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Myocardial infarction after aspirin cessation in stable coronary artery disease patients
International Journal of Cardiology 76 (2000) 257–258 www.elsevier.com / locate / ijcard
Letter to the Editor
Myocardial infarction after aspirin cessation in stable coronary artery disease patients Jean-Philippe Collet MD a
a,b ,
*, Dominique Himbert MD b , Philippe G. Steg MD b
´ ´ ` , 47 Boulevard de l’ Hopital ˆ , 75013 Paris, France Department of Cardiology, Centre Hospitalier Universitaire Pitie-Salpetriere b Department of Cardiology, Centre Hospitalier Universitaire Bichat, Rue Huchard, 75018 Paris, France Received 29 June 2000; accepted 13 September 2000
Abstract Discontinuation of chronic aspirin therapy in stable coronary artery disease patients may lead to acute myocardial infarction within 10 days of withdrawal as a consequence of the progressive recovery of the platelet cyclooxygenase activity which exposes to a rebound effect leading to acute coronary thrombosis. 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Myocardial infarction; Aspirin; Platelets
Patients with coronary artery disease receive longterm aspirin prophylaxis but the optimal duration of treatment and the risks associated with discontinuation are unknown [1]. Although the safety of aspirin withdrawal in patients with angiographically-proven stable coronary disease has never been evaluated, chronic aspirin therapy is often withheld several days before planned surgery to reduce the risk of perioperative bleeding. The mean platelet life span being |10 days, 50% of normally functioning platelets are recovered within 5 days after aspirin withdrawal while platelet thromboxane biosynthesis recovers more rapidly with a level of urinary thromboxane metabolites close to normal after 3 days [2]. We hypothesized that a rebound of coronary thrombotic events may occur in these patients within the 2-week period of platelet functional recovery after
*Corresponding author. Tel.: 133-1-4217-6742; fax: 133-1-42176856. E-mail address: [email protected] (J.-P. Collet).
aspirin cessation. Through a retrospective analysis, we reviewed 475 consecutive patients admitted for acute myocardial infarction (MI) between December 1992 and September 1996, and found 11 patients who had discontinued aspirin therapy within 15 days prior to admission (Table 1). All patients had been on chronic aspirin for symptomatic coronary artery disease. All patients were stable and had been free of acute coronary events for an average of 3.862.9 years. They were either asymptomatic on medical therapy (n55) or with effort angina (n56). Aspirin was discontinued prior to planned surgery in nine patients while two patients stopped taking the medication spontaneously for no medical reason. MI (defined as protracted nitrate-resistant chest pain with ST segment elevation, always confirmed by enzyme assays) occurred within 9.463.2 days of aspirin cessation. Emergency coronary angiography was performed in eight cases and demonstrated complete occlusion of the coronary culprit artery in all. It led to primary PTCA in seven patients and to rescue PTCA in one. The three last patients were treated conserva-
0167-5273 / 00 / $ – see front matter 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00399-5
J.-P. Collet et al. / International Journal of Cardiology 76 (2000) 257 – 258
258
Table 1 Patients characteristics regarding the relation between myocardial infarction and aspirin cessation Age
Treatment duration (years)
Symptomfree interval (years)
68 77
5 2
5 2
68 72 37 70 76 79 66 70
4 3 4 3 8 5 1 4
4 3 4 1.25 8 1 1 2
88
10
70.1612.7 a
4.562.7
10
Surgery
Relation of MI to surgery
Time between MI a and withdrawal (days)
Inguinal hernia Aortofemoral bypass CABG a Colonic surgery None Colonic surgery Hip surgery CABG None Ophthalmic surgery Dental surgery
Per Per
10 10
3.862.9
Pre Post (48 None Post (12 Post (48 Pre None Post (48
h) h) h)
15 10 9 13 6 3 7
h)
Post (48 h)
10 10 9.463.2
CABG, coronary artery bypass grafting; MI, myocardial infarction.
