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- 2. Historia del ácido acetilsalicílico ~400BC Se reconocen sus propiedades antipiréticas y analgésicas 1897 Friedrich Hoffmann sintetiza la forma estable de AAS 1948 El AAS se asocia con la prevención de IM 1971 Sir John Vane descubre el mecanismo de acción del AAS 1915 AAS disponible como analgésico sin prescripción 1988 LA FDA aprueba el AAS en la prevención del IM recurrente ~1500BC Los salicilatos fueron usados por los egipcios como analgésicos 1899 El AAS es comercializado como Aspirina ® AAS, Ácido Acetilsalicílico; FDA, Food and Drug Administration; IM, Infarto de Miocardio
- 3. Metanálisis de ensayos clínicos que proporcionan una base sólida sobre los beneficios de DB-AAS Most patients received low-dose acetylsalicylic acid (DB-AAS). 1. Antiplatelet Trialists' Collaboration. BMJ 1994;308:81–106. 2. Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86. Metanálisis Número de ensayos incluidos Número de pacientes Antiplatelet Trialists’ Collaboration (1994) 1 174 ~100,000 Antithrombotic Trialists’ Collaboration (2002) 2 287 212,000
- 9. Guías 2006 para el tratamiento de la Angina estable
- 10. COURAGE Primary Outcome: Death and Nonfatal MI Boden et al. N Engl J Med 2007 HR 1.05 95% CI 0.87-1.27 P=0.62
- 11. Boden WE et al. N Engl J Med. 2007;356:1503-16. 0.25 0.50 1.00 2.00 1.75 1.50 Medical therapy better PCI better Myocardial infarction Yes No Extent of CAD Multivessel disease Single-vessel disease Diabetes Yes No Angina CCS 0-I CCS II-III Ejection fraction >50% Previous CABG No Yes ≤ 50% Baseline characteristics Hazard ratio (95% CI) COURAGE
- 12. AAS reduce el riesgo del primer infarto o muerte súbita en pacientes con angina estable CV, cardiovascular; LD-ASA, low-dose acetylsalicylic acid; MI, myocardial infarction. Juul-Möller S, et al. Lancet 1992;340:1421–5. Swedish Angina Pectoris AAS Trial (SAPAT) El tratamiento con AAS en pacientes con A.E 34% de reducción en IAM o MS in MI (p=0.003) 39% reducción en IAM no fatal (p=0.006) 32% reducción en episodios CV (p<0.001) 2,035
- 14. ECG
- 16. EFECTO DEL PRE-TRATAMIENTO EN PACIENTES SOMETIDOS A ICP Mehta S et al. Lancet 2001;358:527-33. Steinhubl et al. JAMA 2003;288:2411-20. TRATAMIENTO ANTIAGREGANTE EN INTERVENCIONISMO CORONARIO. DOSIS DE CARGA p=0,01 6,4 4,5 PCI- CURE 300 mgr+ 75 mgr (mediana 10 días) 8,3 8,0 5,8 CREDO 300 mgr <6 h 6-24 h Sin pretratamiento Con pretratamiento p=0,05 Muerte, IAM y revascularización urgente a los 30 días (%) 2 4 6 8 10 %
- 21. Guía
- 22. Resultado
- 25. Antithrombotic Trialists’ Collaboration *Low-dose acetylsalicylic acid was the most widely used antiplatelet agent in the ATTC. ATTC, Antiplatelet Trialists’ Collaboration; CV, cardiovascular; MI, myocardial infarction. Antithrombotic Trialists’ Collaboration . BMJ 2002;324:71–86. reduction in nonfatal reinfarction (p<0.0001) 28% reduction in vascular death (p=0.0006) 15% Antiplatelet therapy Control Nonfatal reinfarction Vascular death Event rate (%) Event rate (%)
- 26. ISIS-2 ISIS-2, Second International Study of Infarct Survival; LD-ASA, low-dose acetylsalicylic acid . Reproduced with permission from Baigent C, et al. BMJ 1998;316:1337–43. 10-year follow-up of ISIS-2 demonstrated that the mortality benefit obtained with 1 month of LD-ASA therapy persisted long term 1 2 3 4 5 6 7 8 9 10 100 90 80 70 60 50 LD-ASA (160mg/day) Control Estimated survival (%) Year since randomization
