The 2012 Scientific Sessions of the American College of Cardiology were held from March 24-27, 2012 in Chicago. This is always a great city for a conference —terrific restaurants, museums and parks—it almost makes you feel as though you are in New York. The McCormick Place Convention Center is another attraction—it is well laid out and easy to navigate. It allows participants to freely move from session to session spending time on what interests them most. The ACC meetings are also well designed with a good mix of science and education and not much scheduled during major trial presentations so attendees are able to hear the trial results without missing out on other presentations. Of course all major trials are now published online on the day of presentation so there is no real need to sit through the talks, but nevertheless it is exciting to hear trials presented by the principal investigators and the discussions between the investigators and the moderator and panel provide valuable insight and perspective. The late breaking trial results are available on http://www.cardiosource.org/News-Media/Meeting-Coverage/ACC/ACC-2012.aspx.
I know the fellows had a good time and made numerous presentations. Louai Razzouk won a prize for his poster presentation entitled “Is Minimal Luminal Area by Intravascular Ultrasound the Critical Determinant of Future MACE in Intermediate Lesions? Insights from PROSPECT”. Medical residents also had an opportunity to present. I was particularly proud of Nick Amoroso who presented ” Mean Platelet Volume is Significantly Associated With Survival Following Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery” and handled the questions of the moderating panel with coolness and aplomb (by his own highly reliable account). Amita Singh had two presentations on triple anti-platelet therapy including cilostazol.
The ACC meetings featured a large number of educational offerings including many specifically linked to the American Board of Internal Medicine Maintenance of Certification program. I do need to renew my boards in interventional cardiology in 2019 so I decided to try a cath lab simulation module worth 10 points out of the 100 needed for recertification. I was particularly interested in the simulation because of my experiences with the Sim center at the VA and the new Sim center that just opened at Bellevue which we have been using for medical student teaching in cardiology. I have always been very skeptical about the educational value of simulations, even though the medical students seemed to be enjoying and learning from them. I was very pleasantly surprised by my experience with cath lab simulation at the ACC. I was told to insert a straight catheter and a straight wire (both very stiff and dangerous feeling) into a femoral sheath in a mannequin. When I felt a “click” I was told to press on the “fluoro” pedal and advance the catheters. Well, a J tipped wire appeared on the screen and I was able to select from a wide variety of catheter shapes and manipulate them into coronary arteries. I was particularly impressed with the coronary images obtained with varying camera angles. We always emphasize to the fellows the importance of obtaining appropriate views to make diagnoses and treat lesions safely—the simulator could let us teach this important lesion without exposing a real patient to excessive contrast and radiation. I then had to perform 4 simulated coronary interventions and ran into many of the complications that we are tested on in the interventional boards and that I lecture about to the fellows (it was helpful to my ego that the proctor explained that complications were programmed in and had nothing to do with my procedural manipulations or choice of balloons, wires, stents and medications ). I “dissected a left main”, “perforated a coronary artery with a guidewire” and “caused slow flow” with a stent expansion. It was reasonably realistic and was a fair test of my ability to recognize problems (it helps when the mannequin says “my chest is hurting”) and respond to them appropriately. I guess that simulations are here to stay and we will be increasingly using them at all levels of medical education.
The ACC meeting includes the Innovations in Intervention (I2) summit sponsored by the ACC and the Cardiology Research Foundation (CRF). This partnership is rather controversial because of the strong ties that CRF has with industry and the live case demonstrations at the I2 summit generate controversy as well. This year, several live cases featured the use of pressure wire for measurement of fractional flow reserve (FFR ) in clinical decision making. I was outraged when the operators decided to go ahead and stent lesions even when the FFR was well in the normal range. Promulgating bad practice and inappropriate use of technology before a wide audience of practitioners and fellows who will take these cases as license to ignore the evidence and make money treating stenoses that are better left alone is thoughtless at best—reprehensible actually. I was disappointed that the panel of experts moderating the live cases had a different response—they concluded that there is still uncertainty and difference of opinion over the value of physiologic assessment of lesions in the cath lab. I differ.
