Norman Lepor

Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study

Background The PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol (LDL‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. Methods and Results Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL‐C target levels were not met. The primary efficacy endpoint was LDL‐C percentage change from baseline to W24. Mean baseline LDL‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P<0.0001 versus placebo). In total, 63.9% and 70.3% of alirocumab‐treated patients achieved their LDL‐C targets at W24. Treatment‐emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection‐site reactions among the most common treatment‐emergent adverse events. Conclusions Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL‐C. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023879.

The evolving utility of intracoronary ultrasound

Abstract We conclude that IVUS imaging has become a method for supporting interventional decision making in our laboratory. By selecting patients for IVUS imaging who are undergoing stent placement, DCA, and laser angioplasty, and who have coronary angiographic lesions of uncertain severity, there has been an increase in the clinical utility of IVUS imaging in our laboratory.

A Prospective, Nonrandomized, Open-Labeled Pilot Study Investigating the Use of Magnesium in Patients Undergoing Nonacute Percutaneous Coronary Intervention with Stent Implantation

Background: Magnesium has recently been shown to inhibit acute stent thrombosis in animal models. This study tested the feasibility of magnesium administration in patients undergoing nonacute percutaneous coronary intervention with stent implantation. Methods: Twenty-one patients undergoing nonemergent percutaneous coronary intervention were enrolled and received intravenous magnesium sulfate (2-g bolus over 20 minutes prepercutaneous coronary intervention, followed by 14 g over 12 hours infusion). Endpoints: safety outcomes-hypotension, bradycardia, bleeding complications and heart block within first 24 hours; angiographic outcomes-acute thrombotic occlusion and need for platelet glycoprotein Ilb/Illa inhibitor bailout; and clinical outcomes-death, myocardial infarction, recurrent ischemia, and need for urgent revascularization at 48 hours and 30 days. Results: No significant effects on heart rate or blood pressure, major bleeding complication, or new electrocardiographic changes were observed. Angiographic thrombus was visualized in two cases, and coronary artery dissection in one case poststent deployment. None of these cases required the use of glycoprotein inhibitors for bailout. Death, myocardial infarction, recurrent ischemia, and need for urgent revascularization were not observed. The serum magnesium level increased from 2.1 ± 0.3 mg/dL at baseline to 3.5 ± 0.8 mg/dL at the end of the infusion (P < .0001). Platelet activation was significantly inhibited at the end of the magnesium sulfate infusion. Conclusion: Intravenous magnesium sulfate has been demonstrated as a feasible and safe agent in patients undergoing nonacute percutaneous coronary intervention with stent implantation. A randomized clinical trial comparing magnesium with glycoprotein inhibitors during percutaneous coronary intervention is warranted.

Intravascular ultrasound imaging of ruptured atherosclerotic plaques in coronary arteries.

Intravascular ultrasound demonstrated plaque ruptures that occurred in regions involved with large complicated atherosclerotic plaques in the coronary artery. Because intravascular ultrasound evaluates both plaque and luminal dimensions, it contributes to our understanding of the pathophysiology of coronary artery disease.

EFFICACY AND SAFETY OF DIFFERENT DOSING REGIMENS OF ALIROCUMAB (STARTING DOSES OF 75 MG EVERY TWO WEEKS AND 150 MG EVERY FOUR WEEKS) VERSUS PLACEBO IN PATIENTS WITH HYPERCHOLESTEROLEMIA NOT TREATED USING STATINS: THE ODYSSEY CHOICE II STUDY

Statins upregulate PCSK9 and increased PCSK9 accelerates target-mediated clearance of PCSK9 monoclonal antibodies; this may limit sustained efficacy when administered every 4 weeks (Q4W). However, patients (pts) not taking a statin may maintain efficacy with Q4W dosing, which could be convenient for

Efficacy and safety of alirocumab in patients with or without prior coronary revascularization: Pooled analysis of eight ODYSSEY phase 3 trials

BACKGROUND AND AIMS Patients with atherosclerotic cardiovascular disease (ASCVD) and prior revascularization are at high risk of further cardiovascular events and may require additional lipid-lowering therapies beyond maximally tolerated statin therapy. We assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in patients with ASCVD, with or without prior coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]). METHODS Data from eight controlled (placebo/ezetimibe) phase 3 ODYSSEY trials were pooled and stratified by trial design: alirocumab 150 mg or 75 mg with possible dose increase to 150 mg (75/150 mg) every 2 weeks (Q2W) versus placebo, and alirocumab 75/150 mg Q2W versus ezetimibe. Most patients received background maximally tolerated statin therapy. RESULTS Among 4629 randomized patients with hypercholesterolemia, 3382 had ASCVD including 2191 with prior revascularization. Although baseline characteristics were comparable between alirocumab and control groups, revascularized patients were more likely to be male, have had prior myocardial infarction/stroke, have higher lipoprotein (a) and PCSK9 levels, and were more often treated with high-intensity statin therapy. Alirocumab significantly reduced low-density lipoprotein cholesterol (LDL-C; primary endpoint; p < 0.0001), lipoprotein (a), non-high-density lipoprotein cholesterol, and apolipoprotein B levels from baseline to week 24 (vs. control), regardless of stratified treatment group or revascularization status. On-treatment LDL-C levels with alirocumab ranged from 45.6 to 64.8 mg/dL. Alirocumab had a similar safety profile regardless of revascularization status, and higher rates of injection-site reactions versus controls. CONCLUSIONS Alirocumab is generally well-tolerated and effective with a similar safety profile in high-risk patients with or without prior revascularization (PCI/CABG).

