The 56th annual scientific session of the American College of Cardiology was held in New Orleans on March 24-27. The site of the meeting had been selected before hurricane Katrina; the ACC re-affirmed its commitment last year when the devastation caused by the storm was still fresh and when future prospects for southern Louisiana were still uncertain. The ACC meeting was by far the largest meeting to have been held at the New Orleans convention center since Katrina; the ACC can be justifiably proud of its role in contributing to the economic recovery of New Orleans. NYU cardiology fellows did their part as well, and led by senior faculty were deeply involved in evidence based investigations of the culinary and festive delights of the “Big Easy”. Word on the street (Bourbon Street that is) has it that alcohol mediated rise in mean cardiology division HDL levels balanced out the massive rise in mean LDL levels resulting from muffuletta, beignet and andouille sausage ingestion.
The major news from the meeting that captured the attention of the media and meeting participants alike were the findings of the COURAGE study. COURAGE made the front page of the New York Times and was featured as the lead article published on line by the New England Journal of Medicine. This study conducted at 50 US and Canadian centers randomized 2287 patients with chronic stable angina to optimal medical therapy alone or optimal medical therapy combined with percutaneous coronary intervention (PCI). There was no difference in the endpoints of death or non-fatal myocardial infarction at a median follow-up of 4.6 years. There was better control of angina with PCI, but at 5 years 74% of the PCI patients and 72% of the medical patients were free of angina. These findings threaten the economic interests of the device manufacturers and the narrowly defined interests of some interventional cardiologists. Not surprisingly, efforts at spin control began even before the findings were presented at the late breaking trials session on Tuesday morning. For example, there were comments made by some prominent figures in the interventional cardiology community that COURAGE patients were not representative and that the findings could not be generalized. Well, we enrolled 64 patients in the COURAGE study at the Manhattan VA and our COURAGE patients were extraordinarily representative of the types of patients with chronic stable angina who come to our cath lab and that you see in your clinics. The findings of COURAGE are in fact generalizable and the study should have a major impact on the practice of medicine in the United States.
To better appreciate what the findings of COURAGE really mean and to separate the hype from the reality it is important to understand that COURAGE was not intended to be an attack on interventional cardiology. The study was in fact in large part designed and carried out by interventional cardiologists (including me) who were interested in better defining patient populations who would benefit from intervention. It is well established that PCI is of enormous benefit to patients with acute coronary syndrome. Furthermore, PCI provides effective and clinically important symptom relief to patients with very severe angina and coronary anatomy suitable for PCI. So the first major lesson to take away from the COURAGE study and that is emphasized by the COURAGE investigators is that PCI continues to be a valuable therapeutic option for large numbers of patients with coronary artery disease. This is supported by the data from the study since over 30% of the medical arm patients in COURAGE had to crossover to revascularization to obtain symptom relief. We just did not know how much benefit (if any) was derived by patients with mild to moderate angina and stable symptoms. Your clinics are full of these types of patients and they are referred for catheterization all the time. We now know that intensive medical therapy is just as good as PCI for these patients.
The second major lesson to take away from the COURAGE study is that medical therapy needs to be intensive! I have always found that the cath lab is a great place to educate patients and practice preventive cardiology. Patients are extraordinarily receptive to messages concerning diet, exercise, smoking cessation and adherence to statin therapy when an 8F sheath is pulled from their femoral artery at the conclusion of an interventional procedure. You are now challenged to deliver the same kind of message to your patients. Mean blood pressure at 5 years in COURAGE patients was 122/70; mean LDL cholesterol was 72.1 mg/dl; statin use was 93% and aspirin use was 94%. Achieve that in your patients and they will do very well.
A major feature of the ACC meeting this year was the large number of negative trials. In part this may due to the growing emphasis on presenting negative studies to avoid the publication bias in favor of positive trials that can distort the clinical significance of novel findings. In part this may be due to the excellent results achieved by current evidence based therapies. Steve Nissen, the new president of the ACC, presented the negative data on torcetrapib, the CETP inhibitor that markedly increases HDL levels. The combination of torcetrapib and atorvastatin results in a nearly perfect lipid profile with a mean HDL of approximately 70 mg/dl and a mean LDL also approximately 70 mg/dl. Nevertheless, this combination does not have favorable effects on coronary atherosclerosis as measured by serial intravascular ultrasound investigations and does not improve clinical outcomes as compared to treatment with atorvastatin alone. The reason for this disappointing outcome is unknown. Torcetrapib does raise blood pressure and Steve Nissen speculated that this elevation in blood pressure may be a marker of deleterious effects of torcetrapib on endothelial function that offsets the beneficial effects on lipids. Is this a drug effect or a class effect? The cardiology community (and Wall Street) is waiting for the answers.
NYU’s own Judy Hochman presented the negative outcome of the TRIUMPH study which showed that the nitric oxide synthase inhibitor tilarginine had no effects on mortality in patients with refractory cardiogenic shock. The FUSION 2 study showed that outpatient nesiritide infusions provide no benefit for patients with advanced heart failure. Similarly, the EVEREST study showed minimal benefit in chronic heart failure from use of the vasopressin antagonist tolvaptan. Patrick Serruys, one of the giants of interventional cardiology presenting disappointing data on a new biodegradable drug-eluting polylactate coronary stent. The idea sounds wonderful; the stent breaks down into lactic acid which is metabolized by the Krebs cycle and so theoretically patients would be free of the risks of late stent thrombosis, stent “jail” of side branches, difficulties with subsequent CABG due to “full metal jacket” coverage of coronary arteries and other as yet unknown long-term deleterious consequences of intravascular foreign bodies. Unfortunately, this new stent is not yet ready for prime time. Serruys implanted the stent into 30 patients and found that the stent actually shrinks over time – so it’s back to the drawing board for that one.
There was some good news on the interventional front however. The SPIRIT 3 trial showed superiority of the XIENCE V everolimus- eluting stent over the Taxus Paclitaxel-eluting stent with respect to in-segment late loss. The XIENCE V is a second generation drug-eluting stent based on a very deliverable Vision stent platform. More importantly, preliminary data suggest that the XIENCE V is rapidly covered by functional endothelial cells and may not be prone to late stent thrombosis. If that turns out to be true, second generation stents would certainly take over from the Taxus and Cypher stents currently in use. A study where a negative finding concealed an important silver lining was the TIMI 36 MERLIN study. This study showed that ranolazine, a blocker of the late sodium current, did not have a favorable impact on the composite endpoint of cardiovascular death or recurrent ischemia in patients hospitalized with an acute coronary syndrome. There was a favorable effect on recurrent ischemia however (13.9% for ranolazine versus 16.1% for placebo) and there were no worrisome safety findings in this study of 6500 patients. Ranolazine slightly prolongs the QT interval and it is reassuring that there were no instances of torsades de pointes in the entire study. In fact, Holter monitor data suggested that ranolazine was anti-arrhythmic. Stay tuned, (Disclosure: the VA was a Merlin site. I have done prior studies on both long-acting and short-acting ranolazine. During fellowship I worked in the lab of Lou Lange, the founder and CEO of CV therapeutics, the company that manufactures ranolazine and sponsored Merlin). I may be biased in favor of ranolazine and not entirely objective, but I do think that this is an effective and safe anti-anginal drug that can be very helpful in the management of selected patients with stable symptoms.
Finally, it is noteworthy that the steering committee of the interventional cardiology group at the ACC selected the OAT study publication in the New England Journal of Medicine as the most important manuscript of the year and invited Judy Hochman to accept an award for this work. All of us at NYU should be very proud of the important contributions Dr. Hochman has made.