The TIMI (Thrombolysis In Myocardial Infarction) investigators did, in
fact, assess ischemic episodes throughout the recording period and found
that there was not a significant difference in the rate of positive ECG
recordings for ischemia (19.9% on ranolazine vs. 21.0% on placebo; p ?
0.21) (3). The investigators did not specifically report the individual
number of symptomatic and silent episodes of myocardial ischemia or
aggregate risk of cardiovascular death or myocardial infarction in the
MERLIN–TIMI 36 trial was similar for patients taking ranolazine and
placebo and in the patient subset that was enrolled with prior chronic
angina, fewer recurrent ischemic episodes were observed in the
significantly greater (4). Thus, the hypothesis that converting symptom-
It would be interesting for the TIMI investigators to address the
specific question of the proportion of the number and duration of
asymptomatic and symptomatic ischemia episodes in patients taking
ranolazine versus placebo from their extensive continuous ECG
database and to correlate these findings with 1-year outcome. This
type of analysis would expand our knowledge on ranolazine treatment
effects and could potentially more completely address the question
that Dr. Conti has raised.
*Peter H. Stone, MD
Bernard R. Chaitman, MD
*Brigham & Women’s Hospital
75 Francis Street
Boston, Massachusetts 02115-6110
1. Stone PH, Chaitman BR, Stocke K, Sano J, DeValut A, Koch GG.
The anti-ischemic mechanism of action of ranolazine in stable ischemic
heart disease. J Am Coll Cardiol 2010;56:934–42.
2. Stern S, Gavish A, Weisz G, et al. Characteristics of silent and
symptomatic myocardial ischemia during daily activities. Am J Cardiol
3. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of
ranolazine on recurrent cardiovascular events in patients with non-ST-
elevation acute coronary syndromes: the MERLIN-TIMI 36 random-
ized trial. JAMA 2007;297:1775–83.
4. Wilson SR, Scirica BM, Braunwald E, et al. Efficacy of ranolazine in
patients with chronic angina observations from the randomized, double-
blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With
Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute
Coronary Syndromes) 36 trial. J Am Coll Cardiol 2009;53:1510–6.
Clopidogrel After Coronary
Artery Bypass Graft Surgery
We recently read the interesting study by Sørensen et al. (1), which
evaluated the efficacy of clopidogrel after coronary artery bypass graft
data from 3,545 patients, the authors reported a lower risk of death
and the combined endpoint of death or recurrent MI in patients who
received clopidogrel after surgery. Based on their results, the authors
recommend that a “focus on discharge clopidogrel treatment of these
patients should be made” (1).
Because their study was nonrandomized, the authors used multi-
ers. Interestingly though, no adjustment was made for the use of on-
or off-pump CABG. In theory, any benefit associated with clopi-
and the prevention of myocardial events. However, clopidogrel did
not significantly reduce the incidence of recurrent MI, cardiovascular
death, or the need for repeat revascularization in this study. How
could clopidogrel lower the risk of death and yet not reduce the
incidence of myocardial events after CABG? Although no explana-
tion was provided by the authors, perhaps this finding relates to
residual confounding. Clopidogrel may have been administered pref-
a better chance for long-term survival.
Sørensen et al. (1) imply in their paper that clopidogrel is
underused after CABG, referring to the current guidelines that
recommend postoperative clopidogrel treatment for 9 to 12 months
for patients who undergo CABG following MI (2). This recommen-
dation was based primarily on data from the Clopidogrel in Unstable
Angina to Prevent Recurrent Ischemic Events (CURE) trial that
reported significantly fewer adverse cardiac events among MI patients
treated with the combination of clopidogrel and aspirin compared
with aspirin alone, even if they ultimately underwent CABG (3).
However, subgroup analysis later revealed that the benefit of com-
bined antiplatelet therapy was entirely preoperative while patients
were awaiting surgery. No benefit was seen for clopidogrel use after
CABG in the CURE trial (4). Therefore, it is not surprising that
many surgeons do not routinely prescribe clopidogrel after CABG.
Because of the lack of prospective data in the field (5), we recently
performed the CASCADE (Clopidogrel After Surgery for Coronary
Artery DiseasE) study (NCT00228423), a randomized, placebo-
controlled trial to evaluate whether the addition of clopidogrel to aspirin
did not significantly reduce vein graft intimal hyperplasia 1 year after
CABG, as assessed by intravascular ultrasound. Although CASCADE
was not powered for angiographic or clinical outcomes, we also did not
see a significant difference in vein graft patency or cardiovascular events
between the 2 treatment groups (7). Power calculations based on
CASCADE determined that a sample size of 8,000 grafts would be
required to demonstrate an improvement in patency with clopidogrel.
We doubt a future trial of this size will ever be performed.
In summary, based on the data available to date, we do not believe
that compelling evidence exists to support the routine use of clopi-
dogrel after CABG.
*Alexander Kulik, MD, MPH
Marc Ruel, MD, MPH
*Lynn Heart and Vascular Institute
Boca Raton Regional Hospital
801 Meadows Road, Suite 104
Boca Raton, Florida 33486
JACC Vol. 58, No. 10, 2011
August 30, 2011:1081–6