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Journal Wrap
The hottest research from various peer-reviewed journals.
ATTR-ACT: Tafamidis Findings Offer Hope For Patients With ATTR-CM
Tafamidis is an effective and safe therapy for treating patients with transthyretin amyloid cardiomyopathy (ATTR-CM), based on findings from the ATTR-ACT trial presented at ESC Congress 2018 and published in the New England Journal of Medicine.
ATTR-CM – a rare, progressive and fatal disease that is either hereditary (mutations in the TTR gene) or acquired – typically presents in patients between 50 and 80 years. Currently there are no approved drugs to improve survival, which on average is three to five years after diagnosis. However, tafamidis has received orphan drug designation from the European Medicines Agency (EMA) and Fast Track designation from the U.S. Food and Drug Administration (FDA). Read More >>>
In ATTR-ACT, researchers randomized 441 patients from 48 centers in 13 countries to receive tafamidis (80 mg), tafamidis (20 mg) or placebo once a day for 30 months. The two tafamidis groups were combined (n=264) and compared with the placebo group (n=177).
Tafamidis significantly reduced the primary composite endpoint of all-cause death and cardiovascular-related hospitalization compared with placebo at 30 days. During the 30-month follow-up, 78 (29.5 percent) patients receiving tafamidis died compared with 76 (42.9 percent) receiving placebo. Rates of cardiovascular-related hospitalizations were 52.3 percent with tafamidis vs. 60.5 percent with placebo.
Regarding secondary outcomes, exercise capacity assessed with the six-minute walk test and health-related quality of life were better with tafamidis than placebo. Additionally, discontinuation of tafamidis due to treatment-related adverse events was less common in the treatment group compared with placebo.
"There are no medications specifically approved for the treatment of transthyretin amyloid cardiomyopathy," said principal investigator Claudio Rapezzi, MD. "Tafamidis improved survival and quality of life, and reduced hospitalizations, indicating that it could be an effective therapy for these patients. A submission to the regulatory authorities for marketing approval is in process as a consequence of this study."
In a related editorial, C. Cristina Quarta, MD, and Scott D. Solomon, MD, FACC, write that the ATTR-ACT findings "offer hope for patients" and "suggest new ways forward in testing therapies for new diseases." However, they also caution that the findings raise further questions "about the mechanism of action of tafamidis, the time course of benefit, and the timing of treatment in the course of a patient's disease" and suggest additional studies "to determine whether there are important therapeutic differences between transthyretin stabilization and transthyretin knockdown."
Maurer MS, Schwartz JH, Gundapaneni B, et al. N Engl J Med 2018;379:1007-16.
APAF-CRT: AV Junction Ablation with CRT Bests Drugs in AFib Patients with Narrow QRS
Atrioventricular (AV) junction ablation plus cardiac resynchronization therapy (CRT) is more successful than pharmacological therapy in reducing heart failure (HF) and hospitalization and improving quality of life in elderly patients with permanent atrial fibrillation (AFib) and narrow QRS, according to research presented at ESC Congress 2018 and published in the European Heart Journal.
Michele Brignole, MD, et al., randomly assigned 102 patients with severely symptomatic permanent AFib (>6 months), narrow QRS (≤110 ms) and at least one hospitalization for HF in the previous year to AV ablation plus CRT (plus defibrillator according to guidelines) or to pharmacological rate-control therapy (plus defibrillator according to guidelines). The primary outcome was the first occurrence of the composite of death due to HF, hospitalization due to HF or worsening HF. Secondary clinical outcomes were total mortality, hospitalization for HF and worsening HF. Read More >>>
Over a median follow-up period of 16 months, the primary composite outcome occurred in 10 patients (20 percent) in the ablation plus CRT arm and in 20 patients (38 percent) in the drug arm. All-cause death or hospitalization for HF occurred in six patients (12 percent) receiving ablation plus CRT and 17 patients (33 percent) receiving drugs (hazard ratio [HR], 0.28; 95 percent confidence interval [CI], 0.11-0.72; p=0.008).
All-cause death occurred in two patients (4 percent) receiving ablation plus CRT and six patients (12 percent) receiving drugs (HR, 0.30; 95 percent CI, 0.06-1.50; p=0.147). Hospitalization for HF occurred in five patients (10 percent) receiving ablation plus CRT and 13 patients (25 percent) receiving drugs (HR, 0.30; 95 percent CI, 0.11-0.78; p=0.024). Compared with the drug arm, ablation plus CRT was associated with a 36 percent decrease in the specific symptoms and physical limitations of AFib at one year of follow-up (p=0.004).
The authors believe these results "are due to the combination of the almost perfect rate regularization achieved by AV junction ablation and CRT pacing, which counteracted the adverse effects of iatrogenic AV block induced by ablation." They add that this therapy should be offered to patients with symptomatic HF refractory to pharmacological therapy who cannot undergo catheter ablation of AFib for the maintenance of sinus rhythm or in whom ablation has failed.
Brignole M, Pokushalov E, Pentimalli F, et al. Eur Heart J 2018;Aug 26:[Epub ahead of print].
