Safety and efficacy of inclisiran in South African patients at high cardiovascular risk: A subanalysis of the ORION phase III clinical trials.

BACKGROUND: Inclisiran significantly reduced low-density lipoprotein cholesterol (LDL-C) in individuals with heterozygous familial hypercholesterolaemia, established atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents (type 2 diabetes, familial hypercholesterolaemia or a 10-year risk of a cardiovascular event ≥20%) in the ORION phase III clinical trials. Infrequent dosing at days 1, 90, 270 and 450 resulted in a mean LDL-C reduction of ~50%. A total of 298 participants from South Africa (SA) were enrolled. Local data are needed to support the use of inclisiran in the SA population, potentially addressing an unmet need for additional LDL-C-lowering therapies. Objectives. To analyse the ORION phase III trial data to assess the efficacy and safety of inclisiran in SA participants. Methods. ORION-9, 10 and 11 were randomised, double-blind, phase III trials. Participants were receiving maximally tolerated statins with or without other lipid-lowering therapies (excluding protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors). Participants were randomised 1:1 to inclisiran sodium 300 mg/284 mg (free acid) or placebo administered at days 1, 90, 270 and 450. The co-primary endpoints were the LDL-C percentage change from baseline to day 510 and the time-averaged percentage change in LDL-C from baseline after day 90 up to day 540. Key secondary endpoints included the absolute change in LDL-C from baseline to day 510, the time-averaged absolute change from baseline after day 90 up to day 540, and changes in other lipids and lipoproteins. Results. The mean age of the participants was 58.6 years (56% male). The mean LDL-C level at baseline was 3.6 mmol/L. At day 510, inclisiran reduced LDL-C levels by 54.2% compared with placebo (95% confidence interval (CI) -61.3 - -47.2; p<0.0001). The corresponding time-averaged reduction in LDL-C was 52.8% (95% CI -57.9 - -47.8; p<0.0001). Treatment-emergent adverse events at the injection site were more common with inclisiran compared with placebo (10.1% v. 0.7%); however, all were mild or moderate in nature and none were persistent. Conclusion. Inclisiran, given in addition to maximally tolerated standard lipid-lowering therapy, is effective and safe and results in robust reductions in LDL-C in SA patients at high cardiovascular risk.

Left atrial appendage closure in patients with atrial fibrillation in whom warfarin is contra-indicated: initial South African experience.

Atrial fibrillation is a common cause of cardiac embolic events, especially stroke. Oral anticoagulation therapy is used to reduce these events. Many patients however are unable to take such therapy. Percutaneous occlusion of the left atrial appendage (the source of 90% of these emboli) is an option in these patients. Presented here are the first 12 patients to have this procedure done in South Africa.

Mechanical thrombo-embolectomy in acute ischaemic stroke: a local experience.

Large-vessel ischaemic strokes have a very poor natural history. Thombolysis is indicated for the treatment of ischaemic stroke but in practice is given to less than 10% of stroke sufferers, and its efficacy in large-vessel occlusion is poor. Mechanical embolectomy is a new therapy that allows attempted revascularisation up to eight hours after stroke onset. With its improved efficacy, it therefore offers some hope to patients admitted with this devastating condition.

A case of rofecoxib-associated stevens-johnson syndrome with corneal and conjunctival changes.

PURPOSE: To report a case of rofecoxib (Vioxx)-associated Stevens-Johnson syndrome with corneal and conjunctival changes. DESIGN: Interventional case report. METHODS: Case report of a 62-year-old woman with systemic lupus erythematosus (SLE) taking rofecoxib for arthritis for 3 weeks. RESULTS: Stevens-Johnson syndrome after 3 weeks of rofecoxib therapy. CONCLUSION: This case report suggests that oral rofecoxib may trigger Stevens-Johnson syndrome, potentially causing symblepharons, corneal neovascularization and cicatricial ectropions.

Parachute mitral valve and a large ventricular septal defect in an asymptomatic adult.

I report here on an asymptomatic 28-year-old man with a parachute mitral valve associated with a significant ventricular septal defect and a stenosing supravalvular mitral ring. This condition has not been reported previously in an asymptomatic adult.

Evidence from gabbro of the Troodos ophiolite for lateral magma transport along a slow-spreading mid-ocean ridge.

The lateral flow of magma and ductile deformation of the lower crust along oceanic spreading axes has been thought to play a significant role in suppressing both mid-ocean ridge segmentation and variations in crustal thickness. Direct investigation of such flow patterns is hampered by the kilometres of water that cover the oceanic crust, but such studies can be made on ophiolites (fragments of oceanic crust accreted to a continent). In the Oman ophiolite, small-scale radial patterns of flow have been mapped along what is thought to be the relict of a fast-spreading mid-ocean ridge. Here we present evidence for broad-scale along-axis flow that has been frozen into the gabbro of the Troodos ophiolite in Cyprus (thought to be representative of a slow-spreading ridge axis). The gabbro suite of Troodos spans nearly 20 km of a segment of a fossil spreading axis, near a ridge-transform intersection. We mapped the pattern of magma flow by analysing the rocks' magnetic fabric at 20 sites widely distributed in the gabbro suite, and by examining the petrographic fabric at 9 sites. We infer an along-axis magma flow for much of the gabbro suite, which indicates that redistribution of melt occurred towards the segment edge in a large depth range of the oceanic crust. Our results support the magma plumbing structure that has been inferred indirectly from a seismic tomography experiment on the slow-spreading Mid-Atlantic Ridge.

Switching patients with glaucoma or ocular hypertension from dual therapy to monotherapy: evaluation of brimonidine as a model.

