<div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" paraid="1255219910" paraeid="{dc1b85f4-d663-4cd9-bae2-5b976b3a2d93}{10}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Patients with ST-segment myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI)<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">don’t</span><span> </span><span class="NormalTextRun SCXW52456907 BCX0">benefit</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>from</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>receiving</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>intravenous nicorandil</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>during intervention</span><span class="NormalTextRun SCXW52456907 BCX0">, the randomized CLEAN trial shows. </span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" paraid="2129699436" paraeid="{dc1b85f4-d663-4cd9-bae2-5b976b3a2d93}{12}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Intravenous nicorandil during<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">PCI<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">doesn’t</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>significantly change the rates of death from cardiac causes, nonfatal heart attack, target vessel revascularization (TVR</span><span class="NormalTextRun SCXW52456907 BCX0">)</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>or unplanned hospitalization 1-year</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>post-procedure.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" paraid="1268500146" paraeid="{dc1b85f4-d663-4cd9-bae2-5b976b3a2d93}{14}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">The investigators — led by Dong Huang, MD, and Hongxian Wu, MD, both<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">from</span><span> </span><span class="NormalTextRun SCXW52456907 BCX0">the Shanghai</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>Institute of Cardiovascular Diseases, China</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>—<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">hypothesized that nicorandil, a potassium-channel opener, may lower the chances of reperfusion injur</span><span class="NormalTextRun SCXW52456907 BCX0">y and microvascular obstruction in STEMI patients.</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>They published their data online in the<span> </span></span></span><em><span class="NormalTextRun SCXW52456907 BCX0">Journal of the American College of Cardiology</span></em><span class="NormalTextRun SCXW52456907 BCX0">.</span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="914461391" paraeid="{4cb434f9-a4a8-4604-9699-edece67c6c90}{99}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">PCI is routinely performed in STEMI patients, but little is known about preventing coronary microvascular obstruction (CMVO) in this<span> </span></span><span class="NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW52456907 BCX0">patient</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>population.<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">Previous</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>clinical trials on the use of nicorandil are small —<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">such as<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">the<span> </span></span></span><a class="Hyperlink SCXW52456907 BCX0" href="https://www.sciencedirect.com/science/article/abs/pii/S0140673607616341" target="_blank" rel="noreferrer noopener"><span data-contrast="none" xml:lang="EN-US" lang="EN-US" class="TextRun Underlined SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0" data-ccp-charstyle="Hyperlink">J</span><span class="NormalTextRun SCXW52456907 BCX0" data-ccp-charstyle="Hyperlink">-WIND</span></span></a><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>trial</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(results<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">published in<span> </span></span></span><span class="NormalTextRun SCXW52456907 BCX0">The Lancet</span><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>in 2007</span><span class="NormalTextRun SCXW52456907 BCX0">)</span></span><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span> </span><span class="NormalTextRun SCXW52456907 BCX0">— but data show nicorandil may improve clinical outcomes in STEMI patients.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" paraid="771172956" paraeid="{dc1b85f4-d663-4cd9-bae2-5b976b3a2d93}{16}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun EmptyTextRun SCXW52456907 BCX0"></span><a class="Hyperlink SCXW52456907 BCX0" href="https://clinicaltrials.gov/study/NCT04665648?id%3DNCT04665648%26amp;amp;viewType%3DCard%26amp;amp;rank%3D1=" target="_blank" rel="noreferrer noopener"><span class="NormalTextRun SCXW52456907 BCX0" data-ccp-charstyle="Hyperlink">CLEAN</span></a><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(Clinical Efficacy and<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW52456907 BCX0">sAfety</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>of intravenous Nicorandil)</span><span class="NormalTextRun SCXW52456907 BCX0">, a multicenter, randomized, double-blind, placebo-controlled trial, took place across 49 medical centers in China between January 2021 and December 2023. </span><span class="NormalTextRun SCXW52456907 BCX0">Participants were included if they were 18-80 years old and had STEMI within 12 hours of experiencing symptoms.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="701467680" paraeid="{fb2a812e-506a-4aa6-a0f5-01ee6a36e154}{80}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Patients<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">in the study<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">were randomized 1:1 to receive intravenous nicorandil (6 mg bolus before reperfusion plus<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">6 mg</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>per hour of infusion for 48 hours) or placebo<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">(matching distribution strategy)</span><span class="NormalTextRun SCXW52456907 BCX0">, and all participants were not allowed to take nicorandil orally during the follow-up period.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="910259048" paraeid="{79ca5011-6d55-485a-910d-16a7bda67ee1}{215}"><span class="NormalTextRun SCXW52456907 BCX0">A composite of cardiovascular death, nonfatal myocardial infarction (MI), TVR or unplanned hospitalization due to heart failure (HF) at 1-year was the primary outcome in the CLEAN trial.</span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="9524644" paraeid="{4266f426-6a4f-4345-948a-07e85d7ba666}{1}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">The trial enrolled and randomized 748 patients to nicorandil<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">(mean age=58.2 years, 85.7% men, mean body mass index [BMI]=25.1)<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">and 755 patients to the placebo group</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(mean age=58.6 years, 83.0% men, mean BMI=25.0)</span><span class="NormalTextRun SCXW52456907 BCX0">.