INSIDE THIS ISSUE OF JACC
Inside This Issue of JACC
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Clinical Trials
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No Interaction Between Statin Metabolism and Efficacy of Clopidogrel.
Several of the widely used statins are primarily metabolized by the cytochrome P450 3A4 isoenzyme (CYP3A4); this enzyme is also necessary for the conversion of clopidogrel to its active metabolite. The CHARISMA trial randomized over 16,000 subjects to clopidogrel or placebo. This retrospective analysis compared the efficacy of clopidogrel in patients taking statins that are primarily metabolized by the CYP3A4 enzyme or via different routes. There was no evidence of an interaction between clopidogrel and the metabolism of statins. Despite theoretical concerns and ex vivo testing suggesting a potential negative interaction with concomitant use of clopidogrel and statins metabolized by CYP3A4, there is no evidence of a clinically significant interaction in this large, placebo-controlled trial. See page 291
. See figure.
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Heart Failure
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EOB Predicts Risk of Sudden Cardiac Death.
Exercise oscillatory breathing (EOB), that is rapid variations in the amount of expired gases during strenuous activity, is thought to represent an imbalance between sympathetic and autonomic stimuli for breathing. Guazzi and colleagues reviewed cardiopulmonary exercise testing (CPET) results from 156 chronic heart failure (CHF) patients who were then followed for clinical outcomes. Survivors had significantly higher peak VO2 and lower VE/VCO2 and were less likely to have EOB. There were no deaths in subjects who did not have EOB, but more than 30% of subjects with EOB died. This maladaptive breathing pattern appears to be a strong predictor of the risk for cardiac mortality in patients with CHF. See page 299
. Figure was originally published in Leite JJ, Mansur AJ, de Freitas HFG, et al. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol 2003;41:2175–81.
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Heart Rhythm Disorders
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Increased Risk of Intracranial Hemorrhage in Non-Whites.
Shen and colleagues studied the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF), looking for interactions between race and the risk of ICH with warfarin. Warfarin was associated with increased ICH risk in all races, but the magnitude of risk was greater among non-whites. The hazard ratio for ICH with whites as referent was 4 for Asians, 2 for Hispanics, and 2 for blacks. These results suggest that non-whites, especially Asians, are at increased risk for ICH when treated with warfarin. See page 309
. See figure.
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Cardiac Imaging
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MSCT Characteristics of Vulnerable Plaques.
There is growing interest in using multislice computed tomography (MSCT) not only to measure percent stenosis, but also to characterize the histology of lesions. Motoyama and colleagues compared culprit lesion characteristics in 38 patients with acute coronary syndromes (ACS) and 33 with stable angina. Positive remodeling, low plaque density, and spotty calcification were significantly more frequent in the ACS lesions. The presence of all 3 characteristics demonstrated a high positive predictive value for association with ACS lesions, and the absence of all 3 demonstrated a high negative predictive value. The computed tomography characteristics of plaques, including positive vascular remodeling, low plaque density, and spotty calcification may be the key to identifying vulnerable lesions. See page 319
. See figure.
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Cardiac Imaging
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MCE Predicts Outcomes in MI Survivors.
Myocardial contrast echocardiography (MCE) detects contrast microbubbles at the capillary level within the myocardium; Dwivedi and colleagues hypothesized that MCE may be a useful risk stratifier in the days following a treated ST-segment elevation myocardial infarction (MI). MCE was performed on 99 subjects, most of which were treated with thrombolytics, an average of 7 days post-MI. The multivariable predictors of cardiac death were increased age, mean coronary luminal diameter stenosis, and areas of decreased signal on MCE. MCE was the only independent risk factor for subsequent MI. See page 327
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Preclinical Studies
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Stent Coated with TGF-ß1 Stimulates Collateral Formation.
Several cytokines, including transforming growth factor (TGF)-ß1, can theoretically stimulate the formation of new collateral circulation, yet clinical trials with these compounds have been disappointing. Grundmann and colleagues hypothesized that by coating a stent with TGF-ß1, high and sustained levels could be obtained where it is most likely to be effective. Using a rabbit hindlimb model, stents with either no coating (bare-metal stents), a polymer-only coating, or a polymer embedded with TGF-ß1 were implanted into the external iliac arteries and then the femoral arteries were occluded. Perfusion measurements 1 week later revealed that collateral conductance was nearly 2 times higher in the TGF-ß1 treatment group than in either control group. After 1 week, there was no evidence of increased in-stent neointima formation. This novel stent delivery of TGF-ß1 may improve collateral circulation formation by increasing the duration of exposure at the critical location. See page 351
. See figure.
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Lack of Evidence of a Clopidogrel–Statin Interaction in the CHARISMA Trial
- Jacqueline Saw, Danielle M. Brennan, Steven R. Steinhubl, Deepak L. Bhatt, Koon-Hou Mak, Keith Fox, Eric J. Topol on behalf of the CHARISMA Investigators
J. Am. Coll. Cardiol. 2007 50: 291-295.
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Exercise Oscillatory Ventilation May Predict Sudden Cardiac Death in Heart Failure Patients
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J. Am. Coll. Cardiol. 2007 50: 299-308.
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Racial/Ethnic Differences in the Risk of Intracranial Hemorrhage Among Patients With Atrial Fibrillation
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Prognostic Value of Myocardial Viability Detected by Myocardial Contrast Echocardiography Early After Acute Myocardial Infarction
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A New Intra-Arterial DeliveryPlatform for Pro-Arteriogenic Compounds to Stimulate Collateral Artery Growth Via Transforming Growth Factor-ß1 Release
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Clinical Trials
Heart Failure
