A comparison between statin with ACE inhibitor or ARB therapy in STEMI patients who underwent successful PCI with drug-eluting stents

Yong Hoon Kim, Ae Young Her, Myung Ho Jeong, Byeong Keuk Kim, Sung Jin Hong, Seunghwan Kim, Chul Min Ahn, Jung Sun Kim, Young Guk Ko, Donghoon Choi, Myeong Ki Hong, Yangsoo Jang

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Abstract

Background and aims: Studies of the comparative clinical outcomes between statin with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in ST-segment elevation myocardial infarction (STEMI) patients are limited. We compared 2-year clinical outcomes between statin with ACEI or ARB therapy in STEMI patients after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: A total of 11,706 STEMI patients were enrolled and separated into two groups: the ACEI group (statin + ACEI, n = 8705) and the ARB group (statin + ARB, n = 3001). The primary endpoint was major adverse cardiac events (MACE) defined as all-cause death, recurrent MI (re-MI), and any coronary revascularization. Secondary endpoints were the individual components of MACE and target vessel failure (TVF). Results: After propensity score-matched (PSM) analysis, two PSM groups (2729 pairs, n = 5458, C-statistic = 0.675) were generated. The cumulative incidences of MACE, re-MI, and any coronary revascularization were similar between the two groups. However, the cumulative incidences of all-cause death (hazard ratio [HR], 1.548; 95% confidence interval [CI], 1.091–2.197; p = 0.014) and cardiac death (HR, 1.850; 95% CI, 1.218–2.811; p = 0.004) were significantly higher in the ARB group compared with the ACEI group after PSM analysis. Conclusions: The combination of statin with ACEI may be the preferred treatment strategy to reduce mortality rates in STEMI patients after successful PCI with DES rather than statin with ARB in this study during a 2-year follow-up period.

Original languageEnglish
Pages (from-to)109-117
Number of pages9
JournalAtherosclerosis
Volume289
DOIs
Publication statusPublished - 2019 Oct

