COREG CR

Coreg Cr Generic Name & Formulations

Legal Class

General Description

Carvedilol (as phosphate) 10mg, 20mg, 40mg, 80mg; ext-rel caps.

Pharmacological Class

Noncardioselective beta-blocker/alpha-1 blocker.

How Supplied

CR caps—30, 90; Tabs—100

How Supplied

Coreg CR

Coreg CR are supplied as hard gelatin capsules in bottles of 20 in the following strengths:

10 mg – white and green capsule shell printed with "GSLGK" and "10 mg"
20 mg – white and yellow capsule shell printed with "GSMHV" and "20 mg"
40 mg – yellow and green capsule shell printed with "GSETX" and "40 mg"
80 mg – white capsule shell printed with "GSF1L" and "80 mg"

Storage

Store at 25°C (77°F); excursions 15° to 30°C (59° to 86°F).

Manufacturer

Woodward Pharma Services LLC

Mechanism of Action

Carvedilol phosphate is a non-selective β-adrenergic blocking agent with α₁-blocking activity. It has no intrinsic sympathomimetic activity.

Coreg Cr Indications

Indications

Mild to severe heart failure (HF), to increase survival and reduce hospitalization risk. To reduce cardiovascular mortality post-MI with left ventricular ejection fraction ≤40%.

Coreg Cr Dosage and Administration

Adult

Take with food in the AM. Swallow whole or may open caps and sprinkle beads on a spoonful of applesauce and take immediately. ≥18yrs: HF: initally 10mg once daily for 2 weeks, may double dose every 2 weeks if tolerated; max 80mg once daily. Reduce dose if pulse<55. Post-MI: initially 20mg once daily; increase to 40mg once daily after 3–10 days if tolerated; then to target dose of 80mg once daily. Low BP or heart rate, or fluid retention: may start at 10mg once daily. Switching from immediate-release carvedilol: see literature. ≥65yrs: switching from highest dose of immediate-release carvedilol (25mg twice daily) to Coreg CR: initially Coreg CR 40mg; if tolerated for ≥2weeks, may increase to 80mg.

Children

<18yrs: not recommended.

Coreg Cr Contraindications

Contraindications

Cardiogenic shock or decompensated HF requiring intravenous inotropic therapy. Asthma, related bronchospastic conditions. 2^nd or 3^rd-degree AV block, sick sinus syndrome, or severe bradycardia, unless paced. Severe hepatic impairment.

Coreg Cr Boxed Warnings

Not Applicable

Coreg Cr Warnings/Precautions

Warnings/Precautions

Peripheral vascular disease. Nonallergic bronchospasm. Diabetes (monitor blood glucose). Hyperthyroidism. Monitor renal function in ischemic heart disease, diffuse vascular disease, underlying renal insufficiency, and/or if systolic BP <100 mmHg. Initiation of therapy may temporarily worsen signs and symptoms; benefits may be delayed for several weeks; may need increased diuretic dose at first. Avoid abrupt cessation. Prinzmetal's angina. Pheochromocytoma. Elderly. Pregnancy. Nursing mothers.

Warnings/Precautions

Cessation of Therapy

Avoid abrupt cessation in patients with coronary artery disease.
Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias may occur in patients with angina after abrupt cessation.
Discontinue Coreg CR over 1 to 2 weeks if possible, and monitor the patient closely when discontinuing Coreg CR and advise to limit physical activity to a minimum. Promptly reinstitute Coreg CR if angina worsens or acute coronary insufficiency develops during discontinuation.

Bradycardia

Bradycardia may occur. Reduce dose of Coreg CR if pulse rate drops <55 beats per minute.

Hypotension

Hypotension and postural hypotension may occur, along with syncope.
To reduce the risk for syncope or excessive hypotension, initiate patients on a low dose of Coreg CR with food and gradually up-titrate.
Avoid driving or handling hazardous tasks when initiating treatment due to a risk for syncope.