A multicenter open-label study investigated the clinical effectiveness and economic feasibility of switching 142 patients from dual therapy to twice-daily monotherapy with brimonidine for glaucoma or ocular hypertension. Evaluations were performed at baseline and 2 (visit 2) and 8 (visit 3) weeks after the switch. Patients completed a questionnaire that rated medication-related visual function and satisfaction (comfort, convenience, vision, ease of remembering to use drops) at each visit. At visit 3, investigators, taking into account IOP measurements, safety, and responses on the questionnaire, recommended whether the patient should remain on brimonidine. A pharmacoeconomic analysis, including the number of visits, cost of medication, and success rates, compared the cost of dual therapy with that of switching to brimonidine monotherapy. Of the 131 patients who completed the study, 77 (59%) had no change or a decrease in IOP from baseline, and 53 (41%) had an increase. Investigators recommended that 77% of the study completers continue to take brimonidine monotherapy. Extending treatment with brimonidine for 12 months would achieve a significant cost savings of 16%. Brimonidine monotherapy is an efficacious and cost-effective alternative to dual therapy for glaucoma and ocular hypertension. Appropriate monotherapy may be as effective as dual therapy for many patients, and a clinically relevant trial such as this may be economically advantageous for testing a switch.

Safety and efficacy comparison of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects with allergic conjunctivitis. Emadine Study Group.

PURPOSE: To determine the efficacy and tolerance of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects. METHODS AND MATERIALS: In a randomized, double-masked, parallel controlled study, emedastine 0.05% ophthalmic solution BID was compared to levocabastine 0.05% ophthalmic suspension BID, for control of the signs and symptoms of allergic conjunctivitis in pediatric subjects ages 3-16. Subjects who met all inclusion and exclusion criteria received masked study medication with instructions to instill drops twice daily, in the morning and evening. A diary was completed by the parents four times daily for the first two and last two weeks of the study. Treatment lasted 42 days. Drug efficacy was assessed at the initial administration in the office at Day 0 and after 3, 7, 14, 30 and 42 days. RESULTS: Overall results showed both drugs have an effect and that emedastine was significantly superior (p < 0.05) to levocabastine for the relief of chemosis on Days 14, 30 and 42; of itching on follow-up Days 30 and 42 (p < 0.05); of redness on Days 30 and 42; for eyelid swelling on Days 14 and 30; and for physician's impression score on Days 7, 14, 30 and 42. CONCLUSION: These results confirm previous preclinical and clinical data on the potent and long acting efficacy of this promising new ophthalmic anti-allergic drug, emedastine in pediatric subjects.

An efficacy and tolerance comparison of emedastine difumarate 0.05% and levocabastine hydrochloride 0.05%: reducing chemosis and eyelid swelling in subjects with seasonal allergic conjunctivitis. Emadine Study Group.

PURPOSE: To compare emedastine ophthalmic solution 0.05% BID to levocabastine ophthalmic suspension 0.05% BID in reducing chemosis, eyelid swelling and other signs and symptoms in subjects with seasonal allergic conjunctivitis. METHODS: In a randomized, double-masked, parallel controlled study, emedastine ophthalmic solution 0.05% BID was compared to levocabastine ophthalmic suspension 0.05% BID for control of chemosis, eyelid swelling and other parameters in the environmental allergy study model. RESULTS: At Days 7, 14, 30 and 42, emedastine was significantly better than levocabastine at controlling chemosis and eyelid swelling (p < 0.05). A statistical trend was seen at Day 3 (0.05 < p < 0.10). Results were clinically relevant at Days 30 and 42. Emedastine was also significantly better at reducing redness and itching at Days 7, 14, 30 and 42 (p < 0.05). CONCLUSION: Emedastine is more efficacious than levocabastine in reducing chemosis, eyelid swelling and other efficacy variables associated with seasonal allergic conjunctivitis.

An evaluation of onset and duration of action of patanol (olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin (loratadine 10 mg) tablets in acute allergic conjunctivitis in the conjunctival allergen challenge model.

PURPOSE: To compare the clinical efficacy of Patanol (olopatadine hydrochloride ophthalmic solution 0.1%) to Claritin (loratadine 10 mg) tablets, in the conjunctival allergen challenge model. METHODS: This was a randomized, double-masked, single center, contralateral controlled, antigen challenge model study. The concentration of allergen that elicited a positive response was determined at Visits 1 and 2 (itching > or = 2 and redness > or = 2 OU). At Visit 3, 29 subjects were randomized into two groups. Fifteen subjects received Claritin tablet and Patanol ophthalmic solution 0.1% in one eye and placebo in the contralateral eye. Fourteen subjects received placebo tablet and Patanol in one eye and placebo in the contralateral eye. One hour after drug administration, subjects were challenged with the antigen that elicited a positive response. At 3, 7, and 10 minutes, itching was subjectively evaluated. At Visit 4, the same procedure was followed as in Visit 3, but antigen challenge occurred 8 hours after drug instillation. RESULTS: Results were analyzed by eye. Eyes treated with Patanol (concomitant with placebo tablet) had significantly lower ocular itching scores when compared to eyes treated with placebo (concomitant with Claritin) at 3, 7 and 10 minutes in the onset of action evaluation (p < 0.05). Eyes treated with Patanol (concomitant with placebo tablet) had significantly lower ocular itching scores at 7 minutes and there was a statistical trend (0.05 < p < 0.1) at 10 minutes in duration of action evaluation. CONCLUSIONS: Patanol therapy was significantly more efficacious than Claritin in reducing ocular itching related to allergic conjunctivitis.