Discontinuation Of Clopidogrel Research Articles

A Case of Stent Thrombosis Occurred at 5 Years after Sirolimus-Eluting Stent Implantation

Drug-eluting stents (DES) have reduced the rate of repeated revascularization of target lesions. For this reason, DES are considered to be superior to bare-metal stents in reducing the restenosis rate. However, some problems have been reported after implantation of DES. One of them, stent thrombosis, has arisen as a fatal complication. Dual antiplatelet therapy is recommended for at least 12 months after implantation of DES to prevent stent thrombosis. Here, we report a case of very late stent thrombosis that occurred 1 week after discontinuation of clopidogrel at 5 years (1832 days) after implantation of a sirolimus-eluting stent.

Incidence and Predictors of Intracranial Hemorrhage After Minor Head Trauma in Patients Taking Anticoagulant and Antiplatelet Medication

The yield of head computed tomography (CT) for patients who suffered head trauma with a presenting Glasgow Coma Scale (GCS) score of 15 has been reported to be low, even in patients who are anticoagulated or on antiplatelet therapy. We undertook this study to (1) determine the frequency of intracranial hemorrhage in anticoagulated patients and patients on antiplatelet therapy and its impact on clinical management, (2) identify predictors of positive imaging findings, and (3) assess potential differences between anticoagulation and antiplatelet therapy. We conducted a retrospective review of the trauma registry at our institution, a Level II trauma center. All trauma registry patients with a minor head injury registered between the years 2004 and 2006 who were taking warfarin or clopidogrel, had a presenting GCS score of 15, and underwent head CT were included in this study. Intracranial hemorrhage on head CT was considered a positive result. One hundred forty-one patients (male, n=67; female, n=74), mean age 79 years (range, 36-101 years), were included in this study. Forty-one patients (29%) were diagnosed with intracranial hemorrhage. Thirty-nine (95%) of these 41 patients underwent reversal and/or discontinuation of clopidogrel and/or warfarin. Five patients required surgical evacuation of an intracranial hemorrhage. Four patients died. Loss of consciousness (Wald=7.468, β=1.179, p=0.008) predicted a positive CT result. Type of medication (warfarin, aspirin, or clopidogrel) did not reach statistical significance as a predictor of positive result. Despite a presenting GCS score of 15, patients with minor head injury from the trauma registry at our institution taking anticoagulation or antiplatelet therapy have a high incidence of intracranial hemorrhage especially after reported loss of consciousness.

Coronary Stenting With the GenousTM Bio-Engineered R StentTM in Elderly Patients - 12-Month Outcomes From the e-HEALING Registry -

We evaluated the Genous™ Bio-engineered R stent™ in elderly patients undergoing non-urgent percutaneous coronary intervention. The elderly have an increased risk of (temporary) discontinuation of clopidogrel, which is associated with a higher risk of developing stent thrombosis (ST). In the e-HEALING registry, 2,651 patients were <65, 1,403 were 65-74 and 869 were ≥ 75 years old. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related car-diac death or myocardial infarction and target vessel revascularization. Secondary outcomes included target lesion revascularization (TLR) and ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. TVF occurred significantly more often in elderly patients compared with younger patients (7.0% in patients aged < 65, 8.8% in patients aged 65-74 and 11.7% in patients aged ≥ 75 years, P<0.001). There was a trend to higher TLR with increasing age (log-rank P=0.06) and no difference in ST. The 1-year results of the Genous stent in a population of elderly patients show a significantly higher TVF rate compared with younger patients, mainly driven by a higher mortality. Although there was a trend to higher TLR rates with increasing age, there was no difference in ST. This attests to the safety of this therapy for the elderly, in whom there could be concerns with administering long-term dual antiplatelet therapy.

