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We previously analyzed five trials on ticagrelor/aspirin versus clopidogrel/aspirin in patients with minor stroke/ TIA in a network meta-analysis. We updated our search and identified 311 new citations with one study for inclusion: CHANCE2 enrolled patients with CYP2C19 loss-of-function alleles and randomized them to ticagrelor/aspirin or clopidogrel/aspirin. Pooling of CHANCE2 with the original studies could not be completed due to violation of NMA assumptions, due to significant inconsistency. This suggests patients with CYP2C19 loss-of-function alleles represent a subpopulation that is inherently different from the general stroke population in their antiplatelet response. Results from CHANCE-2 may not be generalizable without genotype testing.
Precision medicine envisages the integration of an individual’s clinical and biological features obtained from laboratory tests, imaging, high-throughput omics and health records, to drive a personalised approach to diagnosis and treatment with a higher chance of success. As only up to half of patients respond to medication prescribed following the current one-size-fits-all treatment strategy, the need for a more personalised approach is evident. One of the routes to transforming healthcare through precision medicine is pharmacogenomics (PGx). Around 95% of the population is estimated to carry one or more actionable pharmacogenetic variants and over 75% of adults over 50 years old are on a prescription with a known PGx association. Whilst there are compelling examples of pharmacogenomic implementation in clinical practice, the case for cardiovascular PGx is still evolving. In this review, we shall summarise the current status of PGx in cardiovascular diseases and look at the key enablers and barriers to PGx implementation in clinical practice.
A 38-year-old G7P7 is referred by her primary care provider to your high-risk obstetrics clinic for preconception consultation after having angiography and percutaneous coronary intervention (PCI) in your tertiary center for a non-ST elevation myocardial infarction (NSTEMI) 18 months ago. All her children, the youngest aged four years, were delivered vaginally at term prior to emigrating from Africa.
Long-term (>1 year) single antiplatelet therapy with aspirin is effective in reducing the risk of any early recurrent stroke by about one-sixth compared with no antiplatelet therapy. Clopidogrel monotherapy is marginally but significantly more effective than aspirin in reducing major vascular events. Cilostazol is also more effective than aspirin in Asian patients, and its therapeutic efficacy may be augmented by the addition of probucol in patients with ischaemic stroke and high risk of cerebral haemorrhage. The safety and effectiveness of cilostazol in non-Asian patients is not known. Prasugrel monotherapy (3.75 mg daily) is not non-inferior to clopidogrel monotherapy among Japanese patients with non-cardioembolic ischaemic stroke. Dual antiplatelet therapy with aspirin and extended-release dipyridamole is more effective than aspirin monotherapy and equally effective as clopidogrel monotherapy in preventing recurrent stroke. Dual antiplatelet therapy with aspirin and clopidogrel is more effective than aspirin monotherapy in preventing recurrent ischaemic stroke and myocardial infarction in high vascular risk patients, but it also increases the risk of major bleeding which may offset its benefits. Dual antiplatelet therapy with cilostazol added to aspirin or clopidogrel is more effective, and as safe as, aspirin or clopidogrel monotherapy in Japanese patients with non-cardioembolic ischaemic stroke.
Aspirin 160–300 mg daily started within 48 h of onset of acute ischaemic stroke is associated with a small beneficial reduction in recurrent ischaemic stroke (6 fewer per 1000 patients treated) and pulmonary embolism (1.5 fewer per 1000) that outweighs increased risk of bleeding (2 extra symptomatic ICHs and 4 extra major extracranial haemorrhages). The net effect is that, for every 1000 patients treated early with aspirin, 22 have reduced long-term disability, including 11 more achieving full recovery. Only two single antiplatelet regimens have been compared head to head against aspirin alone: cilostazol (a phosphodiesterase inhibitor) performed similarly to aspirin; ticagrelor (a GP IIa/IIIb receptor antagonist) showed tended to reduce ischaemic events but increased minor bleeding and dyspnea. In minor, non-cardioembolic ischaemic stroke or TIA, early dual antiplatelet therapy (DAPT) has shown advantages over early monotherapy. Most well-studied is clopidogrel and aspirin, with similar findings for dipyridamole and aspirin. DAPT reduces all-type (ischaemic and haemorrhagic) recurrent stroke (27 fewer per 1000 treated patients), but minimally increases major extracranial bleedings (3 more per 1000). Confining DAPT to the first 3 w maximizes the benefit to harm ratio. Anticoagulants alone and arterial-dose anticoagulants added to antiplatelet agents offer no net advantages over antiplatelet drugs alone. Venous prophylaxis-dose anticoagulants and aspirin, compared with aspirin alone, reduced recurrent ischaemic stroke more than it tend increased major extracranial haemorrhage.
