Antiplatelet therapy in acute coronary syndromes

Introduction: Coronary thrombosis is a frequent cause of death and myocardial infarction most often explained by superimposition of a platelet-rich thrombus on existing coronary artery disease. Therefore, antiplatelet drugs are essential in the treatment and secondary prevention of acute coronary syndromes (ACS) and during percutaneous coronary intervention. Several novel antiplatelet drugs are now available.

Areas covered: For several years, aspirin and clopidogrel remained the cornerstone of treatment for ACS. However, prasugrel and ticagrelor have a more consistent, faster-acting and more potent antiplatelet effect than clopidogrel, which translates into improved clinical outcomes, although at the expense of an increased bleeding risk. Importantly, some patients experience cardiovascular events despite current antiplatelet treatment, because platelet activation may occur via pathways not inhibited by these agents. Therefore, improved antiplatelet strategies are warranted.

Expert opinion: Despite undisputable benefits of current antiplatelet strategies, a considerable number of patients continue to experience adverse thrombotic events, although clinical outcomes have been improved with new oral P2Y₁₂ antagonists. New drugs have been developed, including intravenous P2Y₁₂ antagonists and oral antagonist targeting the protease-activated receptor-1 platelet activation pathway stimulated by thrombin. This review provides an overview of current and novel antiplatelet strategies and also discusses unmet needs related to antiplatelet therapy for ACS.     

Antiplatelet therapy in secondary stroke prevention

Stroke is the third leading cause of death in the United States. Antiplatelet agents are the mainstays of ischaemic stroke prevention. The therapies recommended for initial therapy include aspirin (50 - 325 mg) daily, the combination of aspirin (25 mg) and extended-release dipyridamole (200 mg) b.i.d., or clopidogrel (75 mg) daily. Ticlopidine 250 mg b.i.d. is approved for stroke prevention but is no longer a first-line therapy. This article reviews the literature on antiplatelet agents for secondary stroke prevention.     

Antiplatelet therapy in secondary stroke prevention

Stroke is the third leading cause of death in the United States. Antiplatelet agents are the mainstays of ischaemic stroke prevention. The therapies recommended for initial therapy include aspirin (50 - 325 mg) daily, the combination of aspirin (25 mg) and extended-release dipyridamole (200 mg) b.i.d., or clopidogrel (75 mg) daily. Ticlopidine 250 mg b.i.d. is approved for stroke prevention but is no longer a first-line therapy. This article reviews the literature on antiplatelet agents for secondary stroke prevention.     

Antiplatelet therapy in acute coronary syndromes

Introduction: Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes in the acute phase and in long-term management. Over the last few years, new antiplatelet drugs have been developed and the therapeutic landscape has rapidly evolved.

Areas covered: We review the available evidence and most recent data concerning all of the principal classes of antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under development).

Expert opinion: This review considers the management of antiplatelet therapy in the light of recent advances, highlighting how to identify patients who will receive the greatest benefit from the older and newer agents, and underscoring the importance of carefully balancing the risks of ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper discusses the potential role of functional and genetic tests in guiding the choice of antiplatelet therapy in a future perspective of ‘personalised medicine’.     

Antiplatelet therapy in acute coronary syndromes

INTRODUCTION: Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes in the acute phase and in long-term management. Over the last few years, new antiplatelet drugs have been developed and the therapeutic landscape has rapidly evolved. AREAS COVERED: We review the available evidence and most recent data concerning all of the principal classes of antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under development). EXPERT OPINION: This review considers the management of antiplatelet therapy in the light of recent advances, highlighting how to identify patients who will receive the greatest benefit from the older and newer agents, and underscoring the importance of carefully balancing the risks of ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper discusses the potential role of functional and genetic tests in guiding the choice of antiplatelet therapy in a future perspective of 'personalised medicine'.     

