Characteristics and Treatments of Patients with Peripheral Arterial Disease Referred to UK Vascular Clinics: Results of a Prospective Registry

BackgroundPeripheral arterial disease (PAD) is often associated with risk factors including cigarette smoking, hypertension and hypercholesterolaemia, and patients have a high risk of future vascular events. Good medical management results in improved outcomes and quality of life, but previous studies have documented sub-optimal treatment of risk factors. We assessed the management of cardiovascular risk factors in patients with PAD referred to specialist vascular clinics.MethodsThis was a prospective, protocol driven registry carried out in UK vascular clinics. Patients who were first-time referrals for evaluation of PAD were eligible if they had claudication plus ankle-brachial pressure index (ABPI) ≤0.9. Statistical associations between key demographic and treatment variables were explored using a chi-squared test.ResultsWe enrolled 473 patients from 23 sites. Mean age was 68 years (SD 10) and 66% were male. Mean estimated claudication distance was 100m, and ABPI was 0.74. Mean systolic blood pressure (SBP) was 155mmHg, and 42% had a SBP >160mmHg. Forty percent were current smokers and half had tried to give up in the prior 6 months, but there was no evidence of a systematic method of smoking cessation. Mean total cholesterol was 5.4 (SD1.2) mmol/l and 30% had levels >6mmol/l. Antiplatelet therapy had been given to 70% and statins to 44%. Prior CHD was present in 29% and these patients had significantly higher use of antiplatelet therapy, statins and ACE-inhibitors.ConclusionsIn spite of attempts to raise awareness about PAD as an important marker of cardiovascular risk, patients are still poorly treated prior to referral to a vascular clinic. In particular, the use of evidence-based treatments is sub-optimal, while hypertension and cigarette smoking are poorly managed. More work needs to be done to educate health professionals about the detection and optimal medical management of PAD

ACE inhibitor use in patients with myocardial infarction. Summary ofevidence from clinical trials

Experimental evidence for the beneficial effects on heart failure of chronic treatment with ACE inhibitors accumulated from early 1980 in experimental models of LV dysfunction secondary to AMI. These studies demonstrated an improvement in hemodynamics, LV remodeling, and mortality with ACE inhibitor treatment. The effect of ACE inhibitors during the acute phase of AMI was less clear, although there was evidence of protection from ischemic damage, possibly mediated by an increase in collateral coronary blood flow

B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease

Background: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use. Methods: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression. Results: Five hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45-3.19; p = 0.0001) and 1.27 for composite events (1.04-1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease. Conclusions: Conventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management. Trial registration: Clinicaltrials.gov, NCT00403351 Registered on 22 November 200

Associations between adding a radial artery graft to single and bilateral internal thoracic artery grafts and outcomes. Insights from the Arterial Revascularization Trial

Background—Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft (CABG) surgery remains unclear. The Arterial Revascularization Trial (ART) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (~20%) also received a RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of SVG to supplement SITA or BITA grafts and outcomes by performing a post-hoc analysis of the ART.  Methods—Patients enrolled in the ART (n=3102) were classified based on conduits actually received (as treated). The analysis included 2737 patients who received a RA graft (RA group, n=632) or SVG only (SVG group, n=2105) in addition to SITA or BITA grafts. The primary endpoint was the composite of myocardial infarction, cardiovascular death and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the two strategies.  Results—MI, cardiovascular death and repeat revascularization cumulative incidence was 2.3% (95%CI 1.1-3.4), 3.5% (95%CI 2.1-5.0) and 4.4% (95%CI 2.8-6.0) in the RA group and 3.4% (95%CI 2.0-4.8), 4.0% (95%CI 2.5-5.6) and 7.6% (95%CI 5.5- 9.7) in the SVG group respectively. The composite endpoint was significantly lower in the RA group (8.8%; 95%CI 6.5-11.0) when compared with the SVG group (13.6%; 95%CI 10.8-16.3) (P=0.005). This association was present when a RA graft was used to supplement both SITA and BITA grafts (interaction P=0.62).  Conclusions—This post-hoc ART analysis showed that an additional RA was associated with lower risk for mid-term major adverse cardiac events when used to supplement SITA or BITA grafts

Disagreement Between Randomized and Observational Evidence on the Use of Bilateral Internal Thoracic Artery Grafting:A Meta-Analytic Approach

