Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial

Konstam, Marvin A.; Neaton, James D.; Dickstein, Kenneth; Drexler, Helmut; Komajda, Michel; Martínez, Felipe A.; Riegger, Günter A.J.; Malbecq, William; Smith, Ronald D.; Guptha, Soneil; Poole‐Wilson, Philip A.

doi:10.1016/s0140-6736(09)61913-9

Cited by 571 publications

(455 citation statements)

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“…Standard heart failure therapy is effective and refers to an angiotensin‐converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a beta‐blocker, and a mineralocorticoid antagonist 2. Even though standard treatment reduces risk of death and heart failure hospitalization by up to 10–37%,3, 4, 5, 6, 7, 8, 9 mortality is high, and many patients suffer from severe symptoms on a daily basis. New and more effective heart failure treatments are needed.…”

Section: Introductionmentioning

confidence: 99%

Eligibility of sacubitril–valsartan in a real‐world heart failure population: a community‐based single‐centre study

2018

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AimsThis study aims to investigate the eligibility of the Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor (ARNI) with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM‐HF) study to a real‐world heart failure population.Methods and resultsMedical records of all heart failure patients living within the catchment area of Umeå University Hospital were reviewed. This district consists of around 150 000 people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at least one echocardiography performed, and 401 patients had an ejection fraction of ≤35% at their latest examination. The major PARADIGM‐HF criteria were applied, and 95 patients fulfilled all enrolment criteria and thus were eligible for sacubitril–valsartan. This corresponds to 5% of the overall heart failure population and 24% of the population with ejection fraction ≤ 35%. The eligible patients were significantly older (73.2 ± 10.3 vs. 63.8 ± 11.5 years), had higher blood pressure (128 ± 17 vs. 122 ± 15 mmHg), had higher heart rate (77 ± 17 vs. 72 ± 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%) than did the PARADIGM‐HF population.ConclusionsOnly 24% of our real‐world heart failure and reduced ejection fraction population was eligible for sacubitril–valsartan, and the real‐world heart failure and reduced ejection fraction patients were significantly older than the PARADIGM‐HF population. The lack of data on a majority of the patients that we see in clinical practice is a real problem, and we are limited to extrapolation of results on a slightly different population. This is difficult to address, but perhaps registry‐based randomized clinical trials will help to solve this issue.

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Section: Introductionmentioning

confidence: 99%

Eligibility of sacubitril–valsartan in a real‐world heart failure population: a community‐based single‐centre study

2018

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“…Furthermore, although randomized, double-blind, trials, may result in recommendations for increases in daily losartan dosages (e.g. Konstam et al (2009) …”

Section: Peerj Preprintsmentioning

confidence: 99%

Summertime dosage-dependent hypersensitivity to an angiotensin II receptor blocker

Forsdyke

2014

Preprint

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Summertime dips in blood pressure (BP), both in normotensive and hypertensive subjects, are well known. However, the dips are small and are not related to particular forms or doses of antihypertensive medication. Nevertheless it is the practice in some quarters to decrease antihypertensive medication in summer, and/or increase in winter. Large scale studies being inconclusive, there are calls for long-term examination of the relationship between environmental temperature and blood pressure in single individuals under medication. While analyzing data from a subject whose BP had been controlled for a decade with the angiotensin-II receptor blocker losartan, an extreme, dosage-dependent, summertime dip came to light. Downward dosage adjustment appeared essential and may have prevent hypotension-related pathology. The benefits of aggressive medication (the "J curve" phenomenon) being debated, the possibility of seasonal hypersensitivity, explicable in terms of differential signaling by countervailing receptors, should be taken into account when considering dosage adjustments in hypertensive subjects.PeerJ PrePrints | http://dx.doi.org/10.7287/peerj.preprints.144v2 | CC-BY 3.0

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“…Small studies that compared the efficacy of therapy with higher‐dose vs. lower‐dose agents have yielded inconsistent or conflicting results 9, 10, 11. Recently, a large‐scale trial, the Heart Failure Evaluation of Angiotensin Antagonist Losartan, demonstrated the superiority of higher‐dose over low‐dose losartan on the primary outcomes of death or hospitalization in patients with systolic heart failure 12. However, the study subjects were limited to patients who were intolerant to ACE inhibitors, precluding extrapolation of the results to the general population.…”

Section: Introductionmentioning

confidence: 99%

The impact of a dose of the angiotensin receptor blocker valsartan on post‐myocardial infarction ventricular remodelling

Park

Kim

et al. 2018

ESC Heart Failure

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AimsAlthough clinical guidelines advocate the use of the highest tolerated dose of angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk–benefit profile of different doses have not been fully identified.Methods and resultsIn this multicentre trial, 495 Korean patients with acute ST segment elevation MI and subnormal left ventricular (LV) ejection fraction (<50%) were randomly allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to 320 mg/day, n = 333) or low‐dose valsartan (80 mg/day, n = 162) treatment. The primary objective was to assess the changes in echocardiographic parameters of LV remodelling from baseline to 12 months after discharge. After treatment, end‐diastolic LV volume (LVEDV) decreased significantly in the low‐dose group, but the difference in LVEDV changes was insignificant between the maximal‐tolerated‐dose and low‐dose groups. End‐systolic LV volume decreased significantly in both groups, to a similar degree between groups. LV ejection fraction rose significantly in both study groups, to a similar degree. Changes in plasma levels of neurohormones were also comparable between the two groups. Drug‐related adverse effects occurred more frequently in the maximal‐tolerated‐dose group than in the low‐dose group (7.96 vs. 0.69%, P < 0.001).ConclusionsIn the present study, treatment with the maximal tolerated dose of valsartan did not exhibit a superior effect on post‐MI LV remodelling compared with low‐dose treatment and was associated with a greater frequency of adverse effect in Korean patients. Further study with a sufficient number of cases and statistical power is warranted to verify the findings of the present study.

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Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial

Cited by 571 publications

References 20 publications

Eligibility of sacubitril–valsartan in a real‐world heart failure population: a community‐based single‐centre study

Eligibility of sacubitril–valsartan in a real‐world heart failure population: a community‐based single‐centre study

Summertime dosage-dependent hypersensitivity to an angiotensin II receptor blocker

The impact of a dose of the angiotensin receptor blocker valsartan on post‐myocardial infarction ventricular remodelling

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