Optimal Timing of Discontinuation of Clopidogrel and Risk of Blood Transfusion After Coronary Surgery - Propensity Score Analysis -

The optimal time delay between last clopidogrel dose and surgery is controversial. The aim of the present study was to analyze the impact of preoperative clopidogrel on the need for blood transfusions with reference to the proper timing of discontinuation. Between January 2005 and December 2010, 1,947 consecutive patients undergoing coronary surgery were enrolled. Of these, 255 patients receiving preoperative clopidogrel were matched to a control group by propensity score analysis. Clopidogrel discontinuation interval before surgery was examined in 1-day increments from 0 to 5 days and >5 days. Patients who discontinued clopidogrel within 5 days of surgery accounted for 91% (211/255). Clopidogrel stop within 5 days before surgery was independently associated with transfusion requirement (P=0.001). Preoperative clopidogrel was not associated with an increased risk of hemorrhagic complications (P=0.696). No differences were observed between patients taking clopidogrel and those not taking clopidogrel with regard to hospital resource utilization and mortality. Patients receiving clopidogrel in association with aspirin did not have an additive risk for transfusion or hemorrhagic complications compared with those on clopidogrel alone (odds ratio [OR], 1.25; 95% confidence interval [CI]: 0.77-2.03; OR, 1.02; 95%CI: 0.38-2.79, respectively). Clopidogrel administration in the 5 days preceding coronary surgery was an independent predictor for increased transfusion requirements, supporting the discontinuation of clopidogrel >5 days before surgery.

Prevalence, Predictors, and Long-Term Prognosis of Premature Discontinuation of Oral Antiplatelet Therapy After Drug Eluting Stent Implantation

To date, limited information is available on the long-term discontinuation rates of antiplatelet therapy after drug-eluting stent implantation. The aim of the present study was to determine the prevalence and predictors of premature discontinuation of oral antiplatelet therapy after drug-eluting stent implantation and to evaluate its effects on long-term prognosis. We studied 1,358 consecutive patients successfully treated with drug-eluting stents and discharged with dual oral antiplatelet therapy. Aspirin was to be maintained lifelong, and clopidogrel was prescribed for 12 months. The patients were followed for 36 months. The prevalence and predictors of aspirin and clopidogrel discontinuation were assessed. Major adverse cardiac events, defined as death, myocardial infarction, destabilizing symptoms leading to hospitalization, and nonfatal stroke, were recorded. Definite, probable, and possible stent thrombosis (ST) and major and minor bleeding were also determined. Of the 1,358 patients, 8.8% had discontinued one or both antiplatelet agents within the first 12 months ("early" discontinuation) and 4.8% had discontinued aspirin after 1 year ("late" discontinuation). Early discontinuation was predicted by in-hospital major bleeding, the use of oral anticoagulants at discharge, and the lack of a statin prescription. Previous stroke was the only independent predictor of late discontinuation. Patients with early discontinuation experienced a greater incidence of major adverse cardiac events (28.6% vs 13.7%, p <0.001) and ST (7.6% vs 3.4%, p = 0.038). All-cause mortality (13.4% vs 4.7%, p <0.001) and cardiovascular death (5% vs 1.2%, p = 0.007) were significantly more frequent among patients with early discontinuation. In patients with late discontinuation, a nonstatistically significant increase was seen in major adverse cardiac events (20% vs 13.3%, p = 0.128) and ST (6.2% vs 3.2%, p = 0.275). In conclusion, premature discontinuation of antiplatelet therapy is relatively common, especially within the first year, and strongly associated with increased cardiovascular events, including ST and death.

Very late stent thrombosis of Sirolimus-eluting stent 59 months after implantation: A first report from the Middle-East and review of literature

Very late stent thrombosis occurs more frequently with drug-eluting stents and tends to occur despite dual antiplatelet therapy or after long periods of clopidogrel discontinuation. Stent thrombosis commonly presents with myocardial infarction or death. We report a 41-year-old Arab male with very late stent thrombosis after 59 months of sirolimus-eluting stent implantation and –49 months after clopidogrel discontinuation despite aspirin continuation, presenting with exertional angina. He underwent successful percutaneous coronary intervention. This case underlines the need for novel stent designs as well as newer therapeutic strategies in preventing very late stent thrombosis among patients receiving drug-eluting stents.

Beware of being caught on the rebound

See also Mylotte D, Peace AJ, Tedesco AT, Mangiacapra F, Dicker P, Kenny D, Foley DP. Clopidogrel discontinuation and platelet reactivity following coronary stenting. This issue, pp 24–32.

Allergic Reactions to Clopidogrel and Cross-Reactivity to Other Agents

Clopidogrel is a widely used antiplatelet agent, particularly after coronary stent implantation. About 1% of patients have allergic or hematologic adverse reactions to clopidogrel. This has important therapeutic implications, as premature discontinuation of clopidogrel is the strongest risk factor for stent thrombosis. Clopidogrel allergy most commonly manifests as a rash. It is important to distinguish this from other causes of rash occurring in patients who have had a recent coronary stent. Although antihistamines and short-term oral corticosteroids are effective in treating most clopidogrel hypersensitivity reactions, some persistent reactions may require discontinuation of clopidogrel. When discontinuation of clopidogrel is required, substitution with an alternative thienopyridine such as ticlopidine traditionally has been performed. However, a recent study suggests that there may be as high as a 27% risk of recurrence of non-life-threatening allergic reactions in such patients, which are usually similar to the allergic reactions that occurred with clopidogrel. No data are available regarding the frequency of cross-reactivity to prasugrel and ticagrelor; these may be potential therapeutic options in some patients.

Prasugrel as alternative treatment strategy in a case with a hypersensitivity reaction to clopidogrel

We report a case with a hypersensitivity reaction to clopidogrel that resolved after clopidogrel discontinuation and recurred on rechallenge. The reaction included fever, tachycardia, rash and mild angioedema. As an alternative to clopidogrel, the more potent thienopyridine prasugrel was administered without any signs of an allergic reaction in the hours, days and weeks following administration.

The Platelet Activity After Clopidogrel Termination (PACT) Study

"Rebound" platelet hyperreactivity after discontinuation of clopidogrel has been proposed to lead to increased thrombotic risk, including late stent thrombosis. However the hypothesis that discontinuation of clopidogrel results in platelet hyperreactivity has never been rigorously tested. We therefore performed a randomized, double-blind, placebo-controlled, crossover study: the Platelet Activity after Clopidogrel Termination (PACT) study. Platelet reactivity in 15 healthy subjects was measured at baseline, during clopidogrel 75 mg or placebo daily for 14 days, and on days 1, 4, 8, 11, 15, and 45 after discontinuation of clopidogrel or placebo. Platelet reactivity was assessed by (1) platelet surface activated GPIIb-IIIa and surface P-selectin (by whole blood flow cytometry) in response to ADP 0.5, 1, and 20 μmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 μmol/L; and collagen/epinephrine 5 μg/mL/5 μmol/L, (2) light transmission aggregation with ADP 2.5, 5, and 20 μmol/L; TRAP 2 and 20 μmol/L; and collagen 6 μg/mL, (3) whole blood impedance aggregation with ADP 1.6 and 6.5 μmol/L; TRAP 4 and 32 μmol/L; and collagen 3.2 μg/mL, and (4) plasma soluble CD40 ligand (by ELISA). Immature platelet fraction was measured in the Sysmex XE-2100. At no time point after discontinuation of clopidogrel was platelet reactivity, as determined by any assay end point, or the immature platelet fraction significantly greater than after discontinuation of placebo. This randomized, double-blind, placebo-controlled, crossover study demonstrates that discontinuation of clopidogrel does not result in "rebound" platelet hyperreactivity, as determined by multiple time points, assays, agonists, and agonist concentrations. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00619073.

Simultaneous dual coronary very late stent thrombosis following noncardiac surgery

Challenges arise in the care of patients with drug-eluting stents (DES) undergoing noncardiac surgery. The risk of bleeding during surgery must be balanced with the risk of stent thrombosis from interrupted dual antiplatelet therapy. We report a case of a patient with simultaneous stent thrombosis in two coronary arteries following discontinuation of clopidogrel for an elective noncardiac surgery 3 years after DES placement.

Clopidogrel hypersensitivity: clinical challenges and options for management

Over 90 million patients have been prescribed clopidogrel since its US FDA approval in 1997. Clopidogrel hypersensitivity affects up to 6% of patients, most commonly in the form of a pruritic rash. Symptoms are severe enough to result in drug discontinuation in 1.5% of patients. Premature discontinuation of clopidogrel is problematic following percutaneous coronary intervention because of the risk of stent thrombosis leading to myocardial infarction and death. Accordingly, the management of patients with clopidogrel hypersensitivity is of significant clinical importance. Conventional clopidogrel desensitization protocols, while successful in most patients, employ a washout period off medication to enable accurate detection of a reaction during the desensitization. However, interruption of therapy is potentially hazardous in patients with recent stent placement. Our clinical experience demonstrates that clopidogrel hypersensitivity can be successfully treated without drug interruption using short-course corticosteroids and antihistamines to enable the development of physiologic tolerance while the medication is continued. The role of newer agents, such as prasugrel, as surrogate therapy in patients with clopidogrel hypersensitivity is yet to be defined.

