The American College of Cardiology 59th Annual Scientific Session, paired with the i2 Summit produced in partnership with CRF, was a rousing success. Held March 14-16, 2010, in Atlanta, GA, the conference featured late breaking research that marked progress on several fronts in the fight against cardiovascular disease.
Hopeful Results with Devices for Structural Disease
Mitral valve repair with the percutaneously delivered MitraClip system treats leaks just as effectively as open surgery, according to results of the EVEREST II trial. One-year clinical success rates, although statistically no worse than surgery, were somewhat lower with the device; its implantation, however, does not preclude future surgery.
Meanwhile, two interventional devices aimed at reducing abnormal heartbeats known as atrial fibrillation (A-fib) continued to show progress.
In updated results from last year, closure of a pouch-like area of the heart known as the left atrial appendage with the Watchman device provided A-fib patients with an alternative to warfarin for stroke prevention. The effect lasted out to almost two years. Importantly, the risk from complications associated with the device declined with growing operator experience and improved patient selection.
Meanwhile, filling an angioplasty balloon with coolant to freeze malfunctioning heart tissue—a technique called cryoballoon ablation—was shown to effectively treat drugresistant A-fib in symptomatic patients. The STOP-AF trial compared optimal drug therapy against treatment of the pulmonary veins with the Arctic Front Cardiac Cryoablation Catheter System. After one year, 69.9% of patients who received cryoablation had no detectable A-fib, no use of nonstudy drugs, and no A-fib treatments compared with 7.9% of those who received drugs alone. There was no difference between the treatments in terms of adverse events.
Fine-Tuning Antiplatelet Drug Therapy
A large registry study has backed up earlier results from the randomized COGENT trial. The newer study showed that in patients on dual antiplatelet therapy (aspirin and the blood thinner clopidogrel) after stenting, simultaneously using proton pump inhibitors (PPIs) to prevent stomach bleeding does not undermine the benefits of dual antiplatelet therapy. At six months, adverse heart-related events were similar whether patients were or were not taking PPIs.
Sounding a similar note of reassurance, combined analysis of results from two randomized trials found that stopping dual antiplatelet therapy at 12 months did not endanger patients implanted with drug-eluting stents (DES). At 19 months, rates of heart attack or heart-related death were similar regardless of whether or not clopidogrel was extended beyond one year. However, the results were not considered definitive.
A meta-analysis of five trials confirmed that high levels of blood platelet reactivity—the tendency for platelets to clot despite drug inhibition—after stenting are associated with inferior results. Specifically, a poor response to clopidogrel resulted in twice the risk of death and heart attack. Whether patients’ elevated platelet reactivity was due to genetics, their clinical condition, or other factors was not examined.
In the randomized CILON-T study, triple antiplatelet therapy (cilostazol added to aspirin and clopidogrel) reduced platelet reactivity compared with standard dual antiplatelet therapy in patients implanted with DES. But at six months, this did not translate into fewer adverse events. In addition, although bleeding levels were equal between the triple and dual regimens, more patients taking cilostazol halted their drug early and/or had increased heart rates.
Additionally, the new antiplatelet drug ticagrelor— which in the PLATO trial proved superior to clopidogrel without increasing bleeding—has now been shown to be a safer alternative to clopidogrel for patients who need urgent bypass surgery and must be quickly withdrawn from antiplatelet drugs. In the study, patients who underwent bypass surgery within seven days of stopping ticagrelor were less likely to die than those who had been taking clopidogrel. Curiously, there was no difference between the groups in terms of heart attack or bypass-related bleeding.
On the anticoagulant front, the MM-WES trial observed that testing for two genes that affect response to warfarin enabled physicians to fine-tune dosing of the drug for patients. Both overall hospitalizations and those specifically related to bleeding or thromboembolism were reduced by about one-third compared with patients who did not undergo testing; the effect was especially strong in patients who had their tests earlier after initiation of warfarin.
Battle of the Stents
An early peek from the SPIRIT IV trial found that, in non-emergency angioplasty patients, the everolimuseluting Xience V stent proved more effective and less expensive than the paclitaxel-eluting Taxus stent. At one year, repeat angioplasty procedures were reduced by 48%, and medical costs, including initial hospitalization and follow-up, were $146 lower with Xience V compared with Taxus.
Results from the MAIN-COMPARE trial, meanwhile, show that the differences in outcomes between stenting and surgery for patients with unprotected left main coronary artery disease hold over the long term. After about five years, the risk of death or a combination of death, heart attack, or stroke remained similar for the angioplasty and bypass surgery groups. But as before, repeat procedures in the same blocked vessel were significantly lower with bypass compared with angioplasty regardless of stent type.
In an extended 18-month report from the SORT OUT III trial, which included a wide range of “realworld” patients, the zotarolimus-eluting Endeavor stent continued to lag behind the sirolimus-eluting Cypher stent for major heart-related adverse events as well as other outcomes except heart-related death and definite cases of blood clots forming inside stents.
And in two-year results from ISAR-TEST-2—which compared Endeavor, Cypher, and the so-called Dual DES (a device combining sirolimus and the antioxidant probucol)—the latter stent continued to show the lowest rate of repeat procedures to clear the same artery blockage. Both Dual DES and Endeavor continued to prevent arteries from renarrowing between years one and two, while Cypher lost some of that ability. Meanwhile, there was no hint of a safety difference among the three stents.
Long-term follow-up from two randomized trials sheds light on the risk of late complications with DES in patients with severe types of heart attack. At three years, the DEDICATION trial showed a higher rate of heart-related death with DES vs. bare-metal stents, while major heart-related adverse events and repeat procedures to clear the same artery blockage were lower with DES. At five years, the PASSION trial found no difference in major heart-related adverse events between Taxus stents and bare-metal stents but observed a slight increase in very late definite cases of blood clots forming within Taxus stents.
Guidance for Practice
A meta-analysis helped resolve inconsistencies among three major randomized trials of patients with heart disease by determining that routinely using early angiography improves long-term outcomes. The alternate strategy involved performing angiography only when angina resisted treatment or a patient had chest pain at rest. High-risk patients had the most to gain, but intermediate- and low-risk patients also experienced lower rates of heart-related death or heart attack.
According to results from the randomized JETSTENT trial, routine thrombectomy (removal of clot with a cutting device) in addition to direct stenting in severe heart attack patients with evidence of blood clot in a coronary artery produces better blood flow to the heart and improves six-month clinical outcomes compared with stenting alone.
Finally, the PREVENT study showed that—contrary to recent reports—hydration with sodium bicarbonate in diabetic patients with kidney dysfunction who are undergoing stenting is no better at protecting against contrast-induced kidney problems than normal saline.
