Somjot S. Brar

Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data.

OBJECTIVESnThe purpose of the study was to systematically evaluate the significance of platelet reactivity on clopidogrel treatment on adverse cardiovascular events using a collaborative meta-analysis using patient-level data for the VerifyNow P2Y12 assay (Accumetrics, San Diego, California).nnnBACKGROUNDnClinical evidence has been controversial regarding the influence of clopidogrel on treatment platelet reactivity and ischemic outcomes.nnnMETHODSnMEDLINE, Scopus, and the Cochrane library databases were searched through January 2010. A database containing individual patient-level time-to-event data was generated from identified studies. The primary outcome of interest was a composite of death, myocardial infarction (MI), or stent thrombosis. Secondary outcomes included the incidence of: 1) death; 2) MI; and 3) stent thrombosis.nnnRESULTSnA total of 6 studies with 3,059 patients was included. In each study, clopidogrel responsiveness was assessed using the same point-of-care assay after percutaneous coronary intervention. The primary endpoint occurred more frequently in higher quartiles of P2Y(12) reaction unit (PRU) values: quartile I, 5.8%; quartile II, 6.9%; quartile III, 10.9%; quartile IV, 15.8% (p < 0.001). Taking quartile I as referent, the hazard ratios (HRs) for the primary endpoint were as follows: quartile II, HR: 1.13 (95% confidence interval [CI]: 0.72 to 1.78; p = 0.60); quartile III, HR: 1.82 (95% CI: 1.20 to 2.75; p = 0.005); quartile IV, HR: 2.62 (95% CI: 1.78 to 3.87; p < 0.001). On a continuous scale, every 10-U increase in PRU was associated with a significantly higher rate of the primary endpoint (HR: 1.04; 95% CI: 1.03 to 1.06; p < 0.0001). According to receiver-operating characteristic curve analysis, a PRU value of 230 appeared to best predict death, MI, or stent thrombosis (p < 0.001). A PRU value ≥230 was associated with a higher rate of the composite primary endpoint (HR: 2.10; 95% CI: 1.62 to 2.73; p < 0.0001), as well as the individual endpoints of death (HR: 1.66; 95% CI: 1.04 to 2.68; p = 0.04), MI (HR: 2.04; 95% CI: 1.51 to 2.76; p < 0.001), and stent thrombosis (HR: 3.11; 95% CI: 1.50 to 6.46; p = 0.002).nnnCONCLUSIONSnIn this collaborative meta-analysis, the level of on-treatment platelet reactivity according to the P2Y(12) assay is associated with long-term cardiovascular events after percutaneous coronary intervention, including death, MI, and stent thrombosis.

Impact of the everolimus-eluting stent on stent thrombosis: a meta-analysis of 13 randomized trials

OBJECTIVESnWe evaluated the impact of the everolimus-eluting stent (EES) on the frequency of stent thrombosis (ST), target vessel revascularization (TVR), myocardial infarction (MI), and cardiac death in randomized controlled trials comparing the EES to non-everolimus-eluting drug-eluting stents (EE-DES).nnnBACKGROUNDnWhether or not the unique properties of the EES translate into reductions in ST remains unknown.nnnMETHODSnWe searched MEDLINE, Scopus, the Cochrane Library, and Internet sources for articles comparing outcomes between EES and non-EE-DES without language or date restriction. Randomized controlled trials reporting the frequency of ST were included. Variables relating to patient and study characteristics and clinical endpoints were extracted.nnnRESULTSnWe identified 13 randomized trials (n = 17,101) with a weighted mean follow-up of 21.7 months. Compared with non-EE-DES, the EES significantly reduced ST (relative risk [RR]: 0.55; 95% confidence interval [CI]: 0.38 to 0.78; p = 0.001), TVR (RR: 0.77; 95% CI: 0.64 to 0.92; p = 0.004), and MI (RR: 0.78; 95% CI: 0.64 to 0.96; p = 0.02). There was no difference in cardiac mortality between the groups (RR: 0.92; 95% CI: 0.74 to 1.16; p = 0.38). The treatment effect was consistent by different follow-up times and duration of clopidogrel use. The treatment effects increased with higher baseline risks of the respective control groups with the strongest correlation observed for ST (R(2) = 0.89, p < 0.001).nnnCONCLUSIONSnIntracoronary implantation of the EES is associated with highly significant reductions in ST with concordant reductions in TVR and MI compared to non-EE-DES. Whether these effects apply to different patient subgroups and DES types merits further investigation.

Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial

BACKGROUNDnThe administration of intravenous fluid remains the cornerstone treatment for the prevention of contrast-induced acute kidney injury. However, no well-defined protocols exist to guide fluid administration in this treatment. We aimed to establish the efficacy of a new fluid protocol to prevent contrast-induced acute kidney injury.nnnMETHODSnIn this randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, we assessed the efficacy of a new fluid protocol based on the left ventricular end-diastolic pressure for the prevention of contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. The primary outcome was the occurrence of contrast-induced acute kidney injury, which was defined as a greater than 25% or greater than 0·5 mg/dL increase in serum creatinine concentration. Between Oct 10, 2010, and July 17, 2012, 396 patients aged 18 years or older undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min per 1·73 m(2) or less and one or more of several risk factors (diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years) were randomly allocated in a 1:1 ratio to left ventricular end-diastolic pressure-guided volume expansion (n=196) or the control group (n=200) who received a standard fluid administration protocol. Four computer-generated concealed randomisation schedules, each with permuted block sizes of 4, were used for randomisation, and participants were allocated to the next sequential randomisation number by sealed opaque envelopes. Patients and laboratory personnel were masked to treatment assignment, but the physicians who did the procedures were not masked. Both groups received intravenous 0·9% sodium chloride at 3 mL/kg for 1 h before cardiac catheterisation. Analyses were by intention to treat. Adverse events were assessed at 30 days and 6 months and all such events were classified by staff who were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01218828.nnnFINDINGSnContrast-induced acute kidney injury occurred less frequently in patients in the left ventricular end-diastolic pressure-guided group (6·7% [12/178]) than in the control group (16·3% [28/172]; relative risk 0·41, 95% CI 0·22-0·79; p=0·005). Hydration treatment was terminated prematurely because of shortness of breath in three patients in each group.nnnINTERPRETATIONnLeft ventricular end-diastolic pressure-guided fluid administration seems to be safe and effective in preventing contrast-induced acute kidney injury in patients undergoing cardiac catheterisation.nnnFUNDINGnKaiser Permanente Southern California regional research committee grant.

Open Versus Endovascular Stent Graft Repair of Abdominal Aortic Aneurysms: A Meta-Analysis of Randomized Trials

OBJECTIVESnThis study sought to evaluate the short-, intermediate-, and longer-term outcomes after endovascular versus open repair of abdominal aortic aneurysms (AAA), including both AAA-related and all-cause mortality.nnnBACKGROUNDnEndovascular stent graft placement for AAA has gained broad acceptance as an alternative to open surgical repair due to a lower perioperative morbidity and mortality. The intermediate- and long-term all-cause and aneurysm-related mortality vary among studies. Thus, we sought to perform a meta-analysis of open versus endovascular repair for treating AAA.nnnMETHODSnElectronic databases were queried for identification of prospective, randomized trials of open surgery versus endovascular stent graft repair of AAA. A total of 10 published papers reporting on 6 studies at different follow-up intervals were identified; they involved 2,899 patients with AAA repair procedures, of whom, 1,470 underwent endovascular stent graft AAA exclusion and 1,429 were treated by open AAA repair.nnnRESULTSnAt 30 days, the pooled relative risk of all-cause mortality was lower in the endovascular group (relative risk [RR]: 0.35, 95% confidence interval [CI]: 0.19 to 0.64) than in the open surgery group. At intermediate follow-up, the all-cause mortality had a nonsignificant difference (RR: 0.78, 95% CI: 0.57 to 1.08), the AAA-related mortality was significantly lower (RR: 0.46, 95% CI: 0.28 to 0.74) and reintervention rates were higher (RR: 1.48, 95% CI: 1.06 to 2.08) in the endovascular group than in the open surgery group. At long-term follow-up, there was no significant difference in all-cause mortality (RR: 0.99, 95% CI: 0.85 to 1.15) or AAA-related mortality (RR: 1.58, 95% CI: 0.20 to 12.74), whereas the significant difference in the rate of reinterventions persisted (RR: 2.54, 95% CI: 1.58 to 4.08).nnnCONCLUSIONSnIn patients randomized to open or endovascular AAA repair, all-cause perioperative mortality, as well as AAA-related mortality at short- and intermediate-term follow-up are lower in patients undergoing endovascular stent graft placement. This was associated with greater reintervention in the endovascular group noted at intermediate follow-up. Long-term survival appears to converge between the 2 groups.

