CORRESPONDENCE: LETTER TO THE EDITOR
Warning on Diuretic Use
Morten Grundtvig, MD, BSc*,
Arne Westheim, MD, PhD,
Torstein Hole, MD, PhD,
Berit Flønæs, RN,
Lars Gullestad, MD, PhD on behalf of the Norwegian Heart Failure Registry
* Innlandet Hospital Trust, Medical Department, A. Sandvigsgt 17, N-2629 Lillehammer, Norway (Email: mgrundtv{at}online.no).
Lainchbury et al. (1) compared the effect of treatment guided by N-terminal pro-B-type natriuretic peptide with intensive clinical management and usual care among 364 patients with chronic heart failure (1). They concluded that intensive management of chronic heart failure, when compared with usual care, improves 1-year mortality. Although there was a modest increase in the doses of beta-blockers, the major difference between the hospital groups was adjustment of the dose of furosemide. One could therefore be left with the impression that the proper treatment of such patients should be an increase in the dose of diuretics. However, this conclusion is based on a low number of events. The overall numbers of deaths (according to Table 4 of Lainchbury et al. [1]) were 7, 6, and 16 in the first year in the N-terminal pro-B-type natriuretic peptide, intensive clinical management, and usual care groups, respectively, and one could therefore not exclude that the findings were due to chance. Lainchbury et al. (1) also needed to explain their other conclusion that hormone-guided treatment selectively improves long-term mortality in patients  75 years of age, because (according to Table 4 of Lainchbury et al. [1]) the numbers of deaths during 3 years were 6, 6, and 12, respectively.
What is more worrisome is the background therapy on which these results are based. The proportion of patients using angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, and spironolactone were 77% to 84%, 65% to 71%, and 12% to 17%, respectively, and the doses of ACEIs/ARBs and beta-blockers were approximately 60% and 40% of recommended doses. In comparison, in the Norwegian Heart Failure Registry among 3,632 patients, mean age 71 years, the proportion of patients using ACEIs/ARBs, beta-blockers, and spironolactone were 87%, 83%, and 27%, respectively, whereas the doses of ACEIs and beta-blockers were 80% and 58% of recommended target doses, respectively. Contrary to the present study where the dose of furosemide increased to nearly 200 mg/day, we were able to reduce the dose from 58 to 53 mg/day during optimization of drug treatment in our population of patients with one-half of the patients in New York Heart Association functional classes III to IV at baseline (2). Moreover, we found the daily dose of diuretics to be an independent predictor of mortality (3). In fact, it was the strongest predictor of mortality adjusted for age, estimated glomerular filtration rate, New York Heart Association functional class, hemoglobin, serum sodium concentration, stroke, and ischemic heart disease. A large number of other variables were not significantly related.
Until it is better documented that the hormone-assisted treatment is better than clinical care, doctors should be cautious to up-titrate the diuretic dose on the basis of this blood test. Because it is now well documented that both the proportion and dosing of ACEIs/ARBs and beta-blockers have an impact on mortality and morbidity, such recommendations should at least be based on prospective, randomized studies where the patients are optimally treated from the start.
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References
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1. Lainchbury JG, Troughton RW, Strangman KM, et al. N-terminal pro–B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) trial J Am Coll Cardiol 2010;55:53-60.[Abstract/Free Full Text]2. Grundtvig M, Gullestad L, Hole T, Flonaes B, Westheim A. Impact of nurse-based heart failure clinics on drug management and hospital admissions by self monitoring through a common database (abstr) Eur Heart J 2008;29(Suppl):760-761. 3. Grundtvig M, Gullestad L, Atar D, Flønæs B, Hole T, Westheim AS. Diuretic doses and mortality in 3,632 patients with stable chronic heart failure (abstr) Circulation 2009;120:S540.
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