Drug-coated Balloon Angioplasty Superior for In-stent Restenosis

For patients with superficial femoral artery (SFA) in-stent restenosis (ISR), drug-coated balloon angioplasty is associated with lower recurrent restenosis rates compared to standard balloon angioplasty, according to a recent study in Circulation.

In the FAIR trial, a multi-center, randomized clinical trial, 119 patients with SFA ISR at five German centers were randomized to undergo either drug-coated balloon angioplasty

(n = 62) or standard balloon angioplasty (n = 57). To be eligible, patients had to have a SFA ISR of up to 20 cm in length and diameter stenosis had to be at least 70% by duplex ultrasound. At baseline, the popliteal artery and one of the infrapopliteal vessels had to be patent (≤ 50% stenosis) for sustained distal run-off. Finally, eligible patients had chronic limb ischemia of Rutherford category 2 to 4.

The primary endpoint of binary recurrent restenosis was 15.4% in the in the drug-coated balloon angioplasty group and 44.7% of the standard balloon angioplasty group. At 12 months, incidences of recurrent restenosis were 29.5% in the drug-coated group and 62.5% in the standard group. Freedom from target lesion revascularization (TLR) was significantly higher in the drug-coated group. At 12 months, clinical improvement by ≥ 1 Rutherford category without the need of TLR was observed in 77.8% of the drug-coated group and 52.3% of the standard group. A total of two patients from the drug-coated and three patients from the standard group died within 12 months. No deaths were procedure-related.

The authors wrote that there were four main findings of the trial. First, drug-coated balloon angioplasty reduced 6-month recurrent restenosis rate by two thirds compared to standard balloon angioplasty, demonstrating superiority. Second, TLR was needed significantly less frequently with drug-coated balloon angioplasty versus standard balloon angioplasty. Next, there was a positive and sustained clinical impact for patients treated with drug-coated balloon angioplasty in terms of Rutherford category improvements. Finally, drug-coated balloon angioplasty for the treatment of ISR was found to be safe.

The authors concluded that, based on these findings, “a clear treatment recommendation can be made for [drug-coated balloon angioplasty] in SFA ISR legions up to 150 mm in length.”

In an editorial comment accompanying the paper, John R. Laird, MD, FACC, and Gagan D. Singh, MD, FACC, wrote that the authors “are to be congratulated for completing this important and carefully done study,” and question whether drug-coated balloons will “become the defacto standard of care” for femoropopliteal ISR. “Ease of use and the promising results from the FAIR trial makes this an attractive option for the treatment of [femoropopliteal ISR],” they wrote. “Avoidance of an additional layer of stent (bare metal, drug eluting, covered) has theoretical advantages, and obviates the need for longer-term dual antiplatelet therapy.” They cautioned, however, that whether drug-”coated” balloons can have “long-lasting angiographic, hemodynamic and clinical improvements in patients with more complex [femoropopliteal ISR]” is far from certain. They concluded that it is “FAIR to assume that drug-coated balloons will play an increasingly important role” in the treatment of femoropopliteal ISR.

Yamaji K, Shiomi H, Moriomoto T, et al. Circulation. 2015;doi:10.1161/CIRCULATIONAHA.115.0171364.

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Studies Show No Difference in Outcomes with Remote Ischemic Preconditioning

Patients undergoing cardiac surgery may not benefit from remote ischemic preconditioning, according to two studies published in the New England Journal of Medicine.

In the ERICCA study, researchers examined outcomes of patients undergoing coronary artery bypass grafting (CABG) with remote ischemic preconditioning. The results of this study were previously published at ACC.15. In the RIPHeart study, the study authors examined the outcomes of patients undergoing upper-limb remote ischemic preconditioning with elective cardiac surgery.

In the ERICCA study, a total of 1,612 patients undergoing CABG with blood cardioplegia were enrolled in the study, with 811 being assigned to the sham control group and 801 to receive remote ischemic preconditioning. The groups had similar baseline characteristics, surgical details and use of cardiovascular medications during follow-up. Interventions were completed in 716 (88.3%) of control participants and 691 (86.3%) of those in the ischemic preconditioning group. All patients in the cohort were included in the analysis of the primary outcome of major adverse cardiac and cerebral events (MACCE) within 12 months.

The researchers found no significant difference between the two groups in respect to the primary endpoint: 26.5% of the ischemic preconditioning group and 27.7% of the control group experienced MACCE. Per-protocol results were similar to the intention-to-treat results, with little evidence of MACCE between the groups. A secondary outcomes analysis showed no significant between-group differences in perioperative myocardial injury, inotrope score, acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life.

The RIPHeart study included a total of 1,403 patients, with 1,385 patients comprising the full analysis set. A total of 692 patients received remote ischemic preconditioning and the 693 members of the control group received sham remote ischemic preconditioning. The two groups were similar at baseline except that a greater proportion of the sham group took cholesterol lowering drugs (62.7% vs. 68.3%). The primary endpoint was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary endpoints included the occurrence of any individual component of the primary end point by day 90.

The researchers found no significant between-differences in the rate of the primary endpoint or in the rate of its components. Estimates of event-free survival were 85.2% in the sham group and 85.0% in the remote ischemic preconditioning group at 30 days after surgery and 84.5% and 84.4%, respectively, at 90 days after surgery. Sub-group analyses did not reveal significant variation in treatment effects according to the type of surgery, the use or nonuse of cholesterol-lowering drugs, the presence of diabetes, or the EuroSCORE. The researchers also found no significant between-group differences with respect to the secondary endpoints. No adverse events related to remote ischemic preconditioning were observed.