- 27. CAPRIE CAPRIE, Clopidogrel versus AAS in Patients at Risk of Ischemic Events; CV, cardiovascular; IS, ischemic stroke; LD-ASA, low-dose acetylsalicylic acid; MI, myocardial infarction; PAD, peripheral arterial disease; RRR, relative risk reduction. CAPRIE Steering Committee. Lancet 1996;348:1329 –3 9. LD-ASA (325mg/day) Clopidogrel (75mg/day) The overall 8.7% RRR (p=0.043) in the composite endpoint (IS, MI, or CV death) with clopidogrel was attributed to a reduction only in the risk of PAD Follow-up (months) Cumulative event rate (%) 0 3 6 9 12 18 15 24 21 27 33 30 36 4 8 12 16 20 19,185
- 28. CAPRIE CAPRIE, Clopidogrel versus AAS in Patients at Risk of Ischemic Events CV, cardiovascular; IS, ischemic stroke; LD-ASA, low-dose acetylsalicylic acid; MI, myocardial infarction; PAD, peripheral arterial disease. CAPRIE Steering Committee. Lancet 1996;348:1329 – 39. Los resultados del CAPRIE favorecen el uso de AAS en pacientes con historia de IAM – 40 – 30 – 20 – 10 0 10 20 30 40 Favors LD-ASA Favors clopidogrel IS Relative risk reduction (%) MI PAD All patients
- 29. CURE : standard LD-ASA with add-on clopidogrel in patients with ACS without ST-segment elevation ACS, acute coronary syndrome; CURE, Clopidogrel in Unstable angina to prevent Recurrent Events; CV, cardiovascular; IS, ischemic stroke; LD-ASA, low-dose acetylsalicylic acid; MI, myocardial infarction; RRR, relative risk reduction. Reproduced with permission from CURE Trial Investigators. N Engl J Med 2001;345:494–502. The benefits of clopidogrel in patients with ACS without ST-segment elevation were observed only when administered in addition to standard LD-ASA therapy Cumulative hazard rate Months of follow-up Placebo + LD-ASA Clopidogrel + LD-ASA 0 3 6 9 12 0.12 0.10 0.08 0.04 0.02 0.14 0.06 18% RRR (p<0.001)
- 30. AAS+clopidogrel en ACTP CREDO, Clopidogrel for the Reduction of Events During Observation; CV, cardiovascular; LD-ASA, low-dose acetylsalicylic acid; MI, myocardial infarction; PCI-CURE, Percutaneous Coronary Intervention-Clopidogrel in Unstable angina to prevent Recurrent Events. 1. Mehta SR, et al. Lancet 2001;358:527–33. 2. Steinhubl SR, et al. JAMA 2002;288:2411–20. 3. Sabatine MS, et al. JAMA 2005;294:1224–32. PCI-CURE 1 2.9 4.4 0.65 (0.43 – 0.96) Muerte CV o IAM tras 30 días post-ACTP PCI-CLARITY 3 3.3 5.4 0.60 (0.38–0.96) CREDO 2 6.0 7.1 0.83 (0.57–1.21) Events (%) Clopidogrel Placebo + LD-ASA + LD-ASA Total 3.9 5.5 0.71 (0.56–0.89) Odds ratio Favors pretreatment Favors no pretreatment 0.25 0.5 1.0 2.0
- 33. La interrupción prematura del tratamiento antiagregante es la causa más importante de trombosis stent y puede desencadenar un infarto agudo de miocardio
- 34. Recomendaciones para la prevención de la discontinuación prematura de la antiagregación en los pacientes tratados con stent coronario Grines CL, et al. Circulation 2007; 115: 813-818
- 38. Estudio IST: 19.435 pacientes IS, ischemic stroke; IST, International Stroke Trial; LD-ASA, low-dose acetylsalicylic acid. IST Collaborative Group. Lancet 1997;349:1569 – 81. reduction in the risk of recurrent IS within 14 days in patients with acute stroke (2p<0.001) 28% LD-ASA Placebo (300mg/day) Incidence of recurrent stroke (%)
- 39. Estudio CAST : 20.655 pacientes CAST, Chinese Acute Stroke Trial; IS, ischemic stroke; LD-ASA, low-dose acetylsalicylic acid. CAST Collaborative Group. Lancet 1997;349:1641 –9. Time starting LD-ASA (160mg/day) after onset of acute IS (hours) Risk reduction of deaths and nonfatal stroke (%) reduction in the risk of recurrent IS (p=0.01) 24% 0–3 4–6 7 – 12 13 – 24 25 – 48
