Ellis Lader

Warfarin Dosage and Vitamin K in Osmolite

Excerpt To the editor: A cause of warfarin antagonism is unappreciated inclusion of vitamin K analogues in commercial dietary supplements. The following case report is pertinent to this point. A 60...

Severe hemolytic anemia in patients with a porcine aortic valve prosthesis

Two patients underwent aortic valve replacement with a porcine bioprosthesis. A few weeks later, both developed severe hemolytic anemia that could not be controlled medically and led to additional valve replacement. In each case, perforation of the bioprosthetic cusps was detected. This type of lesion was probably responsible for this unusual complication in patients with an aortic bioprosthesis.

Usefulness of clinical information to distinguish patients with normal from those with low ejection fractions in heart failure

In this study we used the DIG trial database to determine whether clinical variables used in combination could accurately predict left ventricular EF for individual patients with HF. The prediction model was able to identify within 0.05 (± 5 EF U) the correct numerical EF only 45% of the time. Although categorical analysis showed that nearly all of the 38% of patients who had the lowest predicted EF actually had EF ≤0.45, this method was unreliable for the remaining 62% of patients.

Ice-Water-Induced Arrhythmias in a Patient with Ischemic Heart Disease

Excerpt Current recommendations for managing patients with acute myocardial infarction include the suggestion that they avoid cold drinks (1). There has been little documentation of serious arrhyth...

Effect of smoking on age at the time of coronary artery bypass graft surgery; baseline data results from the ROSETTA-CABG registry

Background Coronary artery disease (CAD) is a leading cause of death. The aetiology of this disease is not known, but many important risk factors have been recognised. Objective To evaluate the effect of smoking on age at the time of coronary artery bypass graft surgery (CABG), and to examine this finding in the light of medical literature. Methods The authors recruited patients immediately after CABG in a prospective, study in 16 centres and enrolled 408 patients, of which 395 were ultimately analysed. Results Among the 395 patients analysed, there were 60 smokers and 335 non-smokers. The smokers were 8.4 years younger than non-smokers at the time of index CABG. The average age of smokers was 55.79.0 years, and that of non-smokers was 64.1±9.9 years (p<0.001). Hyperlipidaemia was present in 76.7% of smokers and 74.6% of non-smokers (p—NS). Hypertension was present in 58.3% of smokers and 63.9% of non-smokers (p—NS). Diabetes mellitus was present in 21.3% of smokers and 29.3% of non smokers (p—NS). Left ventricular ejection fraction was 53.0±10.5% in smokers and 53.3 ±13.8% in non-smokers (p—NS). Myocardial infarction had occurred in 41.7% of smokers and 35.5% of non-smokers (p—NS). Conclusion Smoking accelerates atherosclerosis and coronary thrombosis resulting in severe form of CAD that cannot be managed by medications or PCI, and requires coronary artery bypass graft surgery (CABG) 8.4 years earlier than non-smokers.

Review: Eplerenone is not more effective for reducing mortality than other aldosterone antagonists

Source Citation Chatterjee S, Moeller C, Shah N, et al. Eplerenone is not superior to older and less expensive aldosterone antagonists. Am J Med. 2012;125:817-25. 22840667

Review: Adding clopidogrel to ASA reduces CV morbidity but increases bleeding in patients at high risk for CV events

