Usman Baber

Clinical ResearchClinical TrialsChanges in Plaque Lipid Content After Short-Term Intensive Versus Standard Statin Therapy: The YELLOW Trial (Reduction in Yellow Plaque by Aggressive Lipid-Lowering Therapy)

OBJECTIVESnThis study sought to determine the impact of short-term intensive statin therapy on intracoronary plaque lipid content.nnnBACKGROUNDnStatin therapy significantly reduces the risk for thrombotic events. Whether or not these benefits are attributable toxa0reduction in plaque lipid content remains to be properly documented in human obstructive coronary artery disease (CAD).nnnMETHODSnWe randomized 87 patients with multivessel CAD undergoing percutaneous coronary intervention and at least 1 other severely obstructive (fractional flow reserve [FFR]xa0≤0.8) nontarget lesion (NTL) to intensive (rosuvastatin 40xa0mg daily) or standard-of-care lipid-lowering therapy. NTLs were evaluated at baseline and after 7 weeks of therapy with FFR, near-infrared spectroscopy, and intravascular ultrasound. The primary endpoint was the change in lipid-core burden index at the 4-mm maximal segment (LCBI4mm max), wherever this occurred within the lesion.nnnRESULTSnUpon follow-up, median reduction (95% confidence interval) in LCBI4mm max was significantly greater in the intensive versus standard group (-149.1 [-210.9 to -42.9] vs. 2.4 [-36.1 to 44.7]; pxa0= 0.01). Results remained consistent after adjustment forxa0baseline differences in LCBI between groups and use of change in LCBI across the entire lesion as the dependent outcome.nnnCONCLUSIONSnShort-term intensive statin therapy may reduce lipid content in obstructive lesions. These hypothesis-generating findings warrant confirmation in larger studies with longer follow-up. (Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy [YELLOW]); NCT01567826).

Impact of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention on Short- and Long-Term Outcomes Pooled Analysis From the HORIZONS-AMI and ACUITY Trials

Background—Contrast-induced acute kidney injury (CI-AKI), defined as a serum creatinine increase ≥0.5 mg/dL or ≥25% within 72 hours after contrast exposure, is a common complication of procedures requiring contrast media and is associated with increased short- and long-term morbidity and mortality. Few studies describe the effects of CI-AKI in a large-scale acute coronary syndrome population, and the relationship between CI-AKI and bleeding events has not been extensively explored. We sought to evaluate the impact of CI-AKI after percutaneous coronary intervention in patients presenting with acute coronary syndrome. Methods and Results—We pooled patient-level data for 9512 patients from the percutaneous coronary intervention cohorts of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) multicenter randomized trials. Patients were classified according to CI-AKI development, and cardiovascular outcomes at 30 days and 1 year were compared between groups. A total of 1212 patients (12.7%) developed CI-AKI. Patients with CI-AKI were older, with a more extensive comorbidity profile than without CI-AKI. Multivariable analysis confirmed several previously identified predictors of CI-AKI, including diabetes mellitus, contrast volume, age, and baseline hemoglobin. Mortality rates were significantly higher in the CI-AKI group at 30 days (4.9% versus 0.7%; P<0.0001) and 1 year (9.8% versus 2.9%; P<0.0001), as were rates of 1-year myocardial infarction, definite/probable stent thrombosis, target lesion revascularization, and major adverse cardiac events. Major bleeding (13.8% versus 5.4%; hazard ratio, 2.64; 95% confidence interval, 2.21–3.15; P<0.0001) was also higher in patients with CI-AKI. After multivariable adjustment, results were unchanged. Conclusions—CI-AKI after percutaneous coronary intervention in patients presenting with acute coronary syndrome is independently associated with increased risk of short- and long-term ischemic and hemorrhagic events. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and ACUITY (NCT00093158).

