Recent reports indicate that statins are associated with an increased risk for new-onset diabetes mellitus (DM) compared with placebo and that this relation is dose dependent. The aim of this study ...was to perform a comprehensive network meta-analysis of randomized controlled trials (RCTs) investigating the impact of different types and doses of statins on new-onset DM. RCTs comparing different types and doses of statins with placebo were searched for using the MEDLINE, Embase, and Cochrane databases. A search of RCTs pertinent to this meta-analysis covering the period from November 1994 to October 2012 was conducted by 2 independent investigators using the MEDLINE, Cochrane, Google Scholar, and Embase databases as well as abstracts and presentations from major cardiovascular meetings. Seventeen RCTs reporting the incidence of new-onset DM during statin treatment and including a total of 113,394 patients were identified. The RCTs compared either a statin versus placebo or high-dose versus moderate-dose statin therapy. Among different statins, pravastatin 40 mg/day was associated with the lowest risk for new-onset DM compared with placebo (odds ratio 1.07, 95% credible interval 0.86 to 1.30). Conversely, rosuvastatin 20 mg/day was numerically associated with 25% increased risk for DM compared with placebo (odds ratio 1.25, 95% credible interval 0.82 to 1.90). The impact on DM appeared to be intermediate with atorvastatin 80 mg/day compared with placebo (odds ratio 1.15, 95% credible interval 0.90 to 1.50). These findings were replicated at moderate doses. In conclusion, different types and doses of statins show different potential to increase the incidence of DM.
Coronary artery disease (CAD) is a major challenge in patients with type 2 diabetes (T2D). Coronary computed tomography angiography (CCTA) provides a detailed anatomic map of the coronary ...circulation. Proteomics are increasingly used to improve diagnostic and therapeutic algorithms. We hypothesized that the protein panel is differentially associated with T2D and CAD.
In CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation-a cohort of 528 individuals with no previous cardiovascular event undergoing CCTA), participants were grouped into CAD
(clean coronaries) and CAD
(diffuse lumen narrowing or plaques). Plasma proteins were screened by aptamer analysis. Two-way partial least squares was used to simultaneously rank proteins by diabetes status and CAD.
Though CAD
was more prevalent among participants with T2D (HbA
6.7 ± 1.1%) than those without diabetes (56 vs. 30%,
< 0.0001), CCTA-based atherosclerosis burden did not differ. Of the 20 top-ranking proteins, 15 were associated with both T2D and CAD, and 3 (osteomodulin, cartilage intermediate-layer protein 15, and HTRA1) were selectively associated with T2D only and 2 (epidermal growth factor receptor and contactin-1) with CAD only. Elevated renin and GDF15, and lower adiponectin, were independently associated with both T2D and CAD. In multivariate analysis adjusting for the Framingham risk panel, patients with T2D were "protected" from CAD if female (
= 0.007), younger (
= 0.021), and with lower renin levels (
= 0.02).
We concluded that
) CAD severity and quality do not differ between participants with T2D and without diabetes;
) renin, GDF15, and adiponectin are shared markers by T2D and CAD;
) several proteins are specifically associated with T2D or CAD; and
) in T2D, lower renin levels may protect against CAD.
The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) ...Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.
Atrial fibrillation (AF) is an independent risk factor for thromboembolism and stroke. Women with AF are at a higher overall risk for thromboembolic stroke when compared to men with AF. Recent ...evidence suggests that female sex, after adjusting for stroke risk profile and sex differences in utilisation of anticoagulation, is an independent stroke risk factor in AF. The inclusion of female sex has improved the accuracy of the CHADS2 stroke risk stratification schema (Congestive heart failure, Hypertension, Age 75 years or greater, Diabetes mellitus, and prior Stroke or TIA). The newly revised and validated schema, CHA2DS2-VASc, dichotomises age and incorporates female sex and vascular disease history. The pathophysiological mechanisms to explain this increased risk in women are not well understood. According to Virchow's triad, thrombosis that leads to stroke in AF should arise from three co-existing phenomena: structural abnormalities, blood stasis, and a hypercoagulable state. Herein, we explore the sex differences in the biological processes that lead to thrombus formation as applied to Virchow's Triad. The objective of this review is to describe the potential mechanisms behind the increased risk of stroke in AF associated with female sex.
