Clinical therapeutics
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Clinical therapeutics · Aug 2013
ReviewManagement of acute coronary syndromes in patients with diabetes: implications of the FREEDOM trial.
Diabetes mellitus (DM) is a powerful independent risk factor for multivessel, diffuse coronary artery disease (CAD). The optimal coronary revascularization strategy in DM is not clearly defined, but past trials have suggested an advantage for coronary artery bypass grafting (CABG). Recently, the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial found patients randomized to CABG had lower rates of death and myocardial infarction (MI) compared with those randomized to percutaneous coronary intervention (PCI). ⋯ The optimal revascularization strategy in patients with acute coronary syndrome, diabetes, and multivessel disease, in particular those with ST elevation, is unclear, and not guided by level A (or B) evidence. Currently CABG is favored over PCI, and an individually tailored, collaborative approach, guided by a multidisciplinary heart team, should be employed.
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Clinical therapeutics · Aug 2013
ReviewNew LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes.
Reduction in plasma low-density lipoprotein cholesterol (LDL-C) is a fundamental treatment for the prevention of acute coronary syndromes (ACS). Although statin therapy confers significant protection against ACS in both primary and secondary prevention, a considerable residual risk remains after intensive therapy. In addition, a significant proportion of high-risk patients do not achieve the optimal LDL-C goal recommended in the current guidelines (<1.8 mmol/L). Hence, novel LDL-C-lowering agents that act via mechanisms distinct from HMG-CoA reductase inhibition are under investigation. ⋯ PCSK9, apoB, and MTTP inhibitors can exert potent reductions in plasma LDL-C and apoB concentrations, either as monotherapy or in combination with statins. These effects are particularly relevant to high-risk individuals with marked hypercholesterolemia, such as those with familial hypercholesterolemia. Although the use of mipomersen and lomitapide is limited to severe familial hypercholesterolemia as a replacement for LDL-apheresis, PCSK9 inhibitors are likely to be more widely prescribed in patients at high risk for CVD, especially those who are resistant to or intolerant of high-intensity statin therapy. PCSK9 mAbs are efficacious and have an excellent safety profile, but their long-term impact on cardiovascular events is currently under investigation. Whether PCSK9 mAbs decrease the rates of recurrent cardiovascular events within 3 months following ACS is questionable; however, these agents, unlike statins, may not have pleiotropic benefits on the unstable plaque.
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Clinical therapeutics · Aug 2013
ReviewNew antiplatelet agents and the role of platelet function testing in acute coronary syndromes.
Dual antiplatelet therapy is a guideline mandated for patients with acute coronary syndromes (ACS). Despite its use, thrombotic events continue to occur both early and late. Platelet function testing has been used to define the in vitro effects of new antiplatelet agents, and it has been suggested that it be used to choose therapy. The role of platelet function testing, particularly with newer antiplatelet agents, remains unclear. ⋯ Recent clinical trials have indicated that newer antiplatelet agents have advantages over clopidogrel in the treatment of ACS. Platelet function testing gives us a guide to the timing, efficacy, and variability of therapy and can correlate with poor patient outcomes; however, the use of antiplatelet function testing to tailor therapy does not seem appropriate.
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Clinical therapeutics · Aug 2013
Randomized Controlled Trial Multicenter Study Comparative StudyA randomized, double-blind study of fenofibric acid plus rosuvastatin compared with rosuvastatin alone in stage 3 chronic kidney disease.
Patients with chronic kidney disease (CKD) often have mixed dyslipidemia and high cardiovascular disease risk. Although statins reduce LDL-C, adding a fibrate may further improve lipid parameters. ⋯ The data suggest that, after 16 weeks of therapy, FA + R has an acceptable safety profile and improved TG and HDL-C efficacy versus R. FA + R combination therapy may thus further improve lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. ClinicalTrials.gov identifier: NCT00680017.
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Clinical therapeutics · Aug 2013
Review Meta AnalysisEffects of aggressive statin therapy on patients with coronary saphenous vein bypass grafts: a systematic review and meta-analysis of randomized, controlled trials.
The aim of this study was to investigate the effectiveness and safety of aggressive statin versus moderate statin therapy on patients with saphenous vein grafts (SVGs) in randomized, controlled trials (RCTs). ⋯ Compared with moderate statin therapy, long-term aggressive statin lowered the LDL-C level significantly, further decreased the atherosclerotic progression of SVG, reduced the risks of repeated myocardial infarction and coronary revascularization after CABG, and revealed similar patient compliance and statin-related adverse effects but slightly increased myopathy events and aminotransferase levels.