Research Spotlight

Ono, M., Serruys, P.W., Hara, H., Kawashima, H., Gao, C., Wang, R., Takahashi, K., O’Leary, N., Wykrzykowska, J.J., Sharif, F., Piek, J.J., Garg, S., Mack, M.J., Holmes, D.R., Morice, M.C., Head, S.J., Kappetein, A.P., Thuijs, D., Noack, T., Davierwala, P.M., Mohr, F.W., Cohen, D.J. and Onuma, Y. (2021). “10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease.” J Am Coll Cardiol 77(22): 2761-2773.

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BACKGROUND: The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. OBJECTIVES: The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD). METHODS: In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models. RESULTS: Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; p(interaction) = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; p(interaction) = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: -0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients. CONCLUSIONS: Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode.

https://bhslibrary-primo.hosted.exlibrisgroup.com/primo-explore/openurl?sid=Entrez:PubMed&id=pmid:34116144&vid=01TEXAM-HSC_V1&institution=01TEXAM-HSC&url_ctx_val=&url_ctx_fmt=null&isSerivcesPage=true

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AIMS: Sacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline-directed medical therapy for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β-blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial. METHODS AND RESULTS: Patients with full data on medication use were included. We examined β-blocker and MRA use in patients randomized to sacubitril/valsartan vs. enalapril through 12-month follow-up. New initiations and discontinuations of β-blocker and MRA were compared between treatment groups. Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of β-blocker and MRA at any dose was 87% and 56%, respectively. Mean doses of β-blocker and MRA were similar between treatment groups at baseline and at 6-month and 12-month follow-up. New initiations through 12-month follow-up were infrequent and similar in the sacubitril/valsartan and enalapril groups for β-blockers [37 (9.0%) vs. 42 (10.2%), P = 0.56] and MRA [127 (7.6%) vs. 143 (9.2%), P = 0.10]. Among patients on MRA therapy at baseline, there were fewer MRA discontinuations in patients on sacubitril/valsartan as compared with enalapril at 12 months [125 (6.2%) vs. 187 (9.0%), P = 0.001]. Discontinuations of β-blockers were not significantly different between groups in follow-up (2.2% vs. 2.6%, P = 0.26). CONCLUSIONS: Initiation of sacubitril/valsartan, even when titrated to target dose, did not appear to lead to greater discontinuation or dose down-titration of other key guideline-directed medical therapies, and was associated with fewer discontinuations of MRA. Use of sacubitril/valsartan (when compared with enalapril) may promote sustained MRA use in follow-up.

O’Shaughnessy, J., Sousa, S., Cruz, J., Fallowfield, L., Auvinen, P., Pulido, C., Cvetanovic, A., Wilks, S., Ribeiro, L., Burotto, M., Klingbiel, D., Messeri, D., Alexandrou, A., Trask, P., Fredriksson, J., Machackova, Z. and Stamatovic, L. (2021). “Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study.” Eur J Cancer 152: 223-232.

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AIM: The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). MATERIALS AND METHODS: Patients who completed neoadjuvant P + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. RESULTS: One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5-90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0-50.0 min with SC and 130.0-300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1-3 IV → cycles 4-6 SC: 77.5% → 72.5%; cycles 1-3 SC → cycles 4-6 IV: 77.5% → 63.8%). CONCLUSION: Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion.

Bhatt, A.S., Claggett, B.L., Packer, M., Lefkowitz, M.P., Zile, M.R., McMurray, J.J.V., Solomon, S.D. and Vaduganathan, M. (2021). “Treatment Effects of Sacubitril/Valsartan Compared With Valsartan in Patients with Recent Hospitalization.” J Card Fail Jun 13;S1071-9164(21)00213-X. [Epub ahead of print].

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The Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial demonstrated sacubitril/valsartan modestly lowered total heart failure (HF) hospitalizations and cardiovascular death compared with valsartan in ambulatory HF patients with left ventricular ejection fraction (LVEF) ≥45%.Treatment benefits were greater in patients with lower ejection fractions and post-hoc analyses identified greater benefit in those with recent HF hospitalization. [No abstract; excerpt from article].

Barry, I.P., Barns, M., Verhoeven, E., Wong, J., Dubenec, S., Heyligers, J.M., Milner, R., Shutze, W.P., Bachoo, P., Vlaskovky, P. and Mwipatayi, B.P. (2021). “Excluder Stent Graft-Related Outcomes in Patients with Aortic Neck Anatomy Outside of Instructions For Use (IFU) within the Global Registry for Endovascular Aortic Treatment (GREAT): Mid-term Follow-Up Results.” Ann Vasc Surg Jun 25;S0890-5096(21)00426-X. [Epub ahead of print].

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BACKGROUND: The utilisation rate of endovascular aortic aneurysm repair (EVAR) has increased continuously over the past two decades. EVAR is still performed frequently in patients with an unfavourable proximal seal zone, despite the associated late complications. PURPOSE: We aimed to evaluate the mid-term durability of the GORE® EXCLUDER® AAA Endoprosthesis, featuring the C3 delivery system, in patients with a proximal neck anatomy outside the instructions for use (IFU). PROCEDURES: A retrospective sub-analysis of the Global Registry for Endovascular Aortic Treatment including patients treated for abdominal aortic aneurysms with the GORE® EXCLUDER® AAA Endoprosthesis (W.L. Gore & Associates, Inc, Flagstaff, Arizona) was performed. A “challenging neck” was defined as those treated outside the IFU with an aortic neck length <15 mm and/or aortic neck angle >60°. Cox proportional analyses were used to test for time-to-event differences between those treated within and outside the IFU while accounting for covariates, specifically proximal neck length and neck angle. The main outcomes assessed were 5-year all-cause mortality, 5-year endoleak development (type I or III), and 5-year device-related reinterventions. FINDINGS: Of the 3,324 patients included in the analysis, 411 (12.4%) had a challenging neck and 2,913 (87.6%) did not. The patients in the challenging neck group were significantly older (74.9 years vs. 73.2 years, p=<0.0001) and had a significantly larger aortic aneurysm diameter at the time of the intervention than those treated within the IFU (61.2 mm vs 56.4 mm, p<0.0001), shorter proximal neck length (18 mm vs 30 mm, p<0.0001) and larger infrarenal neck angle (60.8° vs 25.8°, p<0.0001). In the multivariate analysis, brachial access site and challenging neck were not independent risk factors; increased age was associated with a shorter time to mortality (hazard ratio 1.051, 95% confidence interval 1.039-1.062, p<0.0001), as was the use of tobacco (hazard ratio 1.329, 95% confidence interval 1.124-1.571, p=0.0009). The 5-year all-cause mortality (36.2% vs. 27.5%, p=0.002) and aorta-related mortality (3.8% vs 1.1%, p=0.002) were significantly higher in the challenging neck group. The risk of death within 5 years also increased significantly at 1.1% per millimetre increase in the abdominal aortic aneurysm diameter (p=0.0005). Furthermore, the rates of type Ia endoleak development (7% vs. 1.2%, p<0.001) and requirement for reintervention (13.3% vs. 9.7%, p<0.001) were higher in those treated outside the IFU (challenging neck group). CONCLUSIONS: Treatment with the Excluder AAA Endograft outside the IFU was associated with higher 5-year mortality values, increased type Ia endoleak development rates, and a greater need for reintervention compared with treatment within the IFU. This reiterates that fenestrated and open treatments should be strongly considered in cases with aortic neck anatomies outside the IFU. Infrarenal endovascular intervention outside the IFU should only be used when there is no alternative, with meticulous procedural planning and intervention to promote satisfactory outcomes.