Heart Failure/Fluid Retention

During up-titration, the use of carvedilol may cause worsening heart failure or fluid retention. If these symptoms occur, increase diuretics and do not advance the dose of carvedilol until clinical stability resumes.
Occasionally it is necessary to lower the carvedilol dose or temporarily discontinue it.

Non-allergic Bronchospasm

Use caution in patients who do not respond to, or cannot tolerate, other antihypertensive agents. Advise to use the smallest effective dose.

Glycemic Control in Type 2 Diabetes

May mask some of the manifestations of hypoglycemia, particularly tachcardia. Nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. Patients subject to spontaneous hypoglycemia or diabetic patients receiving insulin or oral hypoglycemic agents should be cautioned about these possibilities.
Carvedilol may worsen hyperglycemia in patients with HF and diabetes.
Monitor blood glucose during initiation, dose adjustments, or discontinuing therapy.

Peripheral Vascular Disease

May precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Exercise caution.

Deterioration of Renal Function

In patients with heart failure, the use of carvedilol has rarely resulted in deterioration of renal function.
Risk factors include systolic BP <100mmHg, ischemic heart disease, and diffuse vascular disease, and/or underlying renal insufficiency. Monitor renal function during up-titration, discontinuation, or dose reduction in patients with these risk factors.

Major Surgery

Do not routinely withdraw chronically administered beta-blocker therapy prior to major surgery.
During major surgery, the use of beta-blockers may augment the risk of general anesthesia and surgical procedures due the hearts inability to respond to reflex adrenergic stimuli.

Thyrotoxicosis

May mask clinical signs of hyperthyroidism (eg, tachycardia). Abrupt withdrawal may lead to an exacerbation of hyperthyroidism or may precipitate thyroid storm.

Pheochromocytoma

In patients with pheochromocytoma, initiate an alpha-blocking agent prior to the use of any beta-blocking agent.
Use caution when administering carvedilol to patients suspected of having pheochromocytoma.

Prinzmetal's Variant Angina

Agents with non-selective β-blocking activity may provoke chest pain in patients with Prinzmetal's variant angina.
Use caution in patients suspected of having Prinzmetal's variant angina.

Risk of Anaphylactic Reaction

Patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge while taking beta-blockers.
These patients may be unresponsive to epinephrine used to treat allergic reaction.

Intraoperative Floppy Iris Syndrome (IFIS)

IFIS has been observed during cataract surgery in some patients treated with alpha-1 blockers.

Pregnancy Considerations

Risk Summary

Available data in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes.
There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy.
Use of beta blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depression in the neonate.

Clinical Considerations

Disease-Associated Maternal and/or Embryo-Fetal Risk: Pregnant women with hypertension should be carefully monitored and managed accordingly. Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Fetal/Neonatal Adverse Reactions: Neonates of women with hypertension who are treated with beta-blockers during the third trimester of pregnancy may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Observe newborns for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and manage accordingly.

Nursing Mother Considerations

Risk Summary

No data on the presence of carvedilol in human milk, the effects on the breastfed infant, or the effects on milk production.
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for Coreg CR and any potential adverse effects on the breastfed infant from Coreg CR or from the underlying maternal condition.

Pediatric Considerations

Efficacy of Coreg CR has not been established in patients younger than 18 years.

Coreg Cr Pharmacokinetics

Absorption

Rapidly and extensively absorbed. Absolute bioavailability: approximately 25–35%.

Distribution

>98% plasma protein bound.
Steady-state volume of distribution: approximately 115 L.
Plasma clearance ranges from 500-700 mL/min.

Metabolism

Hepatic (aromatic ring oxidation, glucuronidation).

Elimination

Fecal. Half-life: ~7–10hrs.

