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All other possible information derived from hospital readmission or by the referring physician, relatives, or municipality live registries were entered into the prospective database. Demographic data, clinical characteristics, risk factors and treatment modalities were collected at baseline; occurrence of adverse events, both cardiovascular events and bleeding complications, was recorded at the 1-year follow-up evaluation, as well as the type of therapy given during follow-up, drug-related side effects, duration and compliance to antithrombotic treatments.

Only documented adverse events were considered relevant, as defined in current guidelines and with the date of any event recorded after the baseline visit. Individual data were entered into an electronic case report form including various plausibility checks for the considered variables. The registry was investigators-driven, non-sponsored and was approved by the Ethic Committee of each participating institution.

Bleeding events during or subsequent to the index hospitalization were stratified according to the GUSTO criteria into the following categories: mild not meeting criteria for moderate or severe bleeding , moderate bleeding requiring blood transfusion but not causing hemodynamic compromise , or severe intracranial hemorrhage or bleeding causing hemodynamic compromise [ 5 ]. The GUSTO bleeding events were independently validated by study physicians via medical record review. Survival curves were generated with the use of the Kaplan-Meier method, and the difference between groups was assessed by log-rank test.

Multivariable regression analysis to evaluate the independent contribution of clinical, angiographic, procedural, and therapies to the endpoints was performed by the Cox proportional hazards model.

Primary Prevention

These models take into account the fact that individuals who died are no longer at risk for major bleedings or cardiovascular death i. The proportional hazard assumption was assessed and satisfied graphically by plotting log -log survival curves against log survival time for each predictor category and verifying whether the curves were parallel and, in addition, using time-dependent covariates. All tests were two-sided.

Out of a total population of ACS patients, patients Demographic and clinical characteristics of ACS patients who completed a follow-up according to the antiplatelet treatment at the admission were shown in Table 1.

Antiplatelet Therapy in Acute Coronary Syndrome

Smoking habit was more prevalent in male than in female patients ACS patients treated with monotherapy were more frequently At discharge, the medical therapy was recorded. Diuretics and nitrates were more frequently prescribed in ACS patients with monotherapy than in ACS patients with dual antiplatelet treatment. Conversely, statins were less frequently prescribed in ACS patients with monotherapy than in ACS patients with dual antiplatelet treatment Table 2.

Table 3 summarizes the clinical outcomes during 1-year follow-up. The incidence of re-infarction in this subgroup of patients was 3. Patients with mono-therapy had significantly higher incidence of ischemic events and major bleedings Table 4. The event-free survival curves for all-cause death, cardiovascular death and hemorrhagic complications according to the 4 groups of antiplatelet treatment are shown in Fig 1.

As the number of ACS patients treated with a monotherapy is low, we performed the Cox regression analyses only in patients treated with a dual antiplatelet treatment i. As shown in Tables 5 , 6 and 7 , at the multivariable Cox regression analysis the duration of dual antiplatelet treatments was independently and significantly associated with all-cause mortality, cardiovascular mortality and major bleedings after adjustment of several potential confounders, including the type of dual antiplatelet treatment.

In particular, a 12 month-duration of antiplatelet therapies was more effective in protecting ACS patients from all-cause, cardiovascular mortality and major bleeding complications with respect to a duration from 1 to 6 months. Investigators have defined a priori how to enroll patients: for example, all patients in the first or second week of the month, in order to eliminate possible selection bias. For this reason, this datum mirrors the clinical real world. At hospital discharge, almost the totality of patients was prescribed proton pump inhibitors [more prevalent omeprazole Despite the presence in the literature of data regarding the negative association between clopidogrel and PPI and ticagrelor and PPI [ 8 , 9 , 10 , 11 ] almost the totality of patients was prescribed PPIs.

This datum indicates that from a clinical point of view, clinicians do not worry about the possible ischemic risk associated with the combination between PPIs and dual antiplatelet treatment, whereas the perceived risk of gastrointestinal bleedings prevails. The most prevalent prescription of atorvastatin is in line with literature data and guidelines [ 12 , 13 ].

One hundred and two patients 9.

No patient in the group aspirin plus prasugrel had a history of major or minor bleeding. In diabetics, aspirin plus prasugrel was the less prescribed association, according to recent published data [ 14 ]. These data document that the choice of aspirin and clopidogrel is prevalent in the populations with more frailty: older patients, with a decreased renal function and lower levels of hemoglobin.