Low risk of rebound events after a short course of clopidogrel in acute TIA or minor stroke

The combination of aspirin and clopidogrel is indicated after acute coronary events and possibly for a short period after TIA or minor ischemic stroke. Early discontinuation of clopidogrel results in a transient rebound increase in risk of recurrence in acute coronary syndromes, but there are no published data on any similar rebound effect in patients with TIA or stroke that might inform the design of clinical trials of aspirin and clopidogrel in the acute phase. A 30-day course of aspirin and clopidogrel (both 75 mg daily) was given to high-risk patients with TIA or minor ischemic stroke seen acutely in the EXPRESS study clinic from April 1, 2002, to March 31, 2009. Clopidogrel was stopped after 30 days and aspirin continued. Recurrent events were ascertained at face-to-face follow-up. A total of 320 patients were prescribed a 30-day course of aspirin and clopidogrel acutely after TIA or minor stroke. There were 5 recurrent ischemic strokes and 7 TIAs during the aspirin and clopidogrel treatment period, but no strokes and 4 TIAs during the 30 days after stopping clopidogrel. A similar temporal trend in stroke risk was seen in the 487 patients prescribed aspirin alone in the acute phase, with 12 and 5 strokes in the equivalent time periods. The upper 95% confidence intervals of the observed 0% risk of stroke during the 30 days after stopping clopidogrel was 1.15% overall. Although larger studies are required, our findings suggest there is unlikely to be a large rebound effect after discontinuation of a 30-day course of clopidogrel in acute TIA and minor ischemic stroke. However, planned trials of aspirin and clopidogrel in the acute phase after TIA or stroke should still follow-up beyond the cessation of clopidogrel treatment.

Rotablation in the Drug Eluting Era: Immediate and Long‐Term Results from a Single Center Experience

The aim of this study was to investigate the immediate and long-term outcome of patients who were treated with rotational atherectomy (RA) to facilitate the delivery of drug eluting stents (DES) in heavily calcified lesions. We analyzed 150 consecutive patients who underwent RA and subsequently DES implantation in our institution. The patients had heavily calcified coronary artery lesions requiring plaque modification prior to conventional angioplasty and stent implantation. Rotational atherectomy was performed using the standard Boston Scientific Rotablator system. A 2-burr stepped approach was selected in most of the cases. Following successful modification of the plaque, the angioplasty was performed with a balloon at low pressure to avoid dissection and a DES was implanted. The mean follow up period was 3 years (max. 78 months). Follow-up data included all cause death, stroke, myocardial infarction (MI), recurrent angina, re-hospitalization, target lesion revascularization (TLR), target vessel revascularization (TVR), and long-term duration of dual antiplatelet therapy. The rate of recurrent angina and MI during follow up was low (3.3%) and the overall major adverse cardiac events (MACE) rate was 11.3%. No MACE occurred during hospitalization. There was no relationship between discontinuation of clopidogrel and occurrence of death or MI. The combined approach of RA-DES has a favorable effect when dealing with heavily calcified lesions in both the angiographic and clinical outcomes. No safety concerns are observed up to 6 years.

The Causes and Outcomes of Inadequate Implementation of Existing Guidelines for Antiplatelet Treatment in Patients With Acute Coronary Syndrome: The Experience From Taiwan Acute Coronary Syndrome Descriptive Registry (T‐ACCORD Registry)