In an editorial comment accompanying both studies, Michael Zaugg, MD, and Eliana Lucchinetti, PhD, wrote that “the search for a magic bullet—a cardioprotective strategy that could be successfully administered in addition to the current standard treatment to provide additional benefits—is tantalizing but frustrating, as evidenced by the negative results of [these] two trials.” They added that “the most obvious explanation for the negative results in these two clinical trials is that other cardioprotective pharmacologic agents may have masked the effect of remote ischemic preconditioning or rendered it redundant,” and also wondered whether remote ischemic preconditioning may even be risky.

Zaugg and Lucchinetti concluded that, “in view of these concerns and despite the fact that remote ischemic preconditioning has been praised as safe and has been heavily promoted as the ‘future of cardioprotection’ by some advocates, its safety as a cardioprotective strategy should be carefully investigated in additional, adequately powered studies, specifically in patients undergoing nonsurgical interventions, even if it is applied only at a distance.”

Hausenloy DJ, Candilio L, Evans R, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1413534.
Meybohm P, Bein B, Brosteanu O, et al. N Engl J Med. 2015;doi:10.156/NEJMoa1413579.

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No Benefit From Steroids After Cardiopulmonary Bypass

The steroid methylprednisolone does not affect morbidity or mortality after cardiac surgery with cardiopulmonary bypass, researchers for a recently published Lancet study reported, cautioning against the routine use of steroids for cardiopulmonary bypass.
  
Cardiopulmonary bypass initiates a systemic inflammatory response syndrome, which can lead to adverse clinical outcomes. Steroids can reduce this inflammation, but their effect on clinical outcomes is uncertain.

The Steroids In cardiac Surgery (SIRS) trial, an 80-center international, parallel-group, double-blind, randomized, placebo-controlled study, examined 7,507 high-risk adult patients undergoing cardiopulmonary bypass. Patients were randomized to methylprednisolone (n = 3,755) or placebo (n = 3,752). Baseline characteristics were similar between the groups. A total of 1,587 (21%) patients underwent isolated coronary artery bypass surgery; 2,437 (32%) underwent isolated valvular surgery and 3,379 (45%) underwent combined or other surgery.

After 30 days, 154 (4%) of the methylprednisolone patients and 177 (5%) of the placebo patients had died. Death, myocardial injury, stroke, new renal failure or respiratory failure occurred in 909 (24%) of the methylprednisolone patients and 885 (24%) of the placebo patients. Secondary outcomes of stage 3 renal failure, stroke, new atrial fibrillation, transfusion requirements, infection, gastrointestinal complications, delirium, respiratory failure, and length of intensive care unit or hospital stay did not differ between the groups. Infection, surgical site infection and delirium were the most common adverse events in both groups. Methylprednisolone reduced chest drain output during the first 24 hours after surgery, while peak postoperative serum glucose and postoperative insulin requirements in the first 24 hours after surgery were both increased by the steroid. The 6-month mortality in both treatment groups showed no effect of the methylprednisolone on mortality. The steroid increased the risk of myocardial injury compared to placebo.

In an editorial comment accompanying the paper, Rupert M. Pearse, MD, and Duminda N. Wijeysundera, MD, examined the similarities between the SIRS study and the previous Dexamethasone for Cardiac Surgery (DECS) study. In both studies, no significant benefits from steroids were observed and both showed similar effects on death, acute kidney injury, stroke, myocardial infarction and respiratory failure. Both also show that the potential efficacy of steroids varies with age and that individuals under the age of 65 may see more consistent benefits. Only SIRS showed an increase in myocardial injury after steroid use, but Pearse, Wijeysundera, and the SIRs authors acknowledged that this may be due to the use of the Creatine Kinase Myocardial Band (CK-MB) to monitor this outcome. Pearse and Wijeusindera wrote that the “consistencies in the two trials’ findings might not have occurred by chance. We would recommend that they investigators of both trials collaborate to do an individual patient data meta-analysis to clarify the effects of steroids, especially within the subgroup of younger patients.”

The editorial authors added that the SIRS study “also underlines some wider lessons for clinical trial investigators in perioperative medicine.” Clinical effectiveness trials, they wrote, should only be performed once there is “biological basis for a treatment strategy, in terms of dose, timing, and specific patient population.” They added that debates regarding the value of large trials which frequently fail to confirm the clinical effectiveness of treatment relates to a misunderstanding of the purpose of these trials. They wrote that these trials are meant to “enhance the acuity of clinical evidence on an existing question” and “improve paint care irrespective of their findings.” They concluded that clinical effectiveness trials “prove the value of some treatments, show the marginal benefit and hence non-usefulness of others, and in some case confirm the importance of harms that were previously thought insignificant. With more than 310 million patients undergoing surgery worldwide each year, the need for high-quality clinical trials in perioperative medicine has never been greater.”

Whitlock RP, Devereaux PJ, Teah KH, et al. Lancet. 2015;386:1243-53.

Keywords: CardioSource WorldNews Interventions, Angioplasty, Balloon, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Cardiovascular Agents, Coronary Artery Bypass, Femoral Artery, Inflammation, Ischemic Preconditioning, Methylprednisolone, Research Personnel, Stents

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