| Q ALS transport is indicated for multiple, long bone, pelvic or open fractures q EKG monitor q IV 0.9% NaCl 250 cc hr infusion if lungs clear ; n when patient's condition permits, establish IV access prior to moving patient n if multiple, long bone or pelvic fracture administer 250 cc bolus, repeat as necessary q nitrous oxide for moderate to severe pain.
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Dogrel daily plus placebo twice daily n 161 ; or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily n 159 ; . The primary end point was recurrent ulcer bleeding. After 1 year, recurrent ulcer bleeding had occurred in 13 patients in the clopidogrel group and in 1 patient in the aspirin plus esomeprazole group. The cumulative incidence of recurrent bleeding was 8.6% CI, 4.1% to 13.1% ; in the clopidogrel group and 0.7% CI, 0% to 2.0% ; in the aspirin plus esomeprazole group difference, 7.9 percentage points [CI, 3.4 to 12.4 percentage points]; P 0.001 ; . In summary, aspirin plus esomeprazole therapy was superior to clopidogrel therapy for preventing recurrent ulcer bleeding in patients with a history of bleeding ulcers. Studies in animals have shown that platelet adenosine diphosphatereceptor antagonists, of which clopidogrel is an example, impair the healing of gastric ulcers by suppressing the release of platelet-derived growth factors. Clopidogrel may induce recurrent ulceration in the previously damaged gastric mucosal barrier by this mechanism. In patients who need to take both cardioprotective doses of aspirin and clopidogrel and who are at increased risk for gastrointestinal bleeding because of previous peptic ulceration or risk factors for bleeding ulcers male sex, age 70 years, positive results on tests for H. pylori ; , administration of a proton-pump inhibitor is warranted. Use of the lowest effective dose of aspirin for patients at high risk for gastrointestinal complications is also recommended.
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The bulk of the remaining patients will have events due to the thrombo-embolic complications of atheroma in the neck vessels and in the great vessels. We now understand a great deal more about what is the optimum anti-thrombotic treatment for such patients; all patients with TIA and minor ischaemic strokes should be started on a reasonable dose of aspirin 75300 mg daily ; .2 Once it has been licensed, clopidogrel will be available for those definitely intolerant of aspirin.3 The question will then be, particularly for patients who continue to have attacks despite aspirin and the other interventions discussed below ; , what to do next? The question is, should patients receive either clopidogrel, 3 aspirin plus clopidogrel, 4 or aspirin plus dipyridamole?5 Clopidogrel alone may be somewhat more effective than aspirin, 3 but the more important question of whether it adds anything to aspirin has not yet been addressed.4 A systematic review of the evidence suggested that dipyridamole did not add anything to aspirin2 but a more recent trial5 suggested that it might. An updated systematic review of all of the randomized evidence is urgently needed. Until then, aspirin remains the first-line drug of choice. What about anticoagulants either as first line or for aspirin `failures'? Certainly patients with transient ischaemic attacks or minor ischaemic strokes and atrial fibrillation are very likely to benefit from long-term anticoagulant therapy, aiming for an International Normalized Ratio INR ; between two and four.6 However, the inclusion of this evidence in clinical guidelines has not always been adequately worked out; 7 we need some thoughtful, evidencebased guidelines to ensure that this potentially risky treatment is applied only to those most likely to benefit. Should one use anticoagulants in TIA patients not in atrial fibrillation? Probably not.8, 9 The old trials comparing anticoagulants with controls in such patients are methodologically hopeless, and do not provide definitive evidence.8 A recent trial comparing quite intensive anticoagulant therapy INR 3.04.5 ; with aspirin showed a very clear excess risk of intracranial haemorrhage with anticoagulants.9 A new trial is now being planned to evaluate aspirin.
He Cardiac Arrhythmia Research Program at the PHRI focuses on answering questions related to the best clinical management of patients with atrial fibrillation and other cardiac arrhythmias. Atrial fibrillation is the most common serious disorder of the heart rhythm, affecting one per cent of the population; its most serious consequence is stroke. This research group has focused extensively on the treatment for prevention of stroke in atrial fibrillation and is currently leading two large clinical trials evaluating novel therapies combination of aspirin and clopidogrel and dabigatran, an oral thrombin inhibitor ; for stroke prevention. The group also is interested in the effects of blood pressure lowering in atrial fibrillation. Blood pressure is the most common cause of atrial fibrillation in Canada and other developed countries. However, the pathophysiologic role of hypertension has not been clearly defined; two studies being led by the group are exploring this issue. Prevention of atrial fibrillation by means of cardiac ablation is one of the promising new frontiers in the treatment of atrial fibrillation. This therapy is now increasingly used, but clinical trials to evaluate its effectiveness are just now being started and the group is leading one of the largest trials in this area. The Radiofrequency Ablation versus Antiarrhythmic Drugs for Prevention of Atrial Fibrillation RAAFT ; study being led by Carlos Morillo and Stuart Connolly is assessing 400 patients and is funded by Johnson and Johnson. Cardiac arrhythmias are increasingly treated by means of implanted devices, both defibrillators and pacemakers. This research group has a long-standing interest in device therapy for the management of a number of cardiac arrhythmias and is currently conducting the largest study ever done evaluating device therapy for the prevention of atrial fibrillation and evaluating the ability of cardiac arrhythmia devices to detect silent atrial fibrillation, which might place patients at increased risk of stroke.
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Gorelick PB, Schneck M, Berglund LF, Feinberg W, Goldstone J. Status of lipids as a risk factor for stroke. Neuroepidemiology 1997; 16: 107 RV Heart Protection Study Group. MRC BHF Heart Protection Study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 722. RT Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG, PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease PROSPER ; : a randomised controlled trial. Lancet 2002; 360: 16231630. RT Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA, Stroke Prevention by Aggressive Reduction in Cholesterol Levels SPARCL ; Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549559. RT The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT-LLT ; . JAMA 2002; 288: 29983007. RT Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J, ASCOT investigators. The prevention of coronary events and stroke with atorvastatin in hypertensive subjects with average or below average cholesterol levels. The Anglo-Scandinavian Cardiac Outcomes Trial: Lipid Lowering Arm ASCOT: LLA ; . Lancet 2003; 361: 11491158. RT Borghi C, Dormi A, Veronesi M, Immordino V, Ambrosioni E. Use of lipid-lowering drugs and blood pressure control in patients with arterial hypertension. J Clin Hypertens 2002; 4: 277285. RV Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 2005; 44: 467494. RV Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002; 324: 7186. MA Zanchetti A, Hansson L, Dahlof B, Julius S, Menard J, Warnold I, Wedel H. Benefit and harm of low-dose aspirin in well-treated hypertensives at different baseline cardiovascular risk. J Hypertens 2002; 20: 23012307. CT Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients MATCH ; : randomised, double-blind, placebo-controlled trial. Lancet 2004; 364: 331337. RT Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005; 352: 12931304. RT Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002; 136: 161 MA Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 1419. RV Sanmuganathan PS, Ghahramani P, Jackson PR, Wallis EJ, Ramsay LE. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart 2001; 85: 265271. MA Zanchetti A, Hansson L, Leonetti G, Rahn KH, Ruilope L, Warnold I, Wedel H. Low-dose aspirin does not interfere with the blood pressurelowering effects of antihypertensive therapy. J Hypertens 2002; 20: 10151022. RT Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229234. OS Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16: 434444. OS Knowler WC, Sartor G, Melander A, Schersten B. Glucose tolerance and mortality, including a substudy of tolbutamide treatment. Diabetologia 1997; 40: 680686. OS and lopressor.
Cost Per Weighted Separation CPWS ; is the most useful tool to measure changes in costs. At present CPWS is only produced once a year and over six months after the end of the recording period. NSW Health reports significant problems with delivering CPWS in a timely and regular manner. These lengthy delays severely limit the usefulness of this measure as a monthly monitored performance indicator. However, NSW Health is working towards publishing CPWS on a quarterly and eventually a monthly basis. IPART supports these refinements to data collection and processing. The CPWS is also collected annually by COAG to enable interstate comparisons. In the interim IPART recommends monthly reporting of the cost per admission as a proxy between quarters for the CPWS.
Derlet RW, Richards JR. Overcrowding in Emergency Departments: Problems of the Past Return with a Fury. Emergency Medicine News. 1998, Vol XX 11 ; : Derlet RW. Emergency Medicine Triage IN: e-Medicine on-line publication: : emedicine ; , 1999, Boston Medical Publishing Corporation. Salk ED, Schriger DL, Hubbell KA, Schwartz BL. Effect of Visual Cues, Vital Signs, and Protocols on Triage: A Prospective Randomized Crossover Trial. Annals of Emergency Medicine, 1999 32 6 ; : 655-664. Marrow J. Triage and Casemix in Accident and Emergency Medicine. European Journal of Emergency Medicine 1998 5 1 ; : 53-58. Brillman JC, Doezema D, Tandberg D, Sklar DP, Skipper BJ: Does a Physician's Visual Assessment Change Triage? American Journal of Emergency Medicine 1997, V15: 1, P29-33. Wong TW, Tseng G, Lee LW. Report of an Audit of Nurse Triage in an Accident and Emergency Department. Journal of Accident and Emergency Medicine 1994 11, 91-95 and lotrimin, for example, statin drugs.
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To determine whether pharmaceutical products on the market are officially registered, a sample of at least 100 products available at retail drug outlets must be enumerated. To do this: 1 ; Select a random sample of 10-20 retail drug sales outlets. 2 ; At each retail drug sales outlet select from the shelves 10 products and record the complete names and product specifications. From 100 to 200 products may be identified. If working with more than one enumerator, duplication can be avoided by assigning each enumerator a range of letters of the alphabet, with instructions to select products within the assigned range. The drug registration data base is checked to con!irrn that the products on this list are registered. A smaller sample of 20 products may be further selected, in order to determine the functionality of the computerized or manual drug registration database. The idea is to see whether or not the system can retrieve accurate information concerning the products selected. This is done in the following manner: a ; The list of 100-200 pharmaceutical products is arranged alphabetically and numbered sequentially. 0-J ; Divide the total number of products in this list by the number 20, and round up the fraction if any, this is the sampling interval. c ; Select the first product randomly. 4 Add sampling interval to the sequential number of product previously selected, select product bearing this sequence number. Repeat step d ; until you finish selecting the number of products.
A three-dose graded challenge to clopidogrel, following premedication, was performed on the third day and was well tolerated and metrogel.
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Testify in support of Redux, stressing that obesity is a killer disease that demands long-term treatment. They acknowledge deadly side effects from the drug but say obesity is an even worse killer. FDA advisory committee votes 5-3 against approval because of concerns over Redux's links to a deadly lung disease and possible nerve damage.
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| Lopid od1. Easton JD, Albers GW, Caplan LR, et al. Discussion: Reconsideration of TIA terminology and definitions. Neurology 2004; 62 8 Suppl 6 ; : S29-34. 2. Coull AJ, Lovett JK, Rothwell PM; Oxford Vascular Study. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ 2004; 328: 326. Rothwell PM, Giles MF, Flossmann E, et al. A simple score ABCD ; to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet 2005; 366: 29-36. Featherstone RL, Brown MM, Coward LJ; ICSS Investigators. International carotid stenting study: protocol for a randomised clinical trial comparing carotid stenting with endarterectomy in symptomatic carotid artery stenosis. Cerebrovasc Dis 2004; 18: 69-74. Clopidogrel and modified-release dipyridamole in the prevention of occlusive vascular events. Technology Appraisal 90. NICE guidance. w w w. guidance . 6. Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143: 1-13 and mobic.
8. No visitors allowed. You will be notified of scheduled exceptions to this rule. This includes children and pets. 9. Pairing up with another Drug Court participant for an intimate relationship is strongly discouraged. 10. Smoking is permitted outside only. Place cigarette butts in the ash can provided. 11. No littering in parking lot or in building. You must be responsible for assisting in maintaining the cleanliness of the building. 12. Destroying or defacing property will lead to sanctions and possible criminal charges.
This conference, in this place and at this time, provided the people and President Thabo Mbeki of the Republic of South Africa a historic opportunity to showcase the result of six years of freedom and democracy, and the reality of black and white working together to build a future, but most importantly the chance to see, feel and hear how the country would effectively cope with HIV AIDS without the discrimination, prejudice and stigma that has plagued the United States. This conference gave President Mbeki a forum to raise new and necessary questions associated with the inequalities of making HIV medicines and treatments available to all people, regardless of class, race, gender, sexuality, religious affiliation--and most importantly ability to afford the astronomical cost associated with HIV drugs. This conference provided Mbeki a podium from which to challenge world leaders, governments, pharmaceutical companies, financiers, and world health organizations on their humanitarian rhetoric and the politics of AIDS. Mbeki failed to break those silences and many others. He failed to end the silence on the global mismanagement and inequitable distribution of medicines and treatment options available to all poor people and particularly to the millions of people of color living with HIV. Charles E. Clifton is the new editor of Positively Aware and Director of Communications for Test Positive Aware Network and moduretic.
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Researchers at the national lipid association suggest that patients ask their doctors about their triglyceride levels, since medications like lopid, lifibra, and tricor are available to help lower triglycerides and their associated risks.
1999 ; pharmacol res combination therapy with clopidogrel and aspirin after coronary stenting and ocuflox.
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Method This is a single centre study from cardiovascular catheterization laboratory, Brigham and Women's Hospital, Boston, MA, USA. This centre is a tertiary referral centre and provides 24-hour emergency services for primary angioplasty. All coronary interventions involving DES from 25th April, 2003 to 1st July, 2004 were reviewed for occurrence of SAT. BMS study period included all coronary interventions used BMS from 1st July 2002 to 25th March, 2003. Results A total of 1770 DES procedures and 1335 BMS procedures were performed during the two study periods. SAT occurred in 11 DES patients 0.62% ; and 5 BMS patients 0.37% ; NS ; . The mean time to SAT occurrence was 6.0 days in the DES group and 7.6 days in the BMS group NS ; . Both groups had similar pre-procedural clinical and lesion characteristics. The total stent length and the minimal luminal diameter of the stents post-procedure were 20.7mm and 2.82mm in the DES SAT group and 29.2mm and 2.90mm in the BMS SAT group NS ; . Using a logistic model, three factors influenced the occurrence of SAT in DES cases: 1. Presentation with index AMI OR 3.48, p 0.056 2. Stent diameter 3.0mm OR 2.75, p 0.114 3. Inability to take ASA or clopidogrel OR 3.83, p 0.095 ; . Conclusions SAT occurred in 0.62% of cases after DES implantation and was similar to BMS. Our dataset suggested presentation with index AMI, stent diameter 3.0mm and inability to take dual anti-platelet therapy may predict SAT occurrence. STUDY ON THE PREVALENCE OF SKIN DISEASES AMONG ELDERLY HOMES RESIDENTS AND THE POSSIBLE USE OF STORE-AND-FORWARD TELEDERMATOLOGY IN THIS GROUP OF PATIENTS Dr Chan Wen, Department of Medicine & Therapeutics, Prince of Wales Hospital June 2005 Dermatology & Venerology Exit Assessment Exercise ; Background Skin problems are common in the geriatric population. There was no previous data on the prevalence of skin problems in local geriatric community. Teledermatology had been shown to have potential benefits in various aspects in dermatology services. Elderly homes residents tend to have more difficulty in seeking specialist care and are suitable cases for the study of the use of teledermatology. 1 and oxybutynin.
For these reasons, aspirin and clopidogrel have become essential tools in the management of patients with cardiovascular disease.
6078 per additional QALY. However, although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. To estimate the exact length of time that clopidogrel in addition to standard therapy should be prescribed for patients with non-ST-segment ACS would require a prospective trial that randomised patients to various durations of therapy. This would accurately assess whether a `rebound' phenomenon occurs in patients if clopidogrel were stopped after 3 months of treatment and prednisolone and lopid.
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WE'RE BACK WITH THE ANSWER TO OUR ACCENTHEALTH MINDBENDER! WE ASKED HOW MUCH SLEEP DOES THE AVERAGE ADOLESCENT NEED EACH NIGHT? IS IT: A ; 10 HOURS B ; 9 HOURS C ; 7 HOURS IF YOU ANSWERED "B" YOU'RE RIGHT! MOST ADOLESCENTS NEED BETWEEN EIGHT-AND-A-HALF AND NINE-AND-A-QUARTER HOURS OF SLEEP EACH NIGHT. A LACK OF SLEEP CAN MAKE YOU LOOK TIRED AND FEEL DEPRESSED AND IRRITABLE. AND IT CAN AFFECT YOUR PERFORMANCE IN EVERYTHING FROM TAKING SCHOOL EXAMS TO PLAYING SPORTS OR EVEN VIDEO GAMES. SLEEP IS CONSIDERED FOOD FOR THE BRAIN SO KIDS AND PARENTS, GET INTO A GOOD SLEEP ROUTINE AND MAKE SURE YOU'RE GETTING ENOUGH Z'S! NOW FILL OUT YOUR MINDBENDER SWEEPSTAKES ENTRY FORM IN THIS WAITING ROOM FOR YOUR CHANCE TO WIN FROM ACCENTHEALTH. SOURCE: NATIONAL SLEEP FOUNDATION.
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Aspirin vs clopidogrel in patients at risk for cardiovascular event 19, 185 patients, 3 subgroups with 6, 300 patients each TIA Stroke; myocardial infarction; peripheral arterial occlusive disease ; Mean duration of follow-up: 1.9 years Primary outcome: ischemic stroke, myocardial infarction, or vascular death.
The recently published ACCESS trial, for example, provided evidence that lowering blood pressure is not necessarily detrimental. ACCESS was a double-blind, placebo-controlled, randomised phase II study designed to assess the effect of modest blood pressure reductions with the angiotensin receptor blocker ARB ; candesartan in the early treatment of stroke starting within 72 hours of onset ; in people who were extremely hypertensive. The trial was stopped prematurely because of a major and significant reduction in the composite endpoint of death, cerebral, or cardiac events among cande- Professor Philip Bath sartan-treated patients 9.8% versus 18.7% ; . Candesartan was given in a blinded fashion for a week following the index stroke, and then all hypertensive patients became eligible for candesartan. Oddly, it was much later that the Kaplan-Meier curves for the composite endpoint began to separate, with the early candesartan group showing less events and the difference between the groups increasing with time. Slide 16 ; It is difficult to understand why this happened. ARBs are suspected of having neuroprotective and neuroreparative properties, but, at this point, attributing the benefit to this aspect of an ARB would be "wild speculation." The benefit might be attributable to the multimodal effects of ARBs. These agents, in addition to affecting blood pressure, have vasodilator effects, improve central haemodynamics, and probably have anti-inflammatory and antiplatelet properties. Four large trials, either already underway or in the planning stages, are addressing the issue of blood pressure modification after stroke. The COSSACS n 2900 ; and ENOS n 5000 ; trials are examining the question of whether prior antihypertensive treatment should be continued or stopped in stroke patients, an important question since about half of stroke patients are on a variety of antihypertensive drugs. CHIPPS n 1000 ; will investigate the effects of lisinopril, and, of course, PRoFESS, is investigating telmisartan. In addition to addressing the question of the continuation of previous antihypertensive treatment, the ENOS trial will also evaluate the safety and efficacy of lowering blood pressure with transdermal glyceryl trinitrate 5 mg daily ; during the early treatment phase. Patients with an ischaemic or haemorrhagic stroke and hypertension 140220 mg Hg ; , who receive treatment within 48 hours of onset, will be enrolled. Currently, the outcome is 3-month death or dependency as measured by the mRS. Professor Bath did not believe that lowering blood pressure necessarily reduced perfusion in the region of a stroke, and showed some CT scans to illustrate this. Briefly discussing the PRoFESS trial, Professor Bath suggested that there could be a slightly larger reduction in blood pressure in the dipyridamole arm than in the clopidogrel arm. In a meta-analysis of all the dipyridamole trials n 9102 ; , the agent was associated with a modest improvement in blood pressure. In summary high blood pressure is Slide 16 common, and detrimental in stroke patients. It is unclear whether blood pressure should be altered during the acute phase of stroke. The limited data available indicate that beta blockers and calcium channel blockers are not ideal choices but the angiotensin modifying drugs, and perhaps nitrates, seem more promising. We need a better understanding of the effects of such drugs, for example on cerebral blood flow and haemostasis, and the ongoing studies, including PRoFESS should help us to achieve this.
