Mg In High-risk Patients Research Articles

Principles of angiology in lower extremity arterial disease (LEAD)

Lower extremity arterial disease (LEAD) is afrequent manifestation of atherosclerosis with ahigh risk for cardiovascular events. The measurement of the ankle-brachial index (ABI) should be used as ascreening method for LEAD. A differentiation is made between a stable stage of intermittent claudication and the stage of critical limb ischemia. The control of cardiovascular risk factors is crucial. Particular emphasis should be placed on smoking cessation and lipid-lowering treatment with statins and a target low-density lipoprotein (LDL)-cholesterol level of <55 mg/dl as a core element. In patients with symptomatic LEAD an inhibition of platelet aggregation is indicated. In addition to treatment with clopidogrel 75 mg or with acetylsalicylic acid (ASS) 100 mg in high risk patients the combination of ASS 100 mg and rivaroxaban 2 × 2.5 mg can be indicated. In critical limb ischemia revascularization (percutaneous intervention, operation) is always indicated to prevent amputation. First-line treatment in patients with intermittent claudication is exercise training. Revascularization can be indicated in patients with asevere limitation of walking distance.

THE EFFECTIVENESS OF OUTPATIENT AND HOSPITAL LIPID-LOWERING THERAPY IN PATIENTS WITH HIGH AND VERY HIGH CARDIOVASCULAR RISK DURING 2011-2015

Aim. To estimate the effectiveness of lipid-lowering therapy (LLT) at outpatient and hospital treatment stages in patients at high and very high cardiovascular risk during 2011-2015. Material and methods . In a cross-sectional epidemiological study we analyzed LLT in hospital patients for the period April-May 2011, 2012 and 2015. All data were obtained from randomly selected case-records of patients (n=548; 20% of all hospital patients over the study period). Risk categories of patients as well as target levels of low density lipoprotein (LDL) cholesterol were determined according to the current clinical guidelines for the respective year. Outpatient LLT was administered in local out-patient clinics and hospital one – in the clinic of State Research Centre for Preventive Medicine. Results . The most commonly prescribed group of lipid-lowering drugs was statins, while combined treatment or monotherapy with other lipid-lowering agents were used only in rare cases. From 2011 to 2015 the proportion of patients taking statins before admission increased from 20% to 49.8% (from 23.1% up to 29.6% of patients at high cardiovascular risk and from 28% up to 68.5% of patients at very high cardiovascular risk, respectively). During hospitalization the proportion of individuals receiving statins increased from 49.8% to 72.9%, from 29.6% to 74% and from 68.5% to 95.3% in general group, among patients at high and very high cardiovascular risk, respectively. In 2015 LDL cholesterol target levels were achieved in 14.8% and 7.1% of patients at high and very high risk, respectively. In-hospital rate of simvastatin administration reduced from 33.6% to 0.5%, whereas prescription of atorvastatin and rosuvastatin increased from 31.4% to 64.5% and from 3.6% to 9.9%, respectively. Average dose of statins (in conversion to atorvastatin) increased from 10 mg to 20 mg in high-risk patients and from 10 mg to 40 mg – in very high risk group. Conclusion . Positive trend in frequency of LLT prescription was demonstrated in patients at high and very high cardiovascular risk during 2011-2015. Nevertheless, significant number of patients in out-patient clinics still remains under non-optimal treatment.

Use of selective serotonin re-uptake inhibitors and the heart rate corrected QT interval in a real-life setting: the population-based Rotterdam Study.

Selective serotonin re-uptake inhibitors (SSRIs), specifically citalopram and escitalopram, are thought to cause QTc prolongation, although studies have shown contradictory results. Nevertheless, a maximum citalopram dosage of 20 mg in high risk patients (e.g. >60 years of age) is recommended. We aimed to investigate the association between use of (individual) SSRIs and QTc in a population-based study in older adults. This study, which was part of the prospective Rotterdam Study (period 1991-2012), included participants with up to five electrocardiograms (ECGs). We used linear mixed models to compare QTc F (QT corrected according to Fridericia) measured during use of individual SSRIs with QTc F measured during non-use of any antidepressant. For citalopram, analyses were additionally restricted to a maximum dosage of 20 mg in participants aged 60 years and older. We included 12 589 participants with a total of 26 620 ECGs of which 436 ECGs were made during SSRI use. The mean QTc F was similar during use of any drugs from the SSRI class and during non-use. After stratifying to individual SSRIs, ECGs recorded during use of citalopram had the longest QTc compared with ECGs recorded during non-use (+12.8 ms, 90% CI 7.5, 18.2). This result remained similar in the analysis comprising participants aged 60 years and older with a maximum prescribed daily dosage of 20 mg citalopram. Although no SSRI class effect was observed, use of citalopram was associated with a longer QTc F, even after considering the recommended restrictions. Other SSRIs may not give a clinically relevant QTc F prolongation.

Time to reconsider dabigatran 110 mg in the USA.

Unlike other international regulatory agencies, the US FDA did not approve the dabigatran 110mg dose for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Such decision was based on the review of the results from the RE-LY trial, after which the US FDA concluded there was no subgroup of patients for whom dabigatran 110mg was not inferior to dabigatran 150mg. Recently, observational studies based on US data have found that the safety profile of dabigatran differs between subgroups, considerably more than what was suggested in clinical trials. In addition, post hoc analyses of the RE-LY trial support the use of dabigatran 110mg in high-risk patients, as recommended by the European label. Based on this new evidence, the US FDA should reconsider the approval of the dabigatran 110mg dose. The availability of dabigatran 110mg may be especially favorable for groups of patients for whom dabigatran has been associated with higher risk of bleeding than warfarin, which represent a high proportion of the patients recommended for oral anticoagulation. In addition, the approval of this intermediate strength would increase prescribers' and patients' flexibility in the choice of oral anticoagulant.

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with (n=368) and without (n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effective than rosuvastatin at lowering low-density lipoprotein cholesterol, total cholesterol, non- high-density lipoprotein cholesterol, and apolipoprotein B (all p<0.001). No significant differences in treatment effects were seen between the presence and absence of MetS. In this post-hoc analysis of high-risk hypercholesterolaemic patients the lipid-reducing effects of ezetimibe/simvastatin or rosuvastatin were not altered significantly by the presence of MetS.

Efficacy and Safety of Adding Fenofibrate 160 mg in High-Risk Patients With Mixed Hyperlipidemia Not Controlled by Pravastatin 40 mg monotherapy

Patients with mixed hyperlipidemia and at high risk of coronary heart disease may not achieve recommended low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol goals on statin monotherapy. This study was designed to evaluate the efficacy and safety of a fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy in high-risk patients not at their LDL cholesterol goal on pravastatin 40 mg. In this 12-week, multicenter, randomized, double-blind, double-dummy, parallel-group study, after a run-in on pravastatin 40 mg, 248 patients were randomly assigned to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy. Combination therapy produced significantly greater complementary decreases in non-HDL cholesterol (primary end point) than pravastatin monotherapy (-14.1% vs -6.1%, p = 0.002). Significantly greater improvements were also observed in LDL cholesterol (-11.7% vs -5.9%, p = 0.019), HDL cholesterol (+6.5% vs +2.3%, p = 0.009), triglycerides (-22.6% vs -2.0%, p = 0.006), and apolipoprotein B (-12.6% vs -3.8%, p <0.0001). Significantly more patients receiving the fenofibrate/pravastatin combination therapy than pravastatin alone achieved the LDL cholesterol (<100 mg/dl) and non-HDL cholesterol (<130 mg/dl) goals (p <0.01). Combination therapy was generally well tolerated with incidences of clinical and laboratory adverse experiences similar between the 2 groups. In conclusion, the fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy significantly improved the global atherogenic lipid profile in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy.

Efficacy of Switching from Statin Monotherapy to Ezetimibe/Simvastatin 10/20 mg Versus Rosuvastatin 10 mg in High-Risk Patients Analyzed by Baseline LDL-C

Efficacy of Switching from Statin Monotherapy to Ezetimibe/Simvastatin 10/20 mg Versus Rosuvastatin 10 mg in High-Risk Patients Analyzed by Baseline LDL-C

Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20mg Compared with Rosuvastatin 10mg in High-Risk Patients with and Without Type 2 Diabetes Mellitus (T2DM)

Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20mg Compared with Rosuvastatin 10mg in High-Risk Patients with and Without Type 2 Diabetes Mellitus (T2DM)

Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20mg Compared with Rosuvastatin 10mg in High-Risk Patients with and Without Type 2 Diabetes Mellitus

Synopsis: Many patients at risk of coronary events fail to achieve recommended LDL-C goals with statin monotherapy and are therefore at increased risk of future coronary events. This study evaluated efficacy of switching hypercholesterolemic patients at high cardiovascular risk who failed to achieve adequate lowering of LDL-C with prior statin monotherapy to ezetimibe/simvastatin (EZE/SIMVA) versus rosuvastatin (ROSUVA).

