Jean Marco

Guidelines on the management of stable angina pectoris: executive summary

We thank the authors for raising the interesting discussion regarding the treatment of hypertension in patients with concomitant coronary disease. The J-shaped association between on-treatment blood pressure and risk has been described in longitudinal cohorts of patients with treated hypertension as well as in clinical trial populations, both in on-treatment and control arms. However, it is not absolutely clear that the association is treatmentrelated; in fact, one meta-analysis of seven randomized controlled trials including data on more than 40 000 patients has shown that the J-shaped relationship between blood pressure and mortality was not related to antihypertensive treatment. In this meta-analysis, noncardiovascular death was inversely related to blood pressure (both systolic and diastolic) in contrast to the J-shaped relationships for cardiovascular and total mortality, leading the authors to hypothesize that poor health conditions leading to low blood pressure and an increased risk of death might in part explain the J-shaped curve. Secondly, as discussed in the full-text version of the guidelines, there is accumulating evidence that blood pressure lowering in the ‘normal’ range is associated with improved cardiovascular outcomes in the population with known coronary disease. In the CAMELOT study, patients with coronary disease and mean blood pressure of 129/78 were randomized to enalapril, amlodipine, or placebo. Blood pressure reductions were similar (5/2 mm) in both treatment groups and associated with similar relative reductions in the composite endpoint of cardiovascular death, MI, and stroke, although not statistically significant in either group because of the small sample size. An intravascular ultrasound substudy demonstrated a significant inverse correlation between progression of atherosclerosis and blood pressure reduction even in this normal blood pressure range, with the greatest benefit observed in patients whose blood pressure fell below 120/80. Thus, the task force has felt it important, in the absence of unequivocal evidence to the contrary, to preserve consistency between guidelines on prevention and angina with regard to targets for institution of therapy for hypertension in the presence of coronary disease. No lower limit has yet been identified as a definite cutoff beyond which blood pressure should not be lowered further, although, clearly, symptomatic hypotension or postural hypotension will limit aggressive blood pressure lowering in the lower range.

Guidelines on myocardial revascularization.

Guidelines and Expert Consensus Documents summarize and evaluate all available evidence with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome and the risk benefit ratio of diagnostic or therapeutic means. Guidelines are no substitutes for textbooks and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/ guidelines/rules). Members of this Task Force were selected by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) to represent all physicians involved with the medical and surgical care of patients with coronary artery disease (CAD). A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk benefit ratio. Estimates of expected health outcomes for society are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2. The members of the Task Force have provided disclosure statements of all relationships that might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at European Heart House, headquarters of the ESC. Any changes in conflict of interest that arose during the writing period were notified to the ESC. The Task Force report received its entire financial support from the ESC and EACTS, without any involvement of the pharmaceutical, device, or surgical industry. ESC and EACTS Committees for Practice Guidelines are responsible for the endorsement process of these joint Guidelines. The finalized document has been approved by all the experts involved in the Task Force, and was submitted to outside specialists selected by both societies for review. The document is revised, and finally approved by ESC and EACTS and subsequently published simultaneously in the European Heart Journal and the European Journal of Cardio-Thoracic Surgery. After publication, dissemination of the Guidelines is of paramount importance. Pocket-sized versions and personal digital assistant-downloadable versions are useful at the point of care. Some surveys have shown that the intended users are sometimes unaware of the existence of guidelines, or simply do not translate them into practice. Thus, implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations.

Clinical Efficacy of Polymer-Based Paclitaxel-Eluting Stents in the Treatment of Complex, Long Coronary Artery Lesions From a Multicenter, Randomized Trial. Support for the Use of Drug-Eluting Stents in Contemporary Clinical Practice

Background— Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking. Methods and Results— TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001). Conclusions— The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice.

Intracoronary Stent Implantation Without Ultrasound Guidance and With Replacement of Conventional Anticoagulation by Antiplatelet Therapy 30-Day Clinical Outcome of the French Multicenter Registry

