Synergistic Effect of Combined HMG-CoA Reductase Inhibitor and Angiotensin-II Receptor Blocker Therapy in Patients With Chronic Heart Failure: The HF-COSTAR Trial

Background: It is known that HMG-CoA reductase inhibitors (statins) may have a therapeutic benefit in patients with heart failure (HF). However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients...

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Veröffentlicht in:Circulation Journal 2011, Vol.75(3), pp.589-595
Hauptverfasser: Maejima, Yasuhiro, Nobori, Kiyoshi, Ono, Yuichi, Adachi, Susumu, Suzuki, Jun-ichi, Hirao, Kenzo, Isobe, Mitsuaki, Ito, Hiroshi, for the Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators
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container_end_page 595
container_issue 3
container_start_page 589
container_title Circulation Journal
container_volume 75
creator Maejima, Yasuhiro
Nobori, Kiyoshi
Ono, Yuichi
Adachi, Susumu
Suzuki, Jun-ichi
Hirao, Kenzo
Isobe, Mitsuaki
Ito, Hiroshi
for the Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators
description Background: It is known that HMG-CoA reductase inhibitors (statins) may have a therapeutic benefit in patients with heart failure (HF). However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF. Methods and Results: We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group. Conclusions: Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF. (Circ J 2011; 75: 589-595)
doi_str_mv 10.1253/circj.CJ-10-0804
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However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF. Methods and Results: We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group. Conclusions: Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF. 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However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF. Methods and Results: We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group. Conclusions: Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF. (Circ J 2011; 75: 589-595)</description><subject>Aged</subject><subject>Angiotensin</subject><subject>Angiotensin Receptor Antagonists - pharmacology</subject><subject>Angiotensin Receptor Antagonists - therapeutic use</subject><subject>Chronic Disease</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Electrocardiography</subject><subject>Female</subject><subject>Heart failure</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - physiopathology</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Losartan - pharmacology</subject><subject>Losartan - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pharmacology</subject><subject>Prospective Studies</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Renin-Angiotensin System - physiology</subject><subject>Simvastatin - pharmacology</subject><subject>Simvastatin - therapeutic use</subject><subject>Statin</subject><subject>Treatment Outcome</subject><subject>Ventricular Dysfunction, Left - drug therapy</subject><subject>Ventricular Dysfunction, Left - physiopathology</subject><issn>1346-9843</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0Utv1DAQAGALgegD7pyQb5zcjh3ndVyibnerolZQxNFynMnGS9ZebOewP4L_3GwfcPFYmk8zmhlCPnG44CLPLo0NZnvR3DAODCqQb8gpz2TJZCXg7dO_YHUlsxNyFuMWQNSQ1-_JieBCikKKU_L3x8Fh2NiYrKFXfY8mUd_Txu9a67Cjq2_XrPEL-h27ySQdka7dYFubfKDadXThNtYndNE6tl7PzOD-mPs6evMbA30YMOj9gVpH73Wy6FKkv2waaDME7-aeK9Qh0aW24xTwA3nX6zHix5d4Tn4urx6aFbu9u143i1u2FXWZWF_LHqu2zLWpa1Pl0GV9wQFy0LKQVcW7kqOWZVdiUUOLre4QtcjEzHkBJjsnX57r7oP_M2FMamejwXHUDv0UVVXAXAUkzPLzi5zaHXZqH-xOh4N63eAMls9gG5Pe4D8wT2XNiOrpRKrMVXZ8mhvFQR1P9R8MOih02SNmd43U</recordid><startdate>2011</startdate><enddate>2011</enddate><creator>Maejima, Yasuhiro</creator><creator>Nobori, Kiyoshi</creator><creator>Ono, Yuichi</creator><creator>Adachi, Susumu</creator><creator>Suzuki, Jun-ichi</creator><creator>Hirao, Kenzo</creator><creator>Isobe, Mitsuaki</creator><creator>Ito, Hiroshi</creator><creator>for the Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators</creator><general>The Japanese Circulation Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>2011</creationdate><title>Synergistic Effect of Combined HMG-CoA Reductase