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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Growing recognition of the heterogeneity of clinical conditions associated with non-ST-elevation myocardial infarction &#40;NSTEMI&#41; has led to intense research on this entity in a search for the best therapeutic options&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">NSTEMI is associated with higher rates of morbidity and mortality than other acute coronary syndromes &#40;ACS&#41;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> and thus warrants thorough study&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The article by Gonzales-Cambeiro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> published in this issue of the <span class="elsevierStyleItalic">Journal</span> on the mortality benefit of long-term angiotensin-converting enzyme inhibitors or angiotensin receptor blockers &#40;ACEIs&#47;ARBs&#41; after successful percutaneous coronary intervention &#40;PCI&#41; in NSTEMI gives this question a new impulse&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The authors of this observational study showed that in NSTEMI patients successfully treated by PCI&#44; the use of ACEIs&#47;ARBs was associated with a lower risk of four-year mortality&#46; However&#44; the high rate of multivessel disease&#44; lack of information on the proportion of patients who underwent complete revascularization and on how soon PCI was performed&#44; and the fact that the population was not stratified according to clinical severity by criteria such as the GRACE score&#44; highlight certain variables that require particular attention in the assessment and treatment of this heterogeneous patient group&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The benefit of ACEIs&#47;ARBs as an adjuvant therapy for ST-elevation myocardial infarction &#40;STEMI&#41; has long been known&#44;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">3&#8211;6</span></a> but conclusive evidence of their value in NSTEMI is lacking&#46; The article by Gonzales-Cambeiro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> appears to demonstrate a reduction in all-cause mortality with ACEI&#47;ARB use in this subgroup of ACS patients&#46; But was it the drug treatment alone that was responsible for this benefit&#63; In our opinion there are three factors that could have biased these results&#58; &#40;1&#41; the timing of PCI&#59; &#40;2&#41; the completeness of revascularization&#59; and &#40;3&#41; the duration of antiplatelet therapy&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Let us now examine these three factors in detail&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#40;1&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Analysis of the timing for invasive assessment of patients with non-ST-elevation ACS shows that the best strategy is always to perform it as soon as possible&#44;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">7&#44;8</span></a> although in certain subgroups this is even more important&#44; as timing can have significant effects on medium- and long-term outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> Earlier intervention is associated with lower mortality&#46; Patients with higher clinical risk scores are known to benefit more from an earlier approach&#44;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">7&#8211;9</span></a> but it is these patients who frequently have to wait longer before intervention&#44; since their circumstances are often less favorable in terms of the safety and efficacy of invasive procedures&#46; Among such factors are female gender&#44; advanced age&#44; renal dysfunction and anemia&#46; It can be a temptation not to treat these patients&#44; because they are &#8220;too sick&#8221; or because the risk of intervention is too high&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Consequently&#44; many of the results obtained in groups of consecutive patients do not accurately reflect the effect on the timing of intervention of the combined effect of these different factors&#44; however clearly each of the individual variables involved has been identified and described&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Subgroup analysis according to risk scores and timing of intervention could help to determine the influence of different therapeutic strategies &#40;pharmacological or otherwise&#41; on clinical outcome and prognosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#40;2&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">The second factor relates to the proportion of patients with multivessel disease who did not undergo complete revascularization&#44; which the article states was almost half of both study groups&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The importance of complete revascularization &#40;immediate or staged&#41; in reducing the need for repeat revascularization is accepted in STEMI patients&#44; but there is no solid evidence that this also applies to mortality and reinfarction&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">10&#44;11</span></a> Its impact on mortality as a single endpoint is unknown&#44; although it has been included in combined endpoints&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The available evidence also supports complete revascularization in NSTEMI&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a> and recent studies recommend that revascularization be performed in a single procedure&#44; since a staged approach is associated with a higher rate of major adverse cardiovascular and cerebrovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The study by Gonzales-Cambeiro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> does not specify the number of patients who underwent complete revascularization&#44; and this may have biased the results&#46; Patients who would benefit most from complete revascularization are often those in whom it is more difficult to perform&#44; because of three-vessel disease&#44; diffuse disease&#44; left main disease&#44; left ventricular dysfunction&#44; and similar conditions&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Thus&#44; as in the question of the timing of intervention&#44; the greatest difficulty in deciding the most appropriate approach in accordance with the state of the art comes when dealing with the most complex types of patient&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#40;3&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Thirdly&#44; it is important to discuss antiplatelet therapy&#44; which is of great importance in patients with NSTEMI undergoing PCI&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We know that most patients in Gonzales-Cambeiro et al&#46;&#8217;s study<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> were under dual antiplatelet therapy with aspirin and clopidogrel at hospital discharge&#44; but they do not state what proportion continued this therapy for the full 12 months stipulated&#44; how many discontinued it before&#44; or how many continued it afterwards&#46; The first two cases can affect outcome&#44; while recent data<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a> indicate that the third could have a positive impact on prognosis in selected patients with high ischemic risk and low bleeding risk&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Finally&#44; another factor can have a significant impact on prognosis&#58; left ventricular function&#46; Most of the population in Gonzales-Cambeiro et al&#46;&#8217;s study<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> had preserved &#40;&#62;50&#37;&#41; mean left ventricular ejection fraction &#40;LVEF&#41;&#44; with only a small proportion having LVEF &#8804;40&#37; &#40;less than 10&#37; after propensity score matching&#41;&#46; It thus appears that the mortality rates observed &#40;around 16&#37; in the untreated groups and almost 12&#37; in the treated group&#41;&#44; lower than the 22&#37; predicted&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> may be related to the proportion with preserved LVEF&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Despite this&#44; ACEIs&#47;ARBs would be expected to be less effective in patients with preserved LVEF&#46; However&#44; we are not told the percentage of patients who suffered reinfarction or target lesion failure during follow-up&#44; and it is thus impossible to know how the above factors might have affected the results&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">There is still considerable uncertainty concerning the treatment of NSTEMI&#44; due mainly to the heterogeneity of its presentation and clinical course&#46; Its poor prognosis means that improvements in treatment are particularly important&#46; By three years after the index event&#44; around 22&#37; of NSTEMI patients have died&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> This figure gives us pause for thought&#46;</p></li></ul></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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