High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.

OBJECTIVES: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events. BACKGROUND: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR. METHODS: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month. RESULTS: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70). CONCLUSIONS: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.

Genotypic and phenotypic assessment of platelet function and response to P2Y12 antagonists.

The P2Y12-ADP receptor antagonists are the cornerstone of oral antiplatelet therapy in the secondary prevention of coronary artery disease, especially after acute coronary syndrome or percutaneous coronary intervention. Currently, the therapeutic agents available to block the receptor include clopidogrel and prasugrel; ticagrelor is not available everywhere. Clopidogrel was the gold standard, but recently it has been challenged by prasugrel and ticagrelor. One pitfall of clopidogrel is that in some patients it cannot induce optimal platelet reactivity inhibition in connection with several factors, including some genetic polymorphisms of enzymes participating in its bioabsorption or metabolism. This variability of response can be evaluated by platelet reactivity monitoring. This comprehensive review provides the available data regarding the genotypic and phenotypic interaction with the response to P2Y12-ADP receptor antagonists and discusses the concept of personalized antiplatelet therapy based on a genotypic or phenotypic profile.

Incidence, predictors, and outcome of new, subsequent lesions treated with percutaneous coronary intervention in patients presenting with myocardial infarction.

Despite improving strategies for control of risk factors, progression of atherosclerosis may lead to recurrent cardiac events related to a lesion other than that treated with initial percutaneous coronary intervention (PCI) after ST-elevation myocardial infarction (STEMI). Of 1,007 consecutive patients undergoing primary or rescue PCI for STEMI, 897 who were discharged alive were followed for up to 3 years. Those who underwent nontarget lesion revascularization (non-TLR) were compared with those who did not. Those who underwent a second procedure were followed for an additional 1 year. Altogether, 94 patients (10.5%) required a non-TLR. The median time from the first to the second PCI was 396 days (interquartile range 131 to 533). Subsequent PCI was required for non-STEMI in 46.1% and STEMI in 9.7% of cases. Independent predictors of need for non-TLR were diabetes mellitus, history of coronary bypass surgery, or peripheral vascular disease. By 1 year after the second PCI, 9 patients (9.6%) died, 4 (4.3%) had sustained MI, and 4 (4.3%) had TLR. One of these major adverse events had occurred in 17 (18%). In conclusion, after STEMI, nearly 10% of patients will develop an event that requires subsequent PCI to an unrelated lesion. Patients with diabetes mellitus, history of coronary bypass surgery, or peripheral vascular disease are at increased risk for this event. Aggressive preventive and medical management should be applied to this population for prevention of these subsequent events.

Prognostic value of procedure-related myocardial infarction according to the universal definition of myocardial infarction in saphenous vein graft interventions.

BACKGROUND: In the recently published universal definition of myocardial infarction (MI), a troponin elevation above 3x above the 99th percentile of normal after percutaneous coronary intervention (PCI) is a procedure-related (type 4a) MI. Although troponin rise is common after saphenous vein graft (SVG) PCI, its prognostic value remains undetermined. We aimed to investigate the prognostic value of the universal definition of PCI-related MI in SVG interventions. METHODS: A cohort of 589 unselected consecutives patients with normal preprocedural troponin Ic undergoing isolated SVG PCI with drug-eluting stent implantation was included. Patients were divided into 2 groups according to the peak troponin value post PCI: those with MI defined as a peak troponin value above 3x the 99th percentile of normal post-PCI (MI group, n = 166) and those without (no MI group, n = 423). The primary end point was the rate of major adverse cardiac events including death, MI, and target vessel revascularization at 1-year follow-up. RESULTS: Baseline characteristics were similar between the 2 groups. In the MI group, patients had more complex angiographic features (type C lesions: 44.7 vs 34.8%; P = .006). The rate of direct stenting and distal protection use were similar in the 2 groups (MI vs no MI: 29.2 vs 28.7%; P = .9 and 32 vs 37.5%; P = .24, respectively). Patients in the MI group had a worse inhospital course but a similar 1-year rate of major adverse cardiac events (22.3 vs 19.1%; P = .39). CONCLUSION: Procedure-related MI after PCI, as defined by the universal definition, is associated with an adverse inhospital course but may not predict long-term outcome in SVG PCI.

Prognostic value of the Syntax score in patients undergoing coronary artery bypass grafting for three-vessel coronary artery disease.

BACKGROUND: The Syntax score prognostic value has recently been highlighted in patients undergoing percutaneous coronary intervention (PCI) for multivessel coronary artery disease (CAD), however its prognostic value in patients undergoing coronary artery bypass grafting (CABG) for multivessel CAD is still unknown. The aim of this study was to evaluate the prognostic value of the Syntax score in patients undergoing CABG for 3-vessel CAD. METHODS: A cohort of 320 consecutive patients with multivessel (3-vessel) CAD who were subjected for CABG were included in this study and divided into tertiles according to the Syntax score (<24.5, 24.5-34, and >34). During the 1-year follow-up, cardiovascular events including death, myocardial infarction (MI), and stroke were systematically indexed. The primary end point was the composite criteria death/MI/stroke. RESULTS: The Syntax score ranged from 11-74 with a mean of 31.2 +/- 12.6 and a median of 28.5 [22-38]. Baseline clinical characteristics were similar among the tertiles. No statistical difference was found for the composite criteria death/MI/stroke: 9.4% versus 7.5% versus 10.4% in the groups with a Syntax score <24.5, 24.5-34, and >34, respectively (P = 0.754). CONCLUSION: Unlike for PCI, the Syntax score has a poor prognostic value for severe cardiovascular events in patients undergoing CABG for 3-vessel CAD. Other risk scores should be used to predict the outcome of this population.