Benefits of antiplatelet agents in preventing future cardiovascular events have been well established. However, the prescription pattern of antiplatelet usage in patients with acute coronary syndrome (ACS) is rarely investigated. Hence, Taiwan ACute CORonary Syndrome Descriptive Registry (T-ACCORD Registry) aimed to evaluate medical practices in Taiwan in managing ACS patients. The guidelines of antiplatelet treatment is not properly implanted in the management of ACS patients. This prospective observational study was performed between April 2004 and December 2006 in 27 hospitals in Taiwan. A total of 1331 patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI) discharged from hospitals was analyzed. The patients with older age, lower hemoglobin levels, or previous cardiovascular ischemic diseases were less likely to receive aspirin at discharge, whereas patients with NSTEMI were less likely to receive clopidogrel at discharge. The prescription of dual antiplatelet agents declined rapidly from 61.8% at discharge to 12.6% at 12 months. The most common reason for clopidogrel discontinuation was recorded as physician's judgment. Dual antiplatelet treatment for 9 months or longer was associated with lower 1-year mortality. Percutaneous coronary intervention (PCI) was the only factor leading to dual antiplatelet therapy for at least 9 months. Our registry showed that underlying medical conditions may affect antiplatelet prescriptions at discharge. During the first year following an ACS episode, the prescription rate of dual antiplatelet therapy declined over time, mainly due to physician's judgment leading to the discontinuation of clopidogrel. Adherence to dual antiplatelet treatment was associated with lower total mortality at 1 year.

Antiplatelet therapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. Key messages for clinical practice

Should we interrupt antiplatelet therapy (acetylsalicylic acid [ASA] alone or in combination with clopidogrel) in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal (GI) procedures? The relevant evidence was critically appraised in a recent White Paper from the American College of Gastroenterology and the American College of Cardiology. Clinicians need to qualify and compare 2 competing risks: the increased risk of bleeding if antiplatelet therapy is maintained during the endoscopic GI procedure, vs. the increased risk of cardiovascular (CV) thrombosis if antiplatelet therapy is interrupted or modified in the periprocedural period. ASA treatment may be continued for all endoscopic GI procedures, provided that there is no pre-existing bleeding disorder. Clopidogrel administration could be maintained for low-risk endoscopic GI procedures, such as diagnostic endoscopy of the upper or lower GI tract with or without biopsies. For patients on clopidogrel undergoing high-risk endoscopic GI procedures, such as polypectomy or sphincterotomy, the individualized risk of CV complications from clopidogrel discontinuation should be assessed. During the first month following bare-metal stent implantation or the first 6 (possibly 12) months following drug-eluting stent placement the CV risk is particularly high, therefore elective high-risk endoscopic GI procedures should be deferred accordingly. In all other clinical situations requiring clopidogrel treatment, the risk of CV events is lower than above. Therefore, clopidogrel treatment could be interrupted for 7 to 10 days before the procedure (and restarted as soon as possible after the procedure), provided that ASA treatment is maintained.

Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of ‘bridging’ antiplatelet therapy with tirofiban during temporary withdrawal of clopidogrel

Patients with a recently implanted coronary drug-eluting stent (DES) who need urgent surgery are at increased risk of surgical bleeding unless clopidogrel is discontinued beforehand, but clopidogrel discontinuation has been associated with a high rate of adverse events due to stent thrombosis. This pilot study tested the hypothesis that the i.v. perioperative administration of the short-acting antiplatelet agent tirofiban allows the safe withdrawal of clopidogrel without increasing the rate of surgical bleeding. Phase II study with a Simon two-stage design. Thirty patients with a recently implanted DES [median (range) 4 (1-12) months] and high-risk characteristics for stent thrombosis underwent urgent major surgery or eye surgery. Clopidogrel was to be withdrawn 5 days before surgery, and tirofiban started 24 h later, continued until 4 h before surgery, and resumed 2 h after surgery until oral clopidogrel was resumed. The use of aspirin was decided by the surgeon. There were no cases of death, myocardial infarction, stent thrombosis, or surgical re-exploration due to bleeding during the index admission, with a risk estimate of 0-11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial infarction (TIMI) major and one of TIMI minor bleeding in the postoperative phase; another four patients were transfused without meeting the TIMI criteria for major or minor bleeding. In patients with a recently implanted DES and high-risk characteristics for stent thrombosis needing urgent surgery, a 'bridging strategy' using i.v. tirofiban may allow temporary withdrawal of oral clopidogrel without increasing the risk of bleeding.