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="613715886" paraeid="{06311b7b-8868-4b4f-a2e7-431921eb18a3}{125}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Participants’ most c</span><span class="NormalTextRun SCXW52456907 BCX0">ommon comorbidities</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(nicorandil, placebo)</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>included hypertension</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(56.1%, 55.1%)</span><span class="NormalTextRun SCXW52456907 BCX0">, type II diabetes</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(32.0%, 30</span><span class="NormalTextRun SCXW52456907 BCX0">.</span><span class="NormalTextRun SCXW52456907 BCX0">2%</span><span class="NormalTextRun SCXW52456907 BCX0">)</span><span> </span><span class="NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW52456907 BCX0">and</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>current tobacco-smoking</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>(50.7%, 51.0%)</span><span class="NormalTextRun SCXW52456907 BCX0">.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="222766018" paraeid="{9c485fe0-15fd-4799-9907-ebff4ff34292}{16}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">At 1-year follow-up, 13.1% of nicorandil patients and 13.1% of placebo patients experienced aa<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">component</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>of the primary outcome,<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">indicating</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>no significant differences in safety or efficacy between the two groups (p=</span><span class="NormalTextRun SCXW52456907 BCX0">0.3429).</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="2102004954" paraeid="{893755a7-a356-4df1-b217-c687709542e4}{118}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Each<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">component</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>of the primary outcome was individually assessed as a secondary outcome. No significant between-group differences were<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">observed</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>in the secondary outcomes analysis,<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">but both groups had<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">minor<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">reductions in cardiac death and TVR</span><span class="NormalTextRun SCXW52456907 BCX0"> </span><span class="NormalTextRun SCXW52456907 BCX0">(cardiovascular death hazard ratio [HR]=0.515, 95% confidence interval [CI</span><span class="NormalTextRun SCXW52456907 BCX0">]=0.269-0.983; TVR HR=0.322, 95% CI=0.143-0.727)</span><span class="NormalTextRun SCXW52456907 BCX0">.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="768859864" paraeid="{e7d7d5b0-faaf-4470-b064-d195478ba6df}{83}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Both groups also had similar rates of adverse events.</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>Prespecified subgroup analyses<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">demonstrated</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>no interactions between baseline characteristics and outcomes of the trial.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="622629752" paraeid="{c93e7564-a4fc-4506-af56-29d7d816ff14}{193}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">A key limitation of the CLEAN trial is the timing of the trial itself. Data collection took place during the COVID-19 pandemic. The investigators noted that this did not influence data integrity and completeness, as remote monitoring was used a</span><span class="NormalTextRun SCXW52456907 BCX0">cross sites.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="1215658616" paraeid="{8b0d73a6-9e91-4671-a4d7-e94bd6571a2b}{181}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Additional limitations include the generalizability of the study, as it was solely conducted in China; coronary microvascular resistance (CMR) imaging was not routinely performed; the investigators did not utilize a</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>core laboratory for angiographic or electrocardiogram endpoints; secondary analyses were not adjusted for various comparisons;<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">data were missing</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>for N-term</span><span class="NormalTextRun SCXW52456907 BCX0">inal pro-B-type natriuretic peptide</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>and echocardiography outcomes; and including TVR in the primary outcome may have influenced the neutral results of the study.</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="614404157" paraeid="{4f9c52d4-debf-4847-ad2d-2adf2e38f492}{119}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">The CLEAN trial<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">demonstrated</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>that intravenous nicorandil<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">does not provide<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">additional</span><span class="NormalTextRun SCXW52456907 BCX0"><span> </span>clinical<span> </span></span><span class="NormalTextRun SCXW52456907 BCX0">benefits</span><span> </span><span class="NormalTextRun SCXW52456907 BCX0">in patients with STEMI undergoing PCI, compared with placebo.<span> </span></span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="2041784360" paraeid="{4cb434f9-a4a8-4604-9699-edece67c6c90}{57}"><strong><span class="NormalTextRun SCXW52456907 BCX0">Source:</span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="2056640599" paraeid="{c5859641-83d0-4dd5-9c51-5f1f1447f9d7}{216}"><span class="NormalTextRun SCXW52456907 BCX0">Huang D, Wu H, Lu Y, et al. Intravenous nicorandil in patients with ST-segment elevation myocardial infarction undergoing primary PCI: The CLEAN randomized clinical trial.<span> </span></span><em><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">J Am Coll </span><span class="NormalTextRun SpellingErrorV2Themed SCXW52456907 BCX0">Cardiol</span></span></em><span class="NormalTextRun SCXW52456907 BCX0">. 2026 August 12 (Article in Press).</span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></p> </div> <div class="OutlineElement Ltr SCXW52456907 BCX0"> <p class="Paragraph SCXW52456907 BCX0" lang="EN-US" paraid="1932123246" paraeid="{1fb3aeed-e41a-431a-b5f6-26234652029e}{68}"><strong><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun MacChromeBold SCXW52456907 BCX0"><span class="NormalTextRun SCXW52456907 BCX0">Image Credit: </span><span class="NormalTextRun SpellingErrorV2Themed SCXW52456907 BCX0">mojo_cp</span><span class="NormalTextRun SCXW52456907 BCX0"> – stock.adobe.com</span></span><span class="EOP Selected SCXW52456907 BCX0" data-ccp-props="{"134233117":false,"134233118":false,"201341983":0,"335551550":1,"335551620":1,"335559685":0,"335559737":0,"335559738":0,"335559739":160,"335559740":279}"> </span></strong></p> </div>