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Background After percutaneous coronary intervention (PCI), the antiplatelet drug clopidogrel is frequently used to prevent stent thrombosis. A concern has been raised that atorvastatin may competitively inhibit the metabolism of the prodrug clopidogrel to its active metabolites by the cytochrome P450 3A4 (CYP3A4) enzyme, thereby potentially negating its antiplatelet effect. The 30-day rates of adverse cardiovascular events (composite of death, myocardial infarction, 11 unstable angina, stroke or transient ischemic attack, and repeat revascularization procedures) in unselected 12 patients prescribed clopidogrel after PCI as a function of their exposure to CYP3A4 inhibitors has not been fully resolved. Methods Using the administrative databases from the Province of Quebec, we identified all patients in 1999 and 2000 who received an outpatient prescription for clopidogrel within 5 days of PCI with stenting. Using multiple logistic regression, we compared the odds ratios (OR) of the composite cardiovascular outcome within 30 days of the index PCI between patients prescribed drugs inhibiting CYP3A4 activity and those who were not. Event rates were adjusted for demographic variables, disease severity, associated comorbidities, and other medications. Results The 2927 patients who were prescribed clopidogrel after PCI were included in our cohort. Of these, 727 were prescribed atorvastatin and 2200 were not. There were 33 (4.54%) adverse events in the group prescribed atorvastatin and 68 (3.09%) in the group not prescribed atorvastatin. The adjusted 30-day OR of the composite outcome was 1.65 (95% CI 1.07-2.54) in patients prescribed atorvastatin with clopidogrel compared to those not prescribed atorvastatin. Other drugs that are substrates for CYP3A4 (OR 1.56, 95% CI 1.02-2.37) and a delay in filling the clopidogrel prescription (OR 1.77, 95% CI 1.16-2.70) were also associated with a higher risk. Sex, previous hospitalizations for unstable angina or myocardial infarction, aspirin use, or a history of revascularization (PCI or coronary artery bypass graft) in the 6 months before the index procedure was not statistically associated with adverse outcomes. Conclusions After coronary stenting, a delay in filling the prescription for clopidogrel as well as prescriptions for drugs inhibiting CYP3A4 enzyme activity was associated with adverse cardiovascular events. However, because of the limitations of observational study designs, the clinical significance of these putative drug interactions remains uncertain but merits further investigation.

Summary Background Drug-eluting stents (DES) are associated with lower restenosis rates than bare-metal stents (BMS), but the benefits and safety of the new devices have not been systematically quantified across different trials. We undertook a meta-analysis of randomised trials comparing BMS and stents eluting sirolimus or paclitaxel. Methods A systematic literature search aimed to identify all randomised clinical trials with 6–12 months of clinical follow-up. Results were pooled by a hierarchical Bayesian random-effects model with prespecified stratification for drug and the presence of carrier polymer. The primary outcomes examined were rates of death, myocardial infarction, target-lesion revascularisation, major adverse cardiac events (death, myocardial infarction, and target-vessel revascularisation), and angiographic restenosis. Findings We identified 11 eligible trials involving 5103 patients. The pooled mortality rates were low for both DES and BMS with no evidence of any difference between them (odds ratio 1·11 [95% credible interval 0·61–2·06]). Pooled rates of myocardial infarction showed no between-group difference (0·92 [0·65–1·25]). The rate of major adverse cardiac events was 7·8% with DES and 16·4% with BMS (0·42 [0·32–0·53]), and the angiographic restenosis rates were also lower for DES (8·9% vs 29·3%; 0·18 [0·06–0·40]). The pooled rates of major adverse cardiac events for each DES type and the respective BMS were: for sirolimus, 6·8% versus 21·0% (0·28 [0·17–0·41]); for polymer-based paclitaxel 8·7% versus 16·7% (0·47 [0·25–0·71]); and for non-polymer-based paclitaxel 7·7% versus 9·5% (0·64 [0·42–1·00]). We did not observe higher rates of edge restenosis, stent thrombosis, or late incomplete stent apposition with DES, although the credible intervals were wide. Interpretation Sirolimus-eluting and polymeric paclitaxel-eluting stents are effective at decreasing rates of angiographic restenosis and major adverse cardiac events compared with BMS. However, there is no evidence that they affect mortality or myocardial-infarction rates. They also appear to be safe in the short to medium term, although definitive conclusions are not possible. Larger studies with longer follow-up are needed to define better the role of these new devices.