PREPARE-CALC: Rotational Atherectomy Before DES Feasible
Lesion preparation upfront with rotational atherectomy (RA) before drug-eluting stenting (DES) is possible in all patients with severely calcified coronary lesions and is more commonly successful as a primary strategy compared with modified balloons (MB), according to the PREPARE-CALC trial presented at TCT 2018 and simultaneously published in Circulation: Cardiovascular Interventions.
Mohamed Abdel-Wahab, MB ChB, MSc, et al., randomly assigned 200 patients with myocardial ischemia and severely calcified native coronary lesions undergoing PCI to lesion preparation using either RA (100) or MB (100) followed by DES implantation. The primary endpoint was strategy success, defined as successful stent delivery and expansion with attainment of <20 percent in-stent residual stenosis of the target lesion in the presence of TIMI (Thrombolysis in Myocardial Infarction) 3 flow without crossover or stent failure. The coprimary endpoint was in-stent late lumen loss (LLL), defined as the difference between the postprocedure and nine month in-stent angiographic minimal lumen diameter. Read More >>>
Overall, 278 lesions were treated (1.39 lesions per patient): 137 in the MB group and 141 in the RA group. Strategy success was significantly more common in the RA group (98 percent, vs. 81 percent in the MB group). The relative risk of failure with an MB- vs. RA-based strategy was 9.5 (p=0.0001), and the main driving factor for strategy failure was the need to crossover to RA in the MB group (16 percent vs. 0 percent; p<0.0001). There were no deaths or reinterventions during hospitalization. No significant differences were observed in residual diameter stenosis or acute lumen gain between patients randomized to MB vs. RA.
At nine months, overall mortality was 2 percent in both groups. Mean in-stent LLL was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group. The estimated mean difference in LLL between the MB and RA group was 0.075 mm. "A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters, relatively shorter procedural time, and less irradiation," write the investigators.
Abdel-Wahab M, Toelg R, Byrne RA, et al. Circ Cardiovasc Interv 2018;Sept 24:[Epub ahead of print].
Jury Still Out on OAC Alone in AFib Plus CAD
The OAC-ALONE trial presented at TCT 2018 and published in Circulation attempted to be the first randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation (AFib) and stable coronary artery disease (CAD) beyond one year after coronary stenting. Unfortunately, the trial was terminated due to low patient enrollment, leaving the jury still out on the optimal antithrombotic regimen for this patient group, despite some guideline recommendations for OAC alone.
The prospective, multicenter, open-label, noninferiority trial aimed to randomize 2,000 patients over 12 months to either OAC alone or combined OAC plus single APT. The primary endpoint was a composite of all-cause death, myocardial infarction (MI), stroke or systemic embolism. The secondary endpoint was a composite of primary endpoint or major bleeding using the International Society on Thrombosis and Haemostasis classification. The study was terminated early after only enrolling 696 patients in 38 months. Read More >>>
While noninferiority of OAC alone vs. combined OAC plus APT was not established, of those patients enrolled the primary endpoint occurred in 54 patients (15.7 percent) in the OAC alone group and in 47 patients (13.6 percent) in the combined OAC plus APT group. The major secondary endpoint occurred in 67 patients (19.5 percent) in the OAC alone group and in 67 patients (19.4 percent) in the combined OAC plus APT group. Broken down by event, MI occurred in eight patients in the OAC group, vs. four patients in the OAC plus APT group, while stroke or systemic embolism occurred in 13 patients in the OAC group and 19 patients in the OAC plus APT group. Major bleeding was higher in the OAC plus APT group (36 patients) vs. the OAC group (27 patients).
"Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive," the authors said. "Future larger studies are required to establish the optimal antithrombotic regimen in this population." In a related editorial comment, Gilles Lemesle, MD, PhD, writes that despite the "tantalizing observations" from OAC-ALONE, the issue of which strategy should be considered as default in clinical practice (and for which patients)" is still not settled. However, she notes the findings "will be useful in planning future trials."
Matsumura-Nakano Y, Shizuta S, Komasa A, et al. Circulation 2018;Sept 24:[Epub ahead of print].
Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and Atrial Fibrillation, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Coronary Artery Disease
Keywords: ACC Publications, Cardiology Interventions, Amyloid, Atherectomy, Coronary, Atrial Fibrillation, Atrioventricular Block, Benzoxazoles, Cardiac Resynchronization Therapy, Cardiomyopathies, Catheter Ablation, Confidence Intervals, Constriction, Pathologic, Coronary Artery Disease, Defibrillators, Drug Approval, Embolism, Factor IX, Factor V, Follow-Up Studies, Heart Failure, Hemostasis, Hospitalization, Iatrogenic Disease, Mutation, Myocardial Infarction, Myocardial Ischemia, Orphan Drug Production, Pharmaceutical Preparations, Prealbumin, Prospective Studies, Quality of Life, Research Personnel, Risk, Stents, Stroke, Thrombosis, United States Food and Drug Administration
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