The "smoker's paradox" in patients with acute coronary syndrome: a systematic review

<p>Abstract</p> <p>Background</p> <p>Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival benefit for smokers; that is, the "smoker's paradox". The aim of this study was, therefore, to perform a systematic review of the literature and evidence surrounding the existence of the "smoker's paradox".</p> <p>Methods</p> <p>Relevant studies published by September 2010 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1963) and the Cochrane Central Register of Controlled Trials, with a combination of text words and subject headings used. English-language original articles were included if they presented data on hospitalised patients with defined acute coronary syndrome, reported at least in-hospital mortality, had a clear definition of smoking status (including ex-smokers), presented crude and adjusted mortality data with effect estimates, and had a study sample of > 100 smokers and > 100 non-smokers. Two investigators independently reviewed all titles and abstracts in order to identify potentially relevant articles, with any discrepancies resolved by repeated review and discussion.</p> <p>Results</p> <p>A total of 978 citations were identified, with 18 citations from 17 studies included thereafter. Six studies (one observational study, three registries and two randomised controlled trials on thrombolytic treatment) observed a "smoker's paradox". Between the 1980s and 1990s these studies enrolled patients with acute myocardial infarction (AMI) according to criteria similar to the World Health Organisation criteria from 1979. Among the remaining 11 studies not supporting the existence of the paradox, five studies represented patients undergoing contemporary management.</p> <p>Conclusion</p> <p>The "smoker's paradox" was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era, whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox.</p

Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study

Antiplatelet therapy with clopidogrel has been shown to reduce major adverse cardiac events in acute coronary syndromes and after percutaneous interventions. This effect is not only due to its anti-platelet effect but also possibly due to an anti-inflammatory effect. The effect of clopidogrel cessation after one year of therapy on markers of inflammation has been investigated in diabetics and showed an increase in platelet aggregation as well as hsCRP and surface P-selectin levels. This was an exploratory multicenter prospective open-label single arm study of 98 non-diabetic patients who had received one or more drug eluting stents and were coming to the end of their 12 months course of clopidogrel therapy. The effect of clopidogrel cessation on expression of biomarkers: sCD40L, soluble P-selectin and hsCRP was measured right before clopidogrel cessation (day 0), and subsequently at 1, 2, 3 and 4 weeks after drug withdrawal. A median increase in sCD40L expression from 224 to 324.5 pg/ml was observed between baseline and 4 weeks after clopidogrel cessation, which corresponded to a 39% mean percent change based on an ANCOVA model (P < 0.001). Over the 4 weeks observation period the change in sCD40L expression correlated weakly with soluble P-selectin levels (at 4 weeks Spearman’s correlation coefficient = 0.32; P = 0.0024). Increase in P-selectin expression from baseline was statistically significant at week 1 and 2. Conversely, hsCRP level decreased by 21% at 1 week (P = 0.008) and was still reduced by 18% by 4 weeks (P = 0.062). The change in sCD40L expression appeared to vary with the type of drug eluting stent. Patients treated with drug eluting stents at 1 year after implantation display significant increase in sCD40L and decrease in hsCRP after clopidogrel cessation. Further studies should elucidate if this increase in sCD40L levels reflects solely the removal of the inhibitory effects of clopidogrel on platelet activity or rather an increase in pro-inflammatory state. The latter hypothesis may be less likely given decrease in hsCRP levels. Randomized studies are urgently needed to establish potential link of clopidogrel discontinuation and vascular outcomes

Implantable Cardioverter-Defibrillators for Primary Prevention in Patients With Ischemic or Nonischemic Cardiomyopathy: A Systematic Review and Meta-analysis.

Abstract BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have a role in preventing cardiac arrest in patients at risk for life-threatening ventricular arrhythmias. PURPOSE: To compare ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic or nonischemic cardiomyopathy. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, and EMBASE databases, as well as several Web sites, from 1 April 1976 through 31 March 2017. STUDY SELECTION: Randomized controlled trials, published in any language, comparing ICD therapy with conventional care and reporting mortality outcomes (all-cause, sudden, any cardiac, or noncardiac) in the primary prevention setting. DATA EXTRACTION: 2 independent investigators extracted study data and assessed risk of bias. DATA SYNTHESIS: Included were 11 trials involving 8716 patients: 4 (1781 patients) addressed nonischemic cardiomyopathy, 6 (4414 patients) ischemic cardiomyopathy, and 1 (2521 patients) both types of cardiomyopathy. Mean follow-up was 3.2 years. An overall reduction in all-cause mortality, from 28.26% with conventional care to 21.37% with ICD therapy (hazard ratio [HR], 0.81 [95% CI, 0.70 to 0.94]; P = 0.043), was found. The magnitude of reduction was similar in the cohorts with nonischemic (HR, 0.81 [CI, 0.72 to 0.91]) and ischemic (HR, 0.82 [CI, 0.63 to 1.06]) disease, although the latter estimate did not reach statistical significance. The rate of sudden death fell from 12.15% with conventional care to 4.39% with ICD therapy (HR, 0.41 [CI, 0.30 to 0.56]), with a similar magnitude of reduction in patients with ischemic (HR, 0.39 [CI, 0.23 to 0.68]) and those with nonischemic disease (HR, 0.44 [CI, 0.17 to 1.12]). Noncardiac and any cardiac deaths did not differ significantly by treatment. LIMITATION: Heterogeneous timing of ICD placement; heterogeneous pharmacologic and resynchronization co-interventions; trials conducted in different eras; adverse events and complications not reviewed. CONCLUSION: Overall, primary prevention with ICD therapy versus conventional care reduced the incidence of sudden and all-cause death. PRIMARY FUNDING SOURCE: None