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Table of Contents
GUIDELINE AND CONSENSUS
Year : 2018  |  Volume : 3  |  Issue : 4  |  Page : 138-141

Recommendations for the clinical application of Angiotensin II receptor blocker in patients with coronary heart disease in 2018


1 Department of Cardiology, Peking University First Hospital, Beijing, China
2 Department of Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China
3 Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, China
4 Department of Cardiology, Huashan Hospital Affiliated to Fudan University, Shanghai, China
5 Department of Cardiology, Jinan Central Hospital, Jinan, China
6 Department of Cardiology, People's Hospital of Peking University, Beijing, China
7 Department of Cardiology, Fuwai Hospital of Chinese Academy of Medical Sciences, Beijing, China
8 Department of Cardiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
9 Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai, China
10 Department of Cardiology, Peking Union Medical College Hospital, Beijing, China

Date of Web Publication19-Dec-2018

Correspondence Address:
Yong Huo
Peking University First Hospital, Beijing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cp.cp_34_18

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How to cite this article:
Li J, Chen Y, Gao C, Li Y, Su G, Sun N, Tang Y, Wang J, Wei M, Yan X, Huo Y. Recommendations for the clinical application of Angiotensin II receptor blocker in patients with coronary heart disease in 2018. Cardiol Plus 2018;3:138-41

How to cite this URL:
Li J, Chen Y, Gao C, Li Y, Su G, Sun N, Tang Y, Wang J, Wei M, Yan X, Huo Y. Recommendations for the clinical application of Angiotensin II receptor blocker in patients with coronary heart disease in 2018. Cardiol Plus [serial online] 2018 [cited 2019 Jan 23];3:138-41. Available from: http://www.cardiologyplus.org/text.asp?2018/3/4/138/247956




  Introduction Top


The “China Cardiovascular Disease Report 2016”[1] reported that the number of people suffering from coronary heart disease in China is as high as 11 million, and morbidity and mortality are still on the rise. The BRIG study[2] showed that from 2006 to 2012, the use of antiplatelet drugs and statins in patients with acute coronary syndrome (ACS) in China increased year by year, while the use of angiotensin-converting enzyme inhibitors (ACEI) and Angiotensin II receptor blockers (ARB) in the hospital was slightly less, use was further reduced after the patient was discharged from the hospital and was less than at one-third of the usage after 1 year of discharge.

In ACS and stable coronary heart disease guidelines, it is clearly recommended that patients with different types of coronary heart disease should be treated with the renin-angiotensin-aldosterone system inhibitor (RAASi). In order to better promote the standardized application of RAASi in patients with coronary heart disease in clinical practice, China published the consensus “Application of ACEI in patients with coronary heart disease” in 2015.[3] However, treatment with ARB for coronary heart disease in China has not been studied even though the Chinese population suitable for treatment with ARB is extensive. The ONTARGET[4] study, the VALIANT[5] study, and a newly published meta-analysis, including coronary heart disease patients, consistently show that ACEI and ARB have similar efficacy in reducing the risk of cardiovascular events. Messerli et al.[6] suggested that treatment with ARBs was equivalent to treatment with ACEI in reducing blood pressure, cardiovascular death, all-cause death, and end-stage renal disease risk. The Chinese population has good tolerance to ARB, low incidence of adverse reactions, and has universal applicability. In clinical practice, there are many beneficial RAASi treatment options, and selection is focused on the potential to use the treatment both early and long-term and its efficacy of reducing cardiovascular events, which is currently determined by clinical medical workers. The current study contains clinical recommendations for standard ARB treatment of coronary heart disease and standardized guidelines to improve the clinician's use of RAASi and improve the clinician's understanding of treatment options with ARB. Studies have shown that[7] clinicians do not have a deep understanding of the standardized application of ARB in patients with coronary heart disease and are not familiar with the timing of initiation of treatment, treatment time course, dose adjustment, renal function management, or adverse reaction management. Even in patients with diabetes or high blood pressure, the percentage of patients with ARB prescriptions is only 46.1% and 56.3%. There are major concerns about the treatment of coronary heart disease in patients with normal blood pressure and high-risk groups, especially when combined with other drugs that have an effect on blood pressure and increase the risk of hypotension. Therefore, to further improve the standardized application of ARB in patients with coronary heart disease, we have written this recommendation for clinical application in patients with coronary heart disease and developed a clinical application process for different types of patients with coronary heart disease.

The recommendations for the application of ACEI in coronary heart disease are not repeated here.

Important evidence and requirements for treatment with Angiotensin II receptor blockers in coronary heart disease

Suggest

  • From the evidence-based evidence study, ACEI and ARB have similar effects in patients with coronary heart disease
  • Because the pathophysiological mechanisms of stable coronary heart disease and ACS are not the same, adequate dose therapy is required for ARB.


