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 2437% 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 KaplanMeier 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 KaplanMeier 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, KaplanMeier 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 clopidogrelstatin 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
|