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(3) Palestinian determination to are on the side of justice, including Clopidogrel (n=529) Prasugrel (n=432)
resist occupation by developing their justice in health. These groups do
≤24 h 308 (58%) 266 (62%)
own health services independently of not separate humanitarian, medical,
>24 h to 30 days 48 (9%) 34 (8%)
the Israeli military. or scientific work from solidarity
>30 days to 1 year 154 (29%) 119 (28%)
The fact remains that, as with Palestinians and advocacy
>1 year 16 (3%) 10 (2%)
documented in Israeli military annual for justice and removal of the root
Unknown 3 (1%) 3 (1%)
reports and other sources, health cause of ill health: Israeli occupation
services for Palestinians during this of Palestinian land. It is time for Table: Non-fatal myocardial infarctions not associated with stent thrombosis
in all patients with acute coronary syndrome, by time from percutaneous
period were starved of funds, lacked Israelis, especially Israeli medical and
coronary intervention2
basic medications and equipment, health professionals, to face reality,
and staff were inadequately trained acknowledge the root cause of ill
and insufficient in numbers.2 Indeed, health among both peoples, and work periprocedural (table). Furthermore,
the ex-deputy mayor of Jerusalem, systematically for its removal. when only site-reported events were
Meron Benvenisti, found that the I declare that I have no conflicts of interest. counted, the reduction in the primary
military government’s entire civilian outcome with prasugrel was no longer
budget for Palestinians in 1980 was
Rita Giacaman significant, neither for the STEMI
rita@birzeit.edu
only 1·7% of the total civilian budget subgroup nor the overall ACS cohort.
Institute of Community and Public Health, Birzeit
of the State of Israel, and 0·01% of Also, Montalescot and colleagues
University, Occupied Palestinian Territory
the gross national product of the claim that the bleeding risk was
1 Roy S. De-development revisited: Palestinian
West Bank, and that there had been economy and society since Oslo. similar with prasugrel and clopidogrel.
almost no government investment in J Palestine Stud 1999; 28: 64–82. However, the STEMI subgroup was
infrastructure and development.3 2 Giacaman R. Health conditions and services in underpowered to detect a meaningful
the West Bank and Gaza Strip. United Nations
The improving trends in health Conference on Trade and Development. difference in this safety outcome.
indices began to reverse in the UNCTAD/ECDC/SEU/3. Sept 28, 1994. Given the lack of heterogeneity
3 Benvenisti M. The 1986 report. Jerusalem:
1990s, with stalling infant mortality West Bank Data Base Project, 1986.
between the STEMI patients and the
rates and increasing stunting of 4 Falk R. Israel’s war crimes. The Nation Dec 29, rest of the ACS cohort with regard to
children younger than 5 years. Our 2008. http://www.thenation.com/ both risk and benefit, the risk estimate
doc/20090112/falk?rel=hp_currently
Series referred repeatedly to the (accessed April 17 2009). calculated from the entire study
multiple factors associated with these 5 Harel A. IDF in Gaza: killing civilians, population is more appropriate. In
trends: Israeli military occupation vandalism, and lax rules of engagement. this larger group, both thrombolysis
Haaretz March 19, 2009. http://www.haaretz.
of Palestinian land and its policies com/hasen/spages/1072040.html in myocardial infarction (TIMI) major
and practices; corruption and (accessed April 27, 2009). haemorrhage (hazard ratio 1·32, 95%
mismanagement of the Palestinian CI 1·03–1·68) and fatal haemorrhage
Authority; and a multiplicity of (4·19, 1·58–11·1) unrelated to
donors with different agendas and Prasugrel STEMI coronary-artery bypass grafting were
priorities. significantly increased with prasugrel.3
Our Series provided minimal
subgroup analysis Lastly, although the STEMI subgroup
coverage of the attack on the Gaza In Gilles Montalescot and colleagues’ analysis was prespecified, TRITON-
Strip beginning Dec 27, 2008. report on the subgroup with ST- TIMI 38 was not prospectively design-
We refer correspondents to other segment-elevation myocardial infarc- ed to assess the superiority of prasugrel
accounts relevant to that, such as that tion (STEMI) from TRITON-TIMI 38 over clopidogrel in this population.4
of the UN Human Rights Rapporteur (Feb 28, p 723),1 non-fatal myocardial Because α was not adjusted to account
in the occupied Palestinian territory, infarction was not adequately defined. for the multiple planned and post-hoc
Richard Falk.4,5 This outcome drove most of the comparisons that were made, it is likely
Finally, we agree that Physicians reduction in the primary composite that some of the positive findings are
for Human Rights—Israel is an endpoint seen with prasugrel type 1 errors.1 Thus, any conclusions
outstanding organisation, which versus clopidogrel. Food and Drug drawn from these data must be
works with Palestinian partners on Administration Advisory Committee regarded as exploratory at best.
