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Small randomized trials have demonstrated that radial access reduces access site complications compared to a femoral approach. The objective of this meta-analysis was to determine if radial access reduces major bleeding and as a result can reduce death and ischemic events compared to femoral access. MEDLINE, EMBASE, and CENTRAL were searched from 1980 to April 2008. Relevant conference abstracts from 2005 to April 2008 were searched. Randomized trials comparing radial versus femoral access coronary angiography or intervention that reported major bleeding, death, myocardial infarction, and procedural or fluoroscopy time were included. A fixed-effects model was used with a random effects for sensitivity analysis. Radial access reduced major bleeding by 73% compared to femoral access (0.05% vs 2.3%, OR 0.27 [95% CI 0.16, 0.45], P < .001). There was a trend for reductions in the composite of death, myocardial infarction, or stroke (2.5% vs 3.8%, OR 0.71 [95% CI 0.49-1.01], P = .058) as well as death (1.2% vs 1.8% OR 0.74 [95% CI 0.42-1.30], P = .29). There was a trend for higher rate of inability to the cross lesion with wire, balloon, or stent during percutaneous coronary intervention with radial access (4.7% vs 3.4% OR 1.29 [95% CI 0.87, 1.94], P = .21). Radial access reduced hospital stay by 0.4 days (95% CI 0.2-0.5, P = .0001). Radial access reduced major bleeding and there was a corresponding trend for reduction in ischemic events compared to femoral access. Large randomized trials are needed to confirm the benefit of radial access on death and ischemic events.

A comprehensive international approach to ACAD treatment requires increased research funding, the development of novel treatments, and investment in early detection methods. The focus of management of coronary artery disease needs to shift from the late stages of the disease, coronary artery obstruction and resultant ischaemia and infarction, towards strategies aimed at early prevention, regression, and cure of atherosclerosis ACAD should be seen as a lifetime continuum from early life through to older age Practical and pragmatic research must be promoted and conducted by stakeholders that is inclusive of routine health care using decentralised and adaptive platforms of interventions that allow a greater proportion of diverse patients to be randomised within clinical trials with lifelong follow-up New therapies to eradicate atherosclerosis must be developed The eradication of atherosclerosis is possible with transformative research A global standard of data collection and dissemination to inform population-based decision making in ACAD should be established

Key Points Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel disease Whether patients with STEMI and multivessel disease should receive percutaneous coronary intervention (PCI) of only the culprit vessel or complete revascularization, either in a simultaneous or staged approach, remains uncertain Increasing evidence from randomized controlled trials suggests that multivessel PCI is safe or even beneficial in selected patients, compared with culprit vessel-only PCI Results from adequately-powered randomized controlled trials are still needed to determine the optimal reperfusion strategy in patients with STEMI and multivessel disease The optimal reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease is still uncertain. In this Review, Mehran and colleagues discuss the available evidence on the different treatment options for patients with STEMI and multivessel disease, highlighting current guideline recommendations and providing future directions on reperfusion strategies in these patients. Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel disease. The optimal reperfusion strategy in these patients is still uncertain. Whether percutaneous coronary intervention (PCI) of only the culprit vessel or a strategy of complete revascularization, either in a simultaneous or staged multivessel PCI approach, should be performed remains unclear. Although a large number of observational studies have mostly shown worse clinical outcomes associated with a multivessel PCI approach, increasing evidence from randomized controlled trials suggests that multivessel PCI is safe, while reducing the need for revascularization in selected patients, compared with culprit vessel-only PCI. However, adequately-powered studies are still needed to determine the best treatment strategy in patients with STEMI and multivessel disease, particularly to demonstrate a reduction in the hard end point of death or myocardial infarction. In this Review, we provide a comprehensive summary of current evidence on the different treatment options for patients with STEMI and multivessel disease, highlighting current guideline recommendations and providing future directions on reperfusion strategies in these patients.

Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72–1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28–0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38–0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76–1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43–1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28–0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13–0·71; p=0·006). Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10 064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87–1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76–1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10–2·51], p=0·015). Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.

Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.

Patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease who undergo primary percutaneous coronary intervention (PCI) are most commonly treated with PCI to the culprit lesion only. Whether a strategy of complete revascularization in these patients is superior is unknown. We performed a meta-analysis comparing the benefits and risks of routine culprit-only PCI vs multivessel PCI in STEMI. MEDLINE, EMBASE, ISI Web of Science, and The Cochrane Register of Controlled Trials were searched from 1996 to January 2011. Relevant conference abstracts were searched from January 2002 to January 2011. Studies included STEMI with multivessel disease receiving primary PCI. The primary end point was long-term mortality. Data were combined using a fixed-effects model. Of 507 citations, 26 studies (3 randomized, 23 nonrandomized; 46,324 patients, 7886 multivessel PCI and 38,438 culprit-only PCI) were included. There was no significant difference in hospital mortality with multivessel PCI vs culprit-only PCI (odds ratio [OR] 1.11, 95% CI 0.98-1.25, P = .10 [randomized OR 0.24, 95% CI 0.06-0.91, P = .04; nonrandomized OR 1.12, 95% CI 1.00-1.27, P = .06]). However, if multivessel PCI during index catheterization was performed, hospital mortality was increased (OR 1.35, 95% CI 1.19-1.54, P < .001). When multivessel PCI was performed as a staged procedure, hospital mortality was lower (OR 0.35, 95% CI 0.21-0.59; P < .001; P interaction < .001). Reduced long-term mortality (OR 0.74, 95% CI 0.65-0.85, P < .001[randomized OR 0.61, 95% CI 0.28-1.33, P = .22; nonrandomized OR 0.75, 95% CI 0.65-0.86, P < .001]) and repeat PCI (OR 0.65; 95% 0.46-0.90, P = .01[randomized OR 0.31, 95% CI 0.17-0.57, P < .001; nonrandomized OR 0.88, 95% CI 0.59-1.31, P = .54]) were observed with multivessel PCI. Overall, staged multivessel PCI improved short- and long-term survival and reduced repeat PCI. Still, large randomized trials are required to confirm the benefits of staged multivessel PCI in STEMI.

In a randomized trial, 1059 patients with an acute myocardial infarction with ST-segment elevation presented to hospitals that did not have the capability of performing percutaneous coronary intervention (PCI) and received fibrinolysis. They were then assigned to either immediate transfer to a PCI center for catheterization or transfer only if fibrinolysis failed. The immediate-transfer strategy was associated with significantly fewer ischemic complications at 30 days. In patients with an acute myocardial infarction with ST-segment elevation, routine early angioplasty after fibrinolysis was associated with significantly fewer ischemic complications at 30 days. Primary percutaneous coronary intervention (PCI) is an effective treatment for myocardial infarction with ST-segment elevation when it can be performed rapidly. 1 However, primary PCI is performed at less than 25% of acute care hospitals in the United States. 2 , 3 Many patients with myocardial infarction with ST-segment elevation present to hospitals that do not have the capability of performing PCI and therefore cannot undergo PCI within the timelines recommended in the guidelines 4 ; instead, they receive fibrinolysis as the initial reperfusion therapy. Although the proportion of such patients has decreased in recent years, 27.6% of the patients in the National Registry . . .

Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI −0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI −3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI −7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference −0.7%, 95% CI −7.8% to 6.5%). Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573

Older adults with acute MI are a growing population with unique treatment challenges. Shamir Mehta comments on the findings of the FIRE trial comparing complete revascularization with culprit-lesion–only PCI in adults ≥75 years of age. Older patients with acute myocardial infarction are a rapidly growing population that presents unique treatment challenges for the clinician. 1 Such patients usually have more coexisting illnesses and are more likely to have frailty issues than their younger counterparts. They also present more often with high-risk features such as heart failure and shock, along with multivessel and complex coronary artery disease, and they may have more complications from invasive treatment. Despite these factors, early reperfusion of the culprit vessel with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) and an early invasive strategy in patients with . . .