tively because of admission more than 12 h after symptom onset. The chronological link between aspirin withdrawal and acute MI reported here may not be fortuitous. All patients were stable on medical therapy before aspirin cessation and MI occurred with a delay consistent with the platelet function recovery. MI is generally precipitated by plaque rupture associated with changes in the haemostatic / fibrinolytic balance [3]. Our data support the hypothesis of a rebound effect after aspirin withdrawal leading to acute coronary thrombosis which might have been facilitated by the surgical stress present in seven patients. This superimposed thrombotic tendency is crucial in these patients that are also known to exhibit enhanced thrombin generation which is a potent factor stimulating platelet aggregation and a marker of subsequent coronary events [4]. The average delay between aspirin withdrawal and myocardial infarction is consistent with the rebound of platelet activity described after aspirin cessation in similar patients [5]. Discontinuing chronic aspirin therapy in stable coronary artery disease patients, especially before
surgery, may be associated with a substantial risk of acute myocardial infarction. The magnitude of this risk and the value of alternative measures, such as replacement with heparin or shorter-acting antiplatelet agents, deserve further prospective evaluation.
References [1] Antiplatelet Trialist’s Collaboration Study. Collaborative overview of randomised trials of antiplatelets therapy. Prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994;308:81–106. [2] Fitzgerald GA, Oates JA, Hawiger J, Maas RL, Roberts II U, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest 1983;71:676–88. [3] Fitzgerald DJ, Roy L, Catella F. Platelet activation in unstable coronary disease. N Engl J Med 1986;315:983–9. [4] Lam JYT, Latour JG, Lesperance J, Waters D. Platelet aggregation, coronary disease progression and future coronary events. Am J Cardiol 1994;73:333–8. [5] Vial JH, McLeod LJ, Roberts MS. Rebound elevation in urinary thromboxane B2 and 6-keto-PFF1 alpha exacerbation alter aspirin withdrawal. Prostaglandin Thromboxane Leukot Res 1991;21A:157–60.
Letter to the Editor
Myocardial infarction after aspirin cessation in stable coronary artery disease patients Jean-Philippe Collet MD a
a,b ,
*, Dominique Himbert MD b , Philippe G. Steg MD b
´ ´ ` , 47 Boulevard de l’ Hopital ˆ , 75013 Paris, France Department of Cardiology, Centre Hospitalier Universitaire Pitie-Salpetriere b Department of Cardiology, Centre Hospitalier Universitaire Bichat, Rue Huchard, 75018 Paris, France Received 29 June 2000; accepted 13 September 2000
Abstract Discontinuation of chronic aspirin therapy in stable coronary artery disease patients may lead to acute myocardial infarction within 10 days of withdrawal as a consequence of the progressive recovery of the platelet cyclooxygenase activity which exposes to a rebound effect leading to acute coronary thrombosis. 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Myocardial infarction; Aspirin; Platelets
Patients with coronary artery disease receive longterm aspirin prophylaxis but the optimal duration of treatment and the risks associated with discontinuation are unknown [1]. Although the safety of aspirin withdrawal in patients with angiographically-proven stable coronary disease has never been evaluated, chronic aspirin therapy is often withheld several days before planned surgery to reduce the risk of perioperative bleeding. The mean platelet life span being |10 days, 50% of normally functioning platelets are recovered within 5 days after aspirin withdrawal while platelet thromboxane biosynthesis recovers more rapidly with a level of urinary thromboxane metabolites close to normal after 3 days [2]. We hypothesized that a rebound of coronary thrombotic events may occur in these patients within the 2-week period of platelet functional recovery after
*Corresponding author. Tel.: 133-1-4217-6742; fax: 133-1-42176856. E-mail address: [email protected] (J.-P. Collet).