Coreg Cr Interactions

Interactions

May be potentiated by CYP2D6 inhibitors (eg, quinidine, fluoxetine, paroxetine, propafenone), alcohol (separate by 2 hours). Bradycardia, hypotension with catecholamine depletors (eg, reserpine, MAOIs). Carvedilol levels reduced by rifampin. Increased absorption with cimetidine. Caution with drugs that affect cardiac conduction (esp. diltiazem, verapamil). May potentiate antidiabetic agents. Monitor digoxin, cyclosporine when changing carvedilol dose. Anesthesia.

Coreg Cr Adverse Reactions

Adverse Reactions

Dizziness, edema, hypotension, syncope, bradycardia, AV block, GI upset, hyperglycemia, weight gain, abnormal vision.

Coreg Cr Clinical Trials

Clinical Trials

Mild to Moderate Heart Failure (HF)

Carvedilol was evaluated in patients with mild to moderate HF in 5 multicenter, placebo-controlled trials, and in 1 active-controlled trial (COMET).
There were 4 US multicenter, double-blind, placebo-controlled trials which included 1094 patients with NYHA II-III HF and ejection fraction less than or equal to 0.35. Most of the patients were on digitalis, diuretics, and an ACE inhibitor at trial entry. There was an Australia-New Zealand double-blind, placebo-controlled trial which included 415 patients with less severe HF. All patients tolerated a 2-week course of carvedilol 6.25mg twice daily.
The primary endpoint was either progression of HF (1 US trial) or exercise tolerance (2 US trial and the Australia-New Zealand trial).
Slowing Progression of HF:

One US multicenter trial (366 subjects) had as its primary end point the sum of cardiovascular mortality, cardiovascular hospitalization, and sustained increase in heart failure medications. Heart failure progression was reduced, during an average follow‑up of 7 months, by 48% (P =.008).
In the Australia‑New Zealand trial, death and total hospitalizations were reduced by about 25% over 18 to 24 months.
In the 3 largest U.S. trials, death and total hospitalizations were reduced by 19%, 39%, and 49%, nominally statistically significant in the last 2 trials. The Australia‑New Zealand results were statistically borderline.

Functional Measures:

None of the multicenter trials had NYHA classification as a primary end point, but all such trials had it as a secondary end point. There was at least a trend toward improvement in NYHA class in a l trials.

Subjective Measures:

Health-related quality of life, as measured with a standard questionnaire (a primary end point in 1 trial), was unaffected by carvedilol. However, patients' and investigators' global assessments showed significant improvement in most trials.

Mortality:

Death was not a pre-specified end point in any trial but was analyzed in all trials. Overall, in these 4 US trials, mortality was reduced, nominally significantly so in 2 trials.

The COMET Trial

The COMET trial included 3029 subjects with NYHA class II-IV heart failure (left ventricular ejection fraction less than or equal to 35%) who were randomly assigned to receive either carvedilol (target dose: 25mg twice daily) or immediate-release metoprolol tartrate (target dose: 50mg twice daily). The mean age of the subjects was approximately 62 years, 80% were males, and the mean left ventricular ejection fraction at baseline was 26%. Approximately 96% of the subjects had NYHA class II or III HF.
The primary end points were all-cause mortality and the composite of death plus hospitalization for any reason.
All-cause mortality was 34% in the subjects treated with carvedilol and was 40% in the immediate-release metoprolol group (P =.0017; hazard ratio = 0.83, 95% CI, 0.74-0.93). The effect on mortality was primarily due to a reduction in cardiovascular death. The difference between the 2 groups with respect to the composite end point was not significant (P =.122). The estimated mean survival was 8.0 years with carvedilol and 6.6 years with immediate-release metoprolol.