BACKGROUND Stenting reduces both acute complications of coronary angioplasty and restenosis rates but increases subacute thrombosis rates and hemorrhagic complications when used with coumadin anticoagulation. METHODS AND RESULTS To simplify postcoronary stenting treatment and to reduce these drawbacks, we evaluated the 1-month outcome of a prospective registry of 2900 patients in whom successful coronary artery stenting was performed without coumadin anticoagulation. Patients received 100 mg/d aspirin and 250 mg/d ticlopidine for 1 month. Low-molecular-weight heparin (LMWH) treatment was progressively reduced in four consecutive stages, from 1-month treatment to none. Event-free outcome at 1 month was achieved in 2816 patients (97.1%). Major stent-related cardiac events were subacute closure in 51 patients (1.8%), including death in 12 (0.5%), acute myocardial infarction in 17 (0.6%), and coronary artery bypass graft surgery in 9 (0.3%). Stent thrombosis was more frequent with balloon size of < 3.0 mm (< or = 2.5 mm, 10%; 3.0 mm, 2.3%; > or = 3.5 mm, 1.0%; P < .001), bail-out situations (6.67% versus 1.38%, P < .001), and patients with unstable angina or acute myocardial infarction (2.2% versus 1.12%, P = .02). Bleeding complications that required transfusion, surgical repair, or both occurred in 55 patients (1.9%). Bleeding complications were related to female gender (4.0% versus 1.51%, P < .001), duration of LMWH treatment (3.83% in phase II/III versus 0.69% in phase IV/V, P < .001), sheath size (6F, 0.52%; 7F, 1.04%; > or = 8F, 4.23%; P < .001), bail-out situations (4.76% versus 1.67%, P < .01), and saphenous graft stenting (4.38% versus 1.75%, P = .04). CONCLUSIONS These results suggest that poststenting treatment by ticlopidine/aspirin is an effective alternative to coumadin anticoagulation, achieving low rates of subacute closure and bleeding complications. LMWH treatment does not improve subacute reocclusion rates but increases bleeding complications. Furthermore, as bleeding complications were independently related to sheath size, we suggest that stenting with 6F guiding catheters may prevent local complications. Furthermore, the ticlopidine/aspirin combination allows a low-cost stenting strategy without ultrasound assessment of stent deployment and permits short inhospital stay.

Predictors of in-hospital and 6-month outcome after acute myocardial infarction in the reperfusion era: The primary angioplasty in myocardial infarction (PAMI) trial

OBJECTIVES This study examined the predictors of in-hospital and 6-month outcome after different reperfusion strategies in acute myocardial infarction. BACKGROUND Thrombolytic therapy and primary angioplasty are both widely applied as reperfusion modalities in patients with myocardial infarction. Although it is accepted that restoration of early patency of the infarct-related artery can reduce mortality and salvage myocardium, the optimal reperfusion strategy remains controversial, and the predictors of outcome in the reperfusion era have been incompletely characterized. METHODS At 12 centers, 395 patients presenting within 12 h of onset of acute transmural myocardial infarction were prospectively randomized to receive tissue-type plasminogen activator (t-PA) or undergo primary angioplasty without antecedent thrombolysis. Sixteen clinical variables were examined with univariate and multiple logistic regression analysis to identify the predictors of clinical outcome. RESULTS By univariate analysis, in-hospital mortality was increased in the elderly, women, patients with diabetes and in patients treated with t-PA as opposed to angioplasty. Only advanced age and treatment by t-PA versus angioplasty independently correlated with increased in-hospital mortality (6.5% vs. 2.6%, respectively, p = 0.039 by multiple logistic regression analysis). Similarly, the only variables independently related to in-hospital death or nonfatal reinfarction were advanced age and treatment by t-PA versus angioplasty (12.0% vs. 5.1%, p = 0.02). The reduction in in-hospital death or reinfarction with angioplasty versus t-PA was particularly marked in patients > or = 65 years of age (8.6% vs. 20.0%, p = 0.048). Furthermore, primary management with angioplasty versus t-PA was the most powerful multivariate correlate of freedom from recurrent ischemic events (10.3% vs. 28.0%, p = 0.0001). The independent beneficial effect of angioplasty on freedom from death or reinfarction was maintained at 6-month follow-up (8.2% vs. 17.0%, p = 0.02). CONCLUSIONS In the reperfusion era, the two most powerful determinants of freedom from death, reinfarction and recurrent ischemia after myocardial infarction are young age and treatment by primary angioplasty.

α-Adrenergic Blockade Improves Recovery of Myocardial Perfusion and Function After Coronary Stenting in Patients With Acute Myocardial Infarction

Background—AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. Methods and Results—Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 μg/kg IC (n=10), the α1-blocker urapidil 600 μg/kg IV (n=10), or saline (n=10). Ten patients pretreated with β-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non–IRA-dependent myocardium (from 27±15% to 38±16% and from 40±15% to 45±15%, respectively). Simultaneously, TIMI frame count decre...

