Description
Metoprolol is a relatively beta1-selective beta blocker without intrinsic sympathomimetic activity. It occupies the beta1 adrenoceptors on the heart and blunts the grip of adrenaline and noradrenaline: heart rate, contractile force and conduction all come down. Myocardial oxygen demand falls with them. The relative selectivity for beta1 over beta2 is why metoprolol interferes less with bronchial muscle than non-selective agents. Relative is not absolute, though. The difference washes out as the dose rises.
The difference between succinate and tartrate is not the active substance but the formulation. Metoprolol tartrate is the immediate-release form and is taken two or three times a day, because levels swing considerably between doses. Metoprolol succinate in the ER preparation (also called CR/XL) releases the drug in a controlled way over 24 hours. The result is a flatter profile without the peaks and troughs of the immediate-release form, on one dose a day.
This extended-release form is precisely the one with hard endpoint data behind it. The review by Prakash and Markham summarises MERIT-HF: 3,991 patients with chronic heart failure, NYHA class II to IV and an ejection fraction of 0.40 or less, randomised on top of standard therapy to metoprolol CR/XL or placebo. After a mean of one year, all-cause mortality in the metoprolol group was 34 percent lower. The analysis by Hjalmarson and Fagerberg breaks that down: sudden deaths fell by 41 percent, deaths from worsening heart failure by 49 percent, alongside fewer hospital admissions and fewer days in hospital.
The dosing schedule in those trials is worth noting, because it runs against the reflex of starting a drug at its target dose. The trial protocol described by Wikstrand gives a starting dose of half a 25mg tablet daily in NYHA III to IV and a whole one in NYHA II. Doubling happened only every two weeks, so the target dose of 200mg daily was built up over eight weeks. The early assumption that beta blockers were contraindicated in heart failure was not simply wrong: started too fast they do make the condition worse. It was slow uptitration that turned a contraindication into a standard of care. The review by Adams traces that path through CIBIS-II, MERIT-HF and COPERNICUS.
You can order Metoprolol succinate ER as extended-release tablets with 25mg, 50mg or 100mg per tablet, 10 tablets per blister.
This information is for research and educational purposes only. No medical advice.
Risks & Safety
Beta blockers are not something you take and drop as you feel like it. The two most dangerous moments are the start and the end.
- Do not stop abruptly: Under continuous therapy the body upregulates its beta receptors. Remove the blocker suddenly and an unchanged sympathetic drive meets more receptors than before. Blood pressure spikes, tachycardia, angina and even infarction have been described. Taper over days to weeks, never overnight.
- Titrate in, do not jump in: The MERIT-HF schedule started at 12.5 to 25mg and took eight weeks to reach 200mg. Starting high with impaired pump function makes it worse.
- Asthma and COPD: Beta1 selectivity is relative and dose-dependent. In obstructive airway disease metoprolol can trigger bronchospasm. Anyone who depends on salbutamol or similar beta2 agonists has a real problem here.
- Bradycardia and AV block: Pulse below 50, dizziness, syncope. Combining it with other rate-lowering agents such as verapamil or diltiazem amplifies this considerably.
- Diabetes: Beta blockers can mask the warning signs of hypoglycaemia, because tremor and palpitations are sympathetically mediated. Sweating remains, the rest does not.
- Not a one-to-one swap for the immediate-release form: Succinate ER and tartrate differ in release. Switching is not just a change of name.
- Common adverse effects: Fatigue, cold hands and feet, dizziness, sleep disturbance with vivid dreams and, in men, occasionally erectile problems.
This classification does not replace medical advice. Risk and responsibility for any actual use lie entirely with the buyer.
Studies
- Metoprolol: a review of its use in chronic heart failure - Drugs 2000, Prakash and Markham: review of metoprolol CR/XL in chronic heart failure, with the 34 percent reduction in all-cause mortality in MERIT-HF and the titration schedule from 12.5 to 25mg up to 200mg daily.
- MERIT-HF mortality and morbidity data - Basic Research in Cardiology 2000, Hjalmarson and Fagerberg: analysis of the 3,991 patients, with 41 percent fewer sudden deaths, 49 percent fewer deaths from worsening heart failure and markedly fewer hospital days.
- MERIT-HF - description of the trial - Basic Research in Cardiology 2000, Wikstrand: trial protocol with inclusion criteria, placebo run-in and the eight-week uptitration.
- Beta-blockers in heart failure: how far have we progressed? - Postgraduate Medicine 2002, Adams: context across CIBIS-II, MERIT-HF and COPERNICUS, including the earlier assumption that beta blockers were contraindicated in heart failure.