Premature preoperative discontinuation of antiplatelet drug therapy in cardiovascular risk patients: a preliminary study on the role of P2Y12 receptor monitoring

In high-bleeding risk procedures, discontinuation of antiplatelet drug therapy with clopidogrel may be requested by surgeons, usually 7-10 days before the surgical procedure. New platelet function tests, such as the vasodilator-stimulated phosphoprotein phosphorylation assay, may help to assess the perioperative status of the clopidogrel-specific P2Y12 receptor. Using vasodilator-stimulated phosphoprotein phosphorylation assay, the platelet reactivity index (PRI) was measured in 80 individuals, including 20 healthy volunteers, 20 cardiologic patients under full antiplatelet drug therapy with clopidogrel and aspirin, 20 surgical patients without any antiplatelet drugs and 20 patients under clopidogrel, discontinued 7 days before the surgical procedure. The mean PRI (95% confidence interval) in healthy volunteers was 86 (82-89%) and that in the surgical control group was 77% (72-81%). In cardiologic patients under full antiplatelet therapy, mean PRI was 51% (42-60%). In the clopidogrel discontinuation group, PRI increased from 51% (40-62%) on day 0 to 65% (57-74%) on day 3 and to 76% (69-84%) on day 5. On the morning of surgery, mean PRI was 85% (80-91%). The PRI values on the 5th day were equivalent to those of the surgical control group (mean difference -0.4%, 95% confidence interval -8.6% to 7.8%, P = 0.9). Fifty-five percent of the patients in the discontinuation group had a PRI of more than 50% on day 0. The study using vasodilator-stimulated phosphoprotein phosphorylation assay, one of the new platelet function assays for the assessment of inhibition of platelet P2Y12 receptor, demonstrates that the PRI on day 5 after discontinuation of clopidogrel is equivalent to a surgical control group and it questions the rigid practice of delaying surgery for 7-10 days, particularly in patients without a clopidogrel effect.

Maintenance of Long-Term Clinical Benefit With Sirolimus-Eluting Stents in Patients With ST-Segment Elevation Myocardial Infarction: 3-Year Results of the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) Trial

The aim of this study was to investigate whether the reported favorable 1-year outcome of the sirolimus-eluting stent (SES) versus the bare-metal stent (BMS) in the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) trial, in the setting of ST-segment elevation myocardial infarction (STEMI), is maintained at 3-year follow-up. At present, only long-term registry data, but not randomized trials, on the safety and effectiveness of SES in STEMI patients are available. Overall, 320 STEMI patients were randomized to receive SES or BMS. The primary end point was the incidence of major adverse cardiovascular events (MACE), at 3-year follow-up. The secondary end points were the rate of target lesion revascularization (TLR) and target vessel revascularization (TVR) and target vessel failure (TVF). The incidence of late events, starting from clopidogrel withdrawal, was also investigated. The 3-year incidence of MACE was lower in the SES group compared with the BMS group (12.7% vs. 21%, p = 0.034), as were TLR (7% vs. 13.5%, p = 0.048), TVR (8% vs. 16%, p = 0.027), and TVF (11.5% vs. 20.5%, p = 0.028) rates. The 3-year survival rate free from MACE, TLR, and TVF was significantly higher in the SES group than in the BMS group (87%, 93%, and 89.5% vs. 79%, 86.5%, and 79.5%, respectively, p < 0.05). The lower incidence of adverse events in the SES group was driven by TLR reduction and achieved in the first year of follow-up. The cumulative incidence of death and recurrent myocardial infarction, starting from clopidogrel discontinuation, was comparable in the 2 groups. The clinical benefits of SES have been shown to be greater than those of BMS at 3-year follow-up.

A Double-Blind, Randomized Study on Prevention and Existence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment

The goal of this study was to assess whether a platelet rebound exists and whether it can be attenuated by clopidogrel tapering. Clinical studies have reported a clustering of thrombotic events after stopping clopidogrel treatment. The hypothesis of a rebound phenomenon of platelets has been declared causative, but its existence has never been confirmed. Tapering of clopidogrel over a certain period of time before stopping the drug completely might provide a way to attenuate this supposed phenomenon. Patients (n = 69) receiving clopidogrel treatment due to prior drug-eluting stent placement and planning to stop clopidogrel were recruited in a double-blind, randomized trial. Patients were randomized to either receive a pre-specified tapering regimen (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was assessed with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after randomization. The primary end point was the highest value of adenosine diphosphate-induced PA measured with LTA in the weeks after complete cessation of clopidogrel in both groups. The highest values of adenosine diphosphate-induced PA after complete cessation of clopidogrel were similar between both groups (p = 0.21 with LTA, and p = 0.55 with MEA). Tapering of clopidogrel does not result in lower PA values after clopidogrel withdrawal. The course of PA values after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon of platelets.