Trial Showed Implementation of High Sensitivity Cardiac Troponin Assays and Universal Definition of Myocardial Infarction Recommendations in Patients with Suspected Acute Coronary Syndrome Increased Diagnosis Rate Without a Change in Outcomes

A recent study by Dr. Chapman, published in Circulation, showed that implementation of high sensitivity cardiac troponin (hs-cTn) and the fourth universal definition of myocardial infarction (MI) increased the identification of patients at risk for cardiovascular and non-cardiovascular events, but failed to improve the outcomes. This study warrants the importance of seeking new strategies to improve outcomes in patients with type 2 MI and myocardial injury. Continue reading →

Randomized Trial Shows Prasugrel Associated with Better Endothelial Function and Stronger Platelet Inhibition as Compared to Clopidogrel or Ticagrelor in Patients with ACS Who Undergo Stenting

In a recent randomized, three-arm, parallel, blinded study by Dr. Schnorbus, published in European Heart Journal, prasugrel was associated with improved endothelial function, more potent platelet inhibition, and decreased plasma interleukin (IL)-6 levels in patients undergoing stent placement for acute coronary syndrome (ACS) compared to ticagrelor and clopidogrel. These effects were observed in patients who received prasugrel 2 hours before stenting.

Coronary artery stenting has been associated with impaired coronary and peripheral endothelial function as well as an inflammatory response leading to the release of mediators and subsequent platelet aggregation. These phenomena are associated with in-stent restenosis as well as adverse prognostic outcomes after percutaneous coronary intervention (PCI). Platelet inhibitors, such as P2Y12 receptor inhibitors, are administered prior and after coronary interventions to address these adverse effects. However, previous studies have suggested that differences exist among P2Y12 inhibitors in terms of their efficacy.

In a prospective, single-center study, a total of 90 patients with unstable angina or non-ST elevation myocardial infarction (NSTEMI) undergoing coronary stenting were randomized to receive a single dose of clopidogrel (600mg), prasugrel (60mg), or ticagrelor (180mg) followed by chronic therapy with the same drug. Patients with elevated c reactive protein (CRP), infective or inflammatory disorders, personal history of prior coronary interventions, impaired hepatic/renal function, those with heart failure, and those with ST elevation myocardial infarction (STEMI) were excluded from the study. The primary endpoint of the study was the change in flow-mediated dilation (FMD) of the conduit artery over a period of 1 day, 1 week, and 1 month after PCI. Secondary endpoints were the effect of study medications on macrovascular and microvascular function, platelet aggregation, and inflammatory stress.

The study showed that antiplatelet therapy immediately before stenting was associated with improved FMD without a significant difference among study medications. On the first follow-up after PCI and later follow-up visits, prasugrel was associated with a stronger platelet reactivity inhibition and improved endothelial function. These effects were limited to those who received prasugrel before catheterization. Prasugrel platelet inhibitory effect was more obvious in NSETMI patients than in those with unstable angina. Prasugrel therapy also led to a more pronounced decrease in IL-6 levels. According to the author, “when administered pre-PCI, prasugrel, but not the other agents, limits stent-induced endothelial dysfunction and inflammation in ACS.” This study is limited by its small size and future studies are needed to further confirm these conclusions.

Interim Results of The EVAPORATE Trial Indicate No Change in Low Attenuation Plaque Volume But A Reduction in Total Plaque Volume Following Treatment with Icosapent Ethyl

The interim results of EVAPORATE trial, a study on the effect of Icosapent Ethyl on coronary plaque progression in statin-treated patients with elevated Triglyceride (TG) level (200-499mg/dl), were presented by Dr. Matthew Budoff at the American Heart Association 2019 meeting. Dr. Budoff and his team found that in patients with coronary atherosclerosis treated with statins, the addition of Icosapent Ethyl (Vascepa) was not associated with a change in low attenuation plaque volume but was associated with a decrease in total plaque volume. However, these are preliminary findings and the trial is set for completion at 18 months.

Icosapent Ethyl, a high‐purity eicosapentaenoic acid (EPA) derivative, has been approved as an adjunct to diet for the reduction of TG levels in adults with elevated TG levels. Its utility has been associated with an increase in serum EPA levels, a lower serum TG level as well as a decrease in inflammatory markers. A prior trial investigated the effect of long-term eicosapentaenoic acid (1.8 g/d) on more than 18000 statin-treated patients, in Japan, showed a significant reduction (19%) in the relative risk of major coronary events.

In the EVAPORATE trial, statin-treated patients with coronary atherosclerosis (defined by narrowing≥20% in 1 coronary artery by either invasive angiography or multidetector computed tomography angiography (MDCTA)) and elevated serum TG levels (135-499mg/dl) were enrolled. Exclusion criteria included severe heart failure, hypersensitivity to contrast or fish and renal insufficiency. The primary endpoint of the study was progression rates of low attenuation coronary plaques as measured by MDCTA. The secondary endpoints were the quantitative changes in plaque morphology, inflammatory markers and the relationship between plaque vulnerability and these changes.

A total of 80 individuals participated in the study (40 randomized to receive Icosapent Ethyl and 40 to receive the placebo). Participants were evaluated at baseline, 3 and 9 months of the study. At baseline, each participant underwent a cardiac computed tomography angiography (CCTA) to evaluate plaque morphology and volume as well as its composition. At 9 months, compared to placebo, Icosapent Ethyl slowed low attenuation coronary plaque progression by 21% (p=0.469). Although the primary outcome was statistically insignificant, the study continues until 18 months. Secondary outcomes of the study were promising, including a reduction in total non-calcified plaque volume by 19% (p = 0.01) and a 42% (p <0.0004) reduction in total plaque volume.

