PCSK9 inhibitors: A new era of lipid lowering therapy

Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.

Erythropoietin therapy after out-of-hospital cardiac arrest:A systematic review and meta-analysis

AIM To assess safety and efficacy of early erythropoietin(Epo) administration in patients with out-of-hospital cardiac arrest(OHCA).METHODS A systematic literature search was performed using PubM ed,MEDLINE,EMBASE,EBSCO,CINAHL,Web of Science and Cochrane databases,of all studies published from the inception through October 10,2016.Inclusion criteria included:(1) Adult humans with OHCA and successful sustained return of spontaneous circulation;and(2) studies including mortality/brain death,acute thrombotic events as their end points.Primary efficacyoutcome was "brain death or Cerebral Performance Category(CPC) score of 5".Secondary outcomes were "CPC score 1,and 2-4","overall thrombotic events" and "acute coronary stent thrombosis".RESULTS We analyzed a total of 606 participants(n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials.No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5(OR = 0.77;95%CI:0.42-1.39),CPC score 1(OR = 1.16,95%CI:0.82-1.64),and CPC score 2-4(OR = 0.77,95%CI:0.44-1.36).Epo group was associated with increased thrombotic complications(OR = 2.41,95%CI:1.26-4.62) and acute coronary stent thrombosis(OR = 8.16,95%CI:1.39-47.99).No publication bias was observed.CONCLUSION Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.

Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery

AIM: To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide(SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia. METHODS: A total of 400 patients were randomized into 2 groups; Group A(200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine(0.5%) with ofloxacin(0.3%) combination for 3 wk. Group B(200 patients) received tapering topical loteprednol etabonate(0.5%) along with ofloxacin(0.3%) and ketorolac tromethamine(0.5%) for 3 wk. Outcomes evaluated were intraocular pressure(IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12 wk.RESULTS: Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A(P=0.82) and Group B(P=0.61) and postoperative IOP values in between both groups(P=0.14) at 1 wk. Incidence of cells/flare postoperative was statistically not significant(P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit. CONCLUSION: SCTA appears to be an effective alternative to prolong postoperative topical steroid use.