Clinical therapeutics
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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
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
Randomized Controlled TrialIpragliflozin does not prolong QTc interval in healthy male and female subjects: a phase I study.
Ipragliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, is in development for the treatment of type 2 diabetes mellitus. The International Conference on Harmonisation recommends that the safety investigation of new drugs include characterization of each agent's effects on the QT/QTc interval. ⋯ No clinically meaningful QTc interval prolongation was observed in these healthy subjects who received ipragliflozin doses up to 600 mg/d for 7 days. ClinicalTrials.gov identifier: NCT01232413.
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Clinical therapeutics · Aug 2013
Comparative StudyCost-effectiveness of 12-month treatment with ticagrelor compared with clopidogrel in the management of acute coronary syndromes.
The PLATO (Platelet Inhibition and Patient Outcomes) randomized trial (NCT00391872) in patients with acute coronary syndromes (ACS) reported that ticagrelor (in addition to aspirin) reduced the rate of the composite end point of myocardial infarction (MI), stroke, or cardiovascular death compared with clopidogrel (in addition to aspirin) by 16% over 12 months (P < 0.001). No significant difference in the incidence of major bleeding was noted, but ticagrelor was associated with a higher rate of major bleeding not related to coronary artery bypass grafting. ⋯ When assessed from the perspective of the Australian health care system, ticagrelor is likely to be cost-effective compared with clopidogrel in preventing downstream morbidity and mortality associated with ACS.