Vorapaxar for Prevention of Major Adverse Cardiovascular and Limb Events in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a severe manifestation of atherosclerosis. Patients with PAD are at heightened risk for atherothrombotic complications, including myocardial infarction and stroke (MACE); however, there is also an equal or greater risk of major adverse limb events (MALE), such as acute limb ischemia (ALI) and major amputation. Therefore, there is a need for effective medical therapies to reduce the risk of both MACE and MALE. Recent trials have demonstrated the role of thrombin inhibition in reducing the risk of MACE and MALE in PAD patients. One such medical therapy, vorapaxar, is a potent inhibitor of protease activated receptor-1 which mediates the cellular effects of thrombin. Vorapaxar, used in addition to aspirin, has demonstrated robust reductions in MACE and MALE in PAD patients. In this article, we provide a contemporary review of the current state of PAD and the role of antithrombotic medications in the treatment of PAD, as well as the current clinical data on vorapaxar and strategies to integrate vorapaxar into contemporary medical management of peripheral artery disease.

Medical Therapy for Secondary Prevention of Atherothrombotic Events in Peripheral Artery Disease.

Patients with peripheral artery disease (PAD) are at risk for severe morbidity and mortality, including ischaemic-related events. Furthermore, there is heterogeneity within the PAD population, where the drivers of risk for cardiovascular and limb-specific ischaemic events differ. Patients with PAD with concomitant coronary artery disease are at increased risk for cardiovascular ischaemic events, whereas patients with PAD with a prior history of lower-extremity revascularization are at increased risk for limb-specific ischaemic events. The current therapeutic challenge is identifying these risk factors to tailor therapy optimally for each patient. Additionally, the majority of our current medical therapeutics in patients with PAD have been shown to reduce atherothrombotic events, such as myocardial infarction, stroke and cardiovascular death, with a paucity of medical therapeutics specifically targeting a reduction in limb-specific ischaemic events. Over the past several years, there have been several contemporary clinical trials evaluating antithrombotic agents and their efficacy in reducing limb-specific ischaemic events. Specifically, rivaroxaban, with the addition of aspirin, has emerged as an efficacious therapeutic. In this article, we provide a review of the current clinical burden of PAD, the rationale behind current PAD medical therapeutics and the contemporary trials that have described the benefit of a novel therapeutic in PAD, rivaroxaban.

Effect of rosuvastatin on plasma coenzyme Q10 in HIV-infected individuals on antiretroviral therapy.

BACKGROUND: Coenzyme Q10 (CoQ10) deficiency has been associated with statin-induced myopathy, and supplementation with CoQ10 may reduce inflammation markers. The effects of statins on CoQ10 and its anti-inflammatory properties have not been investigated in HIV-positive patients. OBJECTIVE: The objectives of this study were to examine the effect of rosuvastatin on CoQ10 and CoQ10/LDL ratio over 24-week SATURN-HIV trial, explore the associations between CoQ10 levels and markers of vascular disease, inflammation, and immune activation, and assess whether changes in CoQ10 affected the anti-inflammatory effects of statin therapy or were associated with myalgia symptoms. METHODS: This was a secondary analysis of the SATURN-HIV trial, a 96-week randomized clinical trial of 10 mg daily rosuvastatin vs. placebo in HIV-infected patients on antiretroviral therapy. We assessed the statin treatment effect on CoQ10 levels and CoQ10/LDL ratios and whether changes in these markers were related to myalgias. Relationships between CoQ10, subclinical vascular disease, and biomarkers of inflammation and immune activation were explored using Spearman correlations and multivariable regression models. RESULTS: Overall, 147 patients were included. Median age was 46 years; 78% were male and 68% African American. At baseline, CoQ10 levels and CoQ10/LDL ratio were modestly correlated with markers of HIV disease, immune activation, and carotid distensibility. After 24 weeks of statin therapy, CoQ10 levels decreased (p = 0.002 for between group difference) and CoQ10/LDL ratio increased (p = 0.036). In the statin treatment arm, we did not find evidence of a relationship between changes in CoQ10 or CoQ10/LDL ration and changes in markers of inflammation or immune activation. There was a borderline statistically significant association between changes in CoQ10 and myalgia symptoms [OR 4.0 per 0.1 mg/L decrease in CoQ10, p = 0.07]. CONCLUSION: Twenty-four weeks of 10 mg daily rosuvastatin decreases CoQ10 concentration and increases CoQ10/LDL ratio in HIV-infected patients on antiretroviral therapy.