A number of late breaking interventional trials were presented during the I2 summit. BCIS1 ( Balloon-Pump Assisted Coronary Intervention Study) showed some intriguing hints of long term benefit with intra-aortic balloon pumping in patients undergoing elective high risk PCI. A total of 301 patients with LVEF < 30% undergoing PCI of lesions in vessels supplying > 40% of the myocardium were enrolled, 151 to IABP and 150 to conventional therapy. There was no difference in the primary endpoint of major adverse cardiac events (MACE) at 28 days between the IABP and conventional therapy arms (15.2% vs. 16.0%). Procedural complications were significantly lower in the IABP arm (1.3% vs. 10.7%, p < 0.001), although access site complications (3.3% vs. 0%, p = 0.06) and all bleeds (19.2% vs. 11.3%, p=0.06) tended to be more frequent in the IABP arm. All-cause mortality at 2 years (median 51 months) was significantly lower in the IABP arm at 2 years (27.8% vs. 38.7%, HR 0.66, 95% CI 0.44-0.98; p=0.039). Information on other outcomes at 2 years such as MI, cardiovascular death, and CVA was not available. This may reflect the play of chance, but it does support the notion that balloon pumping may be very useful in the setting of high risk PCI.
The INFUSE-AMI trial evaluated intracoronary abciximab and manual aspiration thrombectomy in the setting of anterior wall STEMI treated with PCI and bivalirudin. This trial seemed highly relevant to interventionalists at NYU all who use bivalirudin for PCI and very frequently perform manual clot aspiration. A total of 452 patients were randomized, 229 to aspiration thrombectomy and 223 to no aspiration thrombectomy, and 229 to intracoronary abciximab, and 223 to no abciximab. The primary outcome of infarct size at 30 days, as assessed by cardiac magnetic resonance imaging (MRI) was significantly lower in the abciximab arm, as compared with the no abciximab arm (15.1 vs. 17.9, p=0.03). There was no difference in infarct size with thrombectomy. None of the treatments were associated with improvement in blood flow and the study was under-powered for clinical end points. This study will not change clinical practice (at least not at NYU). The interventional community here is still waiting for the results of larger ongoing trials before giving up on thrombectomy.
Another trial of interest to NYU interventionalists who are increasingly using cilostazol post PCI for prevention of restenosis and stent thrombosis (think of Amita Singh’s presentations) was the HOST-ASSURE Randomized Trial that evaluated whether triple therapy with aspirin, clopidogrel 75 mg daily, and cilostazol would be noninferior for cardiovascular outcomes at 1 month when compared with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel 150 mg daily. A total of 3,755 patients were randomized at 40 centers in South Korea: 1,879 to triple therapy and 1,876 to DAPT. The primary composite outcome of cardiac death, myocardial infarction (MI), stroke, stent thrombosis (ST), and PLATO (PLATelet inhibition and patient Outcomes) major bleeding was similar between the triple therapy and DAPT arms (1.2% vs. 1.4%, hazard ratio 0.85, 95% confidence interval 0.49-1.48; p < 0.001 for noninferiority, p = 0.57 for superiority). On-treatment platelet reactivity was better with cilostazol at 1 and 30 days following PCI. Cilostazol for 1 month may thus be a viable alternative to double-dose therapy with clopidogrel in patients undergoing DES PCI. Again, not practice changing, but more data indicating that cilostazol may be a safe and effective therapy post PCI (at least in Asian patients where most of the research has been done).
An interventional trial with important public policy implications was the CPORT-E trial which evaluated the safety of PCI done in hospitals without cardiac surgery on site. A total of 18,867 patients were enrolled at 60 centers, 14,149 to PCI at sites without on-site cardiac surgery, and 4,718 to sites with on-site cardiac surgery (72 were unassigned). The median procedure volume at these institutions was 150. Of the patients enrolled, 64% were undergoing PCI for acute coronary syndrome; 23% of the procedures were either urgent or emergent. There was an even distribution between patients with one-, two-, and three-vessel disease (roughly 28-34%); left main PCI was undertaken in 3% of the patients and saphenous vein graft PCI in about 9%. The primary endpoint of all-cause mortality at 6 weeks was noninferior between sites without and with on-site cardiac surgery (0.9% vs. 1.0%, p for noninferiority p = 0.004). At 9 months, rates of MACE (death, myocardial infarction, target vessel revascularization [TVR]) were noninferior (12.1% vs. 11.2%, p for noninferiority = 0.05). The VA has adopted the idea of performing PCI in centers with cardiac surgery on site and trials such as this one will surely lead to approval of small interventional labs throughout the country. Coronary intervention has matured, high volume is probably not a good measure of quality and a cardiac surgery program on site is not necessary for safe performance of PCI.