Aims In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific ...meta-analysis of randomized trials comparing aspirin plus warfarin (A+W) with aspirin alone in such patients. Methods and results MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), A+W did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone OR 0.96 (0.90–1.03), P=0.30, but increased the risk of major bleeds (MB): OR 1.77 (1.47–2.13), P<0.00001. However, in studies with INR of 2–3, A+W was associated with a significant reduction of MAE OR 0.73 (0.63–0.84), P<0.0001, number needed to treat to avoid one MAE=33, albeit at an increased risk of MB OR 2.32 (1.63–3.29), P<0.00001; number needed to harm by causing one MB=100. In both analyses, intracranial bleeding was not significantly increased by A+W when compared with aspirin alone. Conclusion For patients recovering from ACS, a combined strategy of A+W at INR values of 2–3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a ‘double’ anti-platelet strategy or to newer evolving treatments warrants further investigation.
Patients with acute coronary syndromes (ACSs) still experience high rates of recurrent coronary events, particularly, early in their presentation. Statins yield substantial cardiovascular benefits, ...but the optimal timing of their administration, before or after percutaneous coronary intervention (PCI), remains unclear. We aimed to perform a meta-analysis of randomized controlled trials of statin administration before or after PCI versus no statin or low-dose statin in patients with ACS. Primary end points were 30-day all-cause mortality and 30-day myocardial infarction (MI) stratified by pre- and post-PCI statin administration. Secondary end points were major adverse cardiac events (MACEs) or major adverse cardiac and cerebrovascular events (MACCEs). Long-term analysis beyond 30 days was also performed. Twenty randomized controlled trials enrolling 8,750 patients were included. At 30 days, the rate of MI was significantly lower in the statin group (odds ratio OR 0.67, 95% confidence interval CI 0.53 to 0.84, p = 0.0007) with a trend toward reduced mortality (p = 0.06) and significant reductions in MACE and MACCE compared with no or low-dose statin. The 30-day incidence of MI was markedly lower when statins were administered before PCI (OR 0.38, 95% CI 0.24 to 0.59, p <0.0001) rather than after PCI (p = 0.28). The direction and magnitude of the estimates for before and after PCI versus no statin or low-dose statin were sustained at long term, not reaching statistical significance for MI (OR 0.81, 95% CI 0.65 to 1.01, p = 0.06) but with significant reductions in MACE (p = 0.0002). By meta-regression, earlier statin administration correlated significantly with lower risk of MI, MACE, and MACCE at 30 days. In conclusion, the present meta-analysis indicates a time-related impact of statin therapy on clinical outcomes of patients with ACS undergoing PCI: the earlier the administration before PCI, the greater the benefits.
Percutaneous coronary intervention (PCI) is considered a relatively safe procedure associated with low rates of complications, but is inevitably associated with short and mid-to-long term increased ...bleeding risk. Besides the short term risk associated with the arterial access to perform PCI, enhanced bleeding risk persists for several months, given the need for antithrombotic therapy to prevent procedure-related thrombotic complications as well as ischemic recurrences. Bleeding is a powerful harbinger of adverse outcomes. This awareness has fuelled intense research on bleeding reduction strategies, including new PCI devices and techniques as well as new medications and antithrombotic regimens. We here review the mechanisms and prevalence of bleeding in PCI patients, discuss the available evidence from a practical point of view, and explore future perspectives on how to treat and prevent bleeding complications in these patients.Percutaneous coronary intervention (PCI) is considered a relatively safe procedure associated with low rates of complications, but is inevitably associated with short and mid-to-long term increased bleeding risk. Besides the short term risk associated with the arterial access to perform PCI, enhanced bleeding risk persists for several months, given the need for antithrombotic therapy to prevent procedure-related thrombotic complications as well as ischemic recurrences. Bleeding is a powerful harbinger of adverse outcomes. This awareness has fuelled intense research on bleeding reduction strategies, including new PCI devices and techniques as well as new medications and antithrombotic regimens. We here review the mechanisms and prevalence of bleeding in PCI patients, discuss the available evidence from a practical point of view, and explore future perspectives on how to treat and prevent bleeding complications in these patients.
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