1.
LDL cholesterol, statins and PCSK 9 inhibitors.
Gupta, S
Indian heart journal. 2015;(5):419-24
Abstract
Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20-30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through 'Risk evaluation and Mitigation Strategy (REMS)'. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and Bococizumab are under advanced clinical stage IV trials and awaiting approval by FDA and European Medicines Agency.
2.
Impact of lipid-lowering medications and low-density lipoprotein levels on 1-year clinical outcomes after coronary artery bypass grafting.
Quin, JA, Hattler, B, Bishawi, M, Baltz, J, Gupta, S, Collins, JF, Grover, FL, McDonald, G, Shroyer, AL
Journal of the American College of Surgeons. 2013;(3):452-60
Abstract
BACKGROUND Studies investigating lipid-lowering medication (LLM) use and LDL levels in coronary artery bypass grafting patients are limited. STUDY DESIGN The Veterans Affairs Randomized On/Off Bypass Trial's patient records were analyzed for LLM use and 1-year LDL levels. Mortality, acute MI (AMI), and repeat revascularization rates were compared at 1 year between patients with and without LLM at discharge. In addition, AMI, repeat revascularization, and graft patency were compared between patients that did and did not achieve a 1-year LDL target level of <100 mg/dL. RESULTS The LLM data were available for 86.4% (1,904 of 2,203) of patients. Rates of LLM use were 83.4% (1,316 of 1,577) at discharge and 90.0% (1,713 of 1,904) at 1 year. Patients discharged after coronary artery bypass grafting on LLMs had a significantly lower 1-year mortality rate (1.9% vs 5.4%; p < 0.01) than those not discharged on LLM, and 1-year AMI and repeat revascularization rates were not significantly different. Of the patients with 1-year LDL measurements, 69.4% (1,200 of 1,729) achieved an LDL target level of <100 mg/dL. No differences were seen in AMI, revascularization, or graft occlusion rates between patients who achieved target LDL levels and those who did not. CONCLUSIONS Rates of LLM use among veterans post-coronary artery bypass grafting are high. Discharge on LLM might be associated with improved intermediate-term survival. Patients who achieved an LDL target of <100 mg/dL at 1-year did not experience improved 1-year clinical outcomes or graft patency. Longer-term follow-up might reveal differences in cardiac outcomes related to achievement of target LDL levels.
3.
Consequences of succinylcholine administration to patients using statins.
Turan, A, Mendoza, ML, Gupta, S, You, J, Gottlieb, A, Chu, W, Saager, L, Sessler, DI
Anesthesiology. 2011;(1):28-35
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Abstract
BACKGROUND Statins cause structural changes in myocytes and provoke myotoxicity, myopathy, and myalgias. Thus, patients taking statins may be especially susceptible to succinylcholine-induced muscle injury. The authors tested the hypothesis that succinylcholine increases plasma concentrations of myoglobin, potassium, and creatine kinase more in patients who take statins than in those who do not and that succinylcholine-induced postoperative muscle pain is aggravated in statin users. METHODS Patients who took statins for at least 3 months and those who had never used statins were enrolled. General anesthesia was induced and included 1.5 mg/kg succinylcholine for intubation. The incidence and degree of fasciculation after succinylcholine administration were recorded. Blood samples were obtained before induction and 5 and 20 min and 24 h after succinylcholine administration. Patients were interviewed 2 and 24 h after surgery to determine the degree of myalgia. RESULTS The authors enrolled 38 patients who used statins and 32 who did not. At 20 min, myoglobin was higher in statin users versus nonusers (ratio of medians 1.34 [95% CI: 1.1, 1.7], P = 0.018). Fasciculations in statin users were more intense than in nonusers (P = 0.047). However, plasma potassium and creatine kinase concentrations were similar in statin users and nonusers, as was muscle pain. CONCLUSIONS The plasma myoglobin concentration at 20 min was significantly greater in statin users than nonusers, although the difference seems unlikely to be clinically important. The study results suggest that the effect of succinylcholine given to patients taking statins is likely to be small and probably of limited clinical consequence.
4.
Does aggressive statin therapy offer improved cholesterol-independent benefits compared to conventional statin treatment?
Gupta, S
International journal of cardiology. 2004;(2):131-9
Abstract
There is currently intense research interest in the properties of HMG-CoA reductase inhibitors (statins) beyond their well-documented lipid-lowering action. Studies have consistently demonstrated that administration of statin therapy decreases levels of the inflammatory marker C-reactive protein (CRP), a marker associated with an increased risk of cardiovascular events. This effect appears to be independent of the extent of reduction in total or LDL-cholesterol. Statins also appear to improve endothelial dysfunction by increasing endothelium-dependent vasodilatation. There is also evidence that statins inhibit fibrin formation and thrombus development, an effect that which would be clinically beneficial following plaque fissure or rupture. Early preclinical and clinical evidence suggests that there are quantitative differences between statin regimens in terms of their cholesterol-independent properties. Trials comparing equipotent doses of different statins, based on lipid-lowering efficacy, have not reported any differences in cholesterol-independent properties. However, the current evidence base indicates that more aggressive statin regimens are associated with an enhanced anti-inflammatory effect. Intensive lipid-lowering using statin therapy generates a greater reduction in mortality than standard lipid management, and it is possible that enhanced cholesterol-independent effects may account for some of this excess benefit.