Antiplatelet therapy in peripheral artery disease

Peripheral artery disease (PAD) is a term that relates to atherosclerosis and narrowing of the arteries in the lower extremities. The prevalence of PAD is approximately 12% of the adult population. Despite the low rate of peripheral complications and amputation, PAD is complicated by a high rate of cardiovascular events including myocardial infarction, stroke, and vascular death with an annual incidence of about 5%.The detection of PAD is initially based on the appearance of typical symptoms (claudication and critical limb ischemia) related to peripheral arterial insufficiency. However, PAD may also be present in the absence of clinical symptoms (asymptomatic PAD). Accordingly, asymptomatic disease may occur in up to 50% of all patients with PAD. Ankle brachial index (ABI) is a diagnostic test used to evaluate the presence of PAD, defined by an ABI ≤0.90. The ABI is also demonstrated to be useful in the assessment of vascular risk in asymptomatic and symptomatic patients. Antiplatelet therapy remains a key intervention to reduce cardiovascular risk in PAD. Data from Antithrombotic Trialists' Collaboration showed that antiplatelet treatment was associated with a 23% risk reduction of vascular events in overall population with PAD. However, closer scrutiny of these data reveals that nonaspirin antiplatelet drugs, including ticlopidine, clopidogrel, picotamide, and dipyridamole largely drove the benefits in the PAD subgroup. It remains an open issue if PAD represents an atherosclerotic clinical model where aspirin, differently from coronary heart disease, is less effective in reducing atherosclerotic progression. Based on the reported results further trials with aspirin should be done in asymptomatic (ABI ≤0.90) and symptomatic PAD patients. Finally, the role of new antiplatelet drugs such as prasugrel and ticagrelor has not yet been studied in PAD.     

Antiplatelet therapy in peripheral arterial disease

Antiplatelet therapy significantly reduces the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with peripheral arterial disease (PAD) and intermittent claudication, in patients undergoing peripheral grafting, in patients undergoing peripheral angioplasty, and in patients with carotid disease. Aspirin, aspirin plus dipyridamole, ticlodipine, and clopidogrel have been shown to be efficacious in the treatment of PAD. Data from the Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events (CAPRIE) trial demonstrated in 11,592 patients with PAD that patients randomized to clopidogrel 75 mg daily had a 24% significant (p=0.0028) reduction in vascular death, nonfatal myocardial infarction, and nonfatal stroke than patients randomized to aspirin 325 mg daily. These data favor the use of clopidogrel in patients with PAD.     

Antiplatelet therapy in patients with diabetes mellitus

Platelets are key players in arterial thrombosis, and oral antiplatelet therapy is a cornerstone in the treatment and prevention of cardiovascular events. However, although currently approved antiplatelet drugs have proved successful in reducing cardiovascular events, platelet-dependent thrombosis remains an important cause of morbidity and mortality in patients with coronary artery disease. It is well-known that patients with diabetes mellitus (DM) have an increased risk of cardiovascular events and, therefore, understanding the mechanism of action and safety profile of antiplatelet drugs in this high-risk population is of particular interest. There is considerable inter-individual variation in the efficacy of established antiplatelet drugs, and high on-treatment platelet reactivity is associated with an increased risk of cardiovascular events, thus prompting the search for novel drugs against platelet-dependent thrombosis. New antiplatelet treatment strategies include drugs with more efficient and reversible platelet inhibition. This review discusses selective inhibitors of the platelet cyclooxygenase enzyme, thienopyridine and non-thienopyridine inhibitors of the platelet adenosine diphosphate receptor, phosphodiesterase inhibitors, and protease-activated receptor antagonists. An overview of currently available antiplatelet drugs is provided, focusing on benefits and limitations in patients with DM. Furthermore, the rationale for new oral antiplatelet drugs under development is discussed with particular focus on the potential role of these drugs to improve cardiovascular outcomes in patients with DM.     

抗血小板治疗在缺血性脑卒中预防中的应用

抗血小板治疗是缺血性脑卒中(IS)一级和二级预防的重要组成部分,未接受溶栓治疗的急性IS患者应尽早开始阿司匹林治疗.噻吩吡啶类药物及血小板糖蛋白Ⅱ b/Ⅲ a受体抑制剂等单药用于急性IS治疗的安全性和有效性目前尚缺乏足够证据,抗血小板药物联合应用的疗效和可能的风险尚需进一步研究.对无法采用华法林治疗的高危房颤患者,阿司匹林或阿司匹林+氯吡格雷双联治疗是当前比较推崇的补充选择手段.     

