Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure

<div><p>Objective</p><p>Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).</p><p>Methods</p><p>Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.</p><p>Results</p><p>In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; <i>p</i> = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, <i>p</i> = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, <i>p</i> = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, <i>p</i> = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, <i>p</i> = 0.28).</p><p>Conclusion</p><p>Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.</p></div

Study flow chart.

<p>KAMIR, The Korea Acute Myocardial Infarction Registry; MI, myocardial infarction; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention</p

Event-free survival curves.

<p>The Kaplan-Meier curves demonstrate no significant differences between statin and no-statin groups for either 12-month major adverse cardiovascular events (A, overall population; C, propensity-score matched population) or 12-month all cause mortalities (B, overall population; D, propensity-score matched population). MACE, major adverse cardiovascular event; HR, hazard ratio</p

BAY 60–2770 reduces myocardial infarction in a rat IR injury model.

<p>Seven days after reperfusion, the infarct area was visualized using TTC staining from IR-injured and BAY 60–2770 pre-treated hearts (A). Representative TTC images from Nor (n = 10), IR (n = 5), BAY (n = 6) (B). *p < 0.05 between IR and BAY groups. Echocardiographic analysis is shown as percent of EF (C), FS (D), and LVDD (mm, E). *p <0.05, **p <0.005 vs. IR.</p

BAY 60–2770 activates PKG in isolated cardiac tissue.

<p>BAY 60–2770 was perfused at 5 nM or 5 μM for 10 min in a Langendorff system. cGMP (A) and cAMP (B) concentrations in tissue homogenates were measured. Western blot analysis was used to determine VASP phosphorylation at ser239 (C), and the ratio of phospho-VASP to VASP was analyzed (D). PKG activity was examined using the CycLex cGK/PKG Assay (E). All the experiments were performed duplicated or triplicated in 3 animals from each group. *p <0.05, **p <0.005 vs. IR.</p

Echocardiographic analysis.

<p>Echocardiographic analysis.</p

Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism: A randomized controlled crossover trial

<div><p>Objective</p><p>Exploring clinically effective methods to reduce ischemia-reperfusion (IR) injury in humans is critical. Several drugs have shown protective effects, but studies using other interventions have been rare. Electroacupuncture (EA) has induced similar protection in several animal studies but no study has investigated how the effects could be translated and reproduced in humans. This study aimed to explore the potential effect and mechanisms of EA in IR-induced endothelial dysfunction in humans.</p><p>Methods</p><p>This is a prospective, randomized, crossover, sham-controlled trial consisting of two protocols. Protocol 1 was a crossover study to investigate the effect of EA on IR-induced endothelial dysfunction. Twenty healthy volunteers were randomly assigned to EA or sham EA (sham). Flow mediated dilation (FMD) of the brachial artery (BA), nitroglycerin-mediated endothelial independent dilation, blood pressure before and after IR were measured. In protocol 2, seven volunteers were administered COX-2 inhibitor celecoxib (200 mg orally twice daily) for five days. After consumption, volunteers underwent FMD before and after IR identical to protocol 1.</p><p>Results</p><p>In protocol 1, baseline BA diameter, Pre-IR BA diameter and FMD were similar between the two groups (p = NS). After IR, sham group showed significantly blunted FMD (Pre-IR: 11.41 ± 3.10%, Post-IR: 4.49 ± 2.04%, p < 0.001). However, EA protected this blunted FMD (Pre-IR: 10.96 ± 5.30%, Post-IR: 9.47 ± 5.23%, p = NS, p < 0.05 compared with sham EA after IR). In protocol 2, this protective effect was completely abolished by pre-treatment with celecoxib (Pre-IR: 11.05 ± 3.27%; Post-IR: 4.20 ± 1.68%, p = 0.001).</p><p>Conclusion</p><p>EA may prevent IR-induced endothelial dysfunction via a COX-2 dependent mechanism.</p></div

Box plots of the flow-mediated dilatation responses before and after ischemia-reperfusion following administration of celecoxib in the electroacupuncture group (protocol 2).

<p>Box plots of the flow-mediated dilatation responses before and after ischemia-reperfusion following administration of celecoxib in the electroacupuncture group (protocol 2).</p

Results of arterial diameter in protocols 1 and 2.

<p>Results of arterial diameter in protocols 1 and 2.</p

Box plots of the flow-mediated dilatation responses before and after ischemia-reperfusion (protocol 1).

<p>Left: In the sham group, FMD was significantly blunted after IR. Right: Electroacupuncture completely prevented the impairment in endothelium-dependent vasodilation induced by IR. Boxes show interquartile ranges; the lower and upper boundaries of the boxes indicate the 25^th and 75^th percentile levels, respectively, and the horizontal lines within the boxes indicate the median levels. FMD: flow-mediated dilatation, IR: ischemia-reperfusion.</p