Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

Figures & data

Table 1 Clinical trial and guideline basis for compelling indications for individual drug classes

High-risk condition with compelling indicationa	Thiazide-type diuretic	β-Blocker	ACEI	ARB	CCB	Ald Ant	Guideline and/or clinical trial basisb
Heart failure	X	X	X	X		X	ACC/AHA heart failure guidelines, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALES, CHARM
Post-myocardial infarction		X	X			X	ACA/AHA post-myocardial infarction guidelines, BHAT, SAVE, CAPRICORN, EPHESUS
High coronary disease risk	X	X	X		X		ALLHAT, HOPE, ANBP2, LIFE,CONVINCE, EUROPA, INVEST
Diabetes	X	X	X	X	X		NKF-ADA Guidelines, UKPDS, ALLHAT
Chronic kidney disease			X	X			NKF Guidelines, Captopril Trial, RENAAL, IDNT, REIN, AASK
Recurrent stroke prevention	X		X				PROGRESS

Notes:

a Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines; the compelling indication is managed in parallel with the BP.

b Conditions for which clinical trials demonstrate benefit of specific classes of antihypertensive drugs used as part of an antihypertensive regimen to achieve BP goal to test outcomes.

Copyright © 2003. Adapted with permission from Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–1252.

Abbreviations: AASK, African-American Study of Kidney Disease and Hypertension; ACC/AHA, American College of Cardiology/American Heart Association; ACEI, angiotensin-converting enzyme inhibitor; AIRE, Acute Infarction Ramipril Efficacy; Ald Ant, aldosterone antagonist; ALLHAT, Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial; ANBP2, Second Australian National Blood Pressure Study; ARB, angiotensin receptor blocker; BHAT, Beta-Blocker Heart Attack Trial; CAPRICORN, Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction; CCB, calcium channel blocker; CIBIS, Cardiac Insufficiency Bisoprolol Study; CONVINCE, Controlled Onset Verapamil Investigation of Cardiovascular Endpoints; COPERNICUS, Carvedilol Prospective Randomized Cumulative Survival; EPHESUS, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study; EUROPA, European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease; HOPE, Heart Outcomes Prevention Evaluation; IDNT, Irbesartan in Diabetic Nephropathy Trial; INVEST, International Verapamil SR/Trandolapril Study; LIFE, Losartan Intervention for Endpoint Reduction; MERIT-HF, Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure; NKF-ADA, National Kidney Foundation-American Diabetes Association; PROGRESS, Perindopril Protection Against Recurrent Stroke Study; RALES, Randomized Aldactone Evaluation Study; REIN, Ramipril Efficacy in Nephropathy; RENAAL, Reduction in End Points in Noninsulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan; SAVE, Survival and Ventricular Enlargement; SOLVD, Studies of Left Ventricular Dysfunction; TRACE, Trandolapril Cardiac Evaluation; UKPDS, UK Prospective Diabetes Study; Val-HeFT, Valsartan in Heart Failure Trial.

Table 3 Suggested dose equivalences between other β-blockers and carvedilol CR in hypertension

Current β-blocker		Carvedilol CR
		Starting dosea	Uptitration (after several days to one week) as toleratedb
Atenolol		Carvedilol CR	Carvedilol CR
50 mg QDc	Wait 24 hours from last dose of once-daily atenolol	20 mg QD	40 mg QD
≥75 mg QD		40 mg QD	80 mg QD
Metoprolol tartrate
25–50 mg BID	Wait 12 hours from last dose of metoprolol tartrate	20 mg QD	40 mg QD
75–100 mg BID		40 mg QD	80 mg QD
>100 mg BID		40–80 mg QD	80 mg QD
Metoprolol succinate
50–100 mg QD	Wait 24 hours from last dose of metoprolol succinate	20 mg QD	40 mg QD
150–200 mg QD		40 mg QD	80 mg QD
>200 mg QD		40–80 mg QD	80 mg QD

Notes:

a In clinical trials, carvedilol CR was initiated in β-blocker-naive patients at 20 mg. The recommendations in this table are based on the author’s clinical and research experience and, therefore, recommend switching patients already on a medium to high dose of another β-blocker to a medium to high dose of carvedilol CR. A caveat, however: older patients (>65 years), patients with diabetic neuropathy, or those predisposed to orthostatic hypotension should generally start at 20 mg if on a low dose of another β-blocker and 40 mg if on a high dose of another β-blocker. Such patients may then be uptitrated as tolerated; switching directly to 80 mg is not recommended in these patients. Physicians should closely monitor all patients to avoid possible worsening of BP and increases in heart rate after switching to 20 or 40 mg of carvedilol CR, which would call for a quicker uptitration.

b Uptitrate to achieve BP goal. Maximal dose is 80 mg daily (equivalent to 25 mg of carvedilol BID).

c If patients are on a dose of atenolol lower than 50 mg (ie, 25 mg/day) it is unclear what the exact dose of carvedilol CR would be; however, patients at this low a dose should not be started on a dose higher than 20 mg of carvedilol CR.

Notes: Physicians should be guided by their own judgment and experience in choosing doses when switching between drugs.

Abbreviations: BID, twice daily; QD, once daily.

Table 2 Recommended algorithm for replacing carvedilol with carvedilol CR in patients with hypertension

Current dose of carvedilol		Starting dose of carvedilol CRb
6.25 mg (3.125 mg BID)	Wait 12 hoursa	10 mg QD
12.5 mg (6.25 mg BID)		20 mg QD
25 mg (12.5 mg BID)		40 mg QD
50 mg (25 mg BID)		80 mg QD

Notes:

a Suggestion for patients: Take the nighttime dose of carvedilol BID and start carvedilol CR the next morning.

b When switching from carvedilol 12.5 mg or 25 mg BID, a lower starting dose of COREG^® CR may be considered for elderly patients (≥65 years) or those at increased risk of hypotension, dizziness, or syncope. Subsequent titration to higher doses should, as appropriate, be made after an interval of at least two weeks. Recommendations are based on the author’s opinion, Coreg CR prescribing information,⁸² and data from Fonarow.⁸⁸

Abbreviations: BID, twice daily; CR, controlled release; QD, once daily.

COREG CR® (carvedilol phosphate) Extended-release capsules [Prescribing information]Research Triangle Park, NCGlaxoSmithKline, Inc.2008Available at: http://us.gsk.com/products/assets/us_coregcr.pdf Accessed November 6, 2009.

 Google Scholar

FonarowGCProfile of carvedilol controlled-release: A new once-daily formulation of carvedilolExpert Opin Pharmacother200671825332546

 PubMed Web of Science ®Google Scholar