Editorial comment
How much is enough?
Quanto será suficiente?
Gláucia Maria Moraes de Oliveira
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "247" "paginaFinal" => "248" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Gláucia Maria Moraes de Oliveira" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Gláucia Maria Moraes de" "apellidos" => "Oliveira" "email" => array:1 [ 0 => "glauciamoraesoliveira@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Quanto será suficiente?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The guidelines for treatment after myocardial infarction (MI) with or without ST-segment elevation (STEMI or NSTEMI)<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1–3</span></a> recommend the use of beta-blockers for all patients without contraindication because, based on large observational studies and randomized clinical trials, they increase survival rates.</p><p id="par0010" class="elsevierStylePara elsevierViewall">These guidelines recommend high doses of beta-blockers, but this recommendation is not followed in clinical practice, in which about 25% of the recommended dose is prescribed. Although widely used, these lower doses have not been tested in controlled and randomized trials. The question thus arises as to whether smaller doses of beta-blockers achieve the same benefit in reducing mortality, since the increases in survival in the trials were proportional to the decreases in heart rate obtained with incremental doses.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Studies designed to answer the question of the correct beta-blocker dose have provided important information for the follow-up of MI. The Outcomes of Beta-Blocker Therapy After Myocardial Infarction (OBTAIN) registry,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> of 6682 patients in centers in the USA and Canada from 2007 to 2009 with a mean follow-up of 2.1 years, used multivariate and propensity score analysis to assess the results. No improvement was observed in the survival of patients treated with the higher doses of multiple beta-blockers proposed in the randomized trials.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Similarly, a recently published multicenter registry<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> with 5287 patients discharged on beta-blockers after an acute coronary syndrome (ACS) between 1994 and 2013 showed no difference between the two doses analyzed, ≤25% or ≥50% of an equivalent daily dose of 200 mg of metoprolol. The authors analyzed the rates of major adverse cardiac events (MACE), all-cause death, MI, and stroke or equivalent at six months and 24 months of follow-up using multivariate and propensity score analysis. They observed that patients on lower doses had higher rates of myocardial revascularization, an effect that was also seen in the OBTAIN subgroup analysis. The authors further divided the population into two periods, 1993-2003 and 2004-2013, but there was no statistical difference between them.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In this issue of the <span class="elsevierStyleItalic">Journal</span>, Raposeiras-Roubin et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> revisit this question, retrospectively analyzing 2092 ACS patients discharged from a single center, the Álvaro Cunqueiro University Hospital of Vigo, between June 2013 and January 2016, and followed for a mean of 18.6±9.7 months. The patients were prescribed various beta-blockers with a predominance of bisoprolol. No prognostic benefit was noted in terms of mortality for high-dose vs. low-dose beta-blockers.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A meta-analysis published in 2014<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> encompassing sixty clinical trials with 102<span class="elsevierStyleHsp" style=""></span>003 patients compared the effect of beta-blockers at target doses on mortality after MI in the pre- vs. post-reperfusion era, and showed no benefit due to beta-blockers in the post-reperfusion era. Nevertheless, beta-blockers showed benefits for recurrent MI and angina in the reperfusion era, at the expense of increases in heart failure, cardiogenic shock, and drug discontinuation, but appeared to be short term (30 days after discharge).</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the above registries,<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4–6</span></a> which reflect the translation of guidelines into clinical practice, lower doses of beta-blockers were more frequent and equally useful in reducing cardiac mortality and MACE. These doses were probably selected for a variety of reasons, some objective (hemodynamic limitations and associated respiratory conditions such as reactive airways disease), and some subjective, such as fatigue, depression and sexual dysfunction.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">These retrospective registries used robust methods for statistical data analysis, including propensity score analysis and classical regression, to minimize confounding factors such as hypertension, prior STEMI and multivessel coronary artery disease, which are better controlled for in clinical trials. However, they do not provide information on the control of anginal symptoms, blood pressure, heart rate or arrhythmic events, or confirm the extent of patients’ adherence to medication. The mean follow-up of 24 months may not have been sufficient to show significant differences, such as seen in clinical trials.</p><p id="par0045" class="elsevierStylePara elsevierViewall">It is possible that advanced reperfusion therapies, potent antithrombotics, statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, cardiac rehabilitation, and lifestyle and dietary modifications were responsible for the results observed in the registries, although Allen et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> did not observe differences between two periods in the last twenty years.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Several factors are taken into account when considering the optimal dose of beta-blocker therapy: severity and extent of coronary artery disease, presentation (NSTEMI or STEMI) and size of MI, the reperfusion method used (thrombolysis or percutaneous coronary intervention), presence of residual ischemia, additional non-culprit lesions, revascularization procedures needed in the follow-up period, and assessment of cardiac function.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">On the other hand, beta-adrenergic receptor polymorphisms have been discovered that may be responsible for differences in dose-dependent response and beta-blocker metabolism, with hemodynamic effects such as changes in blood pressure and heart rate.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Recently, a new guideline for the management of acute MI in patients presenting with ST-segment elevation has been published that recommends the use of a beta-blocker, started within 24 hours of hospitalization, in patients without contraindication that should be continued after discharge, with class IIa recommendation and level of evidence B. The contraindications are acute heart failure, hemodynamic instability and higher degree AV block, with the recommendation that doses of proven efficacy should be administered.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Further research should be carried out to compare the effects of different doses of beta-blockers and the factors used to select them in order to improve survival and MACE after MI. Until the results of these studies are available, the best strategy is probably to offer patients the maximum dose tolerated, but lower than the target doses used in the randomized trials. Registries such as that of Raposeiras-Roubin et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> support this therapeutic decision while we await publication of new evidence that may change the use of beta-blockers in the follow-up of patients with MI.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P.T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 4 | 9 |
| 2024 October | 26 | 22 | 48 |
| 2024 September | 30 | 23 | 53 |
| 2024 August | 30 | 20 | 50 |
| 2024 July | 28 | 25 | 53 |
| 2024 June | 15 | 20 | 35 |
| 2024 May | 22 | 33 | 55 |
| 2024 April | 24 | 25 | 49 |
| 2024 March | 37 | 27 | 64 |
| 2024 February | 27 | 19 | 46 |
| 2024 January | 21 | 29 | 50 |
| 2023 December | 18 | 25 | 43 |
| 2023 November | 26 | 21 | 47 |
| 2023 October | 17 | 18 | 35 |
| 2023 September | 13 | 20 | 33 |
| 2023 August | 14 | 20 | 34 |
| 2023 July | 20 | 8 | 28 |
| 2023 June | 27 | 9 | 36 |
| 2023 May | 25 | 16 | 41 |
| 2023 April | 9 | 5 | 14 |
| 2023 March | 17 | 45 | 62 |
| 2023 February | 14 | 34 | 48 |
| 2023 January | 17 | 32 | 49 |
| 2022 December | 26 | 52 | 78 |
| 2022 November | 30 | 37 | 67 |
| 2022 October | 22 | 48 | 70 |
| 2022 September | 20 | 62 | 82 |
| 2022 August | 26 | 37 | 63 |
| 2022 July | 26 | 43 | 69 |
| 2022 June | 20 | 28 | 48 |
| 2022 May | 15 | 24 | 39 |
| 2022 April | 22 | 36 | 58 |
| 2022 March | 24 | 41 | 65 |
| 2022 February | 23 | 36 | 59 |
| 2022 January | 22 | 18 | 40 |
| 2021 December | 17 | 26 | 43 |
| 2021 November | 23 | 38 | 61 |
| 2021 October | 22 | 38 | 60 |
| 2021 September | 16 | 21 | 37 |
| 2021 August | 19 | 35 | 54 |
| 2021 July | 16 | 15 | 31 |
| 2021 June | 14 | 31 | 45 |
| 2021 May | 27 | 40 | 67 |
| 2021 April | 44 | 39 | 83 |
| 2021 March | 68 | 29 | 97 |
| 2021 February | 47 | 13 | 60 |
| 2021 January | 29 | 18 | 47 |
| 2020 December | 35 | 10 | 45 |
| 2020 November | 23 | 12 | 35 |
| 2020 October | 14 | 17 | 31 |
| 2020 September | 47 | 8 | 55 |
| 2020 August | 11 | 8 | 19 |
| 2020 July | 44 | 6 | 50 |
| 2020 June | 22 | 7 | 29 |
| 2020 May | 23 | 9 | 32 |
| 2020 April | 23 | 10 | 33 |
| 2020 March | 32 | 19 | 51 |
| 2020 February | 26 | 28 | 54 |
| 2020 January | 18 | 6 | 24 |
| 2019 December | 26 | 8 | 34 |
| 2019 November | 21 | 7 | 28 |
| 2019 October | 15 | 5 | 20 |
| 2019 September | 7 | 12 | 19 |
| 2019 August | 35 | 6 | 41 |
| 2019 July | 26 | 11 | 37 |
| 2019 June | 15 | 14 | 29 |
| 2019 May | 29 | 7 | 36 |
| 2019 April | 20 | 12 | 32 |
| 2019 March | 29 | 22 | 51 |
| 2019 February | 16 | 5 | 21 |
| 2019 January | 8 | 8 | 16 |
| 2018 December | 21 | 9 | 30 |
| 2018 November | 31 | 9 | 40 |
| 2018 October | 58 | 7 | 65 |
| 2018 September | 21 | 10 | 31 |
| 2018 August | 26 | 4 | 30 |
| 2018 July | 10 | 2 | 12 |
| 2018 June | 16 | 2 | 18 |
| 2018 May | 28 | 7 | 35 |
| 2018 April | 12 | 5 | 17 |
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