The ONTARGET study[4] enrolled patients with coronary heart disease or diabetes with other risk factors and found that telmisartan was not inferior to ramipril in reducing cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization. These findings provide further evidence for the equivalence of ACEI and ARB in patients with coronary heart disease. The OPTIMAAL study[8] compared the effects of losartan and captopril on mortality and morbidity in patients with acute myocardial infarction. The relative risk of death in the losartan group was not statistically different from those treated with captopril. VALIANT[5] found that when valsartan treatment was initiated within 12 h–10 days of acute myocardial infarction the prevention of the left ventricular remodeling was comparable to captopril. The risk of fatal or nonfatal atherosclerotic events in patients was comparable to captopril. The 2017 European Society of Cardiology ST-Elevation Myocardial Infarction (STEMI) guidelines[9] specifically recommend valsartan for patients with myocardial infarction with heart failure and/or left ventricular diastolic dysfunction. Although it is also a coronary heart disease, the pathophysiological mechanisms of stable coronary heart disease and ACS are not the same, and there are some differences in treatment needs. Patients with stable coronary heart disease usually have clear atherosclerosis, mainly with impaired endothelial function and plaque progression, and there is obvious renin angiotensin aldosterone system (RAAS) activation in plaque and blood circulation.[9] Patients with ACS usually have hemodynamic abnormalities, and due to myocardial infarction and cardiac tissue RAAS activation, neuroendocrine factors such as inflammatory factors can mediate ventricular remodeling.[10] Treatment for stable coronary heart disease is mainly focused on vascular protection, while ACS requires dual protection of blood vessels and heart. The concentration of Ang II in heart tissue is up to 5 times higher than that in circulating blood.[11] Regardless of the patient's blood pressure level, ARB should be administered. In order to minimize RAAS activation, a full dose should be given if the patient can tolerate it.

The clinical process and recommendations for angiotensin II receptor blockers treatment in patients with coronary heart disease

  • Clinical procedures and recommendations for ARB treatment in patients with ACS.


    1. All patients with ACS who have no contraindications should start ARB treatment early and adjusted to the full or maximally tolerated dose after hemodynamic stabilization
    2. Patients with ACS who have normal blood pressure should also receive ARB treatment to prevent or treat cardiovascular remodeling.


Treatment process

Combined with the operability of clinical research and clinical practice, the following treatment procedures are recommended [Figure 1].
Figure 1: ACS patient ARB treatment process

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Start angiotensin II receptor blockers treatment based on blood pressure level

There will likely be individual differences in blood pressure in patients with ACS. The purpose of using ARB is not only for blood pressure but primarily for the prevention or treatment of cardiovascular remodeling.

Numerous studies have confirmed that patients with systolic blood pressure (SBP) >130 mmHg benefit from RAASi treatment, and patients with SBP 110–130 mmHg can still benefit from RAASi without risk. The PREAMI study[12] found that administering RAASi to patients with acute myocardial infarction with SBP at 120–130 mm Hg improved ventricular remodeling. In the SAVE study,[13] patients with acute myocardial infarction and left ventricular systolic dysfunction had SBPs of 110–120 mmHg, and treatment with RAASi gradually increased blood pressure and significantly reduced the risk of death. Both the ISIS-4 study[14] and a meta-analysis[15] confirmed that patients with acute myocardial infarction benefited from the use of RAASi at BP100–120 mm Hg, but when blood pressure is <100 mm Hg, the benefit is negligible. When SBP is between 110–130 mmHg, careful consideration should be given to the order of treatment if considering the combination of ARB and beta blockers. If the patient's heart rate is <70 bpm, the ARB can be initiated first, and if there is no hypotension, the beta blocker can be initiated.

Treatment course

High-risk groups, such as the elderly, those with anterior wall myocardial infarction, recurrent MI, Killip II and above, heart failure, or STEMI with left ventricular systolic dysfunction should receive long-term ARB treatment. All patients with NSTE-ACS with left ventricular ejection fraction (LVEF) ≤40% or with heart failure, hypertension, and diabetes should receive long-term treatment with ARB. Other patients recommend at least 12 months of ARB treatment. The treatment course is then determined based on the individual condition of the patient.

Clinical recommendations for angiotensin II receptor blockers treatment in patients with stable coronary heart disease

Patients with stable coronary heart disease, especially those with stable LVEF ≤ 40%, heart failure, hypertension, diabetes or chronic kidney disease (CKD), need to receive ARB treatment as soon as possible and adhere to long-term, even lifelong treatment. The main pathophysiological characteristics of stable coronary heart disease are clear atherosclerosis, impaired endothelial function, risk of plaque rupture, and high incidence of acute cardiovascular events. There is still little direct evidence that ARB treatment affects these measures, but there is evidence for improvement with RAASi treatment, especially in patients with ACEI who cannot tolerate or have hypertension and/or cardiac insufficiency. ARB treatment is needed as early as possible to protect the vascular endothelium and to stabilize and reverse plaque. Studies have also found that patients with stable coronary heart disease and hypertension who received omeproxacin 20 mg or valsartan 80 mg for 6 months showed a significant reduction in plaque volume with intravascular ultrasound detection.[16] Studies have found a risk of ventricular remodeling and heart failure in patients with myocardial infarction. Adequate doses of ARB can reduce the risk of ventricular remodeling and heart failure and prevent recurrence of cardiovascular events. According to clinical research and guidelines, stable coronary heart disease patients with LVEF ≤40%, heart failure, hypertension, diabetes, and CKD are considered high-risk and need to receive ARB treatment as soon as possible. Afterward, they need to adhere to long-term, even lifelong treatment to protect the endothelium and stabilize plaques and to prevent cardiovascular events.

