Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease

AbstractTo examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (≥75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course × (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of “ischemic” ST-T changes. This angina score was then validated in an independent patient sample.The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score ≥9. With an ejection fraction <50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%. Thus, a careful summarization of clinical markers of ischemia in the form of an angina score can provide a powerful prognostic tool and may aid clinicians in identifying high risk patients who are candidates for aggressive therapeutic interventions

Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study

Study question What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? Methods This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. Study answer and limitations The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82 955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53 070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35 233) filled at least one prescription for NSAIDs and 45.5% (n=37 771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding. What this study adds In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. Funding, competing interests, data sharing AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation

Clinical judgement and therapeutic decision making

AbstractClinical decision making is under increased scrutiny due to concerns about the cost and quality of medical care. Variability in physician decision making is common, in part because of deficiencies in the knowledge base, but also due to the difference in physicians' approaches to clinical problem solving. Evaluation of patient prognosis is a critical factor in the selection of therapy, and careful attention to methodology is essential to provide reliable information.Randomized controlled clinical trials provide the most solid basis for the establishment of broad therapeutic principles. Because randomized studies cannot be performed to address every question, observational studies will continue to play a complementary role in the evaluation of therapy. Randomized studies in progress, meta analyses of existing data, and increased use of administrative and collaborative clinical data bases will improve the knowledge base for decision making in the future

Metabolic Syndrome and Early-Onset Coronary Artery Disease Is the Whole Greater Than Its Parts?

ObjectivesWe sought to examine the association between the metabolic syndrome (MetS) (defined both by the 2001 National Cholesterol Educational Program Adult Treatment Panel III [ATP-III] definition and the American Heart Association/National Heart, Lung and Blood Institute [AHA/NHLBI] revision incorporating the lower threshold for impaired fasting glucose [IFG]) and early-onset coronary artery disease (CAD).BackgroundThe impact of MetS on premature CAD has not been studied extensively. Lowering the threshold to define the IFG component (from 110 to 100 mg/dl) and the value of the syndrome as a whole versus its individual components are subjects of intense debate.MethodsWe performed a case-control study with 393 early-onset CAD subjects (acute myocardial infarction, angina with ≥50% stenosis, or coronary revascularization) in men under age 46 years or women under age 56 years and 393 control subjects individually matched for gender, age, and race/ethnicity.ResultsBy conditional logistic regression, presence of ATP-III MetS without diabetes (adjusted odds ratio [adj-OR] 4.9; 95% confidence interval [CI] 3.4 to 8.0) and with diabetes (adj-OR 8.0, 95% CI 4.39 to 14.6) was a strong independent determinant of early-onset CAD. Using the AHA/NHLBI revision, these ORs became slightly stronger. However, neither definition of MetS remained significantly associated with early-onset CAD in multivariate models adjusting for individual components.ConclusionsThe presence of MetS imparts a high risk of early-onset clinical CAD, but the prognostic information associated with the syndrome is not greater than the sum of its parts

Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

BackgroundThe choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.ObjectiveTo determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.DesignDecision-analytic model.Data sourcesPublished literature, Medicare claims, and life tables.Target populationPatients having percutaneous coronary intervention for ACS.Time horizonLifetime.PerspectiveSocietal.InterventionFive strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.Outcome measuresDirect medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisThe clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of$35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor).Results of sensitivity analysisStronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.LimitationNo randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.ConclusionGenotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings

Isolated Disease of the Proximal Left Anterior Descending Artery Comparing the Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Surgery

ObjectivesThis study sought to systematically compare the effectiveness of percutaneous coronary intervention and coronary artery bypass surgery in patients with single-vessel disease of the proximal left anterior descending (LAD) coronary artery.BackgroundIt is uncertain whether percutaneous coronary interventions (PCI) or coronary artery bypass grafting (CABG) surgery provides better clinical outcomes among patients with single-vessel disease of the proximal LAD.MethodsWe searched relevant databases (MEDLINE, EMBASE, and Cochrane from 1966 to 2006) to identify randomized controlled trials that compared outcomes for patients with single-vessel proximal LAD assigned to either PCI or CABG.ResultsWe identified 9 randomized controlled trials that enrolled a total of 1,210 patients (633 received PCI and 577 received CABG). There were no differences in survival at 30 days, 1 year, or 5 years, nor were there differences in the rates of procedural strokes or myocardial infarctions, whereas the rate of repeat revascularization was significantly less after CABG than after PCI (at 1 year: 7.3% vs. 19.5%; at 5 years: 7.3% vs. 33.5%). Angina relief was significantly greater after CABG than after PCI (at 1 year: 95.5% vs. 84.6%; at 5 years: 84.2% vs. 75.6%). Patients undergoing CABG spent 3.2 more days in the hospital than those receiving PCI (95% confidence interval: 2.3 to 4.1 days, p &lt; 0.0001), required more transfusions, and were more likely to have arrhythmias immediately post-procedure.ConclusionsIn patients with single-vessel, proximal LAD disease, survival was similar in CABG-assigned and PCI-assigned patients; CABG was significantly more effective in relieving angina and led to fewer repeat revascularizations

The antiangiogenic agent ZD4190 prevents tumour outgrowth in a model of minimal residual carcinoma in deep tissues

BACKGROUND: Tumour cells may persist at the operative site after seemingly adequate surgery. Radiotherapy is often given in an attempt to prevent repopulation, but this modality cannot be relied upon to prevent locoregional recurrence. An alternative strategy is to take advantage of the requirement of tumour cells to develop an independent blood supply and block this process to prevent recurrence. METHODS: In this study, we evaluate the effect of the angiogenesis inhibitor, ZD4190, using a rodent model of residual carcinoma in deep tissues, mimicking the clinical scenario where low numbers of malignant cells persist at the operative site. RESULTS: The tumour burden that could be eliminated was dependent on the site where the cells were implanted. Immediate treatment with ZD4190 prevented outgrowth of up to 2.5 x 10(5) cells in the rectus muscle and 1 x 10(5) in the gastrocnemius, whereas control animals developed large tumours. When more than 2.5 x 10(6) cells were implanted into the rectus or 1 x 10(6) into the gastrocnemius and treatment was maintained for 3 weeks, the carcinomas that developed in ZD4190-treated animals showed a reduced microvessel density and increased necrosis when compared with the vehicle-treated controls, but an infiltrative growth pattern was common. CONCLUSION: These findings suggest that antiangiogenic agents have a role to play in preventing outgrowth of residual carcinoma and are likely to be most effective when the tumour burden is minimal