an equal footing. That is why we documents2 reveal that asymptomatic We declare that we have no conflicts of interest.
included many references to their elevations in cardiac enzymes
reports and those of B’tselem, the accounted for many events, and that
*James Floyd, Sidney Wolfe
jfloyd@citizen.org
Israeli human rights organisation. in all patients presenting with acute
Health Research Group, Public Citizen, Washington,
We wish to make clear that there are coronary syndrome (ACS) most non-
DC 20009, USA
groups and individuals in Israel who fatal myocardial infarctions were
1 Montalescot G, Wiviott SD, Braunwald E, et al, optimum platelet inhibition. Vaso- thrombosis. Although bleeding was also
for the TRITON-TIMI 38 investigators. Prasugrel dilator-stimulated phosphoprotein- similar between the two treatments,
compared with clopidogrel in patients
undergoing percutaneous coronary inter- guided clopidogrel loading of up to four major bleeding after coronary-artery
vention for ST-elevation myocardial infarction 600 mg doses on successive days before bypass grafting was significantly higher
(TRITON-TIMI 38): double-blind, randomised
controlled trial. Lancet 2009; 373: 723–31. intervention achieved greater platelet with prasugrel (p=0·0033).
2 FDA. Briefing materials from Feb 3, 2009, inhibition and reduced subsequent Montalescot and colleagues do not
meeting of FDA Cardiovascular and Renal Drugs cardiovascular events, compared with a provide any information about statin
Advisory Committee. http://www.fda.gov/
ohrms/dockets/ac/09/briefing/2009-4412b1- single 600 mg loading dose.5 and aspirin use in the study groups.
01-FDA.pdf (accessed March 20, 2009). Whether clopidogrel loading is There is compelling evidence2,3 that
3 Wiviott SD, Braunwald E, McCabe CH, et al.
Prasugrel versus clopidogrel in patients with
best given empirically or guided by statins reduce the risk of recurrent
acute coronary syndromes. N Engl J Med 2007; platelet-function testing remains coronary events and improve survival,
357: 2001–15. uncertain, but the optimum dose is particularly during the postoperative
4 Wiviott SD, Antman EM, Gibson CM, et al, for the
TRITON-TIMI 38 investigators. Evaluation of clearly greater than 300 mg. period.4 Aspirin therapy seems to have
prasugrel compared with clopidogrel in patients We have received research funding from Sanofi similar benefits.5 Therefore, we believe
with acute coronary syndromes: design and
rationale for the TRial to assess Improvement in
Aventis. it would be prudent to report the
Therapeutic Outcomes by optimizing platelet
*Mark W I Webster, Patrick Gladding statistics on statin and aspirin therapy
InhibitioN with prasugrel Thrombolysis In in the study groups.
Myocardial Infarction 38 (TRITON-TIMI 38). Mwebster@adhb.govt.nz
Am Heart J 2006; 152: 627–35. We declare that we have no conflicts of interest.
Cardiac Catheterisation & Intervention Unit,
Auckland City Hospital, Auckland 1031, New Zealand
An analysis of patients undergoing
*Asit Baran Shil, Maureen P Strohm
1 Montalescot G, Wiviott SD, Braunwald E, et al, shil@usc.edu
percutaneous coronary intervention for the TRITON-TIMI 38 investigators.