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Figure 3: Cumulative risk of Ischaemic stroke, myocardial infarction, or vascular death A aspirin; C clopidogrel. Vol 348 November 16, 1996.
Table II. Possible Therapeutic Strategies against Prostate Cancer, for example, pregnancy.
Also tell your prescriber if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs and lopressor.
As with aspirin resistance, the concept of clopidogrel resistance stems from investigations that revealed failure of clopidogrel therapy to inhibit ex vivo platelet function as assessed by a given test. Interindividual variability in clopidogrel-induced platelet inhibition has been consistently demonstrated.4951 In a study of 544 patients, Serebruany et al51 showed that the response to clopidogrel was a normal bell-shaped distribution, consistent with polyenvironmental and polygenetic influences on responsiveness.51 Hochholzer et al52 confirmed this wide range of variability in response to clopidogrel in a study of 1, patients. These studies clearly confirm that the ex vivo response to clopidogrel can vary substantially from patient to patient, but whether this variability has clinical implications is not known. Muller et al53 classified patients as nonresponders and semiresponders to clopidogrel defined arbitrarily as a 10% reduction and a 10%29% reduction in platelet aggregation, respectively ; in their study of 105 aspirintreated patients with stable coronary artery disease who underwent elective PCI. Clopidogrel's inhibition of platelet aggregation was determined by the response to 5 mol L and to 20 mol L of ADP-induced aggregation 4 hours after treatment with 600 mg of clopidogrel. The reported prevalence of patients who were nonresponders and semiresponders varied depending on the ADP dose used to induce aggregation.53 Of interest, 2 of the 105 patients studied had acute stent thrombosis and both patients were among those identified as clopidogrel nonresponders. This correlation between thrombotic events and clopidogrel responsiveness as measured by platelet function tests was also supported by Matetzky et al, 54 who evaluated 60 patients with acute ST-elevation MI who were undergoing PCI. Patients in the lowest quartile of responsiveness to clopidogrel had a significantly higher risk of recurrent cardiovascular events.54 Interestingly, another method of platelet function testing used in this study--the DiaMed Impact cone and platelet analyzer DiaMed Israel Ltd ; --did not identify clinically important differences in platelet inhibition.
Risk of stroke when ticlopidine vs. asprin used in high-risk patients suffering prior transient ischemic attack or minor stroke Combined risk of ischemic stroke, heart attack, and vascular death when clopidogrel vs. asprin used in high-risk patients suffering an atherosclerotic vascular event Prevention of recurrent stroke when carotid endarterectomy used in eligible patients with blocked carotid neck ; arteries who suffered a transient ischemic attack.
Patients 9.3% ; in the clopidogrel ASA group, compared with 719 of the 6, 303 patients 11.4% ; in the placebo ASA group. This corresponded to a relative risk RR ; of 0.80 95% CI, 0.72-0.90; p 0.001 ; for the clopidogrel ASA combination.8 This translates to an ARR of 2.1% 95% CI, 1%3.2% ; , which corresponds to an NNT of 47 patients 95% CI, 32-96 ; to prevent one occurrence of the first primary outcome over an average period of nine months. The incidence of the second primary outcome, which included either the first primary outcome or refractory ischemia, was also significantly lower in the group treated with the clopidogrel ASA combination. The second primary outcome was observed in 1, 035 patients in the clopidogrel ASA group 16.5% ; and in 1, 187 patients 18.8% ; in the placebo ASA group. This corresponded to a RR 0.86 95% CI, 0.79-0.94; p 0.001 ; for the clopidogrel ASA combination.8 This translates to a 2.3% ARR 95% CI, 1%-3.6% ; and an NNT of 44 patients 95% CI, 28-104 ; to prevent one occurrence of the second.
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