Edward Fry

Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention

CONTEXT Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. OBJECTIVES To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. DESIGN, SETTING, AND PARTICIPANTS The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. INTERVENTIONS 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. MAIN OUTCOME MEASURES One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. RESULTS At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P =.02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P =.23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P =.051) 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 =.07). CONCLUSIONS 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.

Treatment of Left Anterior Descending Coronary Artery Disease With Sirolimus-Eluting Stents

Background—Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the “reintervention gap” between surgery and percutaneous intervention, making the percutaneous route preferable. Methods and Results—Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P<0.001). One-year major adverse events (defined as cardiac death, Q-wave and non–Q-wave myocardial infarction, or target vessel revascularization) was decreased 59% in the sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to 0.61; P<0.001). Subgroup analysis of 135 patients with proximal LAD lesions showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus-eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major adverse events demonstrated a similar trend, with a 50% decrease compared with control patients (10.4% versus 20.6%, P=NS). Conclusions—Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

First Clinical Application of an Actively Reversible Direct Factor IXa Inhibitor as an Anticoagulation Strategy in Patients Undergoing Percutaneous Coronary Intervention

Background— The ideal anticoagulant should prevent ischemic complications without increasing the risk of bleeding. Controlled anticoagulation is possible with the REG1 system, an RNA aptamer pair comprising the direct factor IXa inhibitor RB006 and its active control agent RB007. Methods and Results— This phase 2a study included a roll-in group (n=2) treated with REG1 plus glycoprotein IIb/IIIa inhibitors followed by 2 groups randomized 5:1 to REG1 or unfractionated heparin. In group 1 (n=12), RB006 was partially reversed with RB007 after percutaneous coronary intervention and fully reversed 4 hours later. In group 2 (n=12), RB006 was fully reversed with RB007 immediately after percutaneous coronary intervention. Femoral sheaths were removed after complete reversal. Patients were pretreated with aspirin and clopidogrel. End points included major bleeding within 48 hours; composite of death, myocardial infarction, or urgent target vessel revascularization within 14 days; and pharmacodynamic measures. All cases were successful, with final Thrombolysis in Myocardial Infarction grade 3 flow and no angiographic thrombotic complications. There were 2 ischemic end points in the REG1 group and 1 in the unfractionated heparin group, with 1 major bleed in the unfractionated heparin group. Median activated clotting time values rose from 151 to 236 seconds after RB006. Administration of the partial RB007 dose reversed anticoagulation to an intermediate activated clotting time value of 186 seconds. Complete reversal with RB007 returned the median activated clotting time value to 144 seconds. Both reversal strategies enabled scheduled femoral sheath removal. Conclusions— This study demonstrates the clinical translation of a novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coronary intervention and provides the basis for further investigation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715455.

Presentation and Therapy of Spontaneous Coronary Artery Dissection and Comparisons of Postpartum Versus Nonpostpartum Cases

Predisposing risk factors, clinical course, and prognosis of spontaneous coronary artery dissection (SCAD) remain poorly understood. We reviewed medical records and coronary angiograms of patients admitted to our institution with the diagnosis of SCAD from 1999 through 2010. A definite diagnosis of SCAD required the agreement of 2 blinded board-certified interventional cardiologists who reviewed all images separately. Baseline characteristics of patients (n = 23) included mean age 45 ± 11 years, female gender in all (100%), history of hypertension in 13 (57%), and postpartum in 7 (30%). Eleven (48%) had ST-segment elevation on initial electrocardiogram. SCAD involved the left main in 5 patients (21.7%), left anterior descending coronary artery in 16 (70%), left circumflex coronary artery in 8 (35%), and right coronary artery in 6 (26%). Four patients (17%) underwent coronary stenting and 6 (26%) required urgent bypass surgery. Comparison between postpartum and nonpostpartum patients revealed significant differences in mean peak troponin levels: 50 ± 34 ng/ml vs 21 ± 23, p = 0.04, mean left ventricular ejection fraction: 34 ± 6% vs 49 ± 9, p <0.01, proximal coronary segment distribution: 6 (86%) vs 3 (19%), p = 0.004, and left anterior descending coronary artery distribution: 7 (100%) vs 9 (56%), p = 0.04, respectively. Repeat coronary angiographies were performed in 11 patients (46%) during a mean follow-up of 39 ± 38 months and 10 (91%) were found to have healed SCAD, including those who had undergone bypass surgery. In conclusion, our patients with SCAD were characterized by female gender, absence of coronary risk factors, and a high rate of vascular healing without residual stenosis. Larger infarct was found in postpartum patients.

A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial

OBJECTIVES We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST). BACKGROUND The optimal antithrombotic regimen for such patients is unknown. METHODS We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization. RESULTS The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001). CONCLUSIONS The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

2016 ACC/ASE/ASNC/HRS/SCAI Health Policy Statement on Integrating the Healthcare Enterprise

Richard J. Kovacs, MD, FACC, Chair Deepak Bhatt, MD, FACC Ralph Brindis, MD, MPH, MACC Paul N. Casale, MD, MPH, FACC Edward T.A. Fry, MD, FACC Paul A. Heidenreich, MD, FACC Jeffrey P. Jacobs, MD, FACC James L. Januzzi, Jr, MD, FACC Amy L. Miller, MD, PhD, FACC Athena Poppas, MD, FACC

Cardiovascular Health System Leadership: An Evolving Model

![Figure][1] ![Figure][1] As 2018 approaches, the American College of Cardiology (ACC) continues to grow its commitment to patients and members through critical work on the College’s next Strategic Plan [(1)][2]. Carrying forward, the central theme will be transformation of care

Percutaneous Saphenous Vein Graft and Arterial Graft Intervention

Despite major advances in the management of these lesions over the past decade, bypass-graft intervention remains a significant challenge. Saphenous vein graft (SVG) intervention in particular has a high complication rate, a consequence of frequent distal embolization, resulting in no-reflow and periprocedural myocardial infarction. Proximal and distal embolic protection devices have been shown to substantially reduce the risk of no-reflow and adverse cardiac events in patients undergoing SVG PCI. In addition, drug-eluting stents (DES), in comparison to bare-metal stents (BMS) in this patient population, attenuate the high rates of target lesion revascularization at least in the short term.

Histologic Basis of Vessel Remodeling after Various Interventional Procedures: A Comparison of Acute (Cracks, Breaks, Tears, Stretching) and Chronic (Tissue Proliferation, Recoil) Changes

During the past two decades, there has been an explosive increase in the number of techniques and devices used to treat obstructed coronary arteries. Since its introduction in 1977 (1), catheter balloon angioplasty has gained wide acceptance as a nonsurgical form of therapy for acutely and chronically obstructed coronary arteries, and this technique forms the centerpiece around which newer tools and techniques have been developed. Of the many interventional devices currently used or under study, their morphologic effects (“remodeling”) on vessel luminal shape or obstruction can be separated into two underlying processes (2): (a) remodeling (“displacing,” “expanding,” “attaching”) and (b) removing (“heating,” “drilling,” “excising”) (Tables 1, 2). This chapter will review acute and chronic changes of remodeling after balloon angioplasty and other interventional techniques.