Background There have been few prospective studies examining the utility of routine exercise treadmill testing (ETT) early after percutaneous coronary intervention (PCI). The objective of this study was to examine the impact of a routine ETT strategy early after PCI on follow-up cardiac events and procedures. Methods We examined 136 patients who underwent routine ETT at 6 weeks post-PCI in the ADORE trial. The ETT was classified as positive, indeterminate, or negative. The Duke Treadmill Score (DTS) was calculated for all patients. Follow-up occurred at 9 months. Results ETT results at 6 weeks were: 32 (23.5%) positive, 24 (17.6%) indeterminate and 80 (58.8%) negative. At 9 months, the composite event rate was 21.9% in those with a positive ETT, 20.8% in those with an indeterminate ETT and 12.5% in those with a negative ETT (p = 0.25 positive vs. negative ETT). The sensitivity of early ETT for predicting clinical events was 41.2%, the specificity was 73.3%, the positive predictive value was 21.9% and the negative predictive value was 87.5%. At 9 months, the cardiac procedure rate was 18.8% in those with a positive test, 13.0% in those with an indeterminate test, and 6.3% in those with a negative test (p = 0.07 positive vs. negative ETT). In a multivariate logistic regression model, coronary stenting during PCI and a ≥ 85% MPHR achieved were found to be inversely associated with clinical events. However, the DTS did not independently predict clinical events. Conclusion Although the statistical power of the study was limited by the small number of clinical events (particularly MI and death), the results of this study support the ACC/AHA guidelines that exercise treadmill testing should not be used routinely after PCI.

This is the second part of a 2-part article that reviews the literature on coated stents and their effects on in-stent restenosis after percutaneous coronary intervention (PCI). Part I of this review discussed the pathophysiology of in-stent restenosis, specific stent coatings, and animal studies investigating coated stents. Part II discusses nonrandomized studies and clinical trials in humans. Studies in humans have examined stents coated with biocompatible materials and drug-eluting stents. Complications and controversies associated with this new technology are also addressed. The risk of developing in-stent restenosis is related to a variety of factors, both clinical and procedural.1–7⇓⇓⇓⇓⇓⇓ On the basis of these risk factors, patients enrolled in both nonrandomized studies and clinical trials have been classified as having a high, intermediate, or low risk of restenosis. Therefore, the binary restenosis rates (>50% diameter stenosis angiographically) and major adverse cardiac event (MACE) rates in human studies vary greatly depending on the overall risk profile of patients enrolled in these studies. ### Non-Randomized Studies #### Stents Coated with Biocompatible Materials The biocompatibility of stents coated with several materials, including carbon, gold, silicon carbide, and phosphorylcholine, has been investigated in humans. The Carbostent (Sorin Biomedica Cardio) is a metal stent coated with a carbon film that is thought to be less thrombogenic than uncoated steel stents.8 Antoniucci et al9 investigated the long-term biocompatibility of the Carbostent in a group of 112 patients with an intermediate risk of developing restenosis. Six-month follow-up revealed low MACE and restenosis rates of 12% and 11%, respectively. A second study in another group of 112 patients at high risk for restenosis resulted in a MACE rate of 20% and a binary restenosis rate of 25% by 6 months.10 These results suggest that the Carbostent is well tolerated in vivo and possibly inhibits neointimal hyperplasia, especially in …

Dreissenid mussels, Dreissena polymorpha and D. bugensis, were found to be infected by the naidid oligochaete Chaetogaster limnaei at four sites in the St. Lawrence River. This is the first report of this species infecting dreissenids anywhere in the world. Most worms inhabited the mantle cavity, where they caused erosion of the mantle and gill epithelia as determined by histopathological examination. Others penetrated various tissues; one had invaded the ovary and was feeding on oocytes and ovarian tissues. Of 606 mussels examined, 166 (27.4%) harbored at least 1 C. limnaei. The prevalence varied between 1% and 80%, depending on the collection site and date. The worms were slightly but significantly more prevalent in D. bugensis than in D. polymorpha. The intensity ranged from 1 to 18 worms per infected host. Variations in prevalence and intensity were not related to the size or sex of the host, but the data did suggest some seasonality.