Effect of Ivabradine on Endothelial Function in Patients with Stable Angina Pectoris: Assessment with the Endo-PAT 2000 Device.

INTRODUCTION: Ivabradine has opened up new possibilities for treating stable angina and chronic heart failure by lowering heart rate. Ivabradine lowers heart rate by selectively inhibiting the I f current in the sinoatrial node. This study aimed to determine whether the decrease in heart rate achieved with ivabradine was accompanied by hemodynamic changes that might lead to an enhancement of endothelial function. METHODS: Thirty patients with stable angina pectoris were included in the study. Ivabradine (5 mg bid) was added to the recommended standard treatment. Endothelial function was assessed at baseline and after 3 months of ivabradine therapy, with an Endo-PAT 2000 device (Itamar Medical, Israel). This device was recently developed for the noninvasive assessment for endothelial dysfunction. We evaluated reactive hyperemia index (RHI), which reflects endothelial function, and augmentation index (AI), which provides an indication of arterial stiffness. RESULTS: The study population consisted of 25 (83.3%) men and five (16.7%) women. The mean age of the patients was 65.4 ± 6.7 years. Twenty-eight (93.3%) patients had a history of myocardial infarction (ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction), 23 (76.6%) had undergone revascularization (percutaneous coronary intervention or coronary artery bypass graft), 16 (53.3%) had type 2 diabetes mellitus, and 29 (96.6%) had arterial hypertension. The mean resting heart rate decreased significantly, from 77 ± 7 bpm at the start of the study to 65 ± 6 bpm after treatment (P < 0.0001). Endothelial function was found to have improved significantly after 3 months of ivabradine therapy. Mean RHI before treatment was 1.54 ± 0.30, suggesting probable endothelial dysfunction, whereas mean RHI at the end of the study was 1.83 ± 0.36 (P < 0.0001). AI also improved significantly on treatment, from 21 ± 20% to 10 ± 21% (P < 0.0001). CONCLUSION: The addition of ivabradine to the treatment regimen of patients with stable angina pectoris both lowered heart rate and improved endothelial function. However, broader, randomized, double-blind, placebo-controlled clinical trials are required to confirm these findings.

Coenzyme Q(10) and selenium in statin-associated myopathy treatment.

The objective of this study was to evaluate the possible benefits of coenzyme Q10 and selenium supplementation administered to patients with statin-associated myopathy (SAM). Sixty eligible patients entered the pilot study. Laboratory examination (CoQ10, selenium, creatin kinase) and intensity of SAM (visual scale) were performed at baseline, after 1 month, and at the end of study at month 3. Plasma levels of CoQ10 increased from 0.81 ± 0.39 to 3.31 ± 1.72 µmol/L in the active group of patients treated by CoQ10, compared with the placebo (p = 0.001). Also, the symptoms of SAM significantly improved in the active group (p < 0.001): the intensity of muscle pain decreased from 6.7 ± 1.72 to 3.2 ± 2.1 (p < 0.01, -53.4 ± 28.2%); muscle weakness decreased from 7.0 ± 1.63 to 2.8 ± 2.34 (p < 0.01, -60 ± 24.0%); muscle cramps decreased from 5.33 ± 2.06 to 1.86 ± 2.42, p < 0.01, -65 ± 28%); tiredness decreased from the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p < 0.01, -82 ± 22%). We did not observe any significant changes in the placebo group. In conclusion, supplementation of statin-treated patients with CoQ10 resulted in a decrease in the symptoms of SAM, both in absolute numbers and intensity. Additional selenium supplementation was not associated with any statistically significant decrease of SAM. However, it is not possible to draw any definite conclusions, even though this study was carried out in double-blind fashion, because it involved a small number of patients.

Slovak trial on cardiovascular risk reduction following national guidelines with CaDUET® (the STRONG DUET study).

INTRODUCTION: The efficacy and safety of single-pill amlodipine/atorvastatin for reducing blood pressure (BP), low-density lipoprotein cholesterol (LDLC), and predicted 10-year cardiovascular (CV) risk have been demonstrated in low CV risk countries. The Slovak Trial on Cardiovascular Risk Reduction Following National Guidelines with CaDUET® (amlodipine besylate/atorvastatin calcium; Pfizer, Morrisville, PA, USA; STRONG DUET) study evaluated its clinical utility in Slovakia, one of the highest CV risk regions in Europe. METHODS: This was a two-phase study involving 100 outpatient cardiologist and internist departments in Slovakia. Phase 1 assessed BP control and CV risk profiles in adults with treated hypertension, and phase 2 was an open-label, multicenter, observational study. In the phase 2 study, patients with treated but uncontrolled hypertension and three or more coronary heart disease risk factors received single-pill amlodipine/atorvastatin (5/10 or 10/10 mg) for 12 weeks. Major outcomes were the percentage of patients achieving target BP (≤140/90 mmHg) and/or LDL-C (≤3 mmol/L) and reductions in predicted 10-year CV risk. RESULTS: Of the 4,672 phase 1 patients, 80.8% had uncontrolled hypertension and 61.4% had dyslipidemia. Of the 1,406 phase 2 patients, 90.3% of patients achieved target BP at week 12, 66.3% achieved target LDL-C, and 60.7% achieved both. The mean 10-year CV risk was reduced by 49% (P < 0.0001); treatment was well-tolerated and safe. CONCLUSION: Single-pill amlodipine/atorvastatin was associated with significant improvements in BP, LDL-C target attainment, and 10-year CV risk in patients with uncontrolled hypertension in Slovakia. The treatment was well-tolerated and safe. Use of single-pill amlodipine/atorvastatin in high CV-risk countries could lead to significant improvements in CV risk management.