Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial.

BACKGROUND: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. METHODS: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. RESULTS: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. CONCLUSION: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).

Generic Clopidogrel Besylate in the Secondary Prevention of Atherothrombotic Events: A 6-month Follow-up of a Randomised Clinical Trial.

BACKGROUND: The aim of the present interim analysis was to compare the clinical efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulphate (CHS) salt in patient groups eligible to receive clopidogrel. METHODS: A 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n=1,864) were screened and 1,800 were enrolled in the trial and randomized to CHS (n=759) or CB (n=798). Primary efficacy end point was the composite of myocardial infarction, stroke or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 6-months follow-up no differences were observed between CB and CHS in primary efficacy end point (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Rates of BARC-1,-2,-3a and -5b bleeding were similar between the two study groups whereas no bleeding events according to BARC-3b, -3c, -4 and -5a were observed in either CHS or CB group. CONCLUSION: The clinical efficacy and safety of the generic CB is similar to that of the innovator CHS salt, thus, it can be routinely used in the secondary prevention of atherothrombotic events for a period of at least 6 months. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE study Clinical Trials.gov Identifier: NCT02126982).

Mitral valve repair results in better right ventricular remodelling than valve replacement for degenerative mitral regurgitation: a three-dimensional echocardiographic study.

INTRODUCTION: Right ventricular (RV) remodelling may be an important determinant of clinical outcome in patients undergoing mitral valve surgery for mitral regurgitation. In the present study we hypothesised that, compared to valve replacement, mitral valve repair for degenerative mitral regurgitation may result in better RV remodelling, as assessed by real-time, three-dimensional echocardiography (RT3DE). METHODS: Forty unselected patients with degenerative mitral valve regurgitation were recruited prospectively. Two-dimensional (2DE) and RT3DE studies were performed prior to surgery and 6 months postoperatively. RV volumes, stroke volume, ejection fraction and mass, as well as RV pressures were calculated. Regression analysis was used to demonstrate the effect of surgical mitral repair and replacement on reverse RV remodelling. RESULTS: Twenty-one patients underwent mitral valve repair and 19 valve replacement. Mean age was 59.5 ± 15.4 years. Five patients who underwent repair (23.8%) developed recurrent MR within 6 months postoperatively. RV systolic pressure was reduced from 39.3 ± 11.9 mmHg, to 25.4 ± 8.3 mmHg after surgery (p=0.027). Compared to preoperative volumes, 6 months after surgery there was a significant reduction in RV diastolic volume and stroke volume (from 106.4 ± 16.3 ml to 80.4 ± 12.1 ml and from 69.2 ± 15.4 ml to 52.2 ± 14.1 ml, respectively, p<0.001), and an increase in RV ejection fraction (from 54.5 ± 9.2% to 67.3 ± 8.5%, p<0.001). Over a 6-month follow-up period there were no deaths. Overall, the functional class was significantly improved in 39/40 patients (97.5%) but there was no difference between the repair and replacement groups. Using a multivariate regression analysis model including all parameters composing RV remodelling postoperatively, mitral valve repair was the strongest predictor of reverse RV remodelling (reduction of RV end-diastolic volume, p<0.01; reduction of RV mass, p<0.01; reduction of tricuspid regurgitant velocity, p=0.019). CONCLUSIONS: Mitral valve repair leads to more favourable reverse RV remodelling, assessed by RT3DE, compared to valve replacement. This may have important clinical implications.

Simvastatin-induced changes in circulating oxidized low-density lipoprotein in different types of dyslipidemia.

Beyond lowering lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) have been shown to possess antioxidant properties, which may explain some of their beneficial effects in reducing atherosclerosis. We sought to determine whether circulating oxidized low-density lipoprotein (ox-LDL) levels differ between subjects with isolated hypercholesterolemia and combined hyperlipidemia, as well as the effect of simvastatin on circulating ox-LDL according to the type of dyslipidemia. Twenty-five subjects with total cholesterol >200 mg/dl and triglycerides <150 mg/dl, and 22 subjects with total cholesterol >200 mg/dl and triglycerides >150 mg/dl were treated with 40 mg simvastatin daily for 3 months. Serum lipids, C-reactive protein, fibrinogen, ox-LDL, and free radicals were measured at baseline and after 3 months of treatment. In both groups studied, simvastatin significantly improved lipids, and reduced C-reactive protein and fibrinogen levels. Free radicals were significantly reduced only in subjects with hypercholesterolemia. Subjects with combined hyperlipidemia had significantly higher baseline levels of ox-LDL compared to those with hypercholesterolemia (64.6 U/l vs 53.5 U/l, P = 0.03). Ox-LDL levels were reduced by 12% in subjects with hypercholesterolemia (P = 0.03) and by 26% in subjects with combined hyperlipidemia (P = 0.001) after simvastatin treatment. In conclusion, subjects with combined hyperlipidemia have increased levels of circulating ox-LDL compared to subjects with isolated hypercholesterolemia. Simvastatin significantly reduced circulating ox-LDL in both groups, but whether this reduction is related to clinical outcomes remains to be shown.