Bibliographical note

Funding Information:
Statins are well-known first-line evidence-based drugs for the management of dyslipidemia and reduction of the risk of cardiovascular events [2,12,13]. In the Swedish registry, it was demonstrated that initiation of statin treatment, at or before hospital discharge, in survivors of AMI is associated with a reduced 1-year mortality rate [14]. Myauchi et al. [15] reported that early statin treatment stabilized the vulnerable plaque and improved the prognosis in patients with acute coronary syndrome. Kim et al. [16] reported statin could reduce the cumulative incidences of MACE, all-cause death, and CD more than in statin non-user after PCI in AMI patients who underwent PCI with new-generation DES regardless of the presence or absence of dyslipidemia. Even though the beneficial roles of ACEI and ARB in STEMI patients are well-known [3.5], the relative superiority on long-term clinical outcomes between ACEI and ARB is still debatable [17,18]. Long-term comparative studies between statin with ACEI or statin with ARB therapy in patients with STEMI after DES implantation are scarce. Terry et al. suggested that treatment with ACEI is beneficial following AMI [19]. Statin and ACEI or ARB mechanism of action overlaps especially in the activation of NO synthase [20]. ACEI catalyze the breakdown of bradykinin to inactive peptides and this process leads to accumulation of bradykinin. Bradykinin exerts numerous beneficial effects on cardiovascular protection including vasodilation and stimulation of NO [4]. Ferrari et al. suggested that the intrinsic effect on bradykinin is increased by ACEI and not by ARB in some meta-anlayses [21]. The cholesterol-independent or ?pleiotropic? effects of statins include the upregulation and activation of endothelial NO synthase, especially in the presence of hypoxia [22,23]. One meta-analysis study [24] demonstrated that the percentage of patients on statin therapy showed no significant relationship with the reduction in outcomes due to ACEI. In addition, in the ARB trials, no statistical significance was found in terms of outcome and percentage of patients on statin therapy. Therefore, regarding the differences of the cumulative incidence of all-cause death and CD between the two groups in this study, we can conclude that the main determinant factor for this mortality difference was the attribution of the beneficial effect of ACEI on cardiovascular mortality reduction itself. Hence, we cautiously suggest that ACEI may be the preferred drugs for reducing mortality compared with ARB in patients with STEMI after DES. This suggestion may be supported by the fact that ARB are involved in selective blockage of the angiotensin II type 1 (AT1) receptor, which leads to unwanted elevation of circulating angiotensin II levels through unopposed stimulation of angiotensin II type 2 (AT2) receptor. Because angiotensin II has a positive inotropic activity, sustained activation of angiotensin II increases myocardial oxygen demand, but causes vasoconstriction of the coronary vasculatures simultaneously. Hence, this leads to further exacerbation of oxygen imbalance and myocardial ischemia after MI, and may result in irreversible myocardial damage [25]. In addition, angiotensin II is related to accelerated initiation and progression of atherosclerosis and increased incidences of cardiac inflammatory plaque instability and thrombus formation compared with ACEI [26,27]. Plaque rupture is the most common type of plaque complication, accounting for about 70% of fatal AMI and/or sudden coronary deaths [28]. Most recently, Magnoni et al. [29] demonstrated that the combination of ACEI and statin (but not ARB) was associated with decresed prevalence of plaque neovascularization in sixty-six patients with asymptomatic carotid artery stetnosis of intermediate severity assessed by contrast-enhanced ultrasound.This research was supported by a fund (2016-ER6304-02) by Research of Korea Centers for Disease Control and Prevention. We would like to acknowledge Dr. Malcom Neill Allison (oallison@msn.com) for editorial assistance. Korea Acute Myocardial infarction Registry (KAMIR) investigators. Myung Ho Jeong, MD, Youngkeun Ahn, MD, Sung Chul Chae, MD, Jong Hyun Kim, MD, Seung-Ho Hur, MD, Young Jo Kim, MD, In Whan Seong, MD, Donghoon Choi, MD, Jei Keon Chae, MD, Taek Jong Hong, MD, Jae Young Rhew, MD, Doo-Il Kim, MD, In?Ho Chae, MD, Jung Han Yoon, MD, Bon-Kwon Koo, MD, Byung-Ok Kim, MD, Myoung Yong Lee, MD, Kee-Sik Kim, MD, Jin-Yong Hwang, MD, Myeong Chan Cho, MD, Seok Kyu Oh, MD, Nae-Hee Lee, MD, Kyoung Tae Jeong, MD, Seung-Jea Tahk, MD, Jang-Ho Bae, MD, Seung-Woon Rha, MD, Keum-Soo Park, MD, Chong Jin Kim, MD, Kyoo-Rok Han, MD, Tae Hoon Ahn, MD, Moo-Hyun Kim, MD, Ki Bae Seung, MD, Wook Sung Chung, MD, Ju-Young Yang, MD, Chong Yun Rhim, MD, Hyeon-Cheol Gwon, MD, Seong-Wook Park, MD, Young-Youp Koh, MD, Seung Jae Joo, MD, Soo-Joong Kim, MD, Dong Kyu Jin, MD, Jin Man Cho, MD, Sang-Wook Kim, MD, Jeong Kyung Kim, MD, Tae Ik Kim, MD, Deug Young Nah, MD, Si Hoon Park, MD, Sang Hyun Lee, MD, Seung Uk Lee, MD, Hang-Jae Chung, MD, Jang-Hyun Cho, MD, Seung Won Jin, MD, Myeong-Ki Hong, MD, Yangsoo Jang, MD, Jeong Gwan Cho, MD, Hyo-Soo Kim, MD and Seung Jung Park, MD.

Funding Information:
This research was supported by a fund ( 2016-ER6304-02 ) by Research of Korea Centers for Disease Control and Prevention .

Publisher Copyright:
© 2019 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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