Antiplatelet therapy: new insights on the secondary prevention of stroke

2019 ◽  
pp. 39-51
Author(s):  
Julián García- Rafanell ◽  
Javier Borja
Keyword(s):  
Secondary Prevention ◽  
Safety Profile ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Double Blind ◽  
Long Term Study ◽  
Long Term Treatment

Antiplatelet agents represent an important part of the therapeutic armamentarium in the prevention of stroke. Among them, aspirin is the gold standard but its chronic use has been associated with gastric intolerance, gastrointestinal and systemic hemorrhages and drug-resistance. Triflusal is a new antiplatelet agent from the family of salicylates but is not derived from aspirin and has a more selective mechanism of action : inhibition of thromboxane A2 in the platelet  with no effect on prostacyclin biosynthesis in the endothelium.  In the quest for the search of new antiplatelet agents, triflusal has shown a similar relative risk reduction than aspirin for the prevention of  stroke but with reduced severe hemorrhagic side effects. The efficacy and better safety profile of triflusal vs aspirin in the secondary prevention of stroke has been demonstrated in major,  randomized and double blind clinical trials and confirmed after a long term study with a mean follow up of 17 years, as well as in  a Cochrane meta-analysis. Aspirin, but not triflusal, increased antihypertensive therapy requirements during long term treatment  in the secondary prevention of stroke. In patients with atrial fibrillation, the combination of oral anticoagulants with triflusal has shown increased efficacy  versus the standard oral single anticoagulation treatment with no increase of haemorrhagic risk.  Studies have shown that the risk of upper gastrointestinal bleeding associated with the use of triflusal was negligible whereas the hemorrhagic risk associated  with the use of aspirin, including low doses aspirin, was evident. Triflusal was well tolerated in asthmatic patients with aspirin-exacerbated –respiratory-diseases. The efficacy of triflusal in secondary prevention of stroke and its better safety profile when compared to aspirin has been recognized in important International Guidelines including the European Stroke Organization Guidelines.

Agomelatine versus escitalopram in major depressive disorders : a randomized double-blind, long term study focusing on sleep satisfaction and emotional blunting

2011 ◽  
Vol 26 (S2) ◽  
pp. 619-619 ◽  
Author(s):  
E. Corruble ◽  
C. Bélaidi ◽  
G.M. Goodwin
Keyword(s):  
Depressive Symptoms ◽  
Depressive Disorders ◽  
Rating Scale ◽  
Statistical Significance ◽  
Controlled Study ◽  
Major Depressive ◽  
Double Blind ◽  
Long Term Study ◽  
Long Term Treatment

The novel antidepressant agomelatine is a MT1/MT2 receptor agonist and a 5HT2c receptor antagonist, whose efficacy is demonstrated in Major Depressive Disorder (MDD) (1). In an international 24-week double-blind randomized controlled study, the effects of agomelatine 25–50 mg/d (n = 164) were compared to those of escitalopram 10-20 mg/d (n = 160) on satisfaction about sleep (Visual Analogic Scale), depressive symptoms (Hamilton Depression Rating Scale (HAM-D)) and emotions in a subset of 45 patients having completed the Oxford Depression Questionnaire (2).Both drugs improved depressive symptoms (mean decrease in HAM-D score from baseline: -19.9 with agomelatine and -19.2 with escitalopram; percentage of remitters: 69.6% with agomelatine and 63.1% with escitalopram, LOCF endpoint) and the satisfaction about sleep. Interestingly, the wellness feeling on waking was more improved with agomelatine as compared to escitalopram (p = 0.025), indicating a better alertness on waking with agomelatine than escitalopram.Moreover, emotional blunting was less frequent with agomelatine as compared to escitalopram: 28% on agomelatine vs 60% on escitalopram felt that their emotions lacked intensity with a trend to statistical significance (p = 0.063) and 16% of patients on agomelatine vs 53% on escitalopram felt that things that they cared about before illness did not seem important any more (p = 0.024). Finally, less patients withdrew due to emergent adverse events with agomelatine (4.3%) as compared to escitalopram (10.6%), (p = 0.029). To conclude, this study shows some potential clinical advantages of agomelatine as compared to escitalopram in the long term treatment of MDD.