- 40. Análisis APTC: 29 estudios reduction in CV events in patients with previous stroke/TIA with antiplatelet agents (2p<0.00001) 22% LD-ASA was the most widely used antiplatelet agent in the APTC. *All risk reductions are versus placebo. 2p<0.00001 for all risk reductions. APTC, Antiplatelet Trialists’ Collaboration; LD-ASA, low-dose acetylsalicylic acid; MI, myocardial infarction; TIA, transient ischemic attack. Antiplatelet Trialists’ Collaboration . BMJ 1994;308:81–106. 22% 36% 23% 14% 0 5 10 15 20 25 30 35 40 MI, stroke, or vascular death Nonfatal MI Nonfatal stroke Vascular death Risk reduction* in patients with previous stroke/TIA (%)
- 43. Guias de recomendación de AAS para prevencón del ACV recurrente AHA/ASA, American Heart Association/American Stroke Association; ESC, European Society of Cardiology; IS, ischemic stroke; LD-ASA, low-dose acetylsalicylic acid; RCP, Royal College of Physicians; TIA, transient ischemic attack. 1. Sacco RL, et al. Circulation 2006;113:409–49. 2. De Backer G, et al. Eur Heart J 2003;24:1601 –10 . 3. Royal College of Physicians. National clinical guidelines for stroke , 2nd edition, 2004. Guidelines Recommendation AHA/ASA, 2006 1 AAS(50–325mg/day) recomendado para todos los pacientes con ACV no cardioembolico o AIT ESC, 2003 2 LD-ASA (50–300mg/day) is recommended in virtually all patients with clinically established cardiovascular disease RCP, 2004 3 AAS(50–300mg/day) ) recomendado para todos los pacientes con ACV no cardioembolico o AIT uqe no reciben ACO
- 47. Frecuencia de ACV en pacientes con Fibrilación Auricular en relación con la edad Framingham Heart Study
- 48. Factores de riesgo para ACV isquémico y Embolia sistémica en la FA no valvular Riesgo relativo ACV previo Diabetes HTA ICC C.Isquémica Edad 2.5 1.7 1.6 1.5 1.4 1.4
- 53. Muchas Gracias
Notas do Editor
- Acetylsalicylic acid (AAS), is one of a family of drugs known as salicylates. The use of salicylates for pain relief can be traced to the Ancient EgypAITns in ~1500BC, and salicylates were recognized to have antipyretic and analgesic properties in ~400BC. In 1897, Friedrich Hoffmann, a chemist working at Bayer, synthesized a stable, powder form of AAS, which, in 1899, was marketed as AAS ® . In 1948, Laurence Craven, a Californian general practitioner, recognized the potenAITl use of AAS for the prevention of coronary thrombosis. In 1971, Sir John Vane discovered the mechanism of action of AAS; an achievement for which he was awarded the Nobel Prize for Medicine in 1982. The Food and Drug Administration approved the use of AAS for the prevention of recurrent myocardial infarction in 1988.
- The Antiplatelet Trialists’ Collaboration and the Antithrombotic Trialists’ Collaboration are the largest published meta-analyses of randomized trials of antiplatelet agents for the secondary prevention of cardiovascular events. These antiplatelet agents included low-dose acetylsalicylic acid (DB-AAS), clopidogrel, ticlopidine, sulfinpyrazone, dipyridamole, and intravenous glycoprotein IIb/IIIa-receptor antagonists; however, DB-AAS was the most-studied antiplatelet agent. 1,2 The Antiplatelet Trialists’ Collaboration analyzed 174 trials involving ~100,000 patients. 1 The Antithrombotic Trialists’ Collaboration analyzed 287 trials involving 212,000 patients. 2 1. Antiplatelet Trialists' Collaboration. BMJ 1994;308:81–106. 2. Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71 –86.
