Practice Update: Cardiology

AHA 2016 23

The PIONEER AF-PCI Trial The management of anticoagulation and antiplatelet therapy in patients with nonvalvular atrial fibrillation undergoing PCI with stent implantation presents a daily challenge, which was addressed in the PIONEER AF-PCI trial (Gibson CM et al. PIONEERAF-PCI. Paper presented at AHA 2016; November 12–16, 2016; New Orleans, USA). This trial randomised 2100 of such patients to one of three arms: rivaroxaban 15 mg once daily + thienopyridine x 12 months, rivaroxaban 2.5 mg twice daily + DAPT x 1, 6, or 12 months (remainder to 12-month aspirin 75–100 mg once daily), or warfarin (INR, 2–3) + DAPT x 1, 6, or 12 months (remainder to 12-month aspirin 75–100 mg once daily). Compared with the last – the standard approach, known as triple therapy – the two other novel anticoagulant (NOAC) approaches were associated with a 40% reduction in TIMI bleeding events (primary endpoint) at no increased risk of death, MI, or stroke (secondary endpoint) and, on post hoc analysis (which needs to be considered as hypothesis-generating), an even 25% reduction in the risk of hospitalisation (related to both a CV and bleeding event). While the first trial with NOACs with important findings, one has to point out

intention-to-treat analyses. In fact, in the on treatment analyses it was associated with a lower risk of cardiovascular events and mortality compared with ibuprofen. Celecoxib was associated with a lower risk of major GI events compared with both naproxen and ibuprofen and a lower risk of serious renal events than ibuprofen and even naproxen in the on-treatment analyses. In the post-hoc analyses of any CV, GI, or renal event, celecoxib had the lowest risk, naproxen had intermediate risk and ibuprofen the highest risk. These findings are striking as they grant absolution to a drug condemned in the cardiovascular community. These charges date back to COX-2 inhibitor story, which made headlines just over a decade ago, pointing out the increased risk of cardiovascular events with these drugs. Vioxx was the prime contender and eventually left the market in 2004; Bextra followed in 2005. This has left Celebrex as the sole COX-2 inhibitor on the US market with stern black box warnings. Other NSAIDs have also been confronted with heightened levels of concern eg, ibuprofen, whereas Naproxen has prevailed in current opinion as one of the safer representatives in his class. PRECISION would attest that it is safer than ibuprofen, but even so, the winner is, this time: celecoxib, but against NSAIDS that also carry a risk.

over three quarters of patients had two or three additional grafts). No significant differences in major cardiovascular outcomes were found over 5 years of follow-up. However, the incidence of sternal wound complication and reconstruction was 2 and 3-fold higher, respectively, with bilateral IMA bypass grafting, and all of these events occurred in the first year and mainly in diabetics and those with high BMI. Of further note, 14% of patients assigned to bilateral IMA underwent single IMA only versus 2.4% of patients assigned to single IMA undergoing bilateral IMA bypass surgery. In summary, adding one more IMA graft to patients undergoing CABG with LIMA grafting does not add further clinical benefit but may increase the risk of sternal wound complication especially in at risk populations. The PRECISION trial This mega trial involved nearly 1000 centres worldwide that enrolled 24,000 osteoathritis or RA patients with CV disease or risk requiring NSAID therapy for at least 6 months. Patients were randomly assigned to celecoxib 100 mg bid, ibuprofen 600 mg tid, or naproxen 375 mg bid in conjunction with esomeprazole. Celecoxib was not inferior to naproxen and ibuprofen with regards to major adverse cardiovascular events in the

that the dose of rivaroxaban was lower than is commonly used. In fact, this reduced dosing was never tested and tried in atrial fibrillation stroke prevention trials. Thus, it is not surprising that it would lead to lower bleeding events; and how effective would it be for stroke prevention? No true comparison was made with the WOEST trial combination of warfarin and clopidogrel ( Lancet 2013;381:1107–1115), a combination which fared better than triple therapy in that particular trial and in this trial. There was no difference with regard to the duration of 1, 6, or 12 months of DAPT; but, as not a randomised comparison, these data are also to be taken with a grain of salt. As the duration was only for 1 year, the question of how to continue thereafter is another, final one. Thus, there is more to be explored, or, speaking in terms of the investigators, to be pioneered. Clinicians, however, are provided now for some first-time and much needed data on the use of NOACs for the large and challeng- ing population of atrial fibrillation patients undergoing PCI.

DECEMBER 2016