Precautions during angiotensin II receptor blockers treatment

Contraindications for angiotensin II receptor blockers treatment

Treatment contraindications for ARB include hypotension (SBP <90 mmHg), hemodynamic instability, hypovolemia, cardiogenic shock, bilateral renal artery stenosis, renal failure (serum creatinine >265 μmol/L), pregnant or lactating women, or an allergy to ARB.

Renal function management

Cardiorenal syndrome is a condition that should be of concern to patients with severe heart disease. Renal function should be assessed when treating patients with coronary heart disease. In the first 2 weeks after ARB treatment, if serum creatinine does not increase by >30% from baseline and remains stable, it is within acceptable limits and treatment should be continued without adjustment. If serum creatinine increases by 30%–50% from baseline, treatment should be continued under close monitoring without adjustment of the dose, if it falls to <30% of baseline within 5–7 days, continue treatment. In the first 2 weeks after ARB treatment, if serum creatinine is increased by >50% from baseline, it is recommended to discontinue ARB treatment and investigate the cause, such as insufficient blood volume or renal artery stenosis. ARB treatment should be reinitiated after subsequent treatment and recovery of serum creatinine.

Blood pressure management

Blood pressure changes during initial treatment should be closely monitored when receiving ARB because hypotension is most likely to occur either at 24–48 h after the first treatment or after increasing the dose. Blood pressure fluctuates greatly in the early stage, especially in patients with acute myocardial infarction, but as the patient's condition stabilizes and heart function improve, blood pressure will gradually rise and then stabilize. When hypotension occurs during treatment (SBP <100 mmHg), the patient can continue to be treated with ARB if the patient is asymptomatic. If there is no fluid retention, consider reducing or suspending diuretics. Then, according to the heart rate, the order of drug reduction and withdrawal of ARB and β blockers should be determined.

Blood potassium management

At the initial application of ARB, or during the incremental process, attention should be paid to monitoring changes in serum potassium, especially in the elderly, in patients with high-dose ARB in combination with renal insufficiency, and in patients with spironolactone. When potassium is >5.0 mmol/L, it is recommended to stop spironolactone.


  Conclusion Top


The efficacy and safety of treatment with ARB in patients with coronary heart disease has been confirmed by several large-scale clinical studies, but clinicians do not fully understand the importance of using ARB in patients with coronary heart disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Weiwei C, Runlin G, Lisheng L, Manlu Z, Wen W, Yongjun W, et al. Summary of China cardiovascular disease report 2016. Chin Circ J 2017;32:521-30.  Back to cited text no. 1
    
2.
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Chen J, Fu G, Fu X, Ge J, Gao W, Han Y, et al. Angiotensin-converting enzyme inhibitors are used in patients with coronary heart disease. Chinese expert consensus. Chin Circ J 2016;31:420-5.  Back to cited text no. 3
    
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ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-59.  Back to cited text no. 4
    
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Messerli FH, Bangalore S, Bavishi C, Rimoldi SF. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use? J Am Coll Cardiol 2018;71:1474-82.  Back to cited text no. 6
    
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Oosterga M, Voors AA, Buikema H, Pinto YM, Haber HE, Ebels T, et al. Angiotensin II formation in human vasculature after chronic ACE inhibition: A prospective, randomized, placebo-controlled study. QUO VADIS investigators. Cardiovasc Drugs Ther 2000;14:55-60.  Back to cited text no. 9
    
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Danser AH, Koning MM, Admiraal PJ, Sassen LM, Derkx FH, Verdouw PD, et al. Production of angiotensins I and II at tissue sites in intact pigs. Am J Physiol 1992;263:H429-37.  Back to cited text no. 11
    
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Ferrari R, Perindopril and Remodeling in Elderly with Acute Myocardial Infarction Investigators. Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: Results of the randomized perindopril and remodeling in elderly with acute myocardial infarction (PREAMI) study. Arch Intern Med 2006;166:659-66.  Back to cited text no. 12
    
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Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ Jr., Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators. N Engl J Med 1992;327:669-77.  Back to cited text no. 13
    
14.
ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) collaborative group. Lancet 1995;345:669-85.  Back to cited text no. 14
    
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Indications for ACE inhibitors in the early treatment of acute myocardial infarction: Systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group. Circulation 1998;97:2202-12.  Back to cited text no. 15
    
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Ishii H, Kobayashi M, Kurebayashi N, Yoshikawa D, Suzuki S, Ichimiya S, et al. Impact of angiotensin II receptor blocker therapy (olmesartan or valsartan) on coronary atherosclerotic plaque volume measured by intravascular ultrasound in patients with stable angina pectoris. Am J Cardiol 2013;112:363-8.  Back to cited text no. 16
    


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