- For the combined outcome of total coronary heart disease (CHD; nonfatal and fatal myocardial infarction and death due to CHD), the meta-analysis of six primary prevention trials demonstrated that the overall risk reduction was in favor of low-dose acetylsalicylic acid (LD-ASA) therapy (odds ratio of 0.77, 95% confidence interval 0.70–0.86). This meta-analysis demonstrated that treatment with LD-ASA was more likely to be beneficial than not beneficial, compared with placebo, in individuals at high risk of first cardiovascular events. Bartolucci AA, et al. Am J Cardiol 2006;98:746–50.
- ECG Basal
- ¿Por qué no utilizar dosis más bajas de Betabloqueantes y asociar Procoralan para un control estricto de la angina, la isquemia, la FC y una reducción de los eventos coronarios? Se aseguraría además el cumplimiento y se mejoraría la calidad de vida. Efectos adversos “leves” como la fatiga son reconocidos como razón justificada para el cambio a Procoralan. Ahora se puede disminuir la dosis y asociar.
- The Swedish Angina Pectoris AAS Trial (SAPAT) was a randomized, double-blind study. The effects of low-dose acetylsalicylic acid (LD-ASA; 75mg/day) or placebo were assessed in 2,035 patients with a history of chronic stable angina but without a history of myocardial infarction (MI), all of whom were treated with sotalol (beta-blocker) for control of symptoms. After a median follow-up of 50 months, treatment with LD-ASA reduced the incidence of MI or sudden death by 34% (p=0.003), nonfatal MI by 39% (p=0.006), and all cardiovascular events by 32% (p<0.001). SAPAT was the first prospective trial in patients with chronic stable angina and provided conclusive evidence of the benefit of pharmacologic treatment with LD-ASA for reducing the risk of first MI in this patient subgroup. Juul-Möller S, et al. Lancet 1992;340:1421–5.
- The Antiplatelet Trialists’ Collaboration 1 and Antithrombotic Trialists’ Collaboration 2 meta-analyses showed antiplatelet agents to be effective in the secondary prevention of cardiovascular (CV) events. Antiplatelets effectively reduced CV mortality (by 15%), 1,2 and the incidences of nonfatal myocardial infarction (by 34%) 1 and nonfatal stroke (by 25%). 2 Low-dose acetylsalicylic acid was the most-studied antiplatelet agent. 1. Antiplatelet Trialists' Collaboration. BMJ 1994;308:81–106. 2. Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71 –86.
- The Antithrombotic Trialists’ Collaboration conducted a meta-analysis of 287 studies comparing antiplatelet regimens with controls or one antiplatelet regimen with another. Low-dose acetylsalicylic acid was the most widely studied antiplatelet drug. The meta-analysis included 18,788 patients with a history of myocardial infarction who received antiplatelet therapy for a mean duration of 27 months. Antiplatelet therapy significantly reduced the risk of nonfatal reinfarction and vascular death by 28% (p<0.0001) and 15% (p=0.0006), respectively. This benefit represents 18 fewer reinfarctions and 14 fewer vascular deaths per 1,000 patients. Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71 –86.
- In a 10-year follow-up of the Second International Study of Infarct Survival (ISIS-2), 1 month of low-dose acetylsalicylic acid (LD-ASA) therapy (160mg/day) was associated with a highly significant reduction in vascular mortality. 1 Most of the survival benefit was accrued during the first 35 days of follow-up (26 fewer deaths per 1,000). 2 There was little further benefit or loss during subsequent years (between 36 days and 10 years), which demonstrated that the mortality benefit obtained with the short course (1 month) of LD-ASA therapy following the onset of acute myocardial infarction, persisted over a long period of time. 2 1. ISIS-2 Collaborative Group. Lancet 1988;2:349–60. 2. Baigent C, et al. BMJ 1998;316:1337–43.