Background The ART (Arterial Revascularization Trial) showed no difference in survival at 10 years between patients assigned to the single versus bilateral internal thoracic artery grafting strategies. This finding is in contrast with the results of most observational studies, where the use of 2 internal thoracic arteries has been associated with improved survival. Methods and Results We selected propensity-matched studies from the most comprehensive observational meta-analysis on the long-term outcomes of patients receiving 1 versus 2 internal thoracic arteries. Individual participant survival data from each study and the ART were reconstructed using an iterative algorithm that was applied to solve the Kaplan-Meier equations. The reconstructed individual participant survival data were aggregated to obtain combined survival curves and Cox regression hazard ratios with 95% CIs. Individual participant survival data were obtained from 14 matched observational studies (24 123 patients) and the ART. The 10-year survival of the control group of ART was significantly higher than that of the matched observational studies (hazard ratio, 0.86; 95% CI, 0.80-0.93). The 10-year survival of the experimental group of ART was significantly lower than that of the bilateral internal thoracic artery group of the observational studies (hazard ratio, 1.11; 95% CI, 1.03-1.20). Conclusions Both the improved outcome of the control arm and the lower beneficial effect of the intervention had played a role in the difference between observational evidence and ART

Off-pump versus on-pump coronary artery bypass grafting: Insights from the Arterial Revascularization Trial

Background: The long-term effects of off-pump coronary artery bypass continue to be controversial because some studies have reported increased adverse event rates with off-pump coronary artery bypass when compared with on-pump coronary artery bypass. The Arterial Revascularization Trial compared survival after bilateral versus single internal thoracic artery grafting. The choice of off-pump coronary artery bypass versus on-pump coronary artery bypass was based on the surgeon's discretion. We performed a post hoc analysis of the Arterial Revascularization Trial to compare 5-year outcomes with 2 strategies. Methods: Among 3102 patients enrolled in the Arterial Revascularization Trial, we selected 1260 patients who underwent off-pump coronary artery bypass versus 1700 patients who underwent on-pump coronary artery bypass with cardioplegic arrest for the present comparison. Primary outcomes were 5-year mortality and incidence of major cardiac and cerebrovascular events, including cardiovascular death, myocardial infarction, cerebrovascular accident, and revascularization after index procedure. Propensity score matching selected 1260 pairs for final comparison. Stratified Cox models were used for treatment effect estimate. Results: Hospital mortality was comparable between off-pump coronary artery bypass and on-pump coronary artery bypass groups (12 [1.0%] vs 15 [1.2%]; P = .7). Conversion rate to on-pump during off-pump coronary artery bypass was 29 of 1260 (2.3%). When compared with off-pump coronary artery bypass not converted, off-pump coronary artery bypass converted to on-pump presented a remarkably higher hospital mortality (10.3% vs 0.7%; P < .001). At 5 years, the mortality rate was 110 (8.9%) versus 102 (8.3%) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.14; 95% confidence interval, 0.86-1.52; P = .35). Incidence of major cardiac and cerebrovascular events was 175 (14.3) versus 169 (13.8) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.05; 95% confidence interval, 0.84-1.31; P = .65). Conclusions: The present post hoc Arterial Revascularization Trial analysis supports the hypothesis that both off-pump coronary artery bypass and on-pump coronary artery bypass are equally effective and safe

One-year costs of bilateral or single internal mammary grafts in the Arterial Revascularisation Trial

Objective: Coronary artery bypass grafting (CABG) using bilateral internal mammary arteries (BIMA) may improve survival over CABG using single internal mammary arteries (SIMA), but may be surgically more complex (and therefore costly) and associated with impaired sternal wound healing. We report, for the first time, a detailed comparison of healthcare resource use and costs over 12 months, as part of the Arterial Revascularisation (ART) Trial.  Methods: 3102 patients in 28 hospitals in seven countries were randomised to CABG surgery using BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected covering surgery, the initial hospital episode, and for 12 months post randomisation. Using UK unit costs, total costs were calculated and compared between trial arms and for subgroups.  Results: Patients randomised to BIMA spent 20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more treatment for sternal wound problems. Mean (SD) total costs per patient at 12 months were £13 839 (£10 534) for BIMA and £12 717 (£9719) for SIMA (mean cost difference £1122, 95% CI £407 to £1838, p=0.002). No tests for interaction between subgroups and treatment allocation were significant.  Conclusions: At 12 months from randomisation, mean costs were approximately 9% higher in BIMA than SIMA patients, primarily due to longer time in theatre and in-hospital stay, and slightly higher costs related to sternal wound problems during follow-up. Follow-up to the primary trial endpoint of 10 years will reveal whether longer-term differences emerge in graft patency or in overall survival

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction