Atorvastatin before percutaneous coronary intervention: A systematic review and meta-analysis.

Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

Rationale and design of the RESTORE trial: A multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial to evaluate the effect of Shenfu injection on myocardial injury in STEMI patients after primary PCI.

BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized in a 1:1 fashion to receive either intravenous Shenfu injection (80mL Shenfu injection + 70mL 5% glucose injection) or placebo group (150mL 5% glucose injection) before reperfusion and followed by once a day until 5 days after PPCI. The primary end point is infarct size assessed by cardiac magnetic resonance (CMR) imaging 5±2 days after PPCI. The major secondary end points include enzymatic infarct size, microvascular obstruction, intramyocardial hemorrhage, left ventricular volume and ejection fraction assessed by CMR, as well as cardiovascular events at 30 days. CONCLUSIONS: The RESTORE trial is sufficiently powered to demonstrate the clinical effects of Shenfu injection on myocardial injury in STEMI patients undergoing PPCI in the contemporary era.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Prophylactic Rivaroxaban Therapy for Left Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Anterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear. METHODS: We randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5 mg twice daily for 30 days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30 days. Net clinical adverse events were assessed at 30 days and 180 days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding. RESULTS: The addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30 days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95% CI: 0.01-0.62; P = 0.015; P < 0.001 for superiority). Net clinical adverse events were lower within 30 days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30 days and 180 days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30 days. CONCLUSIONS: Our results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.

Efficacy of Buqi Huoxue Decoction Combined with Cardiac Rehabilitation Nursing after Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction and Its Influence on Prognosis.

Objective: To investigate the efficacy of the application of Buqi Huoxue Decoction combined with cardiac rehabilitation nursing for patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its influence on the prognosis. Methods: 120 STEMI patients undergoing PCI were randomly divided into control group, cardiac care group, traditional Chinese medicine and western medicine group (TCM + WM group), and comprehensive treatment group. The control group was treated with a conventional antiplatelet therapy. On the basis of the control group, the cardiac care group was combined with cardiac care treatment. The TCM + WM group was combined with Buqi Huoxue Decoction, and the comprehensive treatment group was combined with cardiac rehabilitation care and Buqi Huoxue Decoction. The total clinical effective rate, readmission rate, and adverse reaction rate of the four groups were measured. Moreover, the myocardial injury markers (creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), and α-Hydroxybutyrate dehydrogenase (α-HBDH)), vascular endothelial function indexes (endothelin (ET-1) and vascular endothelial growth factor (VEGF)), cardiac function indexes (left ventricular ejection fraction (LVEF), left ventricle shortening rate (LFS), left ventricular end diastolic diameter (LVEDd), and left ventricular end systolic diameter (LVESd)), and QOL quality of life score (appetite, spirit, sleep, fatigue, and daily life) were measured. Results: The total effective rate of comprehensive treatment group was obviously increased versus to the control group and cardiac care group. The CK-MB, cTnI, α-HBDH, ET-1, LVEDd, and LVESd levels and SAS and SDS scores in the four groups were decreased, and VEGF, LVEF, and FS levels and QOL quality of life scores were increased after treatment. Moreover, the comprehensive treatment group has more significant changes than the other three groups. The readmission rate in comprehensive treatment group was significantly lower than the other three groups, and the difference in the incidence of adverse reactions in the four groups was not statistically significant. Conclusion: Buqi Huoxue Decoction combined with cardiac rehabilitation after PCI has a significant clinical effect on STEMI patients with PCI postoperative treatment, which can effectively reduce myocardial injury, improve the patient's cardiac function and vascular endothelial function, and improve the patient's quality of life, which can better improve the prognosis of patients.