- The CAPRIE (Clopidogrel versus AAS in Patients at Risk of Ischemic Events) trial was designed to assess the efficacy of clopidogrel monotherapy compared with low-dose acetylsalicylic acid (LD-ASA) in 19,185 patients with a history of recent ischemic stroke (IS), recent myocardial infarction (MI), or peripheral arterial disease (PAD). Patients were randomized to receive either clopidogrel (75mg/day) or LD-ASA (325mg/day). The overall relative risk reduction of the composite primary endpoint (IS, MI, or vascular death) was 8.7% in favor of clopidogrel. However, this difference was of only marginal statistical significance (5.32% vs 5.83%; p = 0.043) and was attributed to a significant reduction in the risk of PAD. CAPRIE Steering Committee. Lancet 1996;348:1329–39.
- CAPRIE ( Clopidogrel versus AAS in Patients at Risk of Ischemic Events) subgroup analysis showed the overall statistical significance was attributed to benefits observed in patients with peripheral arterial disease (p=0.0028). The benefit of clopidogrel in patients with previous ischemic stroke (IS) or myocardial infarction (MI) was not significantly greater (IS, p=0.26; MI, p=0.66). In the subgroup of patients with MI at entry into the study, the findings favored LD-ASA; the incidence of IS, MI, or vascular death was higher with clopidogrel therapy than with LD-ASA (5.03% vs 4.84%; relative risk reduction 3.7%; p=0.66). CAPRIE Steering Committee. Lancet 1996;348:1329–39.
- The CURE ( Clopidogrel in Unstable angina to prevent Recurrent Events ) trial assessed the efficacy and safety of clopidogrel combination therapy with low-dose acetylsalicylic acid (LD-ASA) compared with LD-ASA alone in reducing the risk of nonfatal myocardial infarction (MI), ischemic stroke (IS), or death from cardiovascular (CV) causes in 12,562 patients with acute coronary syndrome without ST-segment elevation. The primary endpoint was defined as the composite of nonfatal MI, IS, or death from CV causes. Results show that overall relative risk reduction of MI, IS, or CV death was 18% in favor of clopidogrel + LD-ASA combination therapy (9.3% versus 11.4%; p<0.001). There were no statistical differences in ischemic stroke (IS) and cardiovascular (CV) death between the clopidogrel + low-dose acetylsalicyclic acid (LD-ASA) and LD-ASA only groups: IS, 1.2% vs 1.4%; CV death, 5.1% vs 5.5%, respectively. The overall statistically significant difference observed in the first primary outcome was therefore mainly attributed to the reduction in nonfatal MI: 22% relative risk reduction; 5.2% vs 6.7% for the clopidogrel + LD-ASA and LD-ASA only groups, respectively. It is important to highlight that LD-ASA remains baseline therapy, and additional benefits in patients with ACS without ST-segment elevation can be achieved with the addition of clopidogrel. CURE Trial Investigators. N Engl J Med 2001;345:494–502.
- PCI-CURE (Percutaneous Coronary Intervention- Clopidogrel in Unstable angina to prevent Recurrent Events) , CREDO ( Clopidogrel for the Reduction of Events During Observation) , and PCI-CLARITY (Percutaneous Coronary Intervention- CLopidogrel as Adjunctive Reperfusion TherapY) demonstrated a benefit of administering clopidogrel + low-dose acetylsalicylic acid (LD-ASA) combination therapy in patients undergoing PCI. Although an increased risk of bleeding was associated with combination therapy, the benefits outweighed the risks in these patients. It is important to highlight that LD-ASA remains baseline therapy, and additional benefits in patients undergoing PCI can be achieved with the addition of clopidogrel. 1. Mehta SR, et al. Lancet 2001;358:527–33. 2. Steinhubl SR, et al. JAMA 2002;288:2411–20. 3. Sabatine MS, et al. JAMA 2005;294:1224–32.