Cardiac surgery on site may not be needed for the safe performance of PCI, but consultation with a cardiac surgeon is certainly a good idea for patients with advanced 3 vessel coronary artery disease. The ASCERT study was an observational comparative effectiveness study comparing survival after PCI versus CABG. The investigators linked the American College of Cardiology Foundation National Cardiovascular Data Registry and the Society of Thoracic Surgeons Adult Cardiac Surgery Database to claims data from the Centers for Medicare and Medicaid Services for the years 2004 through 2008. Outcomes were compared with the use of propensity scores and inverse-probability-weighting adjustment to reduce treatment selection bias. Among patients 65 years of age or older who had two-vessel or three-vessel coronary artery disease without acute myocardial infarction, 86,244 underwent CABG and 103,549 underwent PCI. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups (6.24% in the CABG group as compared with 6.55% in the PCI group; risk ratio, 0.95; 95% confidence interval [CI], 0.90-1.00). At 4 years, there was lower mortality with CABG than with PCI (16.4% vs. 20.8%; risk ratio, 0.79; 95% CI, 0.76-0.82). Similar results were noted in multiple subgroups and with the use of several different analytic methods. Residual confounding was assessed by means of a sensitivity analysis. The authors of this study themselves acknowledge that no degree of statistical manipulation can fully acount for bias in such a study. There are unmeasured variables such as frailty that affect both the choice of revascularization options and survival. The growing feeling which is now incorporated into both the CABG and PCI guidelines is that neither randomized trials nor giant registry studies such as ASCERT can adequately guide therapy for individual patients. Rather, a heart team of experienced interventionalists and cardiac surgeons and often general cardiologists as well is best able to incorporate evidence from studies and individual patient characteristics and preferences to select the most appropriate treatment for patients with advanced coronary artery disease.
Well wouldn’t it be wonderful if we could wipe out atherosclerosis and get rid of both interventionalists and cardiac surgeons and all those trials they do (like the ones I have spent my professional career doing). The latest candidate for miracle drug is the monoclonal antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease (PCSK9). PCSK9 binds to and inactivates the hepatic LDL receptor raising serum LDL. The PCSK9 Inhibition in Patients With Primary Hypercholesterolemia on Atorvastatin trial randomized patients 1:1:1:1:1:1 to placebo every 2 weeks (Q2W); the novel anti PCSK9 blocker SAR236553 50, 100, or 150 mg Q2W; or SAR236553 200 or 300 mg every 4 weeks (Q4W) alternating with placebo to mimic Q2W dosing. Randomization was stratified according to atorvastatin dose, to evaluate any effect of background atorvastatin dose on the LDL-C lowering efficacy of SAR236553. Baseline LDL-C was about 125-130 mg/dl in the six arms. Decreases in LDL-C from baseline were: 39.6% with 50 mg Q2W, 64.2% with 100 mg Q2W, 72.4% with 150 mg Q2W dose, 43.2% with 200 mg Q4W, and 47.7% with 300 mg Q4W, versus 5.1% with placebo (p < 0.0001 for all comparisons vs. placebo). Target LDL-C ?100 mg/dl was significantly higher with SAR236553 than placebo (89-100% vs. 16%, p < 0.05). LDL-C reductions with SAR236553 were similar among atorvastatin doses. Changes in high-density lipoprotein cholesterol (HDL-C) were also noted: 6.7% vs. 4.1% vs. 5.5% vs. 6.3% vs. 8.5% vs. -1.0%, respectively (only 50 mg Q2W, 200 mg Q4W, and 300 mg Q4W demonstrated p < 0.05 as compared with placebo). Similarly, reductions in serum triglycerides were noted: 6.6% vs. 5.5% vs. 18.9% vs. 10.8% vs. 8.4% vs. -9.7%, respectively (only 150 mg Q2W had p < 0.05 when compared with placebo). The clinical value of these dramatic changes in lipid profiles will be evaluated in larger trials, but the audience seemed enthusiastic about the potential of the novel target for treatment .
