Diovan Drug Information
Generic name: VALSARTAN
Angiotensin 2 Receptor Blocker [EPC]
Uses of Diovan
Hypertension Diovan ® is indicated for the treatment of hypertension, to lower blood pressure in adults and pediatric patients one year of age and older. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the class to which valsartan principally belongs.
There are no controlled trials in hypertensive patients demonstrating risk reduction with Diovan. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals.
For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease).
These considerations may guide selection of therapy. Diovan may be used alone or in combination with other antihypertensive agents.
Heart Failure Diovan is indicated to reduce the risk of hospitalization for heart failure in adult patients with heart failure (NYHA class II-IV). There is no evidence that Diovan provides added benefits when it is used with an adequate dose of an angiotensin converting enzyme (ACE) inhibitor.
Post-Myocardial Infarction
In clinically stable adult patients with left ventricular failure or left ventricular dysfunction following myocardial infarction, