COMPLETE Trial OCT Substudy: Non-Culprit Lesions with Vulnerable Plaque Morphology Found In Half of Patients with STEMI and Multivessel Disease

The results of the COMPLETE Optical Coherence Tomography Substudy were presented by Dr. Natalia Pinilla-Echeverri at the American Heart Association 2019 meeting. The substudy found that in patients with an ST-elevation myocardial infarction and multivessel coronary artery disease, half of the patients had a non-culprit lesion with vulnerable plaque morphology.

The COMPLETE trial previously demonstrated that routine angiography guided staged a percutaneous coronary intervention (PCI) of non-culprit lesions reduced the composite endpoint of cardiovascular death or myocardial infarction by 26%. However, whether the benefit of routine PCI of non-culprit lesions is, as a result, the non-culprit lesions having characteristics that were consistent with a vulnerable plaque is not known. Optical coherence tomography (OCT) is a form of intracoronary imaging that is able to identify vulnerable plaques. OCT is able to recognize thin cap fibroadenoma (TCFA), an indicator of a vulnerable plaque that is at risk of rupturing. The investigators wanted to identify the prevalence of TCFA in obstructive compared to non-obstructive non-culprit lesions.

In the COMPLETE trial, patients with a STEMI and multivessel disease who underwent successful PCI of the culprit lesion were randomized to either routine staged PCI of all suitable non-culprit lesions with the goal of complete revascularization regardless of whether there were clinical symptoms or evidence of ischemia or culprit-lesion revascularization only. Patients were deemed to have multivessel disease if they had angiographically significant non-culprit vessel disease of a vessel that was at least 2.5mm in diameter. A lesion was considered angiographically significant if it had at least 70% stenosis of the vessel diameter or 50-69% stenosis with a fractional flow reserve of less than 0.8. In this substudy, STEMI patients with stenosis of at least one non-culprit vessel with more than 70% stenosis that was suitable for OCT were identified. After randomization, multivessel OCT imaging was performed on vessels with non-culprit lesions that underwent PCI, additional vessels with or without target non-culprit lesions for PCI, and STEMI vessels with segments more than 50mm that were unstented.

A total of 93 patients and 425 lesions were included in this substudy. The baseline characteristics in the main study were similar to this imaging study. The average age was 61.3, 82.8% were male, 12.9% had diabetes, 64% had 1 residual diseased vessel and 36% had two or more residual diseased vessels. The non-culprit lesions were classified according to whether they had significant stenosis and whether they had a TCFA. Of the lesions with greater than 70% obstruction, 58 (38.7%) had a TCFA and 92 did not. Of the lesions with less than 70% obstruction, 74 (23.2%) had a TCFA and 201 did not. When assessing the prevalence of TCFAs per patient, the investigators found that half of the patients with TCFA had an obstructive non-culprit lesion that contained vulnerable plaque.

In an interview with Dr. Arzu Kalayci, Dr. Pinilla-Echeverri discussed the implications of the study. She said, “this is very important in the STEMI population because we believe the STEMI population has higher rates of future cardiovascular events. IT may all be related to the inflammatory response that is behind [this]. This is telling us that these patients had a definitely higher risk because they had vulnerable plaques far from the culprit segment. This is reassuring that acute coronary syndrome implies a diffuse pathophysiology with vulnerable plaque not only in the culprit segment but in places far away from the culprit lesion. These results support the findings in the COMPLETE trial.” However, this study does have its limitations. The substudy was observational and is affected by confounding and bias. The substudy was not powered to link clinical evens to morphology. Regardless, the findings of this study could potentially explain the benefit of routine PCI of obstructive non-culprit lesions in patients with STEMI and multivessel disease.

Click here to view the study slides.

Click here to listen to Dr. Kalayci and Dr. Pinilla-Echeverri.

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.

ISCHEMIA CKD: No Difference In Outcomes Between Medical and Invasive Approaches to Ischemia in Patients with End Stage Renal Disease

The results of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches – Chronic Kidney Disease were presented by Dr. Sripal Bangalore at the American Heart Association 2019 meeting. Dr. Bangalore and his team showed that in patients with moderate ischemia and end-stage renal disease, an initial invasive strategy with catheterization and possibly percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) did not lead to an improvement in clinical outcomes.

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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

DAPA-HF: Dapagliflozin Improves Heart Failure Outcomes in Patients With HFrEF Regardless of Diabetic Status

Dr. John McMurray presented the results of the DAPA-HF trial at the American Heart Association 2019 Meeting. The study, which was published in the New England Journal of Medicine, showed that dapagliflozin, an SGLT-2 inhibitor, can potentially be used to treat heart failure with reduced ejection fraction (HFrEF) in patients with and without type 2 diabetes.

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BETonMACE: Trial Shows Novel BET Protein Inhibitor Apabetalone Is Safe and Could Potentially Be Used To Improve Cardiovascular Outcomes

During the American Heart Association 2019 meeting, Dr. Kosh Ray presented the results of the BETonMACE trial. Dr. Ray and his teams showed apabetalone, a BET protein inhibitor was safe and well-tolerated and could potentially be used to reduce the risk of major adverse cardiovascular events (MACE).

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Phase 1 Trial Shows RUC-4 (A Novel Subcutaneous GPIIb/IIIa Inhibitor) Achieves Safe, Rapid and Effective Platelet Inhibition

The results of a phase 1 trial that evaluated the safety of RUC-4, a novel subcutaneous GPIIb/IIIa inhibitor, were presented by Dr. Dean Kereiakes at the American Heart Association 2019 meeting. The study showed that in healthy volunteers and subjects on aspirin with stable coronary artery disease (CAD), RUC-4 provided rapid and high-grade platelet inhibition that resolved within 2 hours.