Chlorthalidone Alone or in Fixed Combination with Slow-Release Metoprolol in the Management of Arterial Hypertension: A Long-Term Study of 545 Patients

1989 ◽  
Vol 17 (4) ◽  
pp. 339-349 ◽  
Author(s):  
E. Bichisao ◽  
L. Merlini ◽  
O. Gambini ◽  
D. Alberti ◽  
G. Pollavini
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Diastolic Blood Pressure ◽  
Slow Release ◽  
Fixed Combination ◽  
Combined Therapy ◽  
Double Blind ◽  
Long Term Study ◽  
Long Term Treatment

In a double-blind trial, 545 out-patients with essential hypertension received 25 mg/day chlorthalidone alone (274 patients) or in fixed combination with 200 mg/day slow-release metoprolol (271 patients) for 8 weeks. Both treatments significantly (P<0.001) decreased systolic and diastolic blood pressure; 45.6% of patients receiving chlorthalidone and 82.5% receiving combined therapy had a diastolic blood pressure of less than 95 mmHg. Patients not controlled by chlorthalidone or chlorthalidone plus metoprolol subsequently received chlorthalidone plus metoprolol (137 patients) or chlorthalidone plus metoprolol plus a third drug (34 patients), respectively, for 8 weeks. A total of 79.5% of patients receiving chlorthalidone plus metoprolol and 61.8% receiving chlorthalidone plus metoprolol plus a third drug had a diastolic blood pressure of less than 95 mmHg. Only 5.9% of patients experienced mild to modérate side-effects. Plasma potassium leveis significantly ( P<0.01) decreased during the first 8 weeks only. It is concluded that a diuretic alone or in fixed combination with a β-blocker is effective in the long-term treatment of arterial hypertension.

Why we should not skip aspirin in cardiovascular prevention

2016 ◽  
Vol 36 (01) ◽  
pp. 33-43 ◽  
Author(s):  
K. Schrör
Keyword(s):  
Oral Anticoagulants ◽  
Antiplatelet Agent ◽  
Factor Xa ◽  
Cardiovascular Prevention ◽  
Antiplatelet Agents ◽  
Antiplatelet Medication ◽  
Percutaneous Coronary ◽  
Direct Inhibitors ◽  
Thrombotic Diseases

SummarySince more than 20 years, aspirin is an approved and established first-line antiplatelet medication in cardiovascular prevention. This is partially due to ist unique mode of action which is not shared with any other antiplatelet agent as well by the reliability of its pharmacological efficacy: inhibition of platelet COX-1 and subsequent thromboxane formation in almost every patient. Aspirin acts synergistic with ADP-antagonists in dual antiplatelet therapy of acute coronary syndroms (ACS) and percutaneous coronary interventions (PCI) and is also approved for long-term secondary prevention. Patients with atrial fibrillation are an exception and benefit more from anticoagulants. After the introduction of the new oral anticoagulants (NOACs), i.e. direct inhibitors of factor Xa or thrombin formation, there is a renewed discussion about the role of antiplatelet agents, specifically if additional dual antiplatelet treatment is still necessary for an optimum clinical effect or whether one component, such as aspirin might be skipped in favor of other classes of oral antiplatelet agents, such as ADP-antagonists. The available data are insufficient to recommend this because of a low number of studies and a still uncertain benefit/ risk (bleeding) ratio. More research on aspirin as a chemopreventive appears also to be necessary and is going on, in particular in individuals at high-risk for vascular thrombotic diseases (diabetics, preeclampsia, venous thrombembolism).

