No effect of switching to high-dose rosuvastatin, add-on nicotinic acid, or add-on fenofibrate on serum vitamin D levels in patients with mixed dyslipidemia.

BACKGROUND: Low 25-hydroxy-vitamin D [25(OH)VitD] levels may represent a novel cardiovascular disease risk factor. Several statins may increase 25(OH)VitD concentration. The effect of other lipid-lowering drugs is unknown. AIM: To investigate whether switching to high-dose rosuvastatin, add-on-statin nicotinic acid or add-on-statin fenofibrate would alter 25(OH)VitD levels in patients with mixed dyslipidemia who are already on a conventional statin dose. METHODS: This is a prespecified analysis of a previously published study. Forty-four patients with mixed dyslipidemia not at treatment goal despite treatment with simvastatin 10-40 mg or atorvastatin 10-20 mg or rosuvastatin 5-10 mg were randomly allocated to switch to rosuvastatin 40 mg (n=17), add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) (1000/20 mg first four weeks and 2000/40 mg thereafter) (n=14), or add-on-statin micronized fenofibrate (200 mg) for three months. The endpoint for this analysis was between-group difference in changes in 25(OH)VitD levels. RESULTS: Serum 25(OH)VitD levels did not significantly change in any group. In the switch to the highest dose of rosuvastatin group and the add-on-statin ER-NA/LRPT group there was an insignificant decrease in 25(OH)VitD levels {-4.7% [from 16.8 (3.2-37) to 16.0 (7.9-51.6)] and -14.8% [from 12.8 (2.0-54.8) to 10.9 (2.4-34)], respectively]}, while in the add-on-statin fenofibrate group there was an insignificant increase [+13% (from 14.5 (1.0-42) to 16.4 (4.4-30.4) ng/mL)]. No significant difference between groups was found. CONCLUSION: In patients already on a conventional statin dose, neither switching to high-dose rosuvastatin (40 mg) nor add-on-statin ER-NA/LRPT or fenofibrate were associated with significant changes in 25(OH)VitD serum levels. Hippokratia 2015; 19 (2):136-140.

The incidence and clinical predictors of ACE-inhibitor induced dry cough by perindopril in 27,492 patients with vascular disease.

OBJECTIVES: Our objective was to investigate the actual incidence and clinical determinants of cough leading to discontinuation of ACE-inhibitors. Cough is the most frequent reason to stop ACE-inhibitor treatment. METHODS: We studied 27,492 ACE-inhibitor naïve patients randomized to the ACE-inhibitor perindopril or placebo using individual data of 3 clinical trials. Multivariate logistic regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. RESULTS: In 27,492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor perindopril due to cough (3.9%), 703 patients during run-in period of 4 weeks and 373 patients during a mean four years of follow-up. Significant determinants of cough were female gender (OR 1.92 95% CI 1.68-2.18), age above 65 years (OR 1.53 95% CI 1.35-1.73), and concomitant use of lipid-lowering agents (OR 1.37; 95% CI 1.18-1.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 4.4 (95% CI 3.1-5.4) in the subjects with highest score (i.e. all determinants present). Racial background was not related to a differential incidence of cough in patients of Caucasian or Asian descendent (OR 1.11 95% CI 0.92-1.39). CONCLUSION: This large combined analysis of randomized clinical trials in 27,492 patients showed an overall lower incidence of cough leading to discontinuation of ACE-inhibitors (3.9%) as compared to literature. Clinical determinants of such cough are older age, female gender and concomitant use of lipid-lowering agents. In contrast, racial differences were not related to the incidence of cough.

Is statin-induced diabetes clinically relevant? A comprehensive review of the literature.

In those predisposed to the development of diabetes (the insulin resistant, obese and older patients) statins may increase the risk of developing diabetes. Despite the fact that the conversion to diabetes is generated from post hoc analyses, it seems to be a class effect with a dose-response relationship. However, statins have not been clearly shown to increase diabetic microvascular complications (retinopathy, nephropathy and neuropathy). Thus, the clinical significance of increased glucose levels in patients treated on statins is uncertain. While the exact mechanism for how statins increase the risk of diabetes is unknown, a possible explanation is through a reduction in adiponectin levels. Despite the fact that higher statin doses are more likely to lead to new-onset diabetes, for every case of diabetes caused, there are approximately three cardiovascular events reduced with high dose versus moderate dose statin therapy. Overall, the small risk of developing type 2 diabetes with statin therapy is far outweighed by the potential of statins to decrease cardiac events.