That is, from a clinical point of view, the choice of a less potent antiplatelet in patients perceived at higher risk of bleeding. On the other hand, this association was more used also in patients with higher comorbidities, such as previous peripheral artery disease or myocardial infarction: this choice appears to be less appropriate.

Total and cardiovascular mortality is significantly higher in aspirin plus clopidogrel with respect to the other two associations. At the univariate Cox regression analyses aspirin plus ticagrelor and aspirin plus prasugrel were both associated with a significantly lower risk for total and cardiovascular mortality. Kaplan Meier curves significantly diverge and show a higher and early all-cause mortality within 2 months in patients treated only with aspirin or with aspirin plus clopidogrel: the early timing of the event might underlie the frailty of these patients in which the clinicians decided to use only one antiplatelet drug or the less potent combination of antiplatelet drugs, apparently in disagreement with current guidelines.

The curve of patients treated by aspirin plus clopidogrel diverges in a clear way from those of aspirin plus ticagrelor and aspirin plus prasugrel and shows later events, between 8 and 10 months from diagnosis. As regards as ischemic events at follow-up, the half was registered in aspirin alone and aspirin plus clopidogrel groups. No cerebral ischemic event in patients treated with aspirin plus prasugrel or aspirin plus ticagrelor was registered.

Even recurrent myocardial infarction was documented with a significant more prevalence in aspirin alone group and aspirin plus clopidogrel. Using all scores, data show a paradoxical higher bleeding risk, major and minor, in patients treated with aspirin alone, again according to the frailty of these patients which determined the prescription of a single antiplatelet. These data are clinically relevant as suggest how in the real world the incidence of bleedings in patients treated with the more potent P2Y12 inhibitors do not seem to be higher than with the administration of clopidogrel.

This might reflect the use of these drugs in a populations at lower bleeding risk younger patients, with higher BMI, with higher GFR. Reduced ejection fraction and previous stroke are independent predictors of bleedings in this cohort.

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The duration of dual antiplatelet therapy was confirmed [ 15 , 16 ] to be an independent and strong predictor of both thrombotic and bleeding events. Limitations of the study are: 1 there are considerable baseline differences among the antiplatelet groups which potentially affect the results derived from multiple statistical adjustments; 2 the diagnosis of myocardial infarction is based only on any biomarker increase, ecg or echo abnormalities, excluding myocardial ischemia which may result in small biomarker increase in the absence of myocardial necrosis. In the real world, the datum of a reduced mortality associated with the use of ticagrelor was confirmed and was present also for prasugrel.

On the other hand, no significant higher prevalence of major bleeding events in patients treated with the more potent P2Y12 antiplatelets was documented. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

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Abstract Background Despite great advances with the introduction of ticagrelor and prasugrel in the treatment of acute coronary syndromes ACS , the risk of thrombosis and bleeding remains significant and affects the choice of clinicians in the treatment of the single patient. Methods START- antiplatelet is a prospective, observational registry carried out by seven Italian cardiology institutions on patients admitted for ACS aimed to document the real world treatment of ACS patients, adding also data on month follow-up.

Results The dual antiplatelet treatment most prescribed was aspirin plus ticagrelor Discussion The analysis of the register has documented that both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality but both do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel.

Funding: The author s received no specific funding for this work. Introduction Antiplatelet treatment is a cornerstone of the management of patients with acute coronary syndrome ACS. Material and methods One thousand five hundreds and thirty- seven patients were enrolled in the Register at May 31, A diagnosis of non-STEMI NSTEMI or STEMI was made if ischemic symptoms and one or more of the following were reported: cardiac biomarkers greater than the local laboratory reference range, new ST-T wave changes, new left bundle branch block, pathologic Q waves on the electrocardiogram, or new imaging evidence of loss of viable myocardium or regional wall motion abnormality.

Stroke was defined as loss of neurological function caused by an ischemic or hemorrhagic event with residual symptoms 24 hours after onset or leading to death. Buy eBook. Buy Softcover. Rent the eBook. FAQ Policy. About this book Cardiovascular pharmacotherapy is a fast-moving and complex discipline within cardiology in general.

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Clinicians who care for patients with acute coronary syndrome will gain a better understanding of these therapies after reading this book. Antiplatelet Therapy.

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