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Metoprolol: Cardioprotection and Clinical Benefits
Introduction to Metoprolol
Metoprolol is a beta1-selective beta-blocker widely used in the treatment of cardiovascular diseases, including hypertension, angina pectoris, and chronic heart failure. It is known for its ability to reduce heart rate, myocardial contractility, and blood pressure, thereby decreasing myocardial oxygen demand.
Metoprolol in Acute Myocardial Infarction (AMI)
Early Administration and Infarct Size Reduction
Research has demonstrated that early intravenous administration of metoprolol before reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) significantly reduces infarct size. This cardioprotective effect was observed through magnetic resonance imaging (MRI) and creatine kinase release measurements, showing smaller infarct sizes and improved left ventricular ejection fraction (LVEF) in the metoprolol group compared to controls1 2 3.
Long-term Benefits
The METOCARD-CNIC trial further highlighted the long-term benefits of early metoprolol administration. Patients treated with intravenous metoprolol before reperfusion exhibited higher LVEF, reduced incidence of severe left ventricular systolic dysfunction, and fewer heart failure admissions over a follow-up period of up to two years3. This suggests that early metoprolol administration not only provides immediate cardioprotection but also contributes to better long-term cardiac outcomes.
Mechanisms of Cardioprotection
Myocardial Salvage
Studies involving animal models have shown that metoprolol administered during acute coronary occlusion significantly increases myocardial salvage. This is measured as the difference between the extent of myocardium at risk and myocardial necrosis. The increased myocardial salvage is associated with improved regional and global left ventricular function2 4.
Timing and Route of Administration
The cardioprotective effects of metoprolol are most pronounced when administered intravenously before reperfusion. Comparisons between pre-reperfusion intravenous metoprolol and post-reperfusion oral metoprolol indicate that the former results in significantly larger myocardial salvage and reduced reperfusion injury, highlighting the importance of timing and administration route4.
Metoprolol in Chronic Heart Failure
Improvement in Symptoms and Exercise Tolerance
In patients with chronic heart failure, particularly those with dilated cardiomyopathy, long-term metoprolol therapy has been shown to improve exercise capacity, functional classification, and left ventricular ejection fraction. These benefits were observed in both double-blind, randomized trials and open-label crossover studies6 8.
Reduction in Mortality and Morbidity
The MERIT-HF trial demonstrated that metoprolol controlled-release/extended-release (CR/XL) significantly reduces all-cause mortality, sudden death, and death due to progressive heart failure in patients with stable mild to moderate chronic heart failure. This trial also reported improvements in NYHA functional class, exercise capacity, and quality of life9.
Conclusion
Metoprolol, particularly when administered early and intravenously before reperfusion, offers significant cardioprotective benefits in patients with acute myocardial infarction. It reduces infarct size, increases myocardial salvage, and improves long-term cardiac function. In chronic heart failure, metoprolol improves symptoms, exercise tolerance, and reduces mortality and morbidity. These findings underscore the importance of metoprolol in the management of various cardiovascular conditions.
Sources and full results
Most relevant research papers on this topic
Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial
Early intravenous metoprolol before reperfusion significantly reduces infarct size and increases left ventricular ejection fraction in patients with ST-segment-elevation myocardial infarction.
RCT
Very Rigorous Journal
Highly CitedEarly Metoprolol Administration Before Coronary Reperfusion Results in Increased Myocardial Salvage: Analysis of Ischemic Myocardium at Risk Using Cardiac Magnetic Resonance
Early metoprolol administration during acute coronary occlusion increases myocardial salvage, leading to improved regional and global left ventricular motion recovery.
RCT
Animal StudyHighly CitedLong-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).
Early intravenous metoprolol administration before reperfusion in patients with anterior STEMI leads to higher long-term left ventricular function, reduced severe systolic dysfunction, and fewer heart failure admissions.
RCTHighly CitedThe cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion.
Intravenous metoprolol before coronary reperfusion results in larger myocardial salvage than oral metoprolol initiated early after reperfusion.
RCTAnimal Study
Rigorous JournalPhotodegradation of metoprolol in the presence of aquatic fulvic acids. Kinetic studies, degradation pathways and role of singlet oxygen, OH radicals and fulvic acids triplet states.
Metoprolol photodegradation in the presence of aquatic fulvic acids leads to a 80% decrease in concentration after 72 hours, with OH radicals being the main reactive species responsible for photosensitized degradation.
Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial.
Metoprolol can safely improve symptoms and exercise capacity in patients with dilated cardiomyopathy, with seven out of 20 patients experiencing resolution of heart failure symptoms and doubled their exercise capacity.
RCTHighly CitedPrevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol
Candesartan treatment protects against early decline in global left ventricular function in patients with early breast cancer receiving adjuvant anthracycline-containing regimens.
RCTRigorous JournalHighly CitedEffect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: a randomized, double-blind, placebo-controlled study.
Metoprolol treatment improves myocardial performance and energetics, and favorably alters substrate utilization in patients with nonischemic dilated cardiomyopathy.
RCTHighly CitedMetoprolol
Metoprolol CR/XL effectively decreases mortality and improves clinical status in patients with stable mild to moderate chronic heart failure due to left ventricular systolic dysfunction, and is effective in patients with ischaemic or dilated cardiomyopathy.
RCT