Severe Heart Failure (COPERNICUS)

The COPERNICUS trial included 2289 patients with HF at rest or with minimal exertion and LVEF <25% (mean 20%), despite digitalis (66%), diuretics (99%) and ACE inhibitors (89%) who were randomly assigned to receive placebo or carvedilol.
Patients were up-titrated from a starting dose of 3.125mg twice daily to a maximum tolerated dose or up to 25mg twice daily over 6 weeks.
The primary end point was all-cause mortality, but cause-specific mortality and the risk of death or hospitalization (tota, CV or HF) were also examined.
The trial was stopped after a median follow‑up of 10 months because of an observed 35% reduction in mortality (from 19.7% per patient-year on placebo to 12.8% on carvedilol; hazard ratio 0.65, 95% CI: 0.52 to 0.81, P =.0014, adjusted).
The effect on mortality was principally the result of a reduction in the rate of sudden death among subjects without worsening heart failure.
Fewer subjects on carvedilol than on placebo were hospitalized for any reason (372 vs 432, P =.0029), for cardiovascular reasons (246 vs 314, P =.0003), or for worsening heart failure (198 vs 268, P =.0001).

Left Ventricular Dysfunction following Myocardial Infarction

The double-blind CAPICORN trial included 1959 patients with a recent MI (within 21 days) and LVEF of ≤40%, with (47%) or without symptoms of HF. Patients initially received carvedilol at 6.25mg twice daily then titrated as tolerated to 25mg twice daily. Subjects had to have a systolic blood pressure greater than 90 mm Hg, a sitting heart rate greater than 60 beats per minute, and no contraindication to β‑blocker use.
All‑cause mortality was 15% in the placebo group and 12% in the carvedilol group, indicating a 23% risk reduction in subjects treated with carvedilol (95% CI: 2% to 40%, P =.03).
There was also a significant 40% reduction in fatal or non-fatal myocardial infarction observed in the group treated with carvedilol (95% CI: 11% to 60%, P =.01). A similar reduction in the risk of myocardial infarction was also observed in a meta-analysis of placebo- controlled trials of carvedilol in heart failure.

Coreg Cr Note

Not Applicable

Coreg Cr Patient Counseling

See Literature

Coreg Cr Generic Name & Formulations

Legal Class

General Description

Carvedilol (as phosphate) 10mg, 20mg, 40mg, 80mg; ext-rel caps.

Pharmacological Class

Noncardioselective beta-blocker/alpha-1 blocker.

How Supplied

CR caps—30, 90; Tabs—100

How Supplied

Coreg CR

Coreg CR are supplied as hard gelatin capsules in bottles of 20 in the following strengths:

10 mg – white and green capsule shell printed with "GSLGK" and "10 mg"
20 mg – white and yellow capsule shell printed with "GSMHV" and "20 mg"
40 mg – yellow and green capsule shell printed with "GSETX" and "40 mg"
80 mg – white capsule shell printed with "GSF1L" and "80 mg"

Storage

Store at 25°C (77°F); excursions 15° to 30°C (59° to 86°F).

Manufacturer

Woodward Pharma Services LLC

Mechanism of Action

Carvedilol phosphate is a non-selective β-adrenergic blocking agent with α₁-blocking activity. It has no intrinsic sympathomimetic activity.

Coreg Cr Indications

Indications

Hypertension.

Coreg Cr Dosage and Administration

Adult

Take with food in the AM. Swallow whole or may open capsules and sprinkle beads on a spoonful of applesauce and take immediately. ≥18yrs: initially 20mg once daily, may double dose every 1–2 weeks if tolerated and needed. Max daily dose of 80mg. Switching from immediate-release carvedilol: see literature. ≥65yrs: switching from highest dose of immediate-release carvedilol (25mg twice daily) to Coreg CR: initially Coreg CR 40mg; if tolerated for ≥2weeks, may increase to 80mg.

Children

<18yrs: not recommended.

Coreg Cr Contraindications

Contraindications

Coreg Cr Boxed Warnings

Not Applicable

Coreg Cr Warnings/Precautions

Warnings/Precautions

Peripheral vascular disease. Nonallergic bronchospasm. Diabetes (monitor blood glucose). Hyperthyroidism. Monitor renal function in ischemic heart disease, diffuse vascular disease, underlying renal insufficiency, and/or if systolic BP <100mmHg. Avoid abrupt cessation. Prinzmetal's angina. Pheochromocytoma. Elderly. Neonates. Pregnancy (monitor). Nursing mothers.