Effects of High-Dose Rosuvastatin on Ventricular Remodelling and Cardiac Function in ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: To investigate the effects of high-dose rosuvastatin on ventricular remodelling and cardiac function in ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: From January 2017 to March 2019, the clinical data of 93 patients with STEMI were collected and analysed, with 46 cases in the conventional-dose group (rosuvastatin, 10 mg/d) and 47 cases in the high-dose group (rosuvastatin, 20 mg/d). Blood lipid (TC, TG, LDL-C and HDL-C), serum inflammatory markers (hs-CRP, IL-6, TNF-α and ICAM-1), ventricular remodelling markers (NT-pro BNP, MMP-9, TIMP-4 and Gal-3) and indicators of cardiac function (LVESD, LVESD, LVESV, LVEDV, IVST and LVEF) were collected from all patients at the time of admission and 8 weeks after rosuvastatin treatment. RESULTS: After treatment with rosuvastatin for 8 weeks, compared with those in conventional-dose group, the levels of TC, TG, LDL-C, hs-CRP, IL-6, TNF-α, ICAM-1, NT-pro BNP, MMP-9 and Gal-3 in the high-dose group decreased significantly (P<0.05), while the increase of HDL-C and TIMP-4 levels was more obvious (P<0.05) than that in the conventional-dose group. Moreover, LVEF was significantly higher (P<0.05) and LVESD, LVESD, LVESV, LVEDV and IVST were significantly lower (P< 0.05) after treatment than before treatment in both groups. The improvement of cardiac ultrasound results in the high-dose group was more significant than that in the conventional-dose group (P< 0.05). CONCLUSION: This study suggests that high-dose rosuvastatin was better than conventional-dose rosuvastatin for improving blood lipid metabolism, reducing the inflammatory response, and preventing and treating ventricular remodelling and myocardial fibrosis, indicating that high-dose rosuvastatin had stronger therapeutic effect on STEMI than conventional-dose rosuvastatin.

Metoprolol blunts the time-dependent progression of infarct size.

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

Effects of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).

OBJECTIVE: To conduct a randomized double-blind prospective study to investigate effect of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation AMI after PCI. METHODS: One hundred and ninety-two AMI patients over 60 years old who underwent PCI were randomly divided into six groups: the low atorvastatin group, high atorvastatin group; low rosuvastatin group; high rosuvastatin group; low simvastatin group; high simvastatin group. Demographic data and clinical information as well as coronary angiography parameters were recorded. Plasma levels of CK-MB, BNP, ALT, and TnI were measured at 12 hr, 24 hr, and 1 week after PCI. Major cardiovascular events (MACE) were recorded and analyzed using Kaplan-Meier (K-M) curve. RESULTS: No significant differences were observed in angiographic and procedural characteristics. In all high dose groups, all levels of CK-MB, BNP, ALT, and TnI were significantly lower. However, after 1 week of PCI, only CK-MB, BNP, and TnI showed significant difference between high and low dose groups. Patients in high dose groups had significantly lower rates for surgical or percutaneous intervention, recurrence of angina, and rehospitalization. K-M curve analysis also showed cumulative incidence freedom time of overall MACE in high dose groups was significantly longer. No significant differences were found among different drugs with the same doses. CONCLUSION: Patients with higher doses had lower level of CK-MB, BNP, ALT, and TnI and lower occurrence of MACE after PCI.

Effect of Oral N-Acetylcysteine Supplementation on the Immunity System in Patients with Acute Myocardial Infarction.

