ATLANTA, GA—The American College of Cardiology 59th Annual Scientific Session/i2 Summit held last week from March 14 to 16, 2010, featured late breaking research that marked progress in several clinical areas in patients with cardiovascular disease, ranging from evaluating devices for structural heart disease to sorting out thorny issues surrounding antiplatelet therapy and the long-term effects of different stents.

Hopeful Results with Devices for Structural Disease

Mitral valve repair with the percutaneously delivered MitraClip system (Abbott, Abbott Park, IL) treats mitral regurgitation just as effectively as open surgery, according to results of the randomized EVEREST II trial. One-year clinical success rates, although noninferior to surgery, were somewhat lower with the device; its implantation, however, does not preclude future surgery.

Meanwhile, 2 interventional devices aimed at reducing atrial fibrillation (A-fib) or curbing its consequences continued to show progress.

In updated results from last year’s presentation, closure of the left atrial appendage with the Watchman device (Atritech, Plymouth, MN) provided patients with nonvalvular A-fib an alternative to warfarin for stroke protection out to 23 months. Importantly, the risk from complications associated with device implantation declined with growing operator experience and improved patient selection.

Cryoballoon ablation was shown to effectively treat drug-refractory paroxysmal A-fib in symptomatic patients. The STOP-AF trial compared optimal drug therapy vs. treatment of the pulmonary veins with the Arctic Front Cardiac Cryoablation Catheter System (Medtronic, Minneapolis, MN). In the trial, 69.9% of patients who received cryoablation achieved the primary efficacy endpoint—no detectable A-fib, no use of non-study drugs, and no A-fib interventions—compared with 7.9% of those in the drug therapy arm. There was no difference between the treatments in combined procedural and major safety events.

Among patients with right-to-left shunts due to patent foramen ovale (PFO) and previous ischemic events, a quarter of whom also suffered migraines, a prospective study found that treatment with the Amplatzer PFO Occluder (AGA Medical, Golden Valley, MN) significantly reduced migraine intensity and frequency in more than 80% out to 28 months.

Fine-tuning Antiplatelet Therapy 

A large registry study has backed up the randomized COGENT trial by showing that in patients on aspirin and clopidogrel following PCI, concomitant use of proton pump inhibitors (PPIs)—including specifically omeprazole and esomeprazole—does not undermine the clinical benefit of dual antiplatelet therapy. At 6 months, MACE rates were similar for those who did or did not take PPIs. 

Sounding a similar note of reassurance, combined analysis of data from 2 randomized trials found that stopping dual antiplatelet therapy at 12 months did not endanger patients implanted with DES. At 19-month median follow-up, rates of MI or cardiac death were similar regardless of whether or not clopidogrel was extended beyond 1 year. However, due in part to lack of statistical power, the results were not definitive.

A meta-analysis of 5 trials confirmed that high post-PCI platelet reactivity, as measured by the VerifyNow assay (Accumetrics, San Diego, CA), is associated with worse outcomes. Specifically, a poor response to clopidogrel (typically a 600-mg loading dose), defined by P2Y12 reaction units ranging from 235 to 240, resulted in twice the risk of the composite of death and MI. Whether patients’ elevated platelet reactivity was due to genotype, clinical condition, or other factors was not examined.

In the randomized CILON-T study, triple antiplatelet therapy with cilostazol added to aspirin and clopidogrel reduced platelet reactivity compared with standard dual antiplatelet therapy in patients implanted with DES, but at 6 months this did not translate into fewer ischemic events. In addition, although bleeding was equivalent between the triple and dual regimens, more patients discontinued cilostazol and/or experienced increased heart rate.

Additionally, the potent investigational antiplatelet agent ticagrelor—which in the PLATO trial proved superior to clopidogrel in reducing major events without increasing bleeding—has now been shown to be a safer alternative to the standard thienopyridine for patients who need urgent bypass surgery and must be quickly withdrawn from antiplatelet therapy. In a nonrandomized substudy of PLATO, patients who underwent CABG within 7 days of stopping their study drug were less likely to die if they were taking ticagrelor rather than clopidogrel. Interpretation of this result was clouded by the fact that there was no difference between the groups in rates of MI or CABG-related bleeding. 

On the anticoagulant front, the MM-WES trial observed that testing for 2 genetic variants that affect response to warfarin enabled physicians to fine-tune dosing for patients. Both overall hospitalization and hospitalization related to bleeding/thromboembolism were reduced by about one third compared with historical controls; the effect was especially strong in patients who underwent testing earlier after initiation of warfarin. 

Battle of the Stents

In an interim analysis from the SPIRIT IV trial, in elective PCI patients, the everolimus-eluting Xience V stent (Abbott Vascular, Abbott Park, IL) proved more effective than Taxus (Boston Scientific, Natick, MA) at lower cost. At 1 year, TLR was reduced by 48%, and medical costs, including initial hospitalization and follow-up, were $146 lower with Xience compared with Taxus.

Results from MAIN-COMPARE, meanwhile, show that the differences in outcomes between stenting and surgery for patients with unprotected left main disease in the study hold over the long term. In a median 5.2-year follow-up, the risk of death or a composite of death, Q-wave MI, or stroke remained similar for the PCI and CABG groups, but as with earlier results, TVR was significantly lower with CABG compared with PCI regardless of stent type.

In extended data from the all-comers SORT OUT III trial, at 18 months the zotarolimus-eluting Endeavor stent (Medtronic, Santa Rosa, CA) continued to lag behind Cypher (Cordis/Johnson & Johnson, Miami Lakes, FL) for MACE as well as other outcomes except cardiac death and definite stent thrombosis.

And in 2-year follow-up of ISAR-TEST-2—which compared Endeavor, Cypher, and the so-called Dual DES (a polymer-free device incorporating sirolimus and the antioxidant probucol)—Dual DES continued to show the lowest TLR. Both the novel stent and Endeavor maintained antirestenotic efficacy between years 1 and 2, while that of Cypher declined. Meanwhile, there was no signal of a safety differential among the 3 stents.

Long-term follow-up from 2 randomized trials shed light on the risk of late events with DES in STEMI patients. At 3 years, the DEDICATION trial showed a higher rate of cardiac mortality with DES vs. BMS, while MACE and TLR favored DES. At 5 years, the PASSION trial found no difference in MACE between PES and BMS but observed a slight increase in very late definite stent thrombosis with PES. 

Guidance for Practice

A meta-analysis helped resolve inconsistencies among 3 major randomized trials of NSTE ACS patients by determining that a routine invasive strategy of “early” angiography results in improved long-term outcomes compared with a selective invasive strategy of angiography triggered by refractory angina or ischemia at rest. High-risk patients had the most to gain, but intermediate- and low-risk patients also reaped lower rates of the primary endpoint of cardiovascular death or MI.

According to results from the randomized JETSTENT trial, routine thrombectomy in addition to direct stenting in STEMI patients with evidence of thrombus produces better myocardial perfusion and improves 6-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 PCI is no better at protecting against contrast-induced nephropathy than normal saline.