Antiplatelet agents such as aspirin and clopidogrel are increasingly encountered in clinical practice. Otorhinolaryngological surgeons are involved in the peri-operative decision of whether to continue treatment and risk haemorrhage or to discontinue treatment and risk thrombosis.
Methods:
Literature relating to the risk of spontaneous or operative haemorrhage was reviewed. The morbidity and mortality associated with cessation of agents was evaluated. Published guidelines were also evaluated. A protocol for the management of antiplatelet agents in the peri-operative period, with particular reference to ENT operations, is presented.
Conclusion:
Significant morbidity and mortality is associated with the premature cessation of antiplatelet agents. Data from cardiac surgery suggest that operative blood loss only marginally increases in patients on aspirin and clopidogrel. However, the management of antiplatelet agents in the peri-operative period should be made after multidisciplinary consultation.
Bleeding after cardiac surgery correlates with morbidity and mortality. The aim of this study was to determine the influence of antiplatelet therapy on bleeding and transfusion rates in coronary artery bypass grafting.
Methods
Forty patients receiving aspirin and/or clopidogrel/ticlopidine within 7 days prior to surgery were retrospectively compared to 40 control patients lacking antiplatelet therapy for at least 8 preoperative days. Blood loss was assessed as chest-tube drainage during the first 12 h after surgery. Units transfused were recorded intraoperatively and during stay in the intensive care unit.
Results
Both groups were comparable for pre- and intraoperative data. Irrespective of single or combined antiplatelet therapy, treated patients demonstrated lower fractions of the creatine-kinase isoenzyme MB (5.8 ± 3.1 vs. 8.2 ± 4.1%; P = 0.004) and infarction rates (0 vs. 3; P = 0.240) than control patients, but had significantly more haemorrhages (940 ± 861 mL vs. 412 ± 590 mL; P = 0.002) and transfusion requirements (red cells: 4.5 ± 4.9 vs. 1.5 ± 2.3, plasma: 4.9 ± 6.4 vs. 1.3 ± 2.5, platelets: 1.5 ± 1.3 vs. 0.1 ± 0.2; all P ⩽ 0.001). The differences to control patients were more pronounced for only short antiplatelet therapy free intervals or ongoing antiplatelet therapy (P⩽2 days ⩽ 0.019). For antiplatelet therapy free intervals longer than 2 days, bleeding and transfusion rates (except for platelets) were nonsignificantly higher as compared to control patients (P ⩾ 0.058).
Conclusions
To overcome increased blood loss and transfusion rates, antiplatelet therapy should be discontinued for at least 2 days before elective coronary surgery. Whether patients at high risk for myocardial infarction might benefit from ongoing antiplatelet therapy remains to be investigated.
Despite major advances in the management of acute coronary syndromes (ACS), 1 in 3 Canadians die from cardiovascular disease. In 1998, the total economic burden of cardiovascular illness in Canada was $159 434.5 million dollars — $83 953.9 million in direct costs and $75 479.6 in indirect costs. During the past 20 years, several pharmacologic adjuncts have been investigated with hopes of ameliorating the consequences of ACS. Notably, clopidogrel has become a common component of ACS therapeutic regimens since its introduction in 1998. Both new medications and those already accepted as standard treatment deserve critical evaluation to ensure they are safe and effective.
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