Relationship between outcomes and systolic blood pressure reduction during the first 24 h in acute heart failure syndrome: an exploratory analysis of the Relax-AHF-studies

Relationship between outcomes and systolic blood pressure reduction during the first 24 h in acute heart failure syndrome: an exploratory analysis of the Relax-AHF-studies

Size of the problem:Expenditures on heart failure (HF) ranges between 1-2% of the total healthcare budget in developed countries, and patients hospitalized for acute heart failure syndrome (AHFS) comprise a great deal of this amount. Patients with AHFS have a combined 1-year event rate for all-cause death or hospitalization of 35-40%. Most patients admitted with AHFS have elevated blood pressure, which increases the burden on the heart muscle resulting in reduced pump function, breathlessness, and congestion. Unmet medical needs:Treatment of AHFS has not changed in the past 50 years, and several trials failed to identify new effective drugs. One of many reasons for failure could be that the old drugs are already effective to relieve the heart muscle. Therefore, in addition to testing new drugs, we propose also to examine better strategies that will ensure optimal use of currently effective drugs, for example by defining optimal treatment targets for blood pressure in patients with AHFS.Knowledge gaps:There is a lack of studies to report what blood pressure would be optimal for patients with normal to moderately elevated blood pressure. The current target for treatment in AHFS is decongestion and “relief of symptoms,” which makes a lot of sense, but it is challenging to measure objectively. Instead, we propose that the blood pressure serves as a complementary surrogate target. Current guidelines recommend reducing blood pressure by 25% in patients admitted with AHFS and very high blood pressure above 180 mmHg. Currently, there is no recommended optimal target for blood pressure reduction in patients with AHFS and normal to moderately elevated blood pressure (e.g., 125-180 mmHg). Questions and issues:Blood pressure is an ideal target as it is easy to measure and easy to treat. However, too much blood pressure lowering may cause harm due to reduced organ perfusion and renal dysfunction. Thus, it is not clear what target blood pressure levels would be most optimal.Solutions to the problems:We hypothesize that it is possible to identify an optimal blood pressure target for patients who present with acute heart failure syndrome and systolic blood pressure of A) 125 to 145 mmHg, or B) 146 to 180 mmHg.The objective is to examine: • if a systolic blood pressure of 120 mmHg 6 hours after randomization is associated with the best outcome in group A • if a systolic blood pressure of 130 mmHg 6 hours after randomization is associated with the best outcome in group B • if there exists an alternative systolic blood pressure at 6 hours after randomization that is associated with the best outcome for each of the two groups?Design and methods:Our analysis will take place in a pooled analysis of 4 randomized clinical trials of the Relax-AHF program. The four studies had similar in- and exclusion criteria and a total of 11457 patients. All patients had AHFS and were randomized with approximately 8 hours from presentation to the hospital, and they had a systolic blood pressure between 125 and 180 mmHg at the time of randomization. The primary outcome will be defined as a combined worsening HF or death during 15 days of follow up. Implication:Although this analysis is explorative, it will contribute to the understanding of how to improve the short-term prognosis for patients admitted with AHFS and normal to elevated blood pressure. This could impact future recommendations, although it needs prospective testing to know if it also improves quality of life as well as healthcare expenditures.

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