Discontinuation of Antiplatelet Study Medication and Risk of Recurrent Stroke and Cardiovascular Events: Results from the PRoFESS Study

被引:39
作者
Weimar, Christian [1 ]
Cotton, Dan [3 ]
Sha, Nanshi [3 ]
Sacco, Ralph L. [2 ]
Bath, Philip M. W. [4 ]
Weber, Ralph [1 ,5 ]
Diener, Hans Christoph [1 ]
机构
[1] Univ Duisburg Essen, Dept Neurol, DE-45122 Essen, Germany
[2] Univ Miami, Dept Neurol, Miami, FL USA
[3] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA
[4] Univ Nottingham, Stroke Trials Unit, Nottingham NG7 2RD, England
[5] Alfried Krupp Hosp Essen, Dept Neurol, Essen, Germany
关键词
Ischemic stroke; Antiplatelets; Clinical study; Secondary prevention; Compliance; Adherence; EXTENDED-RELEASE DIPYRIDAMOLE; ISCHEMIC ATTACK; DOUBLE-BLIND; ASPIRIN; CLOPIDOGREL; METAANALYSIS; PREVENTION; TRIAL; ADHERENCE; THERAPY;
D O I
10.1159/000351144
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Several case control studies have reported an increased risk of cardiovascular events following discontinuation of antiplatelet agents in high-risk patients. We therefore sought to investigate the risk of recurrent stroke and cardiovascular events following discontinuation of antiplatelet study medication in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a large randomized secondary stroke prevention study. Methods: The recurrent stroke and cardiovascular event rates following discontinuation of aspirin plus extended-release dipyridamole (ASA + ERDP) or clopidogrel were compared to the event rates in the on-treatment populations (patients who had discontinued their antiplatelet medication due to an outcome event were kept in the on-treatment population in order not to underestimate the on-treatment stroke rate). Results: In 7,212 treated ASA + ERDP patients, the stroke incidence rate for the on-treatment group was 729 strokes with an average exposure of 17,048 person-years (0.12 per 1,000 person-days). For 7,864 treated clopidogrel patients, the stroke incidence rate for the on-treatment group was 737 strokes with an average exposure of 18,715 person-years (0.11 per 1,000 person-days). ASA + ERDP was discontinued in 2,843 patients (in 57.7% due to an adverse event, 28.2% noncompliance, 1.4% loss to follow-up, 4.5% withdrawal of consent and 8.1% other/nonspecified reasons) and clopidogrel was permanently discontinued in 2,176 patients (49.0% due to an adverse event, 34.2% noncompliance, 1.8% loss to follow-up, 5.3% withdrawal of consent and 9.7% other/nonspecified reasons). Within 30 days, a recurrent stroke occurred in 31 patients (0.37 per 1,000 persondays) after discontinuation of ASA + ERDP and in 15 patients (0.24 per 1,000 person-days) after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 0.77% within 30 days after discontinuation of ASA + ERDP and 0.40% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. A combined vascular endpoint (stroke, myocardial infarction, vascular death) occurred in 68 patients (0.82 per 1,000 person-days) within 30 days after discontinuation of ASA + ERDP and in 47 patients (0.75 per 1,000 person-days) within 30 days after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 2.02% within 30 days after discontinuation of ASA + ERDP and 1.83% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. Conclusion: Discontinuation of antiplatelet medication after ischemic stroke should be advocated only when the risk and severity of bleeding clearly outweigh the risk of cardiovascular events. Copyright (C) 2013 S. Karger AG, Basel
引用
收藏
页码:538 / 543
页数:6
相关论文
共 17 条
[1]   A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50 279 patients at risk for coronary artery disease [J].
Biondi-Zoccai, Giuseppe G. L. ;
Lotrionte, Marzia ;
Agostoni, Pierfrancesco ;
Abbate, Antonio ;
Fusaro, Massimiliano ;
Burzotta, Francesco ;
Testa, Luca ;
Sheiban, Imad ;
Sangiorgi, Giuseppe .
EUROPEAN HEART JOURNAL, 2006, 27 (22) :2667-2674
[2]   Low-dose aspirin for secondary cardiovascular prevention -: cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation -: review and meta-analysis [J].
Burger, W ;
Chemnitius, JM ;
Kneissl, GD ;
Rücker, G .
JOURNAL OF INTERNAL MEDICINE, 2005, 257 (05) :399-414
[3]   Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: The prevention regimen for effectively avoiding second strokes trial (PRoFESS) [J].
Diener, Hans-Christoph ;
Sacco, Ralph ;
Yusuf, Salim .
CEREBROVASCULAR DISEASES, 2007, 23 (5-6) :368-380
[4]  
Rodríguez LAG, 2011, NEUROLOGY, V76, P740, DOI 10.1212/WNL.0b013e31820d62b5
[5]   A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) [J].
Gent, M ;
Beaumont, D ;
Blanchard, J ;
Bousser, MG ;
Coffman, J ;
Easton, JD ;
Hampton, JR ;
Harker, LA ;
Janzon, L ;
Kusmierek, JJE ;
Panak, E ;
Roberts, RS ;
Shannon, JS ;
Sicurella, J ;
Tognoni, G ;
Topol, EJ ;
Verstraete, M ;
Warlow, C .
LANCET, 1996, 348 (9038) :1329-1339
[6]   Persistent Use of Secondary Preventive Drugs Declines Rapidly During the First 2 Years After Stroke [J].
Glader, Eva-Lotta ;
Sjolander, Maria ;
Eriksson, Marie ;
Lundberg, Michael .
STROKE, 2010, 41 (02) :397-401
[7]   Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial [J].
Granger, BB ;
Swedberg, K ;
Ekman, I ;
Granger, CB ;
Olofsson, B ;
McMurray, JJV ;
Yusuf, S ;
Michelson, EL ;
Pfeffer, MA .
LANCET, 2005, 366 (9502) :2005-2011
[8]   Randomized Double-Blind Assessment of the ONSET and OFFSET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease The ONSET/OFFSET Study [J].
Gurbel, Paul A. ;
Bliden, Kevin P. ;
Butler, Kathleen ;
Tantry, Udaya S. ;
Gesheff, Tania ;
Wei, Cheryl ;
Teng, Renli ;
Antonino, Mark J. ;
Patil, Shankar B. ;
Karunakaran, Arun ;
Kereiakes, Dean J. ;
Parris, Cordel ;
Purdy, Drew ;
Wilson, Vance ;
Ledley, Gary S. ;
Storey, Robert F. .
CIRCULATION, 2009, 120 (25) :2577-U103
[9]   Adherence to secondary stroke prevention strategies - Results from the German stroke data bank [J].
Hamann, GF ;
Weimar, C ;
Glahn, J ;
Busse, O ;
Diener, HC .
CEREBROVASCULAR DISEASES, 2003, 15 (04) :282-288
[10]   Long-term outcome after ischaemic stroke/transient ischaemic attack [J].
Hankey, GJ .
CEREBROVASCULAR DISEASES, 2003, 16 :14-19