BACKGROUND: inflammation, oxidative stress, and fibrosis play important roles after an acute myocardial infarction (AMI) event. The most studied inflammatory biomarker in cardiovascular disease is C-reactive protein (CRP). It has been demonstrated that myeloperoxidase (MPO) and Galectin-3 (Gal-3) have some essential roles on immune system when an AMI event occurs. We aimed to determine the effect of oral N-acetylcysteine (NAC) supplementation at the dose of 600 mg 3 times daily for 3 consecutive days on the immune system of AMI patients. METHODS: our randomized single-blinded experimental study using pre- and post-treatment evaluations was performed at Dr. Moewardi Hospital, Indonesia, from May to August 2018. Thirty-two patients with AMI and ST segment elevation (STEMI) who received fibrinolytic therapy were included. There were 17 patients received standard therapy plus 600 mg oral NAC supplementation every 8 h for 3 days and 15 patients received standard therapy, which served as the control group. High-sensitivity C-reactive protein (HsCRP), MPO, and Gal-3 levels of both groups were evaluated at admission and after 72 h receiving treatment. RESULTS: HsCRP, MPO, and Gal-3 levels between NAC and control groups at admission were not significantly different; while intergroup differences after 72 h of NAC supplementation were significant (p values of HsCRP, MPO, and Gal-3 levels were 0.0001, 0.001, and 0.017, respectively). Furthermore, in the NAC group, HsCRP, MPO, and Gal-3 levels at 72 h after treatment were significantly different from the corresponding levels at admission (p values: 0.0001, 0.0001, and 0.0001, respectively); the control group did not show these differences. There were also significant intergroup differences between the NAC and control groups regarding HsCRP, MPO, and Gal-3 levels (p values: 0.011, 0.022, and 0.014, respectively). CONCLUSION: oral supplementation of 600 mg NAC every 8 h for 72 h can reduce HsCRP, MPO, and Gal-3 levels in AMI patients receiving fibrinolytic therapy. Results of our study will provide more options for supplementation therapy to improve management of IMA patients.

Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study.

OBJECTIVES: This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. BACKGROUND: OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. METHODS: In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. RESULTS: At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 µm to 87.9 ± 38.1 µm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs. CONCLUSIONS: In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

Clinical Use of Digitalis: A State of the Art Review.

The history of digitalis is rich and interesting, with the first use usually attributed to William Withering and his study on the foxglove published in 1785. However, some knowledge of plants with digitalis-like effects used for congestive heart failure (CHF) was in evidence as early as Roman times. The active components of the foxglove (Digitalis purpurea and Digitalis lanata) are classified as cardiac glycosides or cardiotonic steroids and include the well-known digitalis leaf, digitoxin, and digoxin; ouabain is a rapid-acting glycoside usually obtained from Strophanthus gratus. These drugs are potent inhibitors of cellular membrane sodium-potassium adenosine triphosphatase (Na+/K+-ATPase). For most of the twentieth century, digitalis and its derivatives, especially digoxin, were the available standard of care for CHF. However, as the century closed, many doubts, especially regarding safety, were raised about their use as other treatments for CHF, such as decreasing the preload of the left ventricle, were developed. Careful attention is needed to maintain the serum digoxin level at ≤ 1.0 ng/ml because of the very narrow therapeutic window of the medication. Evidence for benefit exists for CHF with reduced ejection fraction (EF), also referred to as heart failure with reduced EF (HFrEF), especially when considering the combination of mortality, morbidity, and decreased hospitalizations. However, the major support for using digoxin is in atrial fibrillation (AF) with a rapid ventricular response when a rate control approach is planned. The strongest support of all for digoxin is for its use in rate control in AF in the presence of a marginal blood pressure, since all other rate control medications contribute to additional hypotension. In summary, these days, digoxin appears to be of most use in HFrEF and in AF with rapid ventricular response for rate control, especially when associated with hypotension. The valuable history of the foxglove continues; it has been modified but not relegated to the garden or the medical history book, as some would advocate.

Inhaled corticosteroid/long-acting bronchodilator treatment mitigates STEMI clinical presentation in COPD patients.