Desmopressin Tablets in the Treatment of Severe Nocturnal Enuresis in Adolescents

PEDIATRICS ◽  
1994 ◽  
Vol 94 (6) ◽  
pp. 841-846
Author(s):  
Arne Stenberg ◽  
Göran Läckgren
Keyword(s):  
Nocturnal Enuresis ◽  
Term Treatment ◽  
Dose Titration ◽  
Optimal Dosage ◽  
Double Blind ◽  
Long Term Study ◽  
Titration Period ◽  
Long Term Treatment ◽  
Clinically Significant

Background. In recent years the treatment of primary nocturnal enuresis (PNE) with desmopressin (DDAVP) has been promising. The route of administration until now had been intranasal, but because the tablets were introduced for the treatment of diabetes insipidus they have also become available for the treatment of PNE. Objectives. To find the optimal dosage of desmopressin tablets and to compare desmopressin's efficacy with placebo in a group of adolescents with severe monosymptomatic enuresis. The long-term safety of desmopressin was also studied in the same group of patients. Methods. The effect of oral desmopressin (1-deamino-8-D-arginine-vasopressin) (DDAVP® tablets, Minirin®) was investigated in 25 adolescents (ages 11 to 21 years) with severe monosymptomatic nocturnal enuresis. The first part of the dose-ranging study comprised a single-blind dose titration period, followed by a double-blind, crossover efficacy period comparing desmopressin with placebo. The final part was an open long-term study consisting of two 12-week treatment periods. The efficacy of the drug was measured in reductions of the number of wet nights per week. Results. During the first dose-titration period, the majority of the patients were given desmopressin 400 µg, and the number of wet nights decreased from a mean of 4.9 to 2.8. During the double-blind period, a significant reduction of wet nights was observed (1.8 vs 4.1 for placebo). During the two long-term periods, 48% and 53% of the patients could be classified as responders (0 to 1 wet night per week) and 22% and 23.5% as intermediate responders (2 to 3 wet nights per week). No weight gain was observed due to water retention. After cessation of the drug, 44% of the patients had a significant decrease in the number of wet nights. Conclusions. Oral desmopressin has a clinically significant effect on patients with PNE, and therapy is safe when administered as long-term treatment.

scholarly journals CARDIOEMBOLIC STROKE IN LATVIA: PREVENTION AND LONG-TERM OUTCOME

2016 ◽  
Vol 4 ◽  
pp. 615-621
Author(s):  
Elina Pucite ◽  
Kristaps Jurjāns ◽  
Evija Miglāne ◽  
Baiba Luriņa ◽  
Oskars Kalējs ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Mortality Rate ◽  
Secondary Prevention ◽  
Patient Group ◽  
Stroke Prevention ◽  
Oral Anticoagulants ◽  
Antiplatelet Agents ◽  
Preventive Medication ◽  
One Year

INTRODUCTION: Untreated non-valvular atrial fibrillation is one of major causes of stroke. The goal of the study was to evaluate the use of antithrombotic medication stroke prevention and assess long-term stroke outcome.METHODS: This study involved 531 cardio embolic stroke patients of the Paul’s Stradins Clinical University Hospital, Riga, Latvia, in 2014. After discharge the patients or their relatives were interviewed by phone after 30, 90, 180, and 365 days. Standardized questions were asked about the patients’ abilities and use of prescribed secondary prevention medication. The results were compared between patient groups, assigned according to prescribed medications.RESULTS: Of all the patients included in the study, 8.9% were using oral anticoagulants before stroke onset. One year after discharge, 1.44% of patients were not using any preventive medication, 23.56% were using antiplatelet agents, 43.27% warfarin, and 31.73% target-specific oral anticoagulants. The one-year mortality rate was 40.7%. The mortality rate was significantly higher in the patient group using no secondary preventive medication or antiplatelet agents compared to the patient group that used oral anticoagulants.CONCLUSION: Cardio embolic stroke primary and secondary prevention in Latvia is lacking. The study outcomes suggest that action is needed to increase the use of oral anticoagulants in primary stroke prevention in patients with atrial fibrillation. Poor function outcomes, dementia, and patients’ incompliance limits the use of oral anticoagulants in secondary prevention.

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