Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study.

BACKGROUND: The CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI. METHODS: The Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist. RESULTS: Patients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8-16 vs. 8.0, 5.5-11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7-37.6] vs. 11.6 % [6.8-18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR. CONCLUSIONS: Of patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR. TRIAL REGISTRATION: ISRCTN70913605 , Registered 24th February 2011.

Infarct Size Following Treatment With Second- Versus Third-Generation P2Y12 Antagonists in Patients With Multivessel Coronary Disease at ST-Segment Elevation Myocardial Infarction in the CvLPRIT Study.

BACKGROUND: Third-generation P2Y12 antagonists (prasugrel and ticagrelor) are recommended in guidelines on ST-segment elevation myocardial infarction. Mechanisms translating their more potent antiplatelet activity into improved clinical outcomes versus the second-generation P2Y12 antagonist clopidogrel are unclear. The aim of this post hoc analysis of the Complete Versus Lesion-Only PRImary PCI Trial-CMR (CvLPRIT-CMR) substudy was to assess whether prasugrel and ticagrelor were associated with reduced infarct size compared with clopidogrel in patients undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: CvLPRIT-CMR was a multicenter, prospective, randomized, open-label, blinded end point trial in 203 ST-segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention with either infarct-related artery-only or complete revascularization. P2Y12 inhibitors were administered according to local guidelines. The primary end point of infarct size on cardiovascular magnetic resonance was not significantly different between the randomized groups. P2Y12 antagonist administration was not randomized. Patients receiving clopidogrel (n=70) compared with those treated with either prasugrel or ticagrelor (n=133) were older (67.8±12 versus 61.5±10 years, P<0.001), more frequently had hypertension (49% versus 29%, P=0.007), and tended to have longer symptom-to-revascularization time (234 versus 177 minutes, P=0.05). Infarct size (median 16.1% [quartiles 1-3, 10.5-27.7%] versus 12.1% [quartiles 1-3, 4.8-20.7%] of left ventricular mass, P=0.013) and microvascular obstruction incidence (65.7% versus 48.9%, P=0.022) were significantly greater in patients receiving clopidogrel. Infarct size remained significantly different after adjustment for important covariates using both generalized linear models (P=0.048) and propensity score matching (P=0.025). CONCLUSIONS: In this analysis of CvLPRIT-CMR, third-generation P2Y12 antagonists were associated with smaller infarct size and lower microvascular obstruction incidence versus the second-generation P2Y12 antagonist clopidogrel for ST-segment elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN70913605.

Complete Versus Lesion-Only Primary PCI: The Randomized Cardiovascular MR CvLPRIT Substudy.

BACKGROUND: Complete revascularization may improve outcomes compared with an infarct-related artery (IRA)-only strategy in patients being treated with primary percutaneous coronary intervention (PPCI) who have multivessel disease presenting with ST-segment elevation myocardial infarction (STEMI). However, there is concern that non-IRA PCI may cause additional non-IRA myocardial infarction (MI). OBJECTIVES: This study sought to determine whether in-hospital complete revascularization was associated with increased total infarct size compared with an IRA-only strategy. METHODS: This multicenter prospective, randomized, open-label, blinded endpoint clinical trial evaluated STEMI patients with multivessel disease having PPCI within 12 h of symptom onset. Patients were randomized to either IRA-only PCI or complete in-hospital revascularization. Contrast-enhanced cardiovascular magnetic resonance (CMR) was performed following PPCI (median day 3) and stress CMR at 9 months. The pre-specified primary endpoint was infarct size on pre-discharge CMR. The study had 80% power to detect a 4% difference in infarct size with 100 patients per group. RESULTS: Of the 296 patients in the main trial, 205 participated in the CMR substudy, and 203 patients (98 complete revascularization and 105 IRA-only) completed the pre-discharge CMR. The groups were well-matched. Total infarct size (median, interquartile range) was similar to IRA-only revascularization: 13.5% (6.2% to 21.9%) versus complete revascularization, 12.6% (7.2% to 22.6%) of left ventricular mass, p = 0.57 (95% confidence interval for difference in geometric means 0.82 to 1.41). The complete revascularization group had an increase in non-IRA MI on the pre-discharge CMR (22 of 98 vs. 11 of 105, p = 0.02). There was no difference in total infarct size or ischemic burden between treatment groups at follow-up CMR. CONCLUSIONS: Multivessel PCI in the setting of STEMI leads to a small increase in CMR-detected non-IRA MI, but total infarct size was not significantly different from an IRA-only revascularization strategy. (Complete Versus Lesion-Only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605).

Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial.

BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤ 3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival.

Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design.

AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. METHODS AND RESULTS: CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. CONCLUSIONS: The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.

Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial.

OBJECTIVE: The acute administration of high-dose erythropoietin (EPO) on reperfusing ischaemic myocardium has been reported to halve myocardial infarct (MI) size in preclinical studies, but its effect in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) remains unknown. We investigated whether high-dose EPO administered as an adjunct to PPCI reduces MI size. DESIGN: Double-blinded, randomised, placebo-controlled. SETTING: Single tertiary cardiac centre. PATIENTS: Fifty-one ST elevation myocardial infarction patients undergoing PPCI. INTERVENTIONS: Patients were randomly assigned to receive either a single intravenous bolus of EPO (50,000 IU) prior to PPCI with a further bolus given 24 h later (n=26) or placebo (n=25). MAIN OUTCOME MEASURES: MI size measured by 24 h area under the curve troponin T and cardiac magnetic resonance imaging performed on day 2 and at 4 months. RESULTS: EPO treatment failed to reduce MI size (troponin T area under the curve: 114.6±78 µg/ml EPO vs 100.8±68 µg/ml placebo; infarct mass by cardiac magnetic resonance: 33±16 g EPO vs 25±16 g placebo; both p>0.05). Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction (82% EPO vs 47% placebo; p=0.02) and significantly increased indexed left ventricular (LV) end-diastolic volumes (84±10 ml/m(2) EPO vs 73±13 ml/m(2) placebo; p=0.003), indexed LV end-systolic volumes (41±9 ml/m(2) EPO vs 35±11 ml/m(2) placebo; p=0.035) and indexed myocardial mass (89±16 g/m(2) EPO vs 79±11 g/m(2) placebo; p=0.03). At 4 months, there were no significant differences between groups. CONCLUSIONS: High-dose EPO administered as an adjunct to PPCI failed to reduce MI size. In fact, EPO treatment was associated with an increased incidence of microvascular obstruction, LV dilatation and increased LV mass. Clinical Trial Registration Information http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4058 Unique Identifier=Study ID 4058.

Optimal reperfusion strategy for acute myocardial infarction.

Primary percutaneous coronary intervention has proved to be a superior intervention strategy for acute myocardial infarction than pre-hospital thrombolysis. Both strategies are being used in the UK in parallel, and time to intervention is crucial with both strategies. The Myocardial Infarction National Audit Project registry is showing a gradual move towards percutaneous coronary intervention as the strategy of choice when available.