Diet, exercise, chocolate,alcohol in moderation,a few carefully selected pills and injections seem to me to be appropriate methods of prevention. For some patients, however, more drastic methods may be needed. STAMPEDE compared intensive medical therapy to bariatric surgery in patients with type 2 DM who were either obese or overweight. Eligible patients were randomized in 1:1:1 fashion to either intensive medical therapy alone, intensive medical therapy + Roux-en-Y gastric bypass, or intensive medical therapy + sleeve gastrectomy. All patients received intensive medical therapy as defined by the American Diabetes Association (including lifestyle counseling, frequent home glucose monitoring). Use of newer diabetic medications was permitted. The goal was to achieve a glycated hemoglobin (HbA1c) of ?6%, or intolerance to medication. All bariatric procedures were performed by a single surgeon at the Cleveland Clinic, as per standard operating techniques. A total of 150 patients were randomized. However, eight patients withdrew consent and two missed follow-up appointments, resulting in 141 patients in the primary analysis. Of these, 41 received intensive medical therapy alone, 50 underwent gastric bypass, and 50 underwent sleeve gastrectomy. The primary endpoint of achieving HbA1c ?6% at 12 months was significantly higher in the gastric bypass and sleeve gastrectomy arms, as compared with the medical therapy arm (42% vs. 37% vs. 12%, p = 0.002 and p = 0.008, respectively). No difference was noted between the surgical arms (p = 0.59). Interestingly, all successfully treated patients in the gastric bypass arm did so without the use of any medications, whereas 28% in the sleeve gastrectomy arm required concomitant medications. Mean change in HbA1c at 12 months from baseline for intensive medical therapy, gastric bypass, and sleeve gastrectomy was -1.4% vs. -2.9% vs. -2.9%, p < 0.001 for both; mean change in body weight from baseline was -5.4 kg vs. -29.4 kg vs. -25.1 kg, p < 0.001 for both. There was a salutary effect on high-density lipoprotein cholesterol (HDL-C) (% change from baseline: 11.3% vs. 28.5% vs. 28.4%, p < 0.001 for both), triglycerides (% change from baseline: -14% vs. -44% vs. -42%, p = 0.002, p = 0.08, respectively), high-sensitivity C-reactive protein (hs-CRP) (% change from baseline: -33.2% vs. -84% vs. -80%, p < 0.001 for both), and number of antihypertensive and lipid-lowering medications required at 12 months as well. It is clear that bariatric surgery is the most effective therapy (by far) for morbid obesity. The beneficial effects observed in this short term study of less obese but diabetic patients raises many important questions. Are the benefits sustained? Is there a detriment to stopping statins in diabetic patients whose lipid profile improves with surgery? Are the results reproducible in the community? And if this really does turn out to be a valuable therapy, can our nation afford it? Healthy school lunches and gym classes at an early age seems like a better option to me.
Those were just a few of the late breaking trials. There were trials on stem cell therapy for heart failure, on CT angiography in the emergency department as an alternative to traditional evaluation with stress testing, on pacing for neurally mediated syncope with documented asystole and on late outcomes after trans catheter aortic valve replacement among other studies. None of the trials presented this year were truly landmark studies or will be immediately practice changing. But trials with implications for policy such as CPORT-E needed to be presented even though the results were not surprising. CPORT was very controversial when it was first designed and it shows how far the field of interventional cardiology has progressed over the last 10 years that we now accept without question that high quality PCI can be safely done in small community hospitals. That may not be good news for academic centers which would like to keep a monopoly on doing these kinds of procedures, but it probably is good news for patients, and that is the only measure that counts. Academic centers will be needed to develop and evaluate new treatments and to train practitioners to go out into the community and provide those treatments for the benefit of patients. ACC 2012 was an important part of that process and its contribution to the health and welfare of our nation will be felt in the coming year as the attendees return home, think critically about what they have seen, heard and read about at the meetings and apply their new found knowledge to patient care.
Dr. Steven Sedlis is an associate professsor, Department of Medicine, NYU Langone Medical Center
Image courtesy of Wikimedia Commons