Unprotected left main coronary artery stenting: correlates of midterm survival and impact of patient selection.

BACKGROUND The study served to present the in-hospital and six-month clinical outcome and also the long-term survival data of a consecutive series of patients undergoing stenting for unprotected left main coronary artery (LMCA) disease. METHODS Revascularization with coronary bypass surgery has been generally recommended for treatment of left main coronary stenosis. Improvements in angioplasty and coronary stent techniques and equipment may result in the wider applicability of a percutaneous approach. A total of 92 consecutive patients underwent unprotected LMCA stenting between March 1994 and December 1998. For the initial 39 patients (group I) angioplasty was performed only when surgical revascularization was contraindicated. The remaining 53 patients (group II) also included patients in whom surgery was feasible. Patients were followed for 7.3 +/- 5.8 months (median 239 days; range 49 to 1,477 days). RESULTS Compared to group I, group II patients had higher left ventricular ejection fraction (60 +/- 12% vs. 51 +/- 16%, p < 0.01), less severe LMCA stenosis (68 +/- 12% vs. 80 +/- 10%, p < 0.001), lower surgical risk score (13 +/- 7 vs. 20 +/- 7, p < 0.001), and had angioplasty more often performed via the radial approach (88% vs. 23%, p < 0.001) with smaller guiding catheters (6F: 49% vs. 15%; 8F: 2% vs. 77%, p < 0.001). The procedural success rate was 100%. In-hospital mortality was 4% (4 deaths, 3 cardiac). During follow-up there were six deaths, 13 patients required repeat percutaneous transluminal coronary angioplasty (4 LMCA), and two required coronary artery bypass graft surgery. Estimated survival (+/- SEE) was 89 +/- 6.3% at 500 days and 85 +/- 12% at 1,000 days post-stenting. Overall mortality was 3.8% in group II and 20.5% in group I (p < 0.02). CONCLUSIONS Coronary stenting can be performed safely in high-risk individuals with acceptable intermediate-term outcome. It may be feasible to broaden the application of this technique in selected patients needing revascularization for left main coronary disease.

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results

OBJECTIVES The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible atrial fibrillation patients: results from the European PLAATO study

The European PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) study was performed to determine the safety and efficacy of left atrial appendage occlusion by catheter technique. Embolic stroke due to atrial fibrillation is a common observation, especially in the elderly. Most thrombi in atrial fibrillation form in the left atrial appendage (LAA), its occlusion may therefore reduce the incidence of stroke in these patients.

Ticlopidine and aspirin pretreatment reduces coagulation and platelet activation during coronary dilation procedures.

OBJECTIVES It is unknown whether a therapeutic combination of aspirin (ASA) and ticlopidine might effectively decrease activation of hemostasis. BACKGROUND Percutaneous transluminal coronary angioplasty (PTCA), rotational atherectomy and stent implantation are procedures that fracture or ablate endothelium and plaque, a situation that activates hemostasis. METHODS In 85 patients undergoing PTCA for a 77.8 +/- 1% stenosis, we measured markers of coagulation and platelet activation (thrombin-antithrombin complexes [TAT], prothrombin fragment 1 + 2 [F1 + 2] serotonin and the presence of circulating activated platelets reacting with monoclonal antibodies against glycoproteins exposed on platelet membranes). Blood samples were drawn from a peripheral vein and from the coronary ostium before the procedures. Both immediately and 10 min after angioplasty, and 10 min afterward, samples were collected from a probing catheter (0.018 in, [0.46 cm]) positioned beyond the stenosis. All patients were being treated with antianginal drugs and ASA, 250 mg/day. Seventy of them had taken ticlopidine, 250 mg, twice daily for < or = 1 day (< or = 24 h) (n = 28) or for > or = 3 days (> or = 72 h) (n = 42). Heparin (150 U/kg) was administered before angioplasty. Thirty patients underwent PTCA; 15 of them were not treated with ticlopidine and 15 were given ticlopidine (> or = 72 h). Thirty-five patients had stent implantation, 20 rotational atherectomy. RESULTS Before and during the procedures, there was greater thrombin generation (expressed by higher TAT and F1 + 2 plasma levels) in patients not taking ticlopidine or taking it for < or = 24 h (p < 0.05). Platelet activation and plasma serotonin levels were also significantly higher in the no ticlopidine or < or = 24-h ticlopidine groups. CONCLUSIONS The combined use of ticlopidine, ASA and heparin effectively controls activation of coagulation in patients with stable or unstable angina undergoing coronary dilation.