Warnings/Precautions

Cessation of Therapy

Avoid abrupt cessation in patients with coronary artery disease.
Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias may occur in patients with angina after abrupt cessation.
Discontinue Coreg CR over 1 to 2 weeks if possible, and monitor the patient closely when discontinuing Coreg CR and advise to limit physical activity to a minimum. Promptly reinstitute Coreg CR if angina worsens or acute coronary insufficiency develops during discontinuation.

Bradycardia

Bradycardia may occur. Reduce dose of Coreg CR if pulse rate drops <55 beats per minute.

Hypotension

Hypotension and postural hypotension may occur, along with syncope.
To reduce the risk for syncope or excessive hypotension, initiate patients on a low dose of Coreg CR with food and gradually up-titrate.
Avoid driving or handling hazardous tasks when initiating treatment due to a risk for syncope.

Heart Failure/Fluid Retention

During up-titration, the use of carvedilol may cause worsening heart failure or fluid retention. If these symptoms occur, increase diuretics and do not advance the dose of carvedilol until clinical stability resumes.
Occasionally it is necessary to lower the carvedilol dose or temporarily discontinue it.

Non-allergic Bronchospasm

Use caution in patients who do not respond to, or cannot tolerate, other antihypertensive agents. Advise to use the smallest effective dose.

Glycemic Control in Type 2 Diabetes

May mask some of the manifestations of hypoglycemia, particularly tachcardia. Nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. Patients subject to spontaneous hypoglycemia or diabetic patients receiving insulin or oral hypoglycemic agents should be cautioned about these possibilities.
Carvedilol may worsen hyperglycemia in patients with HF and diabetes.
Monitor blood glucose during initiation, dose adjustments, or discontinuing therapy.

Peripheral Vascular Disease

May precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Exercise caution.

Deterioration of Renal Function

In patients with heart failure, the use of carvedilol has rarely resulted in deterioration of renal function.
Risk factors include systolic BP <100mmHg, ischemic heart disease, and diffuse vascular disease, and/or underlying renal insufficiency. Monitor renal function during up-titration, discontinuation, or dose reduction in patients with these risk factors.

Major Surgery

Do not routinely withdraw chronically administered beta-blocker therapy prior to major surgery.
During major surgery, the use of beta-blockers may augment the risk of general anesthesia and surgical procedures due the hearts inability to respond to reflex adrenergic stimuli.

Thyrotoxicosis

May mask clinical signs of hyperthyroidism (eg, tachycardia). Abrupt withdrawal may lead to an exacerbation of hyperthyroidism or may precipitate thyroid storm.

Pheochromocytoma

In patients with pheochromocytoma, initiate an alpha-blocking agent prior to the use of any beta-blocking agent.
Use caution when administering carvedilol to patients suspected of having pheochromocytoma.

Prinzmetal's Variant Angina

Agents with non-selective β-blocking activity may provoke chest pain in patients with Prinzmetal's variant angina.
Use caution in patients suspected of having Prinzmetal's variant angina.

Risk of Anaphylactic Reaction

Patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge while taking beta-blockers.
These patients may be unresponsive to epinephrine used to treat allergic reaction.

Intraoperative Floppy Iris Syndrome (IFIS)

IFIS has been observed during cataract surgery in some patients treated with alpha-1 blockers.

Pregnancy Considerations

Risk Summary

Available data in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes.
There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy.
Use of beta blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depression in the neonate.

Clinical Considerations

Disease-Associated Maternal and/or Embryo-Fetal Risk: Pregnant women with hypertension should be carefully monitored and managed accordingly. Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Fetal/Neonatal Adverse Reactions: Neonates of women with hypertension who are treated with beta-blockers during the third trimester of pregnancy may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Observe newborns for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and manage accordingly.