Effects of Physical Activity and Sedentary Time on the Risk of Heart Failure

Background— Although the benefits of physical activity for risk of coronary heart disease are well established, less is known about its effects on heart failure (HF). The risk of prolonged sedentary behavior on HF is unknown. Methods and Results— The study cohort included 82 695 men aged ≥45 years from the California Men’s Health Study without prevalent HF who were followed up for 10 years. Physical activity, sedentary time, and behavioral covariates were obtained from questionnaires, and clinical covariates were determined from electronic medical records. Incident HF was identified through International Classification of Diseases, Ninth Revision codes recorded in electronic records. During a mean follow-up of 7.8 years (646 989 person-years), 3473 men were diagnosed with HF. Controlling for sedentary time, sociodemographics, hypertension, diabetes mellitus, unfavorable lipid levels, body mass index, smoking, and diet, the hazard ratio (95% confidence interval [CI]) of HF in the lowest physical activity category compared with those in the highest category was 1.52 (95% CI, 1.39–1.68). Those in the medium physical activity category were also at increased risk (hazard ratio, 1.17 [95% CI, 1.06–1.29]). Controlling for the same covariates and physical activity, the hazard ratio (95% CI) of HF in the highest sedentary category compared with the lowest was 1.34 (95% CI, 1.21–1.48). Medium sedentary time also conveyed risk (hazard ratio, 1.13 [95% CI, 1.04–1.24]). Results showed similar trends across white and Hispanic subgroups, body mass index categories, baseline hypertension status, and prevalent coronary heart disease. Conclusions— Both physical activity and sedentary time may be appropriate intervention targets for preventing HF.

Racial/Ethnic Differences in the Prevalence of Atrial Fibrillation Among Older Adults—A Cross-Sectional Study

BACKGROUNDnAtrial fibrillation affects 4% to 8% of individuals over 60 years of age based on studies of predominantly white populations, whether this is true among nonwhite individuals is not clear. This study was undertaken to define racial/ethnic differences in atrial fibrillation prevalence among a large community cohort.nnnMETHODSnThis is a cross-sectional study. In 2008, there were 430,317 members aged 60 years or older in a large California health maintenance organization. By searching International Classification of Diseases, Ninth Revision codes and electronic electrocardiographic archives, we identified all members in this age group with primary, nonvalvular atrial fibrillation. Race/ethnicity data were assigned using health plan enrollment, service utilization, Asian/Hispanic surname and geocoding methods, and was available for 80.5% of members (79.8% of non-atrial fibrillation and 92% of atrial fibrillation), 99% of which were white, black, Asian, or Hispanic. We assessed the age- and gender-specific atrial fibrillation prevalence rates for each racial/ethnic group. The effect of race/ethnicity on atrial fibrillation was analyzed with logistic regression methods adjusting for potential confounders.nnnRESULTSnThe overall atrial fibrillation prevalence was 5.3%. Among members with assigned race/ethnicity data, the prevalence among whites, blacks, Asians, and Hispanics was 8.0%, 3.8%, 3.9%, and 3.6%, respectively. The adjusted odds ratios (95% confidence intervals) of atrial fibrillation among blacks, Asians, and Hispanics with whites as referent were 0.49 (0.47-0.52), 0.68 (0.64-0.72), and 0.58 (0.55-0.61), respectively.nnnCONCLUSIONSnAtrial fibrillation is less prevalent in older nonwhite individuals than whites. White race/ethnicity is associated with significantly greater odds for atrial fibrillation compared to blacks, Asians, and Hispanics, after adjusting for comorbidities associated with the development of atrial fibrillation.

Impact of Routine Angiographic Follow-Up After Percutaneous Coronary Intervention With Drug-Eluting Stents in the SPIRIT III Randomized Trial at Three Years

Routine angiographic follow-up after bare-metal stent implantation has been associated with an increase in coronary revascularization. The impact of angiographic follow-up after drug-eluting stent placement remains poorly characterized. The prospective, randomized, single-blinded SPIRIT III trial assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were assessed by angiographic versus clinical-only follow-up at 8 months ± 28 days and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564 patients were assigned to angiographic follow-up at 8 months ± 28 days and 438 patients underwent clinical follow-up alone. Three-year major adverse cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased twofold at 9 months, but no difference was noted in ID-TLR for either device. Non-ID-TLR was significantly higher in patients in the angiographic group (4.5% vs 1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007) rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The landmark analysis showed no significant differences between the angiographic and clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In conclusion, routine angiographic follow-up in SPIRIT III did not increase rates of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven revascularization rates with angiographic follow-up of patients with PESs, none of the safety end points were adversely affected.

Discontinuation of Long-Term Clopidogrel Therapy Is Associated With Death and Myocardial Infarction After Saphenous Vein Graft Percutaneous Coronary Intervention