BACKGROUND: Patients with myocardial infarction and concomitant COPD are at increased risk of poor clinical outcomes, including death, as compared to patients without COPD. AIM: To investigate and compare the severity of the clinical presentation of ST-segment elevation myocardial infarction (STEMI) and of the short-(7days) and long-term-(end of follow up) mortality in COPD patients treated with inhaled corticosteroids (ICS)/long-acting bronchodilator (LABD) - either long-acting beta2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) - vs. any other inhaled treatments. METHODS: Data from the REAL (Registro Angioplastiche dell'Emilia-Romagna) Registry were obtained from a large prospective study population of 11,118 patients admitted to hospital for STEMI. RESULTS: From January 2003 to June 2009 we identified 2032 COPD patients admitted to hospital for STEMI. Eight hundred and twenty (40%) COPD patients were on ICS/LABD treatment (of which 55% on ICS/LABA) prior to admission. After adjustment for potential confounding factors, ICS/LABD treatment before STEMI was an independent predictor of reduced risk of pulmonary oedema and cardiogenic shock (OR 0.5, 95%CI 0.3-0.72, p<0.01; OR 0.7, 95%CI 0.4-0.9, p=0.03, respectively). ICS/LABD treatment was associated to reduced 7-days mortality (OR 0.54, 95%CI 0.29-0.98, p=0.045) compared to other inhaled regimens. ICS/LABD-treated did not affect long-term (median 4years) mortality. After hospital discharge, the proportion of ICS/LABD treated patients decreased significantly at 6months and afterwards after the STEMI episode. CONCLUSION: Our data provide preliminary evidence that in COPD patients ICS/LABD treatment reduces the severity of STEMI acute-phase clinical manifestations compared to other inhaled treatments.

High-dose atorvastatin versus moderate dose on early vascular protection after ST-elevation myocardial infarction.

BACKGROUND AND AIM: Clinical benefits of early high-dose statin therapy after acute coronary syndromes are widely known; however, there is poor evidence on the specific setting of ST-elevation myocardial infarction (STEMI) and dose-dependent effects of this therapy on endothelial function and inflammatory biomarkers in the most vulnerable phase after acute coronary syndromes: the postdischarge period. In our study, we compared the short-term effects of high (80 mg) vs moderate doses of atorvastatin (20 mg) in patients with STEMI undergoing primary percutaneous coronary intervention on endothelial function and vascular inflammation. The aim of our study was the evaluation of dose-dependent short-term effects. SUBJECTS AND METHODS: We enrolled 52 patients within 48 hours of a STEMI to atorvastatin 80 mg (n=26) or 20 mg (n=26). Every patient underwent endothelial function evaluation by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) index on the first day and 1 month after the STEMI. At the same time, we measured lipid profile and serum levels of high-sensitivity CRP, IL6, TNFα, and oxidized LDL. RESULTS: After 1 month of therapy, we observed differences in high-sensitivity CRP levels (0.04±0.02 mg/dL vs 0.36±0.3 mg/dL, P=0.001), IL6 (1.12±0.93 pg/mL vs 3.13±2.84 pg/mL, P=0.03), and improvement in RH-PAT index (1.96±0.16 vs 1.72±0.19, P=0.002) in the group treated with high-dose vs moderate-dose atorvastatin. There was no significant difference in levels of TNFα or oxidized LDL with atorvastatin 20 mg, while there was a reduction in these variables in the group treated with atorvastatin 80 mg. We observed a correlation between high-sensitivity polymerase chain reaction and RH-PAT index on the 30th day after STEMI (r=0.5, P=0.001). CONCLUSION: Higher dose statin therapy in patients with STEMI undergoing primary percutaneous coronary intervention showed early greater vascular protective effects that moderate dose.

Cardioprotective effect of Malva sylvestris L. in myocardial ischemic/reprefused rats.