Nursing Mother Considerations

Risk Summary

No data on the presence of carvedilol in human milk, the effects on the breastfed infant, or the effects on milk production.
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for Coreg CR and any potential adverse effects on the breastfed infant from Coreg CR or from the underlying maternal condition.

Pediatric Considerations

Efficacy of Coreg CR has not been established in patients younger than 18 years.

Coreg Cr Pharmacokinetics

Absorption

Rapidly and extensively absorbed. Absolute bioavailability: approximately 25–35%.

Distribution

>98% plasma protein bound.
Steady-state volume of distribution: approximately 115 L.
Plasma clearance ranges from 500-700 mL/min.

Metabolism

Hepatic (aromatic ring oxidation, glucuronidation).

Elimination

Fecal. Half-life: ~7–10hrs.

Coreg Cr Interactions

Interactions

Coreg Cr Adverse Reactions

Adverse Reactions

Bradycardia, orthostatic hypotension, dizziness, nasopharyngitis, GI upset, edema.

Coreg Cr Clinical Trials

Clinical Trials

Mild to Moderate Heart Failure (HF)

Carvedilol was evaluated in patients with mild to moderate HF in 5 multicenter, placebo-controlled trials, and in 1 active-controlled trial (COMET).
There were 4 US multicenter, double-blind, placebo-controlled trials which included 1094 patients with NYHA II-III HF and ejection fraction less than or equal to 0.35. Most of the patients were on digitalis, diuretics, and an ACE inhibitor at trial entry. There was an Australia-New Zealand double-blind, placebo-controlled trial which included 415 patients with less severe HF. All patients tolerated a 2-week course of carvedilol 6.25mg twice daily.
The primary endpoint was either progression of HF (1 US trial) or exercise tolerance (2 US trial and the Australia-New Zealand trial).
Slowing Progression of HF:

One US multicenter trial (366 subjects) had as its primary end point the sum of cardiovascular mortality, cardiovascular hospitalization, and sustained increase in heart failure medications. Heart failure progression was reduced, during an average follow‑up of 7 months, by 48% (P =.008).
In the Australia‑New Zealand trial, death and total hospitalizations were reduced by about 25% over 18 to 24 months.
In the 3 largest U.S. trials, death and total hospitalizations were reduced by 19%, 39%, and 49%, nominally statistically significant in the last 2 trials. The Australia‑New Zealand results were statistically borderline.

Functional Measures:

None of the multicenter trials had NYHA classification as a primary end point, but all such trials had it as a secondary end point. There was at least a trend toward improvement in NYHA class in a l trials.

Subjective Measures:

Health-related quality of life, as measured with a standard questionnaire (a primary end point in 1 trial), was unaffected by carvedilol. However, patients' and investigators' global assessments showed significant improvement in most trials.

Mortality:

Death was not a pre-specified end point in any trial but was analyzed in all trials. Overall, in these 4 US trials, mortality was reduced, nominally significantly so in 2 trials.

The COMET Trial

The COMET trial included 3029 subjects with NYHA class II-IV heart failure (left ventricular ejection fraction less than or equal to 35%) who were randomly assigned to receive either carvedilol (target dose: 25mg twice daily) or immediate-release metoprolol tartrate (target dose: 50mg twice daily). The mean age of the subjects was approximately 62 years, 80% were males, and the mean left ventricular ejection fraction at baseline was 26%. Approximately 96% of the subjects had NYHA class II or III HF.
The primary end points were all-cause mortality and the composite of death plus hospitalization for any reason.
All-cause mortality was 34% in the subjects treated with carvedilol and was 40% in the immediate-release metoprolol group (P =.0017; hazard ratio = 0.83, 95% CI, 0.74-0.93). The effect on mortality was primarily due to a reduction in cardiovascular death. The difference between the 2 groups with respect to the composite end point was not significant (P =.122). The estimated mean survival was 8.0 years with carvedilol and 6.6 years with immediate-release metoprolol.

