Initiation of rivaroxaban in patients with nonvalvular atrial fibrillation at the primary care level: the Swiss Therapy in Atrial Fibrillation for the Regulation of Coagulation (STAR) Study.

BACKGROUND: Rivaroxaban has become an alternative to vitamin-K antagonists (VKA) for stroke prevention in non-valvular atrial fibrillation (AF) patients due to its favourable risk-benefit profile in the restrictive setting of a large randomized trial. However in the primary care setting, physician's motivation to begin with rivaroxaban, treatment satisfaction and the clinical event rate after the initiation of rivaroxaban are not known. METHODS: Prospective data collection by 115 primary care physicians in Switzerland on consecutive nonvalvular AF patients with newly established rivaroxaban anticoagulation with 3-month follow-up. RESULTS: We enrolled 537 patients (73±11years, 57% men) with mean CHADS2 and HAS-BLED-scores of 2.2±1.3 and 2.4±1.1, respectively: 301(56%) were switched from VKA to rivaroxaban (STR-group) and 236(44%) were VKA-naïve (VN-group). Absence of routine coagulation monitoring (68%) and fixed-dose once-daily treatment (58%) were the most frequent criteria for physicians to initiate rivaroxaban. In the STR-group, patient's satisfaction increased from 3.6±1.4 under VKA to 5.5±0.8 points (P<0.001), and overall physician satisfaction from 3.9±1.3 to 5.4±0.9 points (P<0.001) at 3months of rivaroxaban therapy (score from 1 to 6 with higher scores indicating greater satisfaction). In the VN-group, both patient's (5.4±0.9) and physician's satisfaction (5.5±0.7) at follow-up were comparable to the STR-group. During follow-up, 1(0.19%; 95%CI, 0.01-1.03%) ischemic stroke, 2(0.37%; 95%CI, 0.05-1.34%) major non-fatal bleeding and 11(2.05%; 95%CI, 1.03-3.64%) minor bleeding complications occurred. Rivaroxaban was stopped in 30(5.6%) patients, with side effects being the most frequent reason. CONCLUSION: Initiation of rivaroxaban for patients with nonvalvular AF by primary care physicians was associated with a low clinical event rate and with high overall patient's and physician's satisfaction.

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.

AIMS: Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. METHODS AND RESULTS: Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. CONCLUSION: This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

Cardiovascular effects of flavanol-rich chocolate in patients with heart failure.

AIMS: Flavanol-rich chocolate (FRC) is beneficial for vascular and platelet function by increasing nitric oxide bioavailability and decreasing oxidative stress. Congestive heart failure (CHF) is characterized by impaired endothelial and increased platelet reactivity. As statins are ineffective in CHF, alternative therapies are a clinical need. We therefore investigated whether FRC might improve cardiovascular function in patients with CHF. METHODS AND RESULTS: Twenty patients with CHF were enrolled in a double-blind, randomized placebo-controlled trial, comparing the effect of commercially available FRC with cocoa-liquor-free control chocolate (CC) on endothelial and platelet function in the short term (2 h after ingestion of a chocolate bar) and long term (4 weeks, two chocolate bars/day). Endothelial function was assessed non-invasively by flow-mediated vasodilatation of the brachial artery. Flow-mediated vasodilatation significantly improved from 4.98 ± 1.95 to 5.98 ± 2.32% (P = 0.045 and 0.02 for between-group changes) 2h after intake of FRC to 6.86 ± 1.76% after 4 weeks of daily intake (P = 0.03 and 0.004 for between groups). No effect on endothelial-independent vasodilatation was observed. Platelet adhesion significantly decreased from 3.9 ± 1.3 to 3.0 ± 1.3% (P = 0.03 and 0.05 for between groups) 2 h after FRC, an effect that was not sustained at 2 and 4 weeks. Cocoa-liquor-free CC had no effect, either on endothelial function or on platelet function. Blood pressure and heart rate did not change in either group. CONCLUSION: Flavanol-rich chocolate acutely improves vascular function in patients with CHF. A sustained effect was seen after daily consumption over a 4-week period, even after 12 h abstinence. These beneficial effects were paralleled by an inhibition of platelet function in the presence of FRC only.

Chronic treatment with long-acting nifedipine reduces vasoconstriction to endothelin-1 in essential hypertension.

Essential hypertension is associated with enhanced biological activity of endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation. Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they improve endothelial function in vivo. We tested whether calcium antagonists also influence the biological activity of ET-1 in essential hypertensive (EH) patients in the presence and absence of hypercholesterolemia. In 9 healthy subjects (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/-8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure: 164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its modification induced by intrabrachial administration of ET-1, phenylephrine, acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas the following higher doses caused a comparable dose-dependent vasoconstriction in EH and NT subjects. The effect of acetylcholine was significantly reduced in EH as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine had similar effects in NT and EH subjects. After chronic treatment with the nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect induced by both ET-1 and phenylephrine was significantly blunted, whereas the response to acetylcholine was significantly increased and the vasodilation to sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further reduced response to acetylcholine compared with normocholesterolemic EH subjects, and the nifedipine gastrointestinal therapeutic system restored the vasodilation to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic treatment with a long-acting dihydropyridine calcium antagonist not only exhibits a blood pressure-lowering effect but also reduces ET-1-induced vasoconstriction and improves endothelium-dependent vasodilation. Those vasculoprotective effects may importantly contribute to a reduction in major clinical events seen during treatment with these compounds.