PURPOSE: The present investigation evaluated the cardioprotective effect of Malva sylvestris L. (MS) on myocardial ischemic/reperfusion (MI/R) in rats. METHODS: All animals were divided into four groups: the sham operated group, ischemia/reperfusion group (MI/R), and the MS (250 and 500mg/kg) treated groups, who received MS 250 and 500mg/kg intragastrically for 15 consecutive days, respectively. At the end of the protocol, concentrations of aspartate transaminase (AST), creatine kinase-MB fraction (CK-MB) and lactate dehydrogenase (LDH) were estimated in serum and the concentrations of other parameters, such as C-reactive protein, macrophage inflammatory protein 1 alpha (MIP-1α), and nitric oxide (NO) were also estimated in the blood. Tissue homogenate concentrations of inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interlukin-1ß (IL-1ß), IL-10 and IL-6 as well as oxidative stress parameters, such as lipid peroxidation, catalase, and superoxide dismutase were estimated in MI/R rats. RESULT: Significant decreases (p<0.01) in AST, LDH, and CK-MB levels were observed in the MS-treated group compared with those in the MI/R group. C-reactive protein and MIP-1α levels decreased in the MS-treated group compared with those in the MI/R group. Plasma NO level was significantly enhanced in the MS-treated group than in the MI/R group. Moreover, treatment with MS significantly reduced TNF-α, IL-1ß, and IL-6 levels and increased IL-10 levels in the MS group compared with the MI/R group. Treatment with MS also attenuated the altered oxidative stress parameters in MI/R rats. CONCLUSION: The present results indicate the cardioprotective effects of MS of reducing oxidative stress and the inflammatory response in MI/R rats.

High versus low dose statin therapy in Indian patients with acute ST-segment elevation myocardial infarction undergoing thrombolysis.

OBJECTIVES: This study sought to compare high dose versus low dose statin therapy in Indian patients with ST-segment elevation myocardial infarction (STEMI) undergoing thrombolysis. BACKGROUND: Randomized trials have demonstrated that statin treatment reduced major adverse cardiac events (MACEs) in patients with stable angina pectoris and acute coronary syndrome. However, randomized studies of statin therapy in Indian patients with STEMI are scarce. METHODS: Of 1859 patients with acute STEMI, 1027 eligible patients were randomized to 80-mg (n=512) or 10-mg (n=515) atorvastatin. Primary end point was 30-day incidence of MACE (death from any cause, myocardial infarction, NSTE-ACS requiring readmission, ischemia driven revascularization, and stroke). Secondary end points included individual components of primary end point and ST-segment resolution at 90min after thrombolysis. RESULTS: Two groups did not differ in primary endpoints of MACEs (8.79% in high dose vs 9.32% in low dose atorvastatin group, OR=0.938, 95% CI=0.612-1.436, P=0.764). With 80mg atorvastatin, there was insignificant reduction in rate of reinfarction, revascularization and death. Stroke and readmission for NSTE-ACS increased in 80mg atrovastatin group, but was not statistically significant. ST-segment resolution was significantly higher in 80-mg atorvastatin arm (45.90% vs. 37.67%; p=0.008). Myalgia was more in 80mg statin group (18.06% vs 7.57%, p=0.0001). CONCLUSIONS: High-dose atorvastatin did not show significant difference of MACEs in STEMI patients undergoing thrombolysis but showed significant improvement in immediate coronary flow depicted by ST-segment resolution. This benefit of high dose statin is to be weighed against greater myalgia, drug discontinuation and cost in Indian patients.

Timely Reperfusion in Stroke and Myocardial Infarction Is Not Correlated: An Opportunity for Better Coordination of Acute Care.

BACKGROUND: Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment-elevation myocardial infarction (STEMI). The degree to which hospital performance is correlated on emergent STEMI and AIS care is unknown. Primary objective of this study was to determine whether there was a positive correlation between hospital performance on door-to-balloon (D2B) time for STEMI and door-to-needle (DTN) time for AIS, with and without controlling for patient and hospital differences. METHODS AND RESULTS: Prospective study of all hospitals in both Get With The Guidelines-Stroke and Get With The Guidelines-Coronary Artery Disease from 2006 to 2009 and treating ≥10 patients. We compared hospital-level DTN time and D2B time using Spearman rank correlation coefficients and hierarchical linear regression modeling. There were 43 hospitals with 1976 AIS and 59 823 STEMI patients. Hospitals' DTN times for AIS did not correlate with D2B times for STEMI (ρ=-0.09; P=0.55). There was no correlation between hospitals' proportion of eligible patients treated within target time windows for AIS and STEMI (median DTN time <60 minutes: 21% [interquartile range, 11-30]; median D2B time <90 minutes: 68% [interquartile range, 62-79]; ρ=-0.14; P=0.36). The lack of correlation between hospitals' DTN and D2B times persisted after risk adjustment. We also correlated hospitals' DTN time and D2B time data from 2013 to 2014 using Get With The Guidelines (DTN time) and Hospital Compare (D2B time). From 2013 to 2014, hospitals' DTN time performance in Get With The Guidelines was not correlated with D2B time performance in Hospital Compare (n=546 hospitals). CONCLUSIONS: We found no correlation between hospitals' observed or risk-adjusted DTN and D2B times. Opportunities exist to improve hospitals' performance of time-critical care processes for AIS and STEMI in a coordinated approach.