OBJECTIVESnThis study sought to examine the pattern of death and myocardial infarction (MI) after clopidogrel cessation in patients undergoing percutaneous coronary intervention (PCI) of the saphenous vein graft (SVG).nnnBACKGROUNDnThe timing and incidence of adverse events by different durations of clopidogrel therapy after SVG PCI remain unknown.nnnMETHODSnThis is a cohort study of patients undergoing SVG PCI between 2000 and 2009, followed for all-cause mortality or MI after stopping clopidogrel. Incidence rates were calculated across different time periods after clopidogrel cessation. Adjusted incidence rate ratios (IRR) were calculated with multivariable regression (piecewise exponential and Poisson).nnnRESULTSnThere were 603 patients who underwent SVG PCI, of which 411 were event-free at the time of clopidogrel cessation. The incidence rate (95% confidence interval: [CI])/1,000 person-days of death or MI after stopping clopidogrel in the time intervals of 0 to 90 days, 91 to 365 days, and 1 to 2 years were 1.26 (95% CI: 0.93 to 1.70), 0.41 (95% CI: 0.30 to 0.56), and 0.41 (95% CI: 0.30 to 0.55), respectively. In multivariable analyses, the overall IRR (95% CI) for death or MI in the 0- to 90-day interval after stopping clopidogrel compared with the 91- to 365-day interval was 2.58 (95% CI: 1.64 to 4.07). Similar results were observed over a broad range of clopidogrel treatment durations (<6 months, 6 months to 1 year, 1 to 2 years, or >2 years). The results were also consistent across subgroups, including sex, stent type, stent diameter, PCI period, and diabetes status. When death alone was evaluated, there remained a significant increase in the event rate in the 0- to 90-day interval compared with the 91- to 365-day interval (IRR: 2.33; 95% CI: 1.32 to 4.11).nnnCONCLUSIONSnA clustering of events was observed in the initial 0 to 90 days after clopidogrel cessation in all treatment durations of clopidogrel investigated after SVG PCI. These results might have important implications in high-risk cohorts undergoing PCI. Additional studies are needed to elucidate the mechanisms underlying the early clustering of events after clopidogrel cessation.

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography

OBJECTIVESnThe aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.nnnBACKGROUNDnCI-AKI is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality. The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during coronary injection.nnnMETHODSnThe AVERT trial was a prospective, multicenter, 1:1 randomized clinical trial in 578 subjects with either baseline estimated glomerular filtration rate 20 to 30 ml/min/1.73 m2 or estimated glomerular filtration rate 30 to 60xa0ml/min/1.73 m2 and at least 2 additional risk factors for CI-AKI. Patients undergoing coronary angiography with planned or possible percutaneous coronary intervention (PCI) were randomized to hydration plus the AVERT system (nxa0=xa0292) or hydration only (nxa0= 286). The primary effectiveness endpoints were: 1) the total CMV used; and 2)xa0thexa0incidence of CI-AKI, defined as axa0≥0.3 mg/dl increase in serum creatinine within 5 days post-procedure.nnnRESULTSnPatient demographics were well balanced between the groups, with mean baseline serum creatinine of 1.6 ± 0.4 mg/dl and 64.9% patients with diabetes mellitus. PCI was performed in 42.2% of procedures, with coronary angiography in the remainder. Use of AVERT resulted in a 15.5% relative reduction in CMV overall (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml; pxa0= 0.02) and a 22.8% relative reduction in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml; pxa0= 0.001). The maximum relative reduction in CMV was 46% (124 ± 48 ml vs. 232 ± 97 ml; pxa0= 0.01) whenxa0≥3 lesions were treated. There were no differences in the rates of CI-AKI (27.0% vs. 26.6%; pxa0= 0.70) between the study groups.nnnCONCLUSIONSnUse of the AVERT system was feasible and safe, with acceptable image quality during coronary angiography and PCI. AVERT significantly reduced CMV, with the extent of CMV reduction correlating with procedural complexity. No significant differences in CI-AKI were observed with AVERT in this trial. (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN [AVERT]; NCT01976299).

Heart Failure Etiology Is Usually Pluricausal Whether or Not There is Associated Coronary Disease.

The heart failure syndrome (HF) has diverse etiologies. In a 22-year study of predictors of HF in 126,235 persons, we attempted to identify etiologic factors independent of associated coronary heart disease (CAD) in 2594 persons hospitalized for the condition. For this purpose, subjects were stratified according to whether CAD was present. Of the subjects, 60% had evidence for CAD (CAD-HF). Because we also wished to study HF predictors in subjects without associated CAD according to specific HF etiology, the paper records of the other 40% of subjects (non-CAD-HF) underwent a detailed review so that we could determine the apparent primary etiology and contributory factors. A random sample of all subjects with CAD-HF underwent a similar paper record review so that we could ascertain contributory factors. The primary etiology among the subjects with non-CAD-HF was categorized as systemic hypertension (HTN) in 354, valve disease in 110, cardiomyopathies (including alcoholic and idiopathic) in 93, other specific miscellaneous in 55, and primary etiology not evident (unclear) in 423. The unclear-group subjects generally had multiple probable contributing factors. In addition to the preponderant etiology in subjects with non-CAD-HF, the mean number of contributory factors was 1.5; among subjects with CAD-HF, the mean number of contributory factors was 1.9. Frequent additional factors, in both CAD-HF and non-CAD-HF, were HTN, diabetes mellitus, atrial fibrillation, and heavy alcohol consumption. These data show that primary HF etiology is often uncertain and that HF etiology is usually multifactorial, whether or not CAD is present.