Coffee blunts mental stress-induced blood pressure increase in habitual but not in nonhabitual coffee drinkers.

Coffee is widely consumed, especially during mental stress conditions. Cardiovascular impact of coffee remains debated because the underlying mechanisms of action are complex. We reported previously differential cardiovascular stimulation of coffee at rest depending on habitual consumption. The present study was designed to evaluate the effects of coffee on cardiovascular response to mental stress. In 15 healthy volunteers (6 habitual, 9 nonhabitual coffee drinkers), we assessed the effect of mental stress on blood pressure (BP), heart rate (HR), and muscle sympathetic activity (MSA) before and after a triple espresso, intravenous caffeine, and placebo in the same subjects. Under baseline conditions, mental stress significantly increases MSA (+2.5+/-0.7 volts per minute; +14.1+/-10.3%), systolic (+11.6+/-4.1 mm Hg) and diastolic BP (+6.4+/-2.0 mm Hg), and HR (+9.6+/-1.8 minutes(-1)). In nonhabitual coffee drinkers, a triple espresso but not caffeine induced an additional increase in systolic BP (+9+/-6.3 mm Hg; P=0.003) during mental stress, whereas in habitual drinkers, the stress-induced BP increase was blunted (+4+/-3.9 mm Hg; P=NS). As a result, nonhabitual coffee drinkers experienced significantly higher BP during mental stress than habitual drinkers (151+/-17.9/83+/-5.6 mm Hg versus 130+/-7.8/74+/-6.7 mm Hg; P<0.05). Caffeine induced similar effects in habitual and nonhabitual coffee drinkers at rest and during mental stress. The response to the cold pressor test was not influenced by coffee drinking in both groups. In conclusion, in nonhabitual coffee drinkers, coffee enhances the cardiovascular response to mental stress with an additional increase in systolic BP, whereas in habitual drinkers, the response is blunted. Caffeine alone does not exert any potentiating effect, confirming that ingredients other than caffeine are partially responsible for the stimulating effect of coffee on the cardiovascular system.

Cardiovascular effects of coffee: is it a risk factor?

Intake of coffee, one of the most common beverages worldwide, is often reported as a cardiovascular risk factor; however, definitive data are lacking. Acute intake of coffee or beverages containing caffeine can increase blood pressure, heart minute volumes, and cardiac index, as well as activate the sympathetic nervous system in nonhabitual coffee drinkers. Interestingly, this is not observed in habitual coffee drinkers. Restriction of coffee or caffeinated beverages is no longer indicated in the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines for the treatment of hypertension. In fact, no clear association between coffee and the risk of hypertension, myocardial infarction, or other cardiovascular diseases has been demonstrated. In contrast to early studies, recent research indicates that habitual moderate coffee intake does not represent a health hazard and may even be associated with beneficial effects on cardiovascular health.

Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking.

BACKGROUND: Coffee is the most abundantly consumed stimulant worldwide. However, its cardiovascular safety remains controversial. Possible health hazards have been related to its main ingredient, caffeine. Activation of the sympathetic nervous system by coffee may enhance cardiovascular risk; however, it is unclear whether this effect of coffee is related to caffeine or other substance(s) also contained in decaffeinated coffee. METHODS AND RESULTS: In 15 healthy volunteers (6 habitual and 9 nonhabitual coffee drinkers) arterial blood pressure (BP), heart rate, and muscle sympathetic nervous activity (MSA) were continuously recorded before and after drinking a triple espresso or a decaffeinated triple espresso or after intravenous administration of caffeine (250 mg) or placebo (saline) in the same subjects. There was a significant time x condition interaction for the intravenous caffeine and placebo conditions for MSA, with caffeine showing a significant increase in MSA at 60 minutes (53.2+/-14.1% total activity) and the placebo group showing no effect. A similar significant time effect was found for coffee drinking (54.1+/-22.5% total activity). Habitual and nonhabitual coffee drinkers demonstrated similar changes in MSA and BP after intravenous caffeine, whereas coffee drinking increased BP in nonhabitual drinkers only, despite comparable increases of MSA and plasma caffeine levels. Nonhabitual coffee drinkers showed similar activation of MSA and BP after caffeine infusion, coffee, or decaffeinated coffee. CONCLUSIONS: Acutely, coffee and caffeine induced comparable increases in MSA and BP in nonhabitual coffee drinkers, whereas habitual coffee drinkers exhibited lack of BP increase despite MSA activation to coffee. Because decaffeinated coffee also increases BP and MSA in nonhabitual drinkers, ingredients other than caffeine must be responsible for cardiovascular activation.