TCT-772 High prevalence of pelvic venous compression syndrome among patients with chronic venous insufficiency and effective treatment with venous stenting

May-Thurner Syndrome is the pathologic compression of the L common iliac vein by the R common iliac artery and has an incidence of 22%, in a cadaver study. Venous compression syndrome (VCS) can also occur in the external iliac, common femoral vein and R sided veins as well. VCS prevalence ranges

TCT-784 An Innovative MRA Technique for Simultaneous Imaging of Artery and Vein for Diagnosis of Venous Compression Syndrome

METHODS From January 2008 to May 2015, a total of 226 consecutive patients with 250 wounds underwent complete angiosome-targeted PTA for only ischemic foot wound and multi-vessel BTK artery disease. We evaluated the clinical outcome of angiosome-targeted single-vessel versus multi-vessel PTA. The primary endpoint was defined as the complete wound healing within 12 months without death before wound healing, unexpected amputation or flap or target vessel revascularization, or death. The secondary endpoint of the study was the major adverse limb event (MALE) at 1 year.

Cardiovascular Magnetic Resonance and Multidetector Computed Tomography

The advanced imaging technologies, cardiovascular computed tomography (using X-ray), and cardiovascular magnetic resonance (using magnetic and radio frequency or RF fields) generally provide more comprehensive and frequently unique clinical information compared with other technologies. They are not used routinely, but rather for specific indications. Since they are more technically advanced, they are more expensive and require additional knowledge for proper acquisition and interpretation. The strength of CCT resides in its ability to provide excellent imaging quality of the large- and medium-sized coronary arteries using IV-administered contrast medium. While CCT utilizes X-rays, the radiation dose is drastically decreasing with improving technology. The strengths of CMR are the ability to visualize morphology, function, perfusion, viability, and metabolism without ionizing radiation, although sometimes requiring IV gadolinium contrast agent. These two technologies have received relatively recent Nobel prizes (one for CT and three for MRI), and both continue to improve with the advent of new software and hardware. This chapter provides a background for most of the commonly employed applications of computed tomography and magnetic resonance imaging of the heart.

TCT-312 Coronary Plaque Regression by 64-Slice Computed Tomography Coronary Angiography (CTCA): Pipe Dream or Real Possibility

Background: Fractional flow reserve (FFR) is a “golden standard” in determining hemodynamic significance of ambiguous lesions and provides guidance on appropriateness of revascularization. The cut-off values for intravascular ultrasound (IVUS) parameters corresponding to FFR of 0.75 or 0.80 are still under investigation. The aim of this study was to determine best IVUS criteria for predicting physiological significance of left main coronary artery (LMCA) stenosis with FFR as the standard. Methods: FFR values during adenosine infusion (at the rate of 140 g/kg/min femoral vein) were calculated in 99 patients aged 58 10 years with an angiographically ambiguous LMCA stenosis. Subsequently, all patients underwent IVUS with automatic pullback at a constant speed of 0.5 mm/sec., from the middle segment of left descending artery (LAD) to the aorto-ostial junction of LMCA. The following IVUS parameters were analyzed: minimum lumen area (MLA, mm), minimum lumen diameter (MLD, mm), the maximum plaque burden (PB, %), and percent area stenosis (%AS, %). Results: The averaged FFR was 0.77 0.10 (range 0.51-0.99). FFR 0.75 was observed in 42 patients (42.4%). Linear regression analysis revealed a strong correlation between the values of FFR and MLA (AUC 0.86, p 0.001), PB (AUC 0.64, p 0.03), %AS (AUC 0.72, p 0.0002) and the MLD (AUC 0.75, p 0.0001). Cut off points for the value of FFR 0.75 were: 5.9 mm for MLA (sensitivity 0.69 and specificity 0.85), 59.7% for PB (sensitivity 0.77 and specificity 0.48), 36% for %AS (sensitivity 0.94 and specificity 0.44) and 2.9 mm for MLD (sensitivity 0.97 and specificity 0.50), respectively. Conclusions: Strong correlation between FFR and LMCA lesion critical IVUS parameters was found in our patient group. MLA value of 5.9 mm in IVUS seems to be a useful criterion for predicting FFR 0.75.