- La causa más importante de trombosis del stent es la discontinuación del tratamiento antiagregante. Las consecuencias son catastróficas ya que los pacientes se pueden presentar con un infarto agudo de miocardio que puede tener consecuencias fatales. Recientemente se ha reunido un grupo de expertos cardiólogos, cirujanos y dentistas americanos y han elaborado un documento para prevenir la discontinuación prematura de la antiagregación en los pacientes tratados con un stent (Circulation 2007; 115: 813-818). La cirugía menor, la limpieza o extracción dentales pueden realizarse sin apenas riesgo de sangrado. Sin necesidad de suspender el tratamiento antiagregante (Oral Sung Oral. Med Oral Pathol Oral Radiol Endod. 2006; 102:326). Se deben retrasar los procedimientos invasivos no urgentes con posibilidad de sangrado importante a un mes en los pacientes tratados con stent de metal, y a doce meses en los pacientes tratados con stents farmacoactivos, en lugar de suspender la antiagregación. En los pacientes en que deba realizarse alguna intervención que obligue a parar la antiagregación con Clopidogrel, la AAS debe mantenerse y el Clopidogrel debe restablecerse tan pronto como sea posible para evitar la trombosis del stents. Los pacientes que han sido tratados con stent farmacoactivo deben continuar con AAS de por vida y de forma continuada.
- CLARITY-TIMI 28 (CLopidogrel as Adjunctive Reperfusion TherapY-Thrombolysis In Myocardial Infarction Study 28) was designed to assess whether the addition of clopidogrel to standard therapy, including low-dose acetylsalicylic acid (LD-ASA) and fibrinolytics, was beneficial in patients presenting with ST-elevation myocardial infarction (STEMI). 1 Results from the CLARITY-TIMI 28 trial demonstrated that combination therapy was associated with a 36% reduction in the odds of the primary endpoint (p<0.001). COMMIT/CCS-2 ( ClOpidogrel and Metoprolol in Myocardial Infarction Trial/Second Chinese Study ) was designed to assess the efficacy of clopidogrel in combination with LD-ASA in patients with suspected MI, compared with LD-ASA alone. 2 Results from the COMMIT/CCS-2 trial demonstrated that clopidogrel + LD-ASA combination therapy was associated with a significant 9% reduction in the odds of the combined primary endpoint (2p=0.002). As a result of these trials, the US Food and Drug Administration approved the use of clopidogrel for patients with acute STEMI. These data have also been submitted to the European Medicines Evaluation Agency for a STEMI indication in the European Union, and a positive opinion from the agency’s Committee for Medicinal Products for Human Use has been received. 3 However, it is important to highlight that clopidogrel remains the add-on therapy; patients are likely to be receiving standard LD-ASA therapy before they are considered to be at high risk, and therefore eligible for that additional administration of clopidogrel. *TIMI Grade Flow is a grading system that defines the level of blood flow through a coronary artery, 0=no perfusion and 1=penetration without perfusion. 1. Sabatine MS, et al. N Engl J Med 2005;352:1179–89. 2. COMMIT Collaborative Group. Lancet 2005;366:1607–21. 3. Pharmaceutical Business Review Online. Sanofi-Aventis and BMS get new US ok for Plavix [press release, 18 August 2006], in www.pharmaceutical-business-review.com.
- IST (International Stroke Trial) was a randomized trial among 19,435 patients with acute ischemic stroke. Patients were randomized to receive low-dose acetylsalicylic acid (LD-ASA; 300mg/day), subcutaneous heparin (5,000 or 12,500IU twice daily), both, or neither within 48 hours of acute stroke. The primary outcomes were death within 14 days and death or dependency at 6 months. LD-ASA was associated with a 28% reduction in the risk of recurrent ischemic stroke within 14 days (2p<0.001) and a 9% reduction in death or nonfatal recurrent stroke (2p=0.02). There was no increase in the risk of hemorrhagic stroke in LD-ASA-treated patients. IST Collaborative Group. Lancet 1997;349:1569–81.
- CAST (Chinese Acute Stroke Trial) was a randomized trial of 20,655 patients with acute ischemic stroke. Patients received low-dose acetylsalicylic acid (LD-ASA; 160mg/day) within 48 hours of acute stroke, which was continued for up to 4 weeks. LD-ASA was associated with a significant 24% reduction in recurrent ischemic stroke (p=0.01), a significant 12% reduction in death or nonfatal stroke (p=0.03), and a 14% reduction in acute death (p=0.04) compared with placebo. Early LD-ASA administration (within 48 hours of onset of acute stroke) was associated with the greatest risk reductions. At 7 –12 hours after acute stroke, a small (3%) increase was found in the risk of death and nonfatal stroke; however, the reason for this is unknown. CAST Collaborative Group. Lancet 1997;349:1641–9.
