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Update on ranolazine in the management of angina.

ABSTRACT: Mortality rates attributable to coronary heart disease have declined in recent years, possibly related to changes in clinical presentation patterns and use of proven secondary prevention strategies. Chronic stable angina (CSA) remains prevalent, and the goal of treatment is control of symptoms and reduction in cardiovascular events. Ranolazine is a selective inhibitor of the late sodium current in myocytes with anti-ischemic and metabolic properties. It was approved by the US Food and Drug Administration in 2006 for use in patients with CSA. Multiple, randomized, placebo-controlled trials have shown that ranolazine improves functional capacity and decreases anginal episodes in CSA patients, despite a lack of a significant hemodynamic effect. Ranolazine did not improve cardiovascular mortality or affect incidence of myocardial infarction in the MERLIN (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome)-TIMI (Thrombolysis In Myocardial Infarction) 36 trial, but significantly decreased the incidence of recurrent angina. More recently, ranolazine has been shown to have beneficial and potent antiarrhythmic effects, both on supraventricular and ventricular tachyarrhythmias, largely due to its inhibition of the late sodium current. Randomized controlled trials testing these effects are underway. Lastly, ranolazine appears to be cost-effective due to its ability to decrease angina-related hospitalizations and improve quality of life.

SUBMITTER: Codolosa JN

PROVIDER: S-EPMC4077852 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Update on ranolazine in the management of angina.

Codolosa J Nicolás JN Acharjee Subroto S Figueredo Vincent M VM

Vascular health and risk management 20140624

Mortality rates attributable to coronary heart disease have declined in recent years, possibly related to changes in clinical presentation patterns and use of proven secondary prevention strategies. Chronic stable angina (CSA) remains prevalent, and the goal of treatment is control of symptoms and reduction in cardiovascular events. Ranolazine is a selective inhibitor of the late sodium current in myocytes with anti-ischemic and metabolic properties. It was approved by the US Food and Drug Admin ...[more]

PMID: 25028555

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Project description:Background: Persistent angina is prevalent in women, who more often present with atypical angina, and experience less relief from antianginal therapies. The impact of ranolazine on female-specific angina is unclear. A single-arm, open-label trial was conducted to quantify the impact of ranolazine on angina in women with ischemic heart disease (IHD). Materials and Methods: Women with IHD and ≥2 angina episodes/week were recruited from 30 U.S. sites. Angina and nitroglycerin (NTG) consumption were assessed using patient-reported diaries, Seattle Angina Questionnaire (SAQ), Duke Activity Score Index (DASI), and Women's Ischemia Symptom Questionnaire (WISQ) at baseline and at 4 weeks of treatment with ranolazine 500 mg twice/day. A modified intent-to-treat analysis and parametric or nonparametric methods were used as appropriate to analyze changes. Results: Of 171 women enrolled, mean age was 65 ± 12 years. Of the 159 women included in the analysis, at week 4 compared to baseline, median angina frequency decreased with ranolazine treatment from 5.0 to 1.5 attacks/week and median change from baseline was -3.3 (95% confidence interval [CI]: -4.0 to -2.5; p ≤ 0.0001). Median NTG consumption decreased from 2.0 to 0.0 per week over the 4 weeks and median change was -1.0 (95% CI: -2.0 to -0.5; p < 0.0001). All five SAQ subscales showed mean improvements: physical limitation 9.2 (standard error [SE] 1.5; p < 0.0001), angina stability 31.8 (SE 2.7; p < 0.0001), angina frequency 17.7 (SE 1.6; p < 0.0001), treatment satisfaction 9.3 (SE 1.6; p < 0.0001), and disease perception 2.9 (SE 0.8; p < 0.0001). DASI score also improved 2.9 (SE 0.8; p = 0.0014). WISQ subscales also showed significant improvements (all p < 0.0001). Thirty-one women reported drug-related adverse events (AEs), predominantly mild to moderate gastrointestinal symptoms. Conclusions: Women with IHD treated with ranolazine for 4 weeks experienced less angina measured by SAQ and WISQ. NTG use decreased, physical activity improved, and treatment satisfaction improved. AEs were consistent with prior reports.

Project description:Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.

Dataset Information

Update on ranolazine in the management of angina.

Publications

Update on ranolazine in the management of angina.

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