Risk for recurrent coronary heart disease and all-cause mortality among individuals with chronic kidney disease compared with diabetes mellitus, metabolic syndrome, and cigarette smokers

BACKGROUNDnLipid-lowering guidelines endorse a low-density lipoprotein cholesterol goal of <100 mg/dL for people with coronary heart disease (CHD). A more stringent threshold of <70 mg/dL is recommended for those with CHD and very high-risk conditions such as diabetes mellitus, metabolic syndrome, or cigarette smoking. Whether chronic kidney disease (CKD) confers a similar risk for recurrent CHD events is unknown.nnnMETHODS AND RESULTSnWe evaluated the risk for recurrent CHD events and all-cause mortality among 3,938 participants ≥45 years with CHD in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Chronic kidney disease was defined by estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by the presence or absence of CKD and any very high-risk condition. Over a median of 4.1 years, the crude incidence (95% CI) of recurrent CHD events were 12.1 (9.0-15.2), 18.9 (15.5-22.3), 35.0 (25.4-44.6), and 34.2 (28.2-40.3) among those without CKD or high-risk conditions; very high-risk conditions alone; and CKD alone and both CKD and very high-risk conditions. After multivariable adjustment, compared with those without CKD or very high-risk conditions, the hazard ratio (95% CI) for recurrent CHD events was 1.45 (1.02-2.05), 2.24 (1.50-3.34), and 2.10 (1.47-2.98) among those with very high-risk conditions alone, CKD alone, and both CKD and very high-risk conditions, respectively. Results were consistent for all-cause mortality.nnnCONCLUSIONSnChronic kidney disease is associated with risk for recurrent CHD events that approximates or is larger than other established very high-risk conditions.

Prognostic Significance of Elevated Baseline Troponin in Patients With Acute Coronary Syndromes and Chronic Kidney Disease Treated With Different Antithrombotic Regimens A Substudy From the ACUITY Trial

Background— Elevation of baseline cardiac troponin in patients presenting with acute coronary syndromes (ACS) confers an adverse prognosis. The prognostic value of troponin elevation in patients with chronic kidney disease (CKD) and ACS is less certain. Methods and Results— In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) trial, 13 819 patients with moderate and high-risk ACS were assigned randomly to receive heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin monotherapy. Among 2179 patients with CKD (creatinine clearance <60 mL/min), baseline troponin elevation was present in 1291 patients (59.2%). Major bleeding and major adverse cardiac events (MACE), including death, myocardial infarction (MI), or unplanned revascularization, were examined according to baseline troponin status and randomization arm. Patients with CKD in whom the baseline troponin level was elevated had significantly higher rates of death, MI, and MACE at 30 days and 1 year compared with CKD patients without elevated baseline troponin. By multivariable analysis, baseline troponin elevation in patients with CKD was an independent predictor of composite death or MI at 30 days (hazard ratio [95% CI]=2.05 [1.48, 2.83], P<0.0001) and 1 year (1.72 [1.36, 2.17], P<0.0001). In CKD patients with baseline troponin elevation, bivalirudin monotherapy compared with heparin plus a GPI significantly reduced the 30-day rates of major bleeding with nonsignificantly different rates of MACE at 30 days and 1 year. Conclusions— In patients with ACS and CKD, baseline troponin elevation is associated with significantly worse short- and long-term clinical outcomes. Bivalirudin monotherapy safely reduces major bleeding in ACS patients with CKD and baseline troponin elevation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Balancing ischaemia and bleeding risks with novel oral anticoagulants

Novel oral anticoagulants (direct thrombin or factor Xa inhibitors) have become alternative options to vitamin K antagonists owing to their predictable and safe pharmacological profiles. In this Review, Baber and colleagues discuss the overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding risk, in patients with atrial fibrillation, venous thromboembolism, or acute coronary syndrome.

Percutaneous Coronary Intervention Outcomes in Very Elderly Patients From a Single Large-Volume Tertiary Care Center, Specifically Focusing on Nonagenarians

Cardiovascular disease remains the leading cause of morbidity and mortality among elderly patients [(1)][1]. Elderly cardiac patients with several comorbidities have been underrepresented in randomized clinical trials. Several large registries have examined outcomes following percutaneous coronary

Clinical and angiographic predictors of haemodynamically significant angiographic lesions: development and validation of a risk score to predict positive fractional flow reserve.

