Apparent Treatment-Resistant Hypertension Across the Spectrum of Heart Failure Phenotypes in the Swedish HF Registry.

Background: Hypertension is common in patients with heart failure (HF), but less is known about resistant hypertension.
Objectives: This study sought to investigate apparent treatment-resistant hypertension (aTRH) in patients with HF in the SwedeHF (Swedish Heart Failure Registry), across the spectrum of HF phenotypes (heart failure with reduced ejection fraction [HFrEF], heart failure with mildly reduced ejection fraction [HFmrEF], and heart failure with preserved ejection fraction [HFpEF]).
Methods: aTRH was defined as systolic blood pressure ≥140 mm Hg (≥135 mm Hg in diabetes) despite treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or sacubitril-valsartan, as well as a calcium-channel blocker and a diuretic; non-treatment-resistant hypertension (TRH) was defined as systolic blood pressure above these thresholds but not on the 3-drug combination; and normal blood pressure was defined as under these thresholds. In each left ventricular ejection fraction (LVEF) category, patient factors associated with aTRH and non-TRH and outcomes (HF hospitalization and cardiovascular death composite, its components, and all-cause death) according to hypertension category were examined.
Results: Among 46,597 patients, aTRH was present in 2,693 (10%), 1,514 (14%), and 1,450 (17%) patients with HFrEF, HFmrEF, and HFpEF, respectively. Older age, obesity, diabetes, and kidney disease were associated with a greater likelihood of aTRH and non-TRH (vs normal blood pressure). Associations were generally similar irrespective of LVEF category. Compared with normal blood pressure, aTRH was associated with a lower adjusted risk of the composite outcome in HFrEF and HFmrEF (HR: 0.79 [95% CI: 0.74-0.85] and HR: 0.86 [95% CI: 0.77-0.96]) but not in HFpEF (HR: 0.93 [95% CI: 0.84-1.04]).
Conclusions: aTRH was most common in HFpEF and least common in HFrEF. Associated patient characteristics were similar irrespective of LVEF category. aTRH (vs normal blood pressure) was associated with a lower risk of first HF hospitalization or cardiovascular death in HFrEF and HFmrEF but not in HFpEF.
Competing Interests: Funding Support and Author Disclosures SwedeHF is funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions, the Swedish Society of Cardiology, and the Swedish Heart-Lung Foundation. No funding agency had any role in the design, conduct, or decision or approval to publish this study. Dr Lund is supported by Karolinska Institutet, the Swedish Research Council (grant 523-2014-2336), the Swedish Heart Lung Foundation (grants 20150557 and 20190310), and the Stockholm County Council (grants 20170112 and 20190525). Dr Jackson is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/18/14/33330). Drs McMurray and Petrie are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). Dr Petrie has received lecture fees from AstraZeneca and Eli Lilly; personal fees from Novo Nordisk, AstraZeneca, NAPP Pharmaceuticals, Takeda Pharmaceutical, Alnylam, Bayer, Resverlogix, and Cardiorentis; and grants and personal fees from Boehringer Ingelheim and Novartis. Dr Jhund has received personal fees from Novartis and AstraZeneca; personal fees and grants from Boehringer Ingelheim; and his employer, the University of Glasgow, has received remuneration from AstraZeneca for work on the DAPA-HF and DELIVER trials. Mr Dahlström has received research grants from AstraZeneca, Pfizer, Boehringer Ingelheim, Boston Scientific, Vifor Pharma, and Roche Diagnostics; and consulting honoraria from Novartis, Amgen, AstraZeneca, and Pfizer all outside of the submitted work. Ms Hage has received consulting fees from Novartis and Roche Diagnostics; and speaker and honoraria from Merck Sharp & Dohme, and is supported by the Swedish Research Council (grant 20180899). Mr Savarese has received grants and personal fees from Vifor; grants and nonfinancial support from Boehringer Ingelheim; personal fees from Società Prodotti Antibiotici; grants and personal fees from AstraZeneca; personal fees from Roche, Servier, GENESIS, Cytokinetics, and Medtronic; and grants from Novartis, Boston Scientific, PHARMACOSMOS, and Merck, outside the submitted work. Dr McMurray reports that his employer, Glasgow University, has been paid by Novartis for his serving as an executive committee member and co–principal investigator of the ATMOSPHERE, PARADIGM-HF, and PARAGON-HF trials and as an executive/steering committee member of the PARADISE-MI and PERSPECTIVE trials (with sacubitril-valsartan) and for meetings/presentations related to these trials, aliskiren, and sacubitril-valsartan. Novartis has also paid for his travel and accommodation for some of these meetings. Glasgow University has also been paid by Novartis for Dr McMurray serving on an advisory board; by Bayer for serving as a steering committee member of the PANACHE trial using neladenoson bialanate (BAY 1067197); by Cardiorentis for serving as a steering committee member and endpoint committee chair for the TRUE-AHF trial and attending meetings related to this trial; by Cardiorentis for travel and accommodation to attend some of these meetings; by Amgen for serving as a steering committee member for the ATOMIC-HF and COSMIC-HF trials and attending meetings related to these trials; by Amgen for travel and accommodation for some of these meetings; by Oxford University (which received a grant from Bayer, which manufactures acarbose) for serving as a steering committee member for the ACE (Acarbose Cardiovascular Evaluation) trial (using acarbose) and attending meetings related to this trial; by Theracos for serving as principal investigator for the BEST trial and attending meetings related to this trial; by Theracos for travel and accommodation to attend some of these meetings; by AbbVie (which manufactures atrasentan) for serving as a steering committee member for the SONAR trial (using atrasentan) and to attend meetings related to this trial; by AbbVie for travel and accommodation to attend some of these meetings; by DalCor Pharmaceuticals for serving as a steering committee member for the Dal-GenE trial and to attend meetings related to this trial; by Pfizer for serving on the data safety monitoring committee for the SPIRE trial and to attend meetings related to this trial; by Merck for serving on the data safety monitoring committee for the MK-3102 program for the VICTORIA trial and for attending meetings related to this trial; by AstraZeneca (which markets dapagliflozin) for serving as principal investigator of DAPA-HF and co–principal investigator of DELIVER and to attend meetings related to these trials; by AstraZeneca for travel and accommodation to attend meetings; by GlaxoSmithKline for serving as co–principal investigator and steering committee member, respectively, for the Harmony-Outcomes trial (albiglutide) and 2 trials, ASCEND-D and ASCEND-ND, using daprodustat, and to attend meetings related to these trials; by GlaxoSmithKline for travel and accommodation to attend some of the meetings; by Bristol Myers Squibb for serving as a steering committee member for the STAND-UP clinical trial (using an HNO donor) on heart failure and to attend meetings related to this trial; by Kings College Hospital (which has received a grant from KRUK and Vifor-Fresenius, which manufacture intravenous iron) for serving as a steering committee member for the PIVOTAL trial (using intravenous iron) and for running the endpoint adjudication committee for this trial; and to attend meetings related to PIVOTAL and for travel and accommodation to attend some of the meetings. All payments were made through consultancies with Glasgow University, and Dr McMurray has not received any personal payments in relation to the trials or drugs. Dr Lund has received research grants from AstraZeneca, Novartis, Boehringer Ingelheim, Boston Scientific, Vifor Pharma, Relypsa, and Pharmacosmos; and consulting/speaker honoraria from AstraZeneca, Novartis, Bayer, Vifor Pharma, Sanofi, Lexicon, MyoKardia, Orion Pharma, Merck/Merck Sharp & Dohme, Respicardia, and Medscape. Ms Benson has reported that she has no relationships relevant to the contents of this paper to disclose.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)