Functional Effects of High Clopidogrel Maintenance Dosing in Patients With Inadequate Platelet Inhibition on Standard Dose Treatment

Updated guidelines on percutaneous coronary intervention recommend increasing the dose of clopidogrel to 150 mg in high-risk patients if <50% platelet inhibition is demonstrated. However, to date, the functional impact of this recommendation has been poorly explored. The aim of this study was to assess the functional implications associated with the use of clopidogrel 150 mg/day in patients with inadequate platelet inhibition while receiving standard 75 mg/day maintenance treatment. Patients with diabetes mellitus have a higher prevalence of inadequate clopidogrel-induced antiplatelet effects and stent thrombosis compared with those without diabetes and were selected for this analysis. Platelet inhibition was assessed using the VerifyNow P2Y12 assay in patients with type 2 diabetes receiving dual-antiplatelet therapy. Patients (n = 17) with <50% platelet inhibition were treated with clopidogrel 150 mg/day for 1 month. Adenosine diphosphate-induced aggregation and the P2Y12 reactivity ratio were also assessed. Platelet function profiles were compared with that of a control group (n = 17) with >or=50% inhibition. Platelet inhibition increased from 27.1 +/- 12% to 40.6 +/- 18% in patients treated with clopidogrel 150 mg/day (p = 0.009; primary end point). All other functional measures also showed enhanced clopidogrel-induced antiplatelet effects. The degree of platelet inhibition achieved after treatment with clopidogrel 150 mg/day varied broadly, and only 35% of patients yielded a degree of platelet inhibition >or=50%. Increasing the dose in patients with inadequate response to clopidogrel did not reach the same degree of antiplatelet effects as those achieved in patients with adequate response while receiving 75 mg/day. In conclusion, the use of a 150 mg maintenance dose of clopidogrel in patients with type 2 diabetes with <50% platelet inhibition is associated with enhanced antiplatelet effects. However, the antiplatelet effects achieved are nonuniform, and a considerable number of patients persist with inadequate platelet inhibition.

Abstract 1032: High Clopidogrel Maintenance Dosing in Patients with Inadequate Platelet Inhibition: Functional Insights on Thienopyridine Usage According to Updated ACC/AHA/SCAI 2005 Guidelines for Percutaneous Coronary Interventions

Background: Clopidogrel under-dosing is a cause of inadequate platelet inhibition. Inadequate clopidogrel-induced antiplatelet effects have been associated with an increased risk of stent thrombosis. Updated guidelines for percutaneous coronary interventions (PCI) recommend to increase the dose of clopidogrel to 150mg in high risk patients if &lt;50% platelet inhibition is demonstrated. However, to date there are no studies which have evaluated the functional impact of this recommendation. The aim of this study was determine the functional impact of a 150mg maintenance dose of clopidogrel in patients with 50% platelet inhibition while in their steady state phase of dual antiplatelet therapy. Methods: Platelet inhibition was screened by means of the VerifyNow P2Y 12 assay in patients in a steady state phase of dual antiplatelet therapy. Patients with &lt;50% platelet inhibition were treated with 150mg of clopidogrel for one-month. Adenosine diphosphate-induced aggregation using light transmittance aggregometry and P2Y 12 reactivity ratio determined by vasodilator-stimulated phosphoprotein-phosphorylation analysis were also performed. Results: A total of 32 patients were screened to identify 20 with &lt;50% platelet inhibition. Platelet inhibition increased from 28.3±12% to 43.2±18% in patients treated with 150mg of clopidogrel (p=0.004; primary endpoint). All other functional measures also showed that a high maintenance dose of clopidogrel reduces platelet function (Table ) . The degree of platelet inhibition achieved following one-month treatment with high dose clopidogrel broadly varied and only eight (40%) patients yielded a degree of platelet inhibition ≥50%. Conclusions: The use of a 150mg maintenance dose of clopidogrel in high risk patients with &lt;50% platelet inhibition increases platelet inhibition. However, the antiplatelet effects achieved are non-uniform and a considerable number of patients persist with elevated platelet function. Platelet function analysis pre and post high clopidogrel maintenance dose therapy

Efficacy and safety of rosuvastatin 40 mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: Results of the POLARIS study

POLARIS investigated the efficacy and safety of rosuvastatin 40 mg and atorvastatin 80 mg in high-risk patients with hypercholesterolemia. Patients ( n = 871) were randomized to rosuvastatin 40 mg/day or atorvastatin 80 mg/day for 26 weeks. The primary endpoint was percentage change in LDL-C levels at 8 weeks. Secondary assessments included safety and tolerability, NCEP ATP III LDL-C goal achievement, change in other lipids and lipoproteins at 8 and 26 weeks, and health economics. Mean LDL-C levels were reduced significantly more with rosuvastatin 40 mg than with atorvastatin 80 mg at 8 weeks (−56% versus −52%, p < 0.001). The proportion of patients achieving the NCEP ATP III LDL-C goal at 8 weeks was significantly higher in the rosuvastatin 40 mg group (80% versus 72%, p < 0.01). Significant differences in the change from baseline in high-density lipoprotein cholesterol (HDL-C) (+9.6% versus +4.4%) and apolipoprotein (Apo)A-I levels (+4.2 versus −0.5) were observed between rosuvastatin and atorvastatin (all p < 0.05). Both treatments were well tolerated. Based on a US analysis, rosuvastatin used fewer resources and delivered greater efficacy. Intensive lipid-lowering therapy with rosuvastatin 40 mg/day provided greater LDL-C-lowering efficacy than atorvastatin 80 mg/day, enabling more patients to achieve LDL-C goals. Rosuvastatin may therefore improve LDL-C goal achievement in high-risk patients with hypercholesterolemia.