AIMSnCoronary revascularisation based upon physiological evaluation of lesions improves clinical outcomes. Angiographic or visual stenosis assessment alone is insufficient in predicting haemodynamic stenosis severity by fractional flow reserve (FFR) and therefore cannot be used to guide revascularisation, particularly in the lesion subset <70%. Accordingly, we sought to identify independent determinants of angiographic intermediate lesions with haemodynamic significance.nnnMETHODS AND RESULTSnWe assessed consecutive intermediate lesions for patients from January 2014 to April 2015 at our institution. Independent predictors of FFR positivity (FFR ≤0.8) were identified and a scoring system formulated. Of 1,023 consecutive lesions (883 patients), 314 (31%) were haemodynamically significant. Characteristics associated with FFR ≤0.8 include male gender, higher SYNTAX score, lesions ≥20 mm, stenosis >50%, bifurcation, calcification, absence of tortuosity and smaller reference diameter. A user-friendly integer score was developed with the five variables demonstrating the strongest association. On prospective validation (in 279 distinct lesions), the increasing value of the score correlated well with increasing haemodynamic significance (C-statistic 0.85).nnnCONCLUSIONSnWe identified several clinical and angiographic characteristics and formulated a scoring system to guide the approach to intermediate lesions. This may translate into cost savings. Larger studies with prospective validation are required to confirm our results.

Antiplatelet treatments: recent evidence from randomized controlled trials

Purpose of review To provide an overview of selected randomized studies reported over the last 2 years evaluating antiplatelet therapies in patients with either acute or stable manifestations of atherosclerosis. Recent findings From large outcome trials included evidence for reduced risk of ischemic events associated with use of ticagrelor and aspirin versus aspirin alone, albeit with an increased bleeding risk in patients with stable coronary artery disease and history of myocardial infarction. No benefit regarding ischemic outcomes could be demonstrated for ticagrelor monotherapy compared with aspirin or clopidogrel in patients with stroke or peripheral vascular disease, respectively. Results from pharmacokinetic/pharmacodynamic studies suggest that switching from prasugrel to ticagrelor is safe, regardless of the use of a loading dose, and that loading with prasugrel or ticagrelor compared with clopidogrel leads to more prompt and potent platelet inhibition in patients undergoing ad hoc percoutaneous coronary intervention. No evidence could be demonstrated for the prognostic value of routine platelet function monitoring to adjust antiplatelet therapy. Summary Large outcome trials demonstrated various effects of antithrombotic strategies including ticagrelor on clinical outcomes across patient populations. Pharmacokinetic/pharmacodynamic studies confirmed a more prompt and potent platelet inhibition after loading with the new P2Y12 inhibitors versus clopidogrel, and suggested the safety of switching from prasugrel to ticagrelor.

Plaque Morphology Predictors of Side Branch Occlusion After Main Vessel Stenting in Coronary Bifurcation Lesions: Optical Coherence Tomography Imaging Study.

Side branch (SB) occlusion remains a major complication of bifurcation lesion treatment. Although plaque and carina shift are suggested as mechanisms of SB occlusion [(1)][1], little is known about underlying plaque morphology and composition of the main vessel (MV) and its potential impact on SB

Should P2Y12 inhibitors be given for 12 months in acute coronary syndrome

Purpose of review To provide updates regarding the optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS). Recent findings Within the past years, five moderate-sized randomized controlled trials evaluated different DAPT durations after percutaneous coronary intervention. These studies included a significant percentage of ACS patients that varied from 30 to 75% depending on the study. Results suggest that in selected populations prolonging DAPT does not offer additional protection from ischemic events and increases bleeding complications. However, results from a large-scale registry illustrate that DAPT durations beyond 6 months are associated with lower cardiovascular risk. Moreover, a multicenter registry demonstrated that the context underlying DAPT cessation is an additional correlate of outcomes after stent implantation. Summary Current guidelines suggest 12 months of DAPT after an initial presentation with ACS. Emerging evidence suggest that in selected populations shorter duration might be acceptable.