Severe Heart Failure (COPERNICUS)

The COPERNICUS trial included 2289 patients with HF at rest or with minimal exertion and LVEF <25% (mean 20%), despite digitalis (66%), diuretics (99%) and ACE inhibitors (89%) who were randomly assigned to receive placebo or carvedilol.
Patients were up-titrated from a starting dose of 3.125mg twice daily to a maximum tolerated dose or up to 25mg twice daily over 6 weeks.
The primary end point was all-cause mortality, but cause-specific mortality and the risk of death or hospitalization (tota, CV or HF) were also examined.
The trial was stopped after a median follow‑up of 10 months because of an observed 35% reduction in mortality (from 19.7% per patient-year on placebo to 12.8% on carvedilol; hazard ratio 0.65, 95% CI: 0.52 to 0.81, P =.0014, adjusted).
The effect on mortality was principally the result of a reduction in the rate of sudden death among subjects without worsening heart failure.
Fewer subjects on carvedilol than on placebo were hospitalized for any reason (372 vs 432, P =.0029), for cardiovascular reasons (246 vs 314, P =.0003), or for worsening heart failure (198 vs 268, P =.0001).

Left Ventricular Dysfunction following Myocardial Infarction

The double-blind CAPICORN trial included 1959 patients with a recent MI (within 21 days) and LVEF of ≤40%, with (47%) or without symptoms of HF. Patients initially received carvedilol at 6.25mg twice daily then titrated as tolerated to 25mg twice daily. Subjects had to have a systolic blood pressure greater than 90 mm Hg, a sitting heart rate greater than 60 beats per minute, and no contraindication to β‑blocker use.
All‑cause mortality was 15% in the placebo group and 12% in the carvedilol group, indicating a 23% risk reduction in subjects treated with carvedilol (95% CI: 2% to 40%, P =.03).
There was also a significant 40% reduction in fatal or non-fatal myocardial infarction observed in the group treated with carvedilol (95% CI: 11% to 60%, P =.01). A similar reduction in the risk of myocardial infarction was also observed in a meta-analysis of placebo- controlled trials of carvedilol in heart failure.

Coreg Cr Note

Not Applicable

Coreg Cr Patient Counseling

See Literature

Coreg Cr

PAGE CONTENTS

Coreg Cr Generic Name & Formulations

Legal Class

General Description

Pharmacological Class

See Also

How Supplied

How Supplied

Storage

Manufacturer

Mechanism of Action

Coreg Cr Indications

Indications

Coreg Cr Dosage and Administration

Adult

Children

Coreg Cr Contraindications

Contraindications

Coreg Cr Boxed Warnings

Coreg Cr Warnings/Precautions

Warnings/Precautions

Warnings/Precautions

Pregnancy Considerations

Nursing Mother Considerations

Pediatric Considerations

Coreg Cr Pharmacokinetics

Absorption

Distribution

Metabolism

Elimination

Coreg Cr Interactions

Interactions

Coreg Cr Adverse Reactions

Adverse Reactions

Coreg Cr Clinical Trials

Clinical Trials

Coreg Cr Note

Coreg Cr Patient Counseling

Coreg Cr Generic Name & Formulations

Legal Class

General Description

Pharmacological Class

See Also

How Supplied

How Supplied

Storage

Manufacturer

Mechanism of Action

Coreg Cr Indications

Indications

Coreg Cr Dosage and Administration

Adult

Children

Coreg Cr Contraindications

Contraindications

Coreg Cr Boxed Warnings

Coreg Cr Warnings/Precautions

Warnings/Precautions

Warnings/Precautions

Pregnancy Considerations

Nursing Mother Considerations

Pediatric Considerations

Coreg Cr Pharmacokinetics

Absorption

Distribution

Metabolism

Elimination

Coreg Cr Interactions

Interactions

Coreg Cr Adverse Reactions

Adverse Reactions

Coreg Cr Clinical Trials

Clinical Trials

Coreg Cr Note

Coreg Cr Patient Counseling

Images