Inhibitor and Angiotensin-II Receptor Blocker Therapy in Patients With Chronic Heart Failure</title><author>Maejima, Yasuhiro ; Nobori, Kiyoshi ; Ono, Yuichi ; Adachi, Susumu ; Suzuki, Jun-ichi ; Hirao, Kenzo ; Isobe, Mitsuaki ; Ito, Hiroshi ; for the Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j297t-f94fe8b75ac99c850d3f610050a464881d71ea47d7e690bebadeea232c99160c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aged</topic><topic>Angiotensin</topic><topic>Angiotensin Receptor Antagonists - pharmacology</topic><topic>Angiotensin Receptor Antagonists - therapeutic use</topic><topic>Chronic Disease</topic><topic>Drug Synergism</topic><topic>Drug Therapy, Combination</topic><topic>Electrocardiography</topic><topic>Female</topic><topic>Heart failure</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - physiopathology</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Losartan - pharmacology</topic><topic>Losartan - therapeutic use</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pharmacology</topic><topic>Prospective Studies</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Renin-Angiotensin System - physiology</topic><topic>Simvastatin - pharmacology</topic><topic>Simvastatin - therapeutic use</topic><topic>Statin</topic><topic>Treatment Outcome</topic><topic>Ventricular Dysfunction, Left - drug therapy</topic><topic>Ventricular Dysfunction, Left - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maejima, Yasuhiro</creatorcontrib><creatorcontrib>Nobori, Kiyoshi</creatorcontrib><creatorcontrib>Ono, Yuichi</creatorcontrib><creatorcontrib>Adachi, Susumu</creatorcontrib><creatorcontrib>Suzuki, Jun-ichi</creatorcontrib><creatorcontrib>Hirao, Kenzo</creatorcontrib><creatorcontrib>Isobe, Mitsuaki</creatorcontrib><creatorcontrib>Ito, Hiroshi</creatorcontrib><creatorcontrib>for the Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators</creatorcontrib><creatorcontrib>Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maejima, Yasuhiro</au><au>Nobori, Kiyoshi</au><au>Ono, Yuichi</au><au>Adachi, Susumu</au><au>Suzuki, Jun-ichi</au><au>Hirao, Kenzo</au><au>Isobe, Mitsuaki</au><au>Ito, Hiroshi</au><au>for the Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators</au><aucorp>Heart Failure by Coadministration of Statin and Angiotensin-II Receptor Blocker (HF-COSTAR) Trial Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic Effect of Combined HMG-CoA Reductase Inhibitor and Angiotensin-II Receptor Blocker Therapy in Patients With Chronic Heart Failure: The HF-COSTAR Trial</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2011</date><risdate>2011</risdate><volume>75</volume><issue>3</issue><spage>589</spage><epage>595</epage><pages>589-595</pages><issn>1346-9843</issn><eissn>1347-4820</eissn><abstract>Background: It is known that HMG-CoA reductase inhibitors (statins) may have a therapeutic benefit in patients with heart failure (HF). However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF. Methods and Results: We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group. Conclusions: Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF. (Circ J 2011; 75: 589-595)</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>21242642</pmid><doi>10.1253/circj.CJ-10-0804</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Angiotensin
Angiotensin Receptor Antagonists - pharmacology
Angiotensin Receptor Antagonists - therapeutic use
Chronic Disease
Drug Synergism
Drug Therapy, Combination
Electrocardiography
Female
Heart failure
Heart Failure - drug therapy
Heart Failure - physiopathology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Losartan - pharmacology
Losartan - therapeutic use
Male
Middle Aged
Pharmacology
Prospective Studies
Renin-Angiotensin System - drug effects
Renin-Angiotensin System - physiology
Simvastatin - pharmacology
Simvastatin - therapeutic use
Statin
Treatment Outcome
Ventricular Dysfunction, Left - drug therapy
Ventricular Dysfunction, Left - physiopathology
title Synergistic Effect of Combined HMG-CoA Reductase Inhibitor and Angiotensin-II Receptor Blocker Therapy in Patients With Chronic Heart Failure: The HF-COSTAR Trial
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