Requirement for emergent coronary artery bypass surgery following percutaneous coronary intervention in the stent era.

Performance of percutaneous coronary intervention (PCI) at centers without cardiothoracic surgery is a contentious issue. Although this practice allows greater access to care, there are safety concerns. The aim was to assess the requirement for emergent coronary artery bypass grafting (CABG) after PCI and characterize patients at highest risk using independent predictors. The study population consisted of 21,957 unselected patients who underwent PCI from August 1994 (Food and Drug Administration stent approval) to January 2008 at a single medical center. Patients requiring emergent CABG (defined as within 24 hours of the index procedure) were identified. Logistic regression analysis was performed to assess for independent correlates of emergent CABG. Emergent CABG was required in 90 patients (cumulative incidence 0.41%). Indications for CABG included triple-vessel disease, dissection, acute closure, perforation, and failure to cross. These patients had significantly higher in-hospital cardiac death rates (7.8% vs 0.7%; p <0.01) and higher rates of Q-wave myocardial infarction, neurologic events, and renal insufficiency. Independent correlates of emergent CABG after PCI were acute ST-segment elevation myocardial infarction presentation, cardiogenic shock, triple-vessel disease, and type C lesion. Risk assessment based on these predictors identified 0.3% of the patient population to have a 9.3% cumulative incidence of emergent CABG. In conclusion, the need for emergent CABG after PCI in the stent era was low and was associated with poor in-hospital outcomes. Risk was nonuniform, with 0.3% of the study population, characterized by acute presentation and complex coronary disease, at heightened risk of emergent surgery.

Impact of "nuisance" bleeding on clopidogrel compliance in patients undergoing intracoronary drug-eluting stent implantation.

Premature cessation of clopidogrel is a strong risk factor for drug-eluting stent thrombosis in patients undergoing percutaneous coronary intervention. The impact that superficial or "nuisance" bleeding may have on clopidogrel compliance has not been described. The study population consisted of 2,360 unselected patients undergoing successful drug-eluting stent implantation. Nuisance bleeding, defined as easy bruising, bleeding from small cuts, petechia, and ecchymosis, was assessed during routine clinical follow-up. Internal and alarming bleeding was recorded. Cessation of clopidogrel as a consequence of such bleeding was then assessed. Study population characteristics were 66.1% men, mean age 64.5 +/- 11.8 years, diabetes mellitus in 31.1%, smoking in 18.5%, systemic hypertension in 81.8%, dyslipidemia in 87.9%, history of coronary artery disease in 49.1%, chronic renal insufficiency in 8.7%, and acute myocardial infarction in 10.8%. A total of 837 patients reported bleeding events (incidence 32.4%) of which 85.7% were nuisance, 13.6% were internal, and 0.7% were alarming. Rate of clopidogrel discontinuation as a result of bleeding in the nuisance bleeding group was 11.1%. In conclusion, superficial or nuisance bleeding is common in patients taking dual antiplatelet therapy after percutaneous coronary intervention. Overall, 11.1% of patients with nuisance bleeding discontinued clopidogrel. Greater education and follow-up in this patient subset may lead to improved compliance with clopidogrel therapy.

Vascular brachytherapy for patients with drug-eluting stent restenosis.

BACKGROUND: The rate of drug-eluting stent (DES) in-stent restenosis (ISR) exceeds 10% in complex subsets of patients and lesions. The optimal management of DES ISR remains undetermined. Vascular brachytherapy (VBT) is proven to be effective for the treatment of bare metal stent ISR but its outcome for DES ISR has not been established. METHODS: Ninety-nine consecutive patients who presented with ISR following DES implantation in 122 lesions were subjected to conventional percutaneous coronary intervention with adjunct VBT using either beta radiation (Beta Rail in 74 patients [82.2%] and the Galileo system in 13 patients [14.4%]) or gamma radiation (Checkmate system in 3 patients [3.3%]). Patients were followed clinically for major adverse cardiac events (MACE) during 1-year follow-up. RESULTS: A high proportion of patients in this cohort presented with complex ISR; 31.1% had recurrences of ISR to the same site, 55% had diffuse or proliferate pattern of restenosis, and 23 lesions (18.9%) were located in a saphenous vein graft. Procedural success and uneventful in-hospital course were documented in all patients post VBT. At 12 months' follow-up, the target lesion revascularization (TLR) rate was 11% and the overall MACE rate was 26%. Patients with multiple episodes of ISR to the same site had a TLR of 16% and MACE rate of 35.5%. CONCLUSIONS: VBT for the treatment of DES ISR was found to be effective and safe and should be considered for the treatment of DES ISR, in particular in complex patients with multiple recurrences.