Effects of combination therapy of statin and N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Acute myocardial infarction (AMI) is a risk factor for contrast-induced nephropathy (CIN). We investigated whether pretreatment with statin, N-acetylcysteine (NAC) and sodium bicarbonate (NaHCO3) reduces the risk of CIN. METHODS: We conducted a prospective trial and enrolled a total of 334 ST-segment elevation myocardial infarction (STEMI) patients. Patients were divided into four groups: Group I (statin 40mg), Group II (statin 80mg), Group III (statin 80mg plus NAC 1200mg) and Group IV (regimen of group III plus NaHCO3 154mEq/L). CIN was defined as ≥25% or ≥0.5mg/dL increase in serum creatinine from the baseline within the 72h after PCI. RESULTS: CIN occurred in 72 (21.6%) patients. The incidence of CIN was the lowest in the group III (14.3%), and multivariate analysis showed the lower incidence of CIN in group III compared to Group I [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.13-0.64, p=0.002]. Admission hyperglycemia [(AHG)>198mg/dL] (OR 2.20, 95% Cl 1.20-3.68, p=0.011) and the use of intra-aortic balloon pump (IABP) (OR 4.20, 95% CI 1.38-12.78, p=0.016) were independent predictors for CIN. The CIN (OR 9.00, 95% CI 1.30-62.06, p=0.026) was an independent predictor for in-hospital mortality. CONCLUSIONS: Combination of high-dose statin plus NAC was associated with lower incidence of CIN in patients with STEMI who underwent primary PCI compared to statin only.

Mangafodipir as a cardioprotective adjunct to reperfusion therapy: a feasibility study in patients with ST-segment elevation myocardial infarction.

AIMS: The aim of the present study was to examine the feasibility of applying the catalytic antioxidant mangafodipir [MnDPDP, manganese (Mn) dipyridoxyl diphosphate] as a cardioprotective adjunct to primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation (STE) myocardial infarction (STEMI). Both MnDPDP and a metabolite (Mn dipyridoxyl ethyldiamine) possess properties as mitochondrial superoxide dismutase mimetics and iron chelators, and combat oxidative stress in various tissues and conditions. METHODS AND RESULTS: The study tested MnDPDP (n = 10) vs. saline placebo (n = 10), given as a brief intravenous (i.v.) infusion prior to balloon inflation during pPCI in patients with STEMI. Mangafodipir was well tolerated and did not affect heart rate or blood pressure. Despite longer ischaemic time (205 vs. 144 min, P = 0.019) in the MnDPDP group, plasma biomarker releases were identical for the two groups. With placebo vs. MnDPDP, mean STE resolutions were 69.8 vs. 81.9% (P = 0.224) at 6 h and 73.1 vs. 84.3% (P = 0.077) at 48 h. Cardiac magnetic resonance revealed mean infarct sizes of 32.5 vs. 26.2% (P = 0.406) and mean left ventricular (LV) ejection fractions of 41.8 vs. 47.7% (P = 0.617) with placebo vs. MnDPDP. More LV thrombi were detected in placebo hearts (5 of 8) than MnDPDP-treated hearts (1 of 10; P = 0.011). CONCLUSIONS: Mangafodipir is a safe drug for use as an adjunct to reperfusion therapy. A tendency to benefit of MnDPDP needs confirmation in a larger population. The study revealed important information for the design of a Phase II trial.