Gregory Pavlides

Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization

BACKGROUND The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial

BACKGROUND Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. METHODS TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide. Patients with non-ST-elevation acute coronary syndrome who were selected for management without [corrected] revascularisation were randomly assigned to clopidogrel or prasugrel.The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months. In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not. FINDINGS 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis. 3085 (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan-Meier analysis (281/3085 [12·8%] vs 480/4158 [16·5%], adjusted hazard ratio [HR] 0·63, 95% CI 0·53-0·75; p<0·0001). The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10·7%] vs 159/1561 [14·9%], HR 0·77, 95% CI 0·61-0·98; p=0·032) but did not differ between groups in patients who did not have angiography (242/2096 [16·3%] vs 238/2062 [16·7%], HR 1·01, 0·84-1·20; p=0·94; pinteraction=0·08). Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort. INTERPRETATION Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention. FUNDING Daiichi Sankyo, Eli Lilly.

Comparison of Fractional Flow Reserve Assessment With Demand Stress Myocardial Contrast Echocardiography in Angiographically Intermediate Coronary Stenoses.

Background—Real-time myocardial contrast echocardiography (RTMCE) directly measures capillary flow (CBF), which in turn is a major regulator of coronary flow and resistance during demand or hyperemic stress. Although fractional flow reserve (FFR) was developed to assess the physiological relevance of an epicardial stenosis, it assumes maximal microvascular vasodilation and minimal resistance during vasodilator stress. Therefore, we sought to determine the relationship between CBF assessed with RTMCE during stress echocardiography and FFR in intermediate coronary lesions. Methods and Results—Sixty-seven vessels with 50% to 80% diameter stenoses by quantitative coronary angiography in 58 consecutive patients were examined with FFR and RTMCE (mean age, 60±13 years). RTMCE was performed using an incremental dobutamine (n=32) or exercise (n=26) stress protocol, and myocardial perfusion was assessed using a continuous infusion of ultrasound contrast. The presence or absence of inducible perfusion defects and wall motion abnormalities were correlated with FFR. Mean percent diameter stenosis was 60±9%. Eighteen stenoses (27%) had an FFR ⩽ 0.8. Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28 of the 49 stenoses (57%) that were FFR had abnormal CBF, and 24 (49%) had abnormal wall motion in the corresponding coronary artery territory during stress echocardiography. Conclusions—In a significant percentage of intermediate stenoses with normal FFR values, CBF during demand stress is reduced, resulting in myocardial ischemia.

Ostial coronary occlusion during TAVR in bicuspid aortic valve, should we redefine what is a safe ostial height?

Article history: Received 10 February 2016 Accepted 19 March 2016 Available online 24 March 2016 by the bicuspid leaflets (Fig. 2, A). We were able to wire down the RCA and performed percutaneous transluminal coronary angioplasty (PTCA) followed by stenting with a drug eluting stent with restoration of normal flow (Fig. 2, B). As the TEE showed more than mild perivalvular leak, we performed TAVR post-dilatationwith significant improvement. The patients post-operative course was complicated with a complete

Role of Invasive Functional Assessment in Surgical Revascularization of Coronary Artery Disease

In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography. The data on the role of invasive functional assessment in guiding surgical revascularization are limited. In this review, we discuss the diagnostic and prognostic significance of invasive functional assessment in patients considered for coronary artery bypass grafting. In addition, we critically discuss ongoing and future clinical trials on the role of invasive functional assessment in surgical revascularization.

Prevalence and Predictive Value of Microvascular Flow Abnormalities after Successful Contemporary Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction

Background Although microvascular flow abnormalities have been observed following epicardial recanalization in acute ST‐segment elevation myocardial infarction (STEMI), the prevalence and severity of these abnormalities in the current era of rapid percutaneous coronary intervention (PCI) has not been evaluated. The objective of this study was to assess microvascular perfusion (MVP) following successful primary PCI in patients with STEMI and how it affects clinical outcome. Methods In this single‐center, retrospective study, 170 patients who successfully underwent emergent PCI for STEMI were assessed using real‐time myocardial contrast echocardiography using a continuous infusion of intravenous commercial microbubbles (3% Definity). Three patterns of myocardial contrast replenishment were observed following intermittent high–mechanical index impulses: infarct zone replenishment within 4 sec (normal MVP), delays in contrast replenishment but normal plateau intensity (delayed MVP [dMVP]), and both delays in replenishment and reduced plateau intensity (microvascular obstruction [MVO]). Changes in left ventricular ejection fraction at 6 months and clinical event rate at 12 months (death, recurrent infarction, need for defibrillator placement, or heart failure admission) were compared. Results Normal MVP was seen in 62 patients (36%), dMVP in 49 (29%), and MVO in 59 (35%). Left anterior descending coronary artery infarct location was the only parameter independently associated with dMVP or MVO, independent of age, cardiac risk factors, door‐to‐dilation time, pre‐PCI Thrombolysis In Myocardial Infarction flow grade, and thrombus burden. A dMVP pattern had a similar reduction in left ventricular ejection fraction as MVO at hospital discharge but had recovery of left ventricular ejection fraction at 6 months and a greater than fourfold lower event rate than the MVO group (P < .001). Conclusions MVO and dMVP are frequently seen following contemporary successful PCI for STEMI, especially following left anterior descending coronary artery infarction. Despite a similar area at risk, a dMVP pattern has better functional recovery and clinical outcome than MVO. HighlightsThe frequency of MVO was analyzed in acute STEMI patients treated with primary PCI.Despite successful angiographic recanalization, 35% of patients still had MVO.MVO was associated with a fourfold higher risk for adverse events at follow up.Patients with reduced microvascular flow, but not MVO, had a favorable outcome.The severity of microvascular flow abnormality may risk‐stratify STEMI patients.

Acute right ventricular myocardial infarction

ABSTRACT Introduction: Acute right ventricular myocardial infarction (RVMI) is observed in 30–50% of patients presenting with inferior wall myocardial infarction (MI) and, occasionally, with anterior wall MI. The clinical consequences vary from no hemodynamic compromise to severe hypotension and cardiogenic shock depending on the extent of RV ischemia. Areas covered: The pathophysiological mechanisms, diagnostic steps, and novel therapeutic approaches of acute RVMI are described. Expert commentary: Diagnosis of acute RVMI is based on physical examination, cardiac biomarkers, electrocardiography, and coronary angiography, whereas noninvasive imaging modalities (echocardiography, cardiac magnetic resonance imaging) play a complementary role. Early revascularization, percutaneous or pharmacological, represents key step in the management of RMVI. Maintenance of reasonable heart rate and atrioventricular synchrony is essential to sustain adequate cardiac output in these patients. When conventional treatment is not successful, mechanical circulatory support, including right ventricle assist devices, percutaneous cardiopulmonary support, and intra-aortic balloon pump, might be considered. The prognosis associated with RVMI is worse in the short term, compared to non-RVMI, but those patients who survive hospitalization have a relatively good long-term prognosis.

Instantaneous wave-free ratio versus fractional flow reserve

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Acute Coronary Syndromes in Patients with Atrial Fibrillation and Heart Failure. Could Novel Oral Anticoagulants be the Solution of the Optimal Antithrombotic Therapy Puzzle

The patients experiencing an acute coronary event are exposed to increased risk of thromboembolic events. That risk becomes substantially greater when AF fibrillation and heart failure are present as well. Dual antiplatelet therapy remains the gold standard in the treatment of patients with ACS. The combination of an oral anticoagulant agent with dual antiplatelet therapy is proven to be more effective in prevention of further antithrombotic events but is followed by increased risks of clinically significant bleeding thus it is not suggested in the treatment of ACS. However, it has been proven beneficial in patients with AF who present with an acute coronary episode. NOACs have proved to be at least as effective as vitamin K antagonists in protecting patients with atrial fibrillation from thromboembolic events without increased risk of major bleeding. However, only data on the effectiveness of NOACS in patients with ACS and AF have been quite contradictory. Even more, the data on the effect of NOACS in patients with concomitant HF and AF who present with an acute coronary event is almost lacking from current bibliography. In this review, we attempt to describe the available data of the use of NOACS in patients with AF and HF who experience an ACS and to address the need for further studies in this area.