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia--Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR).

BackgroundMany patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia.MethodsA total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ≥ 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety.ResultsRosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or renal insufficiency were recorded.ConclusionIn high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.

W16-P-051 Rosuvastatin 40 MG versus atorvastatin 80 MG in high-risk patients with hypercholesterolaemia: Early results of the POLARIS study

W16-P-051 Rosuvastatin 40 MG versus atorvastatin 80 MG in high-risk patients with hypercholesterolaemia: Early results of the POLARIS study

Enalapril for congestive heart failure

In a randomized, double-blind trial, 253 patients with congestive heart failure (New York Heart Association class IV) received either enalapril (n = 127) or placebo (n = 126) in addition to their existing therapeutic regimens (consisting of digitalis, diuretics, and vasodilators other than angiotensin-converting enzyme inhibitors). The study was discontinued prematurely for ethical reasons because of the much lower mortality among the patients receiving enalapril (n = 50) than among those receiving placebo (n = 68) (p < 0.003). The important reduction in mortality was observed among patients dying from progressive heart failure. Follow-up ranged from 1 day to 20 months (average 188 days). The reduction in mortality was associated with general improvements in the symptoms and signs of left and right ventricular heart failure, reduction of heart size, improvements in New York Heart Association classification, reduction of concurrent cardiovascular medication, and reduction of hospital admissions and days spent in the hospital. The overall withdrawal rate was low, and was comparable in the 2 treatment groups (16%; enalapril, n = 22, placebo, n = 18). Symptomatic hypotension was observed in 17% (n = 21) of the enalapril group vs 0% of the placebo group. Hypotension was the reason for withdrawal of enalapril therapy in 7 patients. After the initial dose of enalapril was reduced to 2.5 mg in high-risk patients, hypotension necessitated withdrawal in only 3.2% of the patients. Hyperkalemia was observed exclusively among patients with concurrent use of potassium-sparing agents. At initiation of therapy, serum creatinine levels increased more frequently in the enalapril group than in the placebo group, but was the reason for withdrawal of treatment in only 3 and 2 patients, respectively. A long-term progressive increase in serum creatinine levels was not observed. Hyponatremia at baseline was associated with an increased risk for mortality in patients receiving placebo, but not in those receiving enalapril. It is concluded that enalapril, added to conventional therapy, reduces morbidity and mortality from severe progressive heart failure.

Tolerability of enalapril in congestive heart failure

In a double-blind, randomized trial, 253 patients with heart failure (New York Heart Association functional class IV) received either enalapril (n = 127) or placebo (n = 126) in addition to their conventional therapeutic regimens (digitalis, diuretics and vasodilators other than angiotensin-converting enzyme inhibitors). Enalapril was administered in a dose of 2.5 to 40 mg/day. The placebo group was administered placebo tablets in addition to their conventional therapeutic regimen. The study was discontinued prematurely for ethical reasons because of the highly significant (p = 0.003) difference in mortality between the enalapril (n = 50) and placebo groups (n = 68). The important reduction was observed among patients dying from progressive heart failure. Follow-up ranged from 1 day to 20 months (average 188 days). The reduction in mortality was associated with general improvements in symptoms and signs of left and right ventricular heart failure, reduction of heart size, improvements in New York Heart Association classification, reduction of concurrent cardiovascular medication, and reduction in the number of hospital admissions and duration of hospitalization. The overall rate of withdrawal from the study was low and was comparable in the 2 treatment groups (16%). Induced hypotension was an intentional part of the treatment, and symptomatic hypotension was observed in 17% of treated patients vs 0% of the placebo group. Hypotension was the reason for withdrawal in 7 patients. After the initial dose of enalapril was reduced to 2.5 mg in high-risk patients, hypotension was the reason for withdrawal in only 3% of all patients. Hyperkalemia was observed exclusively among patients concurrently using potassium-sparing agents.(ABSTRACT TRUNCATED AT 250 WORDS)