In an interview with Dr. C. Michael Gibson, Dr. Budoff discussed the primary findings of the trial. He noted that the increase in serum EPA levels significantly increased in those receiving Icosapent Ethyl and this increase was associated with a coronary plaque regression as well as an anti-inflammatory effect.

This study limited by some points. First, the follow-up duration was shorter than prior studies. Second, the primary endpoint was not statistically significant at the interim time point. The ultimate result of this trial may further define the potential clinical benefits of Icosapent Ethyl on atherosclerotic disorders.

Click here to view the study slides.

Click here to listen to Dr. Budoff and Dr. Gibson discuss the findings of the study.

Intensive LDL Lowering With a Goal of < 70mg/dl Is Superior to Moderate Lowering for Secondary Prevention of Ischemic Stroke Patients 8.5% of patients assigned to the group with intensive LDL lowering suffered from recurrent MACE including recurrent ischemic stroke compared to 10.9% of patients in the modest control approach

A randomized parallel-group trial comparing intensive LDL-C lowering to modest lowering for prevention of major adverse cardiovascular events (MACE) in patients with recent ischemic stroke in the setting of atherosclerosis has shown that an aggressive LDL-C reduction strategy with a goal of < 70mg/dl is superior to modest reduction approach which targets a range of 90-110 mg/dl.

Results of the Treat Stroke to Target Trial (TST trial) which enrolled 2860 patients (32% females) with a median follow-up of 3.5 years were presented by Dr. Amarenco (Department of Neurology and Stroke Center, Bichat Hospital, France) at AHA 2019 and simultaneously published in The New England Journal of Medicine.

Patients with established atherosclerotic cardiovascular disease (ASCVD) and ischemic stroke within the past 3 months or transient ischemic stroke (TIA) within the past 15 days (modified Rankin score of 0-3) were randomized in 1:1 fashion to statin therapy with either a goal LDL-C of < 70 mg/dl (n =1430) or 90-110 mg/dl (n = 1430).

The primary efficacy endpoint of the trial was composite of MACE (nonfatal cerebral infarction or stroke of undetermined origin, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary-artery revascularization, TIA treated with urgent carotid revascularization, or CV death). The primary outcome occurred in 8.5% of patients assigned to the group with intensive LDL lowering compared to 10.9% of patients in the modest control approach (adjusted hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.04). Mean LDL-C levels at baseline were 135 mg/dl for both groups and at 3.5 years for the intensive vs. modest treatment groups were 65 vs. 96 mg/dl (p < 0.05). Secondary outcomes were occurrence of MI, need for urgent revascularization, all-cause mortality, intracranial hemorrhage, and newly diagnosed diabetes mellitus. Rates of intracranial hemorrhage (1.3% vs. 0.9% [p > 0.05]) and new-onset diabetes mellitus (7.2% vs. 5.7% [p > 0.05]) were numerically higher with more aggressive control, but not statistically significant.

The present study highlights the clinical benefit obtained by a tighter control of plasma LDL levels for secondary prevention of stroke. Previously, the SPARCL trial showed that in patients who have had a stroke within the prior one to six months without coronary artery disease, treatment with 80 mg atorvastatin led to a lower incidence of recurrent MACE including fatal and nonfatal strokes. In the Heart Protection Study (HPS), simvastatin 40mg did not show benefit in secondary stroke protection, but in HPS, patients were enrolled after a mean of 4.3 years of having a cerebrovascular accident, whereas the greatest risk for recurrent strokes resides within the first year of suffering from a cerebrovascular accident. Though findings from the current TST trial are in line with the SPARCL trial in terms of reduction of recurrent MACE, the SPARCL trial saw an increase in the incidence of hemorrhagic strokes in the treatment arm, while the present TST clinical trial revealed no rise in hemorrhagic stroke rates in patients despite achieving more aggressive reductions in their serum LDL-C levels.

The authors ask the readers to interpret the results of the TST trial while considering the fact that the study was stopped prematurely due to insufficient funding at 3.5 years and did not reach the goal of 385 events, instead, 277 primary events were recorded for the analysis. In addition, secondary endpoints could not be tested due to the failure of hierarchical clustering of endpoints.

GALILEO-4D: Rivaroxaban-Aspirin Based Anti-Thrombotic Therapy Post-TAVR Protects From Valve Leaflet Motion Abnormalities Rivaroxaban based strategy led to decreased prosthetic valve leaflet thickening and motion reduction following TAVR performed for severe aortic valve stenosis

An expanded analysis of 231 patients from the GALILEO trial comparing rivaroxaban-aspirin based anti-thrombotic therapy with clopidogrel-aspirin based dual anti-platelet therapy post transcatheter aortic valve replacement (TAVR), has shown that the rivaroxaban based regimen protects from valve leaflet motion abnormalities. The rivaroxaban based strategy led to decreased prosthetic valve leaflet thickening and motion reduction following TAVR performed for severe aortic valve stenosis. Continue reading →

GALILEO: Rivaroxaban Based Anti-thrombotic Strategy Associated with Increased Risk of Death or Thromboembolic Events and Bleeding Compared to Antiplatelet Based Strategy in Patients with TAVR

The results of the GALILEO trial were presented by Dr. George Dangas at the American Heart Association 2019 meeting. The trial, which was stopped early, showed that in patients with a successful transcatheter aortic valve replacement (TAVR), a rivaroxaban-based strategy was associated with excessive ischemic and bleeding events.