Question In patients with, or at high risk for, cardiovascular (CV) disease, what are the benefits and harms of adding clopidogrel to aspirin (ASA) to prevent CV events? Review scope Included studies compared ASA plus clopidogrel with ASA alone or plus placebo for >30 days in patients with coronary disease, ischemic cerebrovascular disease, or peripheral artery disease or those at high risk for atherothrombotic disease. Studies that included other platelet aggregation inhibitors as cointerventions or that included patients with coronary stents were excluded. Primary outcomes were CV and all-cause mortality, myocardial infarction (MI), ischemic stroke, and adverse events. Secondary outcomes included major and minor bleeding. Review methods This is an update of a 2011 review. MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, www.clinicaltrials.gov (all to Jul 2017); World Health Organization International Clinical Trials Registry Platform (Oct 2017); and reference lists were searched for randomized controlled trials (RCTs) with follow-up 30 days. 15 RCTs (n =33970), ranging in size from 20 to 15603 patients, met the selection criteria. Clopidogrel dose was 75 to 100 mg/d, and ASA dose was 70 to 325 mg/d; duration of treatment ranged from 6 weeks to 3.4 years. Of the 15 RCTs, 10 described adequate random sequence generation, 9 reported adequate allocation concealment, 9 reported adequate blinding, and all 15 adequately addressed incomplete outcome data. Main results The main results are in the Table. Conclusion In patients with, or at high risk for, cardiovascular disease, adding clopidogrel to aspirin therapy reduces myocardial infarction and ischemic stroke but increases bleeding. Clopidogrel plus aspirin (ASA) vs ASA alone in patients with, or at high risk for, cardiovascular disease* Outcomes Number of trials (n) Weighted event rates At a median 6 to 12 mo Clopidogrel + ASA ASA alone RRR (95% CI) NNT (CI) Cardiovascular mortality 7 (31903) 3.7% 3.8% 2% (10 to 12) Not significant Myocardial infarction 6 (16175) 4.6% 5.8% 22% (10 to 31) 80 (52 to 176) Ischemic stroke 5 (4006) 6.3% 8.6% 27% (9 to 41) 44 (26 to 148) RRI (CI) NNH (CI) All-cause mortality 9 (32908) 5.3% 5.3% 5% (13 to 25) Not significant Major bleeding 10 (33300) 3.0% 2.1% 44% (25 to 64) 110 (81 to 176) Minor bleeding 8 (14731) 6.6% 3.2% 103% (75 to 136) 30 (25 to 38) *Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article. Commentary Upon reviewing the meta-analysis by Squizzato, my first thought was, Your honor, this question has been asked and answered. Over the past 2 decades, studies examining the risks and benefits of adding clopidogrel to ASA have shown variable benefits but always increased bleeding risk. This makes sense: Adding P2Y12 inhibitors or other anticoagulants to ASA to reduce atherothrombotic complications predictably increases bleeding complications. The meta-analysis by Squizzato and colleagues provides further evidence of the increased bleeding risk that comes from combining a P2Y12 inhibitor, in this case clopidogrel, with ASA. The heterogeneity of patient populations included in the meta-analysis is striking; trials included stable patients with risk factors, non-ST elevation MI, or stroke and patients who had coronary artery bypass grafting. As with many other studies, the meta-analysis showed that adding clopidogrel to ASA reduces risk for MI and ischemic stroke, more so in more acutely ill patients and not at all in stable patients with risk factors, and increases bleeding risk in all patients. Mortality benefits were probably lost in the heterogeneous population studied. Moving forward, we need to examine the benefits and potential harms of adding anticoagulants (1), thrombin-receptor inhibitors (2), or more potent P2Y12 inhibitors (3) to ASA. Enough with clopidogrel already!

Glargine did not reduce CV events more than standard care in patients with dysglycemia

Source Citation ORIGIN Trial Investigators, Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319-28. 22686416

Daily n-3 fatty acid supplements did not reduce CV events in high-risk patients with dysglycemia

Source Citation ORIGIN Trial Investigators, Bosch J, Gerstein HC, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367:309-18. 22686415

809-4 Impact of diabetes on 12-month outcomes following coronary artery bypass graft surgery: Results from the routine versus selective exercise treadmill testing after coronary artery bypass grafting (ROSETTA-CABG) registry

Background. To identify the impact of deep strernal wound infection (DSWI) on long-term survival after coronary artery bypass grafting (CABG). Methods. We studied 3760 consecutive patients who underwent isolated CABG between 1992 and 2002. Patients with CABG and no DSWI were compared with those who developed DSWI. Long-term survival data were obtained from the National Death Index. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for DSWI was determined by logistic regression analysis and each patient with DSWI was then matched to 10 patients without DSWI. Results. Forty patients (1.1%) developed DSWI. Multivariate logistic regression analysis found that the independent predictors of DSWI were diabetes mellitus (odds ratio (OR) 5.5; P<0.001), hemodynamic instability (OR 4.0; P=0.026), use of bilateral internal thoracic arteries (OR 2.6; P=0.010), endocarditis and/or sepsis (OR 29.9; P<0.001) and dialysis (OR 3.4; P=0.049). There were no differences in thirty-day mortality between matched groups. Patients with DSWI had longer length of stay (35.0 versus 16.4 days; P<0.001). Kaplan-Meier curves of the two matched groups are shown in figure. After adjustment for pre, intra and postoperative factors, the adjusted hazard ratio of long-term mortality for patients with DSWI was 2.44 (95%CI 1.51-3.92; P<0.001). Conclusions. We found that DSWI after CABG operations was associated with increased long-term mortality. 11:30 a.m.