Coronary bifurcation lesions treated with simple or complex stenting: 5-year survival from patient-level pooled analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study.

AIMS: Randomized trials of coronary bifurcation stenting have shown better outcomes from a simple (provisional) strategy rather than a complex (planned two-stent) strategy in terms of short-term efficacy and safety. Here, we report the 5-year all-cause mortality based on pooled patient-level data from two large bifurcation coronary stenting trials with similar methodology: the Nordic Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study: old, new, and evolving strategies (BBC ONE). METHODS AND RESULTS: Both multicentre randomized trials compared simple (provisional T-stenting) vs. complex (culotte, crush, and T-stenting) techniques, using drug-eluting stents. We analysed all-cause death at 5 years. Data were collected from phone follow-up, hospital records, and national mortality tracking. Follow-up was complete for 890 out of 913 patients (97%). Both Simple and Complex groups were similar in terms of patient and lesion characteristics. Five-year mortality was lower among patients who underwent a simple strategy rather than a complex strategy [17 patients (3.8%) vs. 31 patients (7.0%); P = 0.04]. CONCLUSION: For coronary bifurcation lesions, a provisional single-stent approach appears to be associated with lower long-term mortality than a systematic dual stenting technique.

Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.

Nonalcoholic fatty liver disease and vascular risk.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, which is strongly associated with obesity and diabetes. The risk of cardiovascular disease is increased in NAFLD and represents the main cause of death in these patients. However, given the shared features between NAFLD, the metabolic syndrome and traditional cardiovascular risk factors, uncertainty exists as to whether NAFLD is an independent risk factor for increased cardiovascular disease. RECENT FINDINGS: Multiple epidemiological and case-control studies now demonstrate that NAFLD is associated with increased vascular risk, independently of conventional cardiometabolic risk factors. Evidence also suggests a graded association between NAFLD severity and increased vascular risk. However, given the heterogeneous disease spectrum of NAFLD, these findings have limitations with respect to accuracy of diagnosis and staging of NAFLD in most studies. SUMMARY: Although accumulating evidence points to NAFLD emerging as a novel cardiovascular risk factor, more research is needed to find suitable noninvasive biomarkers of NAFLD severity to allow better risk-stratification based on cardiovascular outcomes. Furthermore, with no established pharmacological treatment option for NAFLD currently available, any potential treatment must show efficacy not only in slowing liver disease progression, but also in ameliorating adverse cardiovascular outcomes.

Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British Bifurcation Coronary Study: old, new, and evolving strategies.

BACKGROUND: The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. METHODS AND RESULTS: Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64+/-10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach. CONCLUSIONS: When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

Does the Routine Availability of CT-Derived FFR Influence Management of Patients With Stable Chest Pain Compared to CT Angiography Alone?: The FFRCT RIPCORD Study.

OBJECTIVES: This study sought to determine the effect of adding computed tomography-derived fractional flow reserve (FFRCT) data to computed tomography angiographic (CTA) data alone for assessment of lesion severity and patient management in 200 patients with chest pain. BACKGROUND: Invasive and noninvasive tests used in the assessment of patients with angina all have disadvantages. The ideal screening test for patients presenting for the first time with chest pain would describe both coronary anatomy and the presence of ischemia and would be readily accessible, low cost, and noninvasive. METHODS: Two hundred patients with stable chest pain underwent CTA for clinical reasons, and FFRCT was calculated. Three experienced interventional cardiologists assessed the CTA result for each patient and by consensus developed a management plan (optimal medical therapy, percutaneous coronary intervention, coronary artery bypass graft surgery, or more information required). FFRCT data for each vessel were then revealed, and the interventional cardiologists made a second plan by consensus, using the same 4 options. The primary endpoint for the study was the difference between the 2 strategies. RESULTS: Overall, after disclosure of FFRCT data there was a change in the allocated management category on the basis of CTA alone in 72 cases (36%). This difference is explained by a discordance between the CTA- and FFRCT-derived assessments of lesion severity. For example, FFRCT was >0.80 in 13 of 44 vessels (29.5%) graded as having a stenosis >90%. In contrast, FFRCT was ≤0.80 in 17 of 366 vessels (4.6%) graded as having stenosis ≤50%. CONCLUSIONS: This study demonstrates proof of concept that the availability of FFRCT results has a substantial effect on the labeling of significant coronary artery disease and therefore on the management of patients compared to CTA alone. Further studies are needed to determine whether FFRCT has potential as a noninvasive diagnostic and management screening tool for patients with stable chest pain.

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.

Simple or complex stenting for bifurcation coronary lesions: a patient-level pooled-analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study.

BACKGROUND: Controversy persists regarding the correct strategy for bifurcation lesions. Therefore, we combined the patient-level data from 2 large trials with similar methodology: the NORDIC Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study (BBC ONE). METHODS AND RESULTS: Both randomized trials compared simple (provisional T-stenting) versus complex techniques, using drug-eluting stents. In the simple group (n=457), 129 patients had final kissing balloon dilatation in addition to main vessel stenting, and 16 had T-stenting. In the complex group (n=456), 272 underwent crush, 118 culotte, and 59 T-stenting techniques. A composite end point at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of the simple versus 17.3% of the complex group (hazard ratio 1.84 [95% confidence interval 1.28 to 2.66], P=0.001). Procedure duration, contrast, and x-ray dose favored the simple approach. Subgroup analysis revealed similar composite end point results for true bifurcations (n=657, simple 9.2% versus complex 17.3%; hazard ratio 1.90 [95% confidence interval 1.22 to 2.94], P=0.004), wide-angled bifurcations >60 to 70° (n=217, simple 9.6% versus complex 15.7%; hazard ratio 1.67 [ 95% confidence interval 0.78 to 3.62], P=0.186), large (≥2.75 mm) diameter side branches (n=281, simple 10.4% versus complex 20.7%; hazard ratio 2.42 [ 95% confidence interval 1.22 to 4.80], P=0.011), longer length (>5 mm) ostial side branch lesions (n=464, simple 12.1% versus complex 19.1%; hazard ratio 1.71 [95% confidence interval 1.05 to 2.77], P=0.029), or equivalent sized vessels (side branch <0.25 mm smaller than main vessel) (n=108, simple 12.0% versus complex 15.5%; hazard ratio 1.35 [95% confidence interval 0.48 to 3.70], P=0.57). CONCLUSIONS: For bifurcation lesions, a provisional single-stent approach is superior to systematic dual stenting techniques in terms of safety and efficacy. A complex approach does not appear to be beneficial in more anatomically complicated lesions.

Dual antiplatelet therapy in cardiovascular disease: does aspirin increase clinical risk in the presence of potent P2Y12 receptor antagonists?

Aspirin is now widely accepted as the first-line antithrombotic platelet therapy for at-risk individuals. During the last decade or so it has also become established that co-administering antagonists of the ADP receptor P2Y(12) with aspirin further reduces the risk of acute thrombotic events. By the nature of its evolution, this therapeutic approach assumes that P2Y(12) receptor antagonists will be added to aspirin, and this therefore dominates the design of clinical trials. This strategy has resulted in the generation of a large body of clinical evidence showing the benefit of aspirin plus P2Y(12) receptor antagonists, largely from studies with clopidogrel and more recently from those with prasugrel and ticagrelor, but with obvious limitations in terms of residual ischaemic event rates and bleeding complications. It is our hypothesis, however, that when administered in the presence of potent P2Y(12) receptor antagonists, aspirin could actually increase total cardiovascular risk, although this has never been tested in large outcome studies. Clearly, this potentially negative interaction could be of relevance to millions of patients.

Drug-eluting stents for the treatment of in-stent restenosis--'real world' double centre experience in consecutive patients.

OBJECTIVES: We evaluated clinical outcome of consecutive patients with in stent restenosis (ISR) treated with drug-eluting stents (DES) at two intervention centres from April 2002 to April 2004, reflecting 'real world' practice. BACKGROUND: ISR is the major limitation to successful long-term outcome after implantation of bare metal stents during percutaneous coronary intervention (PCI). The optimal strategy for the treatment of ISR has yet to be determined. METHODS: 121 consecutive patients with significant ISR were treated with DES. Sirolimus DES were used in 60 patients and paclitaxel DES in the remainder. All patients were followed up to evaluate the incidence of major adverse cardiac events (MACE), angina class and clinically driven angiography. Data were collected between 7 and 27 months after the procedure (mean follow up of 16.5 months). RESULTS: Overall MACE rate at 16.5 months was 13.2% (16 patients) including 4 deaths (3%). Fifteen (12.3%) patients underwent clinically driven angiography. Eight patients (6.6%) developed ISR within the treated segment, of whom, four underwent further PCI and 4 CABG. Mean Canadian angina class decreased from 2.46+/-0.7 pre-procedure to 0.69+/-0.6 at follow up. All patients achieved an improvement in angina, with 59% being rendered angina free and 87% free of MACE. There were no differences in clinical outcome in those who received a paclitaxel and sirolimus DES. CONCLUSIONS: The use of DES implantation for the treatment of ISR is safe, effective and associated with low recurrence rates in a 'real world' large cohort of patients with a complex mix of anatomical and clinical factors.

Failure to monitor ticlopidine: the case for clopidogrel.

AIM: Ticlopidine remains unlicensed for use in coronary artery stenting. Haematological monitoring at two-weekly intervals of all patients taking ticlopidine is recommended because of the risk of neutropaenia. The authors assessed their ability to monitor a two-week course of ticlopidine given to patients undergoing coronary stenting procedures. METHODS AND RESULTS: One hundred and forty-one unselected consecutive patients undergoing coronary stenting procedures were prescribed ticlopidine 250 mg twice daily for two weeks, in addition to aspirin. Prior to discharge home they and their GPs were given written information outlining the side-effects of ticlopidine and the monitoring procedures required. One hundred and thirty-three patients (94%) completed the full two-week course of ticlopidine; three (2.4%) developed significant neutropaenia (neutrophil count <0.5 x 10(9)/mm(3)). Patient compliance with full blood count monitoring was 85% at two weeks and 80% at four weeks. Two patients (1.4%) suffered subacute stent thrombosis. At six months, there were no deaths, one (0.7%) myocardial infarction and nine patients (6%) requiring target vessel revascularization. CONCLUSION: A two-week course of ticlopidine is well tolerated and does not appear to be associated with an increase in adverse cardiac events. However, even with a dedicated monitoring team, adequate haematological follow-up was achieved in only 80% of patients. The need for a licensed antiplatelet agent which has a lower side-effect profile and does not require haematological monitoring is obvious.