European Heart Journal Advance Access originally published online on July 25, 2005
European Heart Journal 2005 26(18):1932; doi:10.1093/eurheartj/ehi434
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Combined pharmacologic treatment with clopidogrel and statin for patients with acute coronary syndrome: is there a survival advantage?
Department of Physiology
Faculty of Medicine
National University of Singapore
Block MD9
2 Medical Drive
Singapore 117597
Singapore
Tel: +65 9237 7529
Fax: +65 6778 8161
E-mail address: phszama{at}nus.edu.sg
Department of Medical Imaging
St Vincents Hospital
Melbourne
Australia
Department of Medical Imaging
St Vincents Hospital
Melbourne
Australia
Department of Physiology
Faculty of Medicine
National University of Singapore
Block MD9
2 Medical Drive
Singapore 117597
Singapore
We read with great interest the retrospective study by Lim et al.1 on the impact of combined treatment of anti-platelet drugs and statin on the clinical outcomes of patients with acute coronary syndrome (ACS). The authors in their study suggest that despite the possibility of competitive drug interaction between statin and clopidogrel,2 the combination of clopidogrel and statin has beneficial synergetic effects on the mortality of patients with non-ST-segment elevation ACS.
Randomized controlled trials over the past 20 years clearly show that aspirin, beta-blocker, ACE-inhibitor, and statin therapies prevent recurrent coronary events in patients with ACS.3,4 In particular, statins have been associated with a substantial reduction of vascular morbidity and mortality. The benefits of statin therapy have been demonstrated in patients with coronary artery disease, hypertension, diabetes, and in those with elevated, averaged,5 or even near-normal LDL-cholesterol levels.6 Statins are known to promote an overall 24–37% reduction in the relative risk for coronary events, independent of other confounding variables such as age and sex (for review refer to Gotto7). Thus, statins are recommended in the current therapeutic guidelines for the treatment of ACS.3,4
Data provided by Lim et al.1 show that the 6-month mortality estimated by the Kaplan–Meier curve was significantly lower in group IV (aspirin+clopidogrel+statin) compared with group II (aspirin+clopidogrel). We would like to make the following important notes: (1) the benefits of statins, beta-blockers, and ACE-inhibitors on the morbidity and mortality of patients with ACS have been well documented, (2) a statistically significant greater number of group IV patients compared with group II were on beta-blockers and ACE-inhibitors in the study conducted by Lim et al.,1 and (3) ex vivo studies of clopidogrel and statin drug interactions show significant inhibition of clopidogrel metabolism but not statin efficacy.
Therefore, this suggests that the low mortality observed by Lim et al.1 within group IV compared with group II could be simply attributed to the independent statin effect and/or to the effect of beta-blockers and ACE-inhibitors. The Lim et al.1 study shows that statin significantly reduces the mortality in the ‘treated’ group IV compared with the ‘non-treated’ group II, and aspirin+clopidogrel could be considered as a background for both groups. In addition, the mortality rate of group III (aspirin+statin) and group II (aspirin+clopidogrel) were 3.6 and 4.4%, respectively. This further indicates the value of statin therapy in patients with ACS.
The Kaplan–Meier curve in the Lim et al.1 study shows only the unadjusted mortality for group II vs. group IV. ‘Restricting the main study comparisons to the two groups in whom clopidogrel was used’, as stated by the authors, might not be sufficient to evaluate the synergistic effect of the drugs of interest on overall mortality. To investigate the additive and/or synergetic effect of clopidogrel and statin, Kaplan–Meier plot should include the adjusted mortality of all the four groups studied by Lim et al.
In conclusion, the retrospective study conducted by Lim et al.1 in ACS patients makes it difficult to draw the conclusion that a ‘clinically’ superior effect exists for clopidogrel–statin drug combination. Moreover, the conclusion of additive or synergetic effects of the combined two drugs on the clinical outcomes of patients with ACS warrants further investigation.
References
- Lim MJ, Spencer FA, Gore JM, Dabbous OH, Agnelli G, Kline-Rogers EM, Dibenedetto D, Eagle KA, Mehta RH. Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry. Eur Heart J 2005;26: 1063–1069.
[Abstract/Free Full Text] - Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DGM, Guyer KE, Bates ER. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug—drug interaction. Circulation 2003;107:32–37.
[Abstract/Free Full Text] - Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004;110:e82–e292.
[Free Full Text] - Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW, McFadden E, De Feyter PJ, Specchia G, Ruzyllo W; Task Force on the Management of Acute Coronary Syndromes of the European Society of Cardiology. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002;23:1809–1840.
[Free Full Text] - Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001–1009.
[Abstract/Free Full Text] - The HPS Study Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals. Lancet 2002;360:7–22.[CrossRef][Web of Science][Medline]
- Gotto AM. Statin therapy: where are we? Where do we go next? Am J Cardiol 2001;87(suppl.):13B–18B.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||