Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study

Kinlay, Scott; Schwartz, Gregory G.; Olsson, Anders; Rifai, Nader; Sasiela, William J.; Szarek, Michael; Ganz, Patricia A.; Libby, Peter

doi:10.1161/01.cir.0000136588.62638.5e

Cited by 149 publications

(52 citation statements)

References 33 publications

(38 reference statements)

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“…High levels of sCD40L had been shown to be associated with cardiovascular events 12,13 and identified patients with acute coronary syndromes (ACS) at heightened risk of death and recurrent myocardial infarction (MI). 14 Our data were consistent with previous studies 5,15 that sCD40L was significantly higher in patients with UAP, and levels of sCD40L were higher in coronary circulation than in system circulation.…”

Section: Discussionmentioning

confidence: 99%

Transcoronary concentration gradient of sCD40L and hsCRP in patients with coronary heart disease

Wang

Tan

et al. 2007

Clinical Cardiology

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SummaryBackground: Recent studies indicated that local inflammation played a pivotal role in the pathogenesis of coronary heart disease. Soluble CD40 ligand (sCD40L) and hsC-reactive protein (hsCRP) are important inflammatory mediators. However, whether they can reflect local coronary inflammation is unclear.Hypothesis: We hypothesized that transcoronary concentration gradient of sCD40L could reflect local inflammation in patients with coronary heart disease (CHD) more reliably.Methods: Forty subjects were divided into unstable angina pectoris (UAP) group (n = 20), stable angina pectoris (SAP) group (n = 10), and controls (n = 10). Blood samples were collected from the coronary sinus (CS), aortic root (AO), and femoral vein (FV). The coronary circulation was expressed as CS-AO difference, while system circulation was expressed as FV-AO difference. sCD40L and hs-CRP were measured.

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Section: Discussionmentioning

confidence: 99%

Transcoronary concentration gradient of sCD40L and hsCRP in patients with coronary heart disease

Wang

Tan

et al. 2007

Clinical Cardiology

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“…29 The acute anti-inflammatory effects of statins resulting in plaque stabilization are thought to be the basis for prevention of recurrent vascular events in coronary artery disease. 30,31 The effects of statin therapy on infarct size have been previously reported in retrospective studies. 32,33 In one study, a smaller infarct volume was associated with the interaction between statin pretreatment and the presence of diabetes in patients with stroke.…”

Section: Discussionmentioning

confidence: 98%

Statin Therapy Does Not Affect the Radiographic and Clinical Profile of Patients with TIA and Minor Stroke

Asdaghi

Coulter²,

Modi³

et al. 2015

AJNR Am J Neuroradiol

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“…11 Indeed, when Brigham investigators examined samples for CD40 ligand, a proinflammatory mediator, from subjects enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study, they demonstrated that not only were particularly high levels of CD40 ligand associated with recurrent events, but, notably, the excess risk attributed to them was eliminated by the high-dose (80-mg/d) atorvastatin therapy. 12 Furthermore, in patients with acute or impending stroke, data from mouse models of cerebral ischemia show that acute termination of statin treatment results in a rapid loss of protection independent of lipid lowering. 13 Thus, further prospective studies of those who are unable to continue with statin therapy in acute settings for both coronary and cerebral ischemia are needed.…”

Section: See P 2333mentioning

confidence: 99%

Stopping Statins

Stone

2004

Circulation

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H ow can you safely enroll subjects on statin therapy with coronary heart disease (CHD) for a clinical trial that randomizes subjects to this therapy only after a suitable dietary lead-in/drug-washout period? This vexing problem confronted the investigators of the Treating to New Targets (TNT) study. 1 Their concern was prompted by the alarming report of Heeschen and colleagues, 2 who found a nearly 3-fold increase (2.93 [95% CI, 1.64 to 6.27]; Pϭ0.005) in the risk of death and nonfatal myocardial infarction (MI) in those in whom statin drugs were not continued after admission with an acute coronary syndrome. 2 A follow-up letter to the editor revealed that this was a statistical rather than a clinical phenomenon. In approximately one third of the study population, missing data for troponin T at baseline were excluded from the multivariate model used to adjust for possible confounding factors. A reanalysis showed only a nonsignificant trend toward greater cardiac risk with abrupt statin discontinuation. 3 The authors concluded that there was insufficient evidence to support their original conclusions. Nonetheless, this raised questions about potential deleterious effects of stopping statins in both acute and chronic CHD patients. See p 2333Fortunately, the authors of the TNT trial seized on the opportunity afforded to them by their study design to see if there were significant adverse effects from statin withdrawal in their study of subjects with stable CHD. 4 TNT is an ongoing, large-scale trial with a double-blind parallel group design comparing 2 doses of atorvastatin (10 and 80 mg once daily) to determine clinical end point differences. This large effort enrolled 16 619 in a dietary lead-in/drug-washout period and, of these, 15 432 eligible subjects began treatment with atorvastatin 10 mg/d on an open-label basis. Of the participants who entered the dietary lead-in/drug-washout period, 57% were currently receiving statin therapy and had their statin therapy discontinued. When event rates for CHD were carefully examined, it was determined that statins could be safely withdrawn, as the 30-day Kaplan-Meier event rate of 0.20% for the combined end point of CHD death, nonfatal MI, resuscitated cardiac arrest, and fatal or nonfatal stroke during the washout phase was not significantly different from the 0.26% rate seen in the open-label phase with the participants on atorvastatin 10 mg/d.Was this concern biologically plausible? Statins are the popular name given to a class of cholesterol-lowering drugs known as HMG-CoA reductase inhibitors. 5 They inhibit the enzyme HMG-CoA reductase, which is critically involved in the rate-limiting step of cholesterol biosynthesis in the liver. Within weeks of starting treatment with a statin, there is a decreased rate of cholesterol synthesis that leads to an upregulation of low-density lipoprotein (LDL) receptors and a resultant fall in blood cholesterol levels. LDL cholesterol (LDL-c) and intermediate-density lipoprotein levels fall in a dose-dependent fashion (available stat...

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Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study

Cited by 149 publications

References 33 publications

Transcoronary concentration gradient of sCD40L and hsCRP in patients with coronary heart disease

Transcoronary concentration gradient of sCD40L and hsCRP in patients with coronary heart disease

Statin Therapy Does Not Affect the Radiographic and Clinical Profile of Patients with TIA and Minor Stroke

Stopping Statins

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