Antiplatelet therapy: thrombin receptor antagonists

Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. Multiple pathways contribute to platelet activation. Aspirin, an irreversible inhibitor of thromboxane A2 synthesis, in combination with clopidogrel, an inhibitor of P2Y(12) adenosine diphosphate platelet receptors, represent the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. Although these agents have demonstrated significant clinical benefit, the increased risk of bleeding and the recurrence of thrombotic events represent substantial limitations. Thrombin is one of the most important platelet activators. The inhibition of protease-activated receptor 1 showed a good safety profile in preclinical studies. In fact, phase II studies with vorapaxar (SCH530348) and atopaxar (E5555) showed no increase of bleeding events in addition to the current standard-of-care of antiplatelet therapy. Although the results of phase III trials for both drugs are awaited, this family is a promising new addition to the current clinical practice for patients with atherothrombotic disease, not only as an alternative, but also as additional therapy.     

Antiplatelet therapy: in search of the 'magic bullet'

The central importance of platelets in the development of arterial thrombosis and cardiovascular disease is well established. No other single cell type is responsible for as much morbidity and mortality as the platelet and, as a consequence, it represents a major target for therapeutic intervention. The growing awareness of the importance of platelets is reflected in the increasing number of patients receiving antiplatelet therapy, a trend that is likely to continue in the future. There are, however, significant drawbacks with existing therapies, including issues related to limited efficacy and safety. The discovery of a 'magic bullet' that selectively targets pathological thrombus formation without undermining haemostasis remains elusive, although recent progress in unravelling the molecular events regulating thrombosis has provided promising new avenues to solve this long-standing problem.     

Antiplatelet therapy: present status and future prospects

The excessive accumulation of platelets at sites of vascular injury is a key event in the development of arterial thrombosis, the principal pathogenic mechanism underlying the acute coronary syndromes and ischaemic stroke. In combination, these disorders are the leading causes of morbidity and mortality in the industrialised world and, as a consequence, the platelet is a major therapeutic target in the management of cardiovascular disease. This perspective focuses on the present state of antiplatelet therapy and potential future strategies to improve the safety and efficacy of antiplatelet agents.     

二氢麦角毒治疗老年脑血管疾病71例

用二氢麦角毒治疗老年脑血管病71例,男49例,女22例,年龄67±6a(56-82a),1.5mg,tid,po。对照组51例,用氟桂嗓10mg,qn,po,疗程6.8±2.9wk(4-12wk)。以神经功能缺损恢复程度及认知和机能能力评分为标准,前者冶疗脑梗死的有效率明显优于后者(P<0.05),对脑动脉硬化2组均有效(P>0.05),对多发性脑梗死性痴呆提高认知能力也有疗效,副作用少。     

Antiplatelet therapy: glycoprotein IIb/IIIa receptor antagonists

The glycoprotein IIb/IIIa antagonists are potent drugs that inhibit platelet aggregation. They are formulated as monoclonal antibodies and synthetic peptides for intravenous use in patients undergoing high-risk angioplasty procedures and in patients with unstable coronary syndromes. Orally active agents are now being evaluated in clinical trials.     

Vascular effects of calcium antagonists. Uses in some cerebrovascular disorders

1. Smooth muscle contraction is related to the intracellular free Ca2+ concentration. 2. Potential dependent Ca2+ channels (PDCs) are generally more sensitive to Ca2+-antagonists (CAts) than receptor-operated Ca2+ channels (ROCs). However, there exists a wide variation in the sensitivity of ROCs and CAts, which largely depends on the vessel studied. 3. Cerebral and coronary arteries seem to be very sensitive to CAts. 4. New dihydropyridines possess selectivity for the cerebrovascular bed. 5. The vasospasm subsequent to subarachnoid hemorrhage appears to be sensitive to CAts. 6. CAts prevent or reduce the neurologic alterations elicited by cerebral ischemia, and some of them induce beneficial effects in the prophylaxis of migraine.