Reducing risk of stroke in patients with acute coronary syndrome: is screening for asymptomatic carotid disease useful?

Stroke is a rare but severe event after acute coronary syndrome. Relations between both arterial territories are still discussed but prevalence of asymptomatic carotid stenosis potentially implicated in the mechanism of stroke is under-investigated. This study aimed to determine the prevalence of asymptomatic carotid stenosis in that population and review the value of screening in a view to potential surgical correction or other preventive therapies. Systematic carotid Doppler ultrasound screening was implemented on 152 consecutive patients admitted to the intensive care unit due to acute coronary syndrome. Fifty-two percent of patients had at least one carotid artery stenosis determined using the NASCET method. Forty-three percent had at least one carotid stenosis <30%, 6% had mild (30-60%) stenosis, and 2.6% had high-grade (>60%) stenosis. Existence of carotid stenosis was associated with age, diabetes mellitus, hypertension, and with the extent of the coronary atherosclerosis (left main artery stenosis). In multivariate analysis, age and diabetes were independently associated with existence of a carotid stenosis. When ultrasound screening was restricted to patients identified by multivariate analysis, the prevalence of carotid stenosis potentially requiring surgical treatment rose to 4.6%. The frequency of asymptomatic carotid atherosclerosis was high in this population but lesions were mild. While the small number of high-grade lesions indicates that systematic screening is not to be recommended, screening of patients aged >65 years or with diabetes, or both, with a view to surgery may be envisaged, since the role of mild stenosis in the occurrence of stroke remains debatable.

Two-year outcome of patients treated with sirolimus- versus paclitaxel-eluting stents in an unselected population with coronary artery disease (from the REWARDS Registry).

Multiple studies comparing sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with coronary artery disease have been performed. Despite these comparisons, it remains uncertain whether a differential in long-term efficacy and safety exists. Unselected patients treated exclusively with 1 drug-eluting stent type were enrolled in the Registry Experience at the Washington Hospital Center with Drug-Eluting Stents. There were 2,099 patients (3,766 lesions) treated with SES and 1,079 patients (1,850 lesions) treated with PES. Patients were followed at 30 days, 1 year, and 2 years for the clinical endpoints of death, myocardial infarction, target vessel revascularization, and definite and definite/probable stent thrombosis. Patients in the SES group had more dyslipidemia, history of congestive heart failure, and ostial lesions; patients treated with PES had more previous coronary artery bypass surgery, unstable angina, and type C lesions. At 2 years, unadjusted major adverse cardiac events (MACE) (22.6% vs 21.1%, p = 0.3) and target vessel revascularization (13.3% vs 11.2%, p = 0.1) were comparable. The incidence of definite stent thrombosis was higher in the SES group (1.8% vs 0.9%, p = 0.05) driven by early events. Similar results were seen after adjustment for baseline differences: MACE (hazard ratio 1.1, 95% confidence interval [CI] 0.9 to 1.3, p = 0.5), definite stent thrombosis (hazard ratio 2.3, 95% CI 1.0 to 5.2, p = 0.05), and target vessel revascularization (hazard ratio 1.1, 95% CI 0.9 to 1.4, p = 0.4). The incidence and rate of late stent thrombosis (>30 days) were similar (0.7% vs 0.5%, p = 0.4 and 0.24%/year, both groups, respectively). In conclusion, no major differential in long-term safety or efficacy was detected between SES and PES; both stent types were efficacious in reducing revascularization but were limited by a small continual increase in late stent thrombosis.

Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials.

OBJECTIVES: To improve the evaluation of the possible antiarrhythmic effect of statins, we performed a meta-analysis of randomized trials with statins on the end point of incidence or recurrence of atrial fibrillation (AF). BACKGROUND: The use of statins had been suggested to protect against AF in some clinical observational and experimental studies but has remained inadequately explored. METHODS: A systematic review of controlled trials with statins was performed. Eligible studies had to have been randomized controlled parallel-design human trials with use of statins that collected data on incidence or recurrence of AF. RESULTS: Six studies with 3,557 patients in sinus rhythm were included in the analysis. Three studies investigated the use of statins in patients with a history of paroxysmal AF (n = 1) or persistent AF undergoing electrical cardioversion (n = 2), and 3 investigated the use of statins in primary prevention of AF in patients undergoing cardiac surgery or after acute coronary syndrome. Incidence or recurrence of AF occurred in 386 patients. Overall, the use of statins was significantly associated with a decreased risk of AF compared with control (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18 to 0.85, p = 0.02). Benefit of statin therapy seemed more marked in secondary prevention of AF (OR 0.33, 95% CI 0.10 to 1.03, p = 0.06) than for new-onset or postoperative AF (OR 0.60, 95% CI 0.27 to 1.37, p = 0.23). CONCLUSIONS: Use of statins was significantly associated with a decreased risk of incidence or recurrence of AF in patients in sinus rhythm with a history of previous AF or undergoing cardiac surgery or after acute coronary syndrome.