- The Antiplatelet Trialists’ Collaboration was a meta-analysis of 145 studies comparing antiplatelet regimens with controls and 29 studies comparing one antiplatelet regimen with another. Low-dose acetylsalicylic acid (LD-ASA; 75–325mg/day) was the most widely studied antiplatelet drug. In more than 10,000 patients with prior stroke or transient ischemic attack, antiplatelet therapy was associated with a significant 22% reduction in the risk of stroke, myocardial infarction, or vascular death ( 2p<0.00001 ). In addition, antiplatelet therapy significantly reduced the risk of nonfatal stroke in all patients by 23% (2p<0.00001). The Antiplatelet Trialists’ Collaboration concluded that there was “no other drug regimen in these trials that has shown to be more effective than LD-ASA alone.” Antiplatelet Trialists' Collaboration. BMJ 1994;308:81–106.
- MATCH ( Management of ATherothrombosis with Clopidogrel in High-risk patients ) was a randomized, double-blind, placebo-controlled trial to compare low-dose acetylsalicylic acid (LD-ASA) + clopidogrel with clopidogrel monotherapy. Overall, 7,599 high-risk patients with recent transient ischemic attack (TIA) or ischemic stroke and at least one additional vascular risk factor were randomized to clopidogrel (75mg/day) and LD-ASA (75mg/day) or to clopidogrel (75mg/day) and placebo. LD-ASA therapy with add-on clopidogrel had no additional benefit over clopidogrel alone in the reduction of the combined primary endpoint of ischemic stroke, myocardial infarction, vascular death, or rehospitalization for an acute event. The combined primary endpoint was reached in 16.7% of patients in the group receiving clopidogrel alone compared with 15.7% in patients receiving LD-ASA + clopidogrel therapy. The overall relative risk reduction was 6.4% with clopidogrel alone. However, this represents a nonsignificant absolute risk reduction of only 1% (p=0.244). The occurrence of stroke or death from any cause (secondary outcomes) was also comparable between the two groups (p=0.790 and p=0.992, respectively). The design of MATCH was such that it did not reflect clinical practice — in clinical practice, LD-ASA is considered the standard first-line antiplatelet agent, and clopidogrel is the add-on therapy. Diener H-C, et al. Lancet 2004;364:331–7.
- CARESS (Clopidogrel and AAS for Reduction of Emboli in Symptomatic carotid Stenosis) was a randomized, double-blind trial to compare low-dose acetylsalicylic acid (LD-ASA) and add-on clopidogrel with LD-ASA monotherapy among subjects with 50% carotid stenosis and who had experienced a transient ischemic attack (TIA) or stroke within the previous 3 months. CARESS used transcranial Doppler ultrasound (TCD) to detect microembolic signals (MES), which are indicative of future stroke and TIA. Patients were screened by TCD and, if MES were detected, they were randomized to LD-ASA + clopidogrel or to LD-ASA monotherapy. At day 7, 43.8% of combination therapy patients were MES-positive compared with 72.7% of monotherapy patients (relative risk reduction 39.8%; 95% confidence interval 13.8–58.0; p=0.0046). There were no significant differences in life-threatening, major, or intracranial hemorrhage between combination therapy and LD-ASA monotherapy, but combination therapy was associated with a nonsignificant 2-fold increase in minor bleeds. CARESS was a very small study and treatment was administered for only 7 days, so it confirms benefits only in limited short-term use. It is hard to assess safety outcomes when treatment is given for only a short period—it is not known whether the incidence of bleeding complications would have increased if treatment was continued for longer. Markus H, et al. Circulation 2005;111:2233–40.
- Antiplatelet agents are a key component of stroke prevention in patients with transient ischemic attack (TIA) or stroke. Long-term prevention strategies for stroke rely on antiplatelet therapy to prevent the enlargement of existing clots and the formation of new clots. Low-dose acetylsalicylic acid is first-line treatment for the prevention of recurrent ischemic stroke or TIA.