aspirin cessation. Through a retrospective analysis, we reviewed 475 consecutive patients admitted for acute myocardial infarction (MI) between December 1992 and September 1996, and found 11 patients who had discontinued aspirin therapy within 15 days prior to admission (Table 1). All patients had been on chronic aspirin for symptomatic coronary artery disease. All patients were stable and had been free of acute coronary events for an average of 3.862.9 years. They were either asymptomatic on medical therapy (n55) or with effort angina (n56). Aspirin was discontinued prior to planned surgery in nine patients while two patients stopped taking the medication spontaneously for no medical reason. MI (defined as protracted nitrate-resistant chest pain with ST segment elevation, always confirmed by enzyme assays) occurred within 9.463.2 days of aspirin cessation. Emergency coronary angiography was performed in eight cases and demonstrated complete occlusion of the coronary culprit artery in all. It led to primary PTCA in seven patients and to rescue PTCA in one. The three last patients were treated conserva-
0167-5273 / 00 / $ – see front matter 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00399-5
J.-P. Collet et al. / International Journal of Cardiology 76 (2000) 257 – 258
258
Table 1 Patients characteristics regarding the relation between myocardial infarction and aspirin cessation Age
Treatment duration (years)
Symptomfree interval (years)
68 77
5 2
5 2
68 72 37 70 76 79 66 70
4 3 4 3 8 5 1 4
4 3 4 1.25 8 1 1 2
88
10
70.1612.7 a
4.562.7
10
Surgery
Relation of MI to surgery
Time between MI a and withdrawal (days)
Inguinal hernia Aortofemoral bypass CABG a Colonic surgery None Colonic surgery Hip surgery CABG None Ophthalmic surgery Dental surgery
Per Per
10 10
3.862.9
Pre Post (48 None Post (12 Post (48 Pre None Post (48
h) h) h)
15 10 9 13 6 3 7
h)
Post (48 h)
10 10 9.463.2
CABG, coronary artery bypass grafting; MI, myocardial infarction.
tively because of admission more than 12 h after symptom onset. The chronological link between aspirin withdrawal and acute MI reported here may not be fortuitous. All patients were stable on medical therapy before aspirin cessation and MI occurred with a delay consistent with the platelet function recovery. MI is generally precipitated by plaque rupture associated with changes in the haemostatic / fibrinolytic balance [3]. Our data support the hypothesis of a rebound effect after aspirin withdrawal leading to acute coronary thrombosis which might have been facilitated by the surgical stress present in seven patients. This superimposed thrombotic tendency is crucial in these patients that are also known to exhibit enhanced thrombin generation which is a potent factor stimulating platelet aggregation and a marker of subsequent coronary events [4]. The average delay between aspirin withdrawal and myocardial infarction is consistent with the rebound of platelet activity described after aspirin cessation in similar patients [5]. Discontinuing chronic aspirin therapy in stable coronary artery disease patients, especially before
surgery, may be associated with a substantial risk of acute myocardial infarction. The magnitude of this risk and the value of alternative measures, such as replacement with heparin or shorter-acting antiplatelet agents, deserve further prospective evaluation.
References [1] Antiplatelet Trialist’s Collaboration Study. Collaborative overview of randomised trials of antiplatelets therapy. Prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994;308:81–106. [2] Fitzgerald GA, Oates JA, Hawiger J, Maas RL, Roberts II U, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest 1983;71:676–88. [3] Fitzgerald DJ, Roy L, Catella F. Platelet activation in unstable coronary disease. N Engl J Med 1986;315:983–9. [4] Lam JYT, Latour JG, Lesperance J, Waters D. Platelet aggregation, coronary disease progression and future coronary events. Am J Cardiol 1994;73:333–8. [5] Vial JH, McLeod LJ, Roberts MS. Rebound elevation in urinary thromboxane B2 and 6-keto-PFF1 alpha exacerbation alter aspirin withdrawal. Prostaglandin Thromboxane Leukot Res 1991;21A:157–60.