AFFIRM trial. 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion were randomly assigned to receive treatment aimed at rate control or rhythm control.

Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs. The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs. After a mean (�SD) of 2.3�0.6 years, 39 percent of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10 percent of the 256 patients in the rate-control group. The primary end point occurred in 44 patients (17.2 percent) in the rate-control group and in 60 (22.6 percent) in the rhythm-control group.

The 90 percent (two-sided) upper boundary of the absolute difference in the primary end point was 0.4 percent (the prespecified criterion for noninferiority was 10 percent or less). The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups.

The study concluded that rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion.

Editorial to Affirm & Race

An accompanying editorial of the two trials, (affirm AND RACE) pointed out that all RACE patients and most AFFIRM participants had already had an episode of AF before enrollment, pointing to the propensity of recurrent arrhythmias. As such the findings from these two trials may not apply to people with first episode of arrhythmia.

Intracoronary progenitor cell infusion in reperfused post MI patients has beneficial effect on remodeling

Experimental studies suggest that transplantation of blood-derived or bone marrow-derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown and hence was studied by Hoelzer et al.

20 patients with reperfused acute myocardial infarction (AMI) were randomized to receive intracoronary infusion of either bone marrow-derived (n=9) or circulating blood-derived progenitor cells (n=11) into the infarct artery 4.3�1.5 days after AMI. Transplantation of progenitor cells was associated with a significant increase in global left ventricular ejection fraction from 51.6�9.6% to 60.1�8.6% (P=0.003), improved regional wall motion in the infarct zone (PPercutaneous transcatheter implantation of aortic valve prosthesis feasible

The design of a percutaneous implantable prosthetic heart valve has become an important area for investigation. A percutaneously implanted heart valve (PHV) composed of 3 bovine pericardial leaflets mounted within a balloon-expandable stent was developed. After ex vivo testing and animal implantation studies, the first human implantation was performed in a 57-year-old man with calcific aortic stenosis, cardiogenic shock, subacute leg ischemia, and other associated noncardiac diseases. Valve replacement had been declined for this patient, and balloon valvuloplasty had been performed with nonsustained results.

With the use of an antegrade transseptal approach, the PHV was successfully implanted within the diseased native aortic valve. With accurate and stable PHV positioning, there was no impairment of the coronary artery blood flow or of the mitral valve function. There was mild paravalvular aortic regurgitation. Immediately and at 48 hours after implantation, valve function was excellent, resulting in marked hemodynamic improvement. Over a follow-up period of 4 months, the valvular function remained satisfactory as assessed by sequential transesophageal echocardiography, and there was no recurrence of heart failure. However, severe noncardiac complications occurred, including a progressive worsening of the leg ischemia, leading to leg amputation with lack of healing, infection, and death 17 weeks after PHV implantation.

Nonsurgical implantation of a prosthetic heart valve can be successfully achieved with immediate and midterm hemodynamic and clinical improvement. After further device modifications, additional durability tests, and confirmatory clinical implantations, PHV might become an important therapeutic alternative for the treatment of selected patients with nonsurgical aortic stenosis.®