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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.

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ISCHEMIA: No Reduction in Cardiovascular Event in Patients with Stable Coronary Artery Disease Who Undergo Invasive Therapy

The results of the ISCHEMIA trial were presented by Dr. Judith Hochman at the American Heart Association 2019 meeting. The study demonstrated that in stable patients, there was no difference in cardiac event rates in patients who underwent invasive procedures as compared to those who were managed conservatively.

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COLCOT: Colchicine Reduced Cardiovascular Events in Patients with Recent Myocardial Infarction

The results of the COLCOT trial were presented by Dr. Jean-Claude Tardif at the American Heart Association 2019 conference and published in the New England Journal of Medicine. The study showed that in patients with a recent myocardial infarction, colchicine led to a significantly lower risk of ischemic cardiovascular events than placebo.

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Enhanced Vasospasm And Reduced Vasodilator Function Linked To Worse Outcomes In Patients With Non-Obstructive Coronary Arteries In patients with vasospastic angina, high IMR (≥ 18) correlated with increased incidence of major adverse cardiovascular events

A single center study that included 187 patients who presented with angina-like chest pain and nonobstructive coronary arteries on diagnostic angiography, has shown that co-existence of high microvascular resistance index (IMR) and vasospasm is associated with an increased incidence of major adverse cardiovascular events (MACE – defined as cardiac death, nonfatal myocardial infarction, and hospitalizations). Rho-kinase activation thought to underlie mechanisms leading to high IMR in this patient population.
The 187 patients included in the study had a median follow-up of 893 days. Continue reading

Mouse Study Shows High Saturated Fat Diet May Promote Arrhythmias By Activating NADPH Oxidase 2 Dietary Saturated Fat Promotes Arrythmia by Activating NADPH Oxidase2

In an original article written by Leroy C. Joseph et al, it was found the molecular mechanisms of cardiac metabolism to arrhythmia and NAPDH Oxidase2(NOX2) deletion or pharmacological inhibition can prevent arrhythmia caused due to the ingestion of a high saturated fat diet. The results of the study were published in Circulation: Arrhythmia and Electrophysiology. Continue reading

Study Demonstrates Decreasing Medical Therapy Utilization Among Veteran Patients Treated with PCI Over 5 Years A cohort analysis of medication utility and the association between medication utility and MACE

11/6/2019- Joe X. Xie et. al recently published the results of a Veterans cohort study in Circulation. They were able to show a meaningful decline in the rate of important 4 post-PCI medication utilization (beta-blockers, statins, ACEI/ARB, and P2Y12 inhibitor) among Veterans in a follow-up period of 5 years, with the highest decrease in medication utility after the first year of PCI. They also showed continuous consumption of all these medications is associated with a decreased rate of major adverse cardiac events (MACE).

Medical therapy utilization and association between medical therapy and MACE were the study’s primary outcomes. They included 57,900 patients who underwent staged PCI, defined as PCI on a non-STEMI lesion and if the PCI is being performed on a segment that had not been treated before. They excluded patients who were in the setting of cardiogenic shock, those who did not survive the index hospitalization following PCI, patients who obtain all their medications outside the VA, or those with a documented allergy to any of the four medication classes of interest. The majority were white elderly males, they usually used tobacco (62%), and most of them had comorbidities including hypertension (89.4%), diabetes mellitus (47.1%), and hyperlipidemia (88.4%) as main comorbidity factors. The mean duration of follow-up was 5 years. During an average follow-up of 5 years, a total of 24,364 patients experienced MACE which was defined as the first occurrence of all-cause death, rehospitalization for MI, rehospitalization for stroke, or repeat revascularization throughout the follow-up. They found a statistically significant correlation between death reduction and stroke rehospitalization and medication utility up to 5 years after PCI but not rehospitalization for MI. In their analysis, Xie and his colleagues calculated that less than 60% of the patients undergoing PCI receive all 4 medication classes at discharge (β-blocker, statin, ACE inhibitor/ARB, and P2Y12 inhibitor), with a gradual decrease of medication utility for approximately 20% of statins, β-blockers, and ACE inhibitor/ARBs over the subsequent 5 years post-PCI. This rate was reported to decrease to approximately 70% for the use of P2Y12 inhibitors.

Previously, there was little evidence available concerning the rate of long-term use of medical therapy following PCI. It has been shown that there is a suboptimal medication adherence by patients 6-12 months after PCI. Xie et al. also showed that all the described medication therapy classes were associated with decrease in the MACE risk even at 5 years post-PCI. They also noticed that all 4 classes of medications were associated with decreased MACE rates.

The data shown by Xie et al. can help with understanding patient compliance to medications, and to implement methods to increase the compliance. Further studies for non-VA patients are recommended.

Registry Data Demonstrates No Difference in Survival Between Extracorporeal CPR and Conventional CPR in Patients With Out of Hospital Cardiac Arrest

A study led by Dr. Wulfran Bougouin published in the European Heart Journal analyzed out of hospital cardiac arrests (OHCA) and compared outcomes in patients who received and did not receive extracorporeal cardiopulmonary resuscitation (CPR). Dr. Bougouin and his team found that 4% of OHCAs were treated with extracorporeal-CPR and this was not associated with an increased hospital survival rate.

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