Prasugrel compared with clopidogrel in USC Keck School of Medicine, Los Angeles,
for ST-elevation myocardial infarction patients undergoing percutaneous coronary CA 90015, USA
enrolled in TRITON-TIMI 381 found intervention for ST-elevation myocardial
infarction (TRITON-TIMI 38): double-blind, 1 Montalescot G, Wiviott SD, Braunwald E, et al,
that cardiovascular events were fewer for the TRITON-TIMI 38 investigators. Prasugrel
randomised controlled trial. Lancet 2009;
with prasugrel than with clopidogrel. 373: 723–31. compared with clopidogrel in patients under-
going percutaneous coronary intervention for
The benefit accrued soon after the 2 Patti G, Colonna G, Pasceri V, Pepe LL,
ST-elevation myocardial infarction (TRITON-
Montinaro A, Di Sciascio G. Randomized trial
procedure. Two aspects of the study of high loading dose of clopidogrel for
TIMI 38): double-blind, randomised controlled
trial. Lancet 2009; 373: 723–31.
design favoured the more potent and reduction of periprocedural myocardial
infarction in patients undergoing coronary 2 Scandinavian Simvastatin Survival Study
faster-acting prasugrel: few patients Group. Randomised trial of cholesterol
intervention: results from the ARMYDA-2
were given a thienopyridine more (Antiplatelet therapy for Reduction of lowering in 4444 patients with coronary heart
MYocardial Damage during Angioplasty) disease: the Scandinavian Simvastatin Survival
than 30 min before the intervention, Study (4S). Lancet 1994; 344: 1383–89.
study. Circulation 2005; 111: 2099–106.
and the clopidogrel loading dose was 3 Cuisset T, Frère C, Quilici J, et al. Benefit of 3 Long-Term Intervention With Pravastatin in
only 300 mg. 600-mg loading dose of clopidogrel on Ischaemic Disease (LIPID) Study Group.
platelet reactivity and clinical outcomes in Prevention of cardiovascular events and death
At the time of the study, a clopidogrel with pravastatin in patients with coronary
patients with non-ST-segment elevation acute
loading dose of 600 mg had been coronary syndrome undergoing coronary heart disease and a broad range of initial
stenting. J Am Coll Cardiol 2006; 48: 1339–45. cholesterol levels. N Engl J Med 1998;
shown to achieve greater platelet 339: 1349–57.
4 Gladding PA, Webster MWI, Zeng I, et al. The
inhibition and reduce post-procedure antiplatelet effect of higher loading and 4 Le Manach Y, Godet G, Coriat P, et al. The
adverse events than 300 mg, leading maintenance dose regimens of clopidogrel: impact of postoperative discontinuation or
the Plavix Response IN Coronary intervention continuation of chronic statin therapy on
most interventional cardiologists to cardiac outcome after major vascular surgery.
(PRINC) trial. J Am Coll Cardiol Intv 2008;
give 600 mg in their clinical practice 1: 612–19. Anesth Analg 2007; 104: 1326–33.
5 The RISC Group. Risk of myocardial infarction
when adequate pretreatment was not 5 Bonello L, Camoin-Jau L, Arques S, et al.
and death during treatment with low dose
Adjusted clopidogrel loading doses according
possible.2,3 Since then, higher-dose to vasodilator-stimulated phosphoprotein aspirin and intravenous heparin in men with
regimens have been assessed. Studies phosphorylation index decrease rate of major unstable coronary artery disease. Lancet 1990;
adverse cardiovascular events in patients with 336: 827–30.
of a single 900 mg loading dose were clopidogrel resistance: a multicenter
inconclusive. We found that a 1200 mg randomized prospective study. J Am Coll Cardiol
loading dose, given as 600 mg followed 2008; 51: 1404–11. Authors’ reply
by another 600 mg 2 h later to In response to James Floyd and
overcome saturable gastric absorption, Gilles Montalescot and colleagues Sidney Wolfe, the definitions and
achieved significantly more rapid and report results from the TRITON- composites of clinical endpoints in
complete platelet inhibition within TIMI 38 trial,1 which show that prasu- TRITON-TIMI 38 were prespecified1 and
4–7 h than a single 600 mg dose.4 grel (compared with clopidogrel) results accepted as valid by the US Food and
Serial platelet-function testing has in significant reductions in 30-day Drug Administration and the European
confirmed that high clopidogrel doses rates of all-cause and cardiovascular Medicines Agency before the start of
can sometimes be needed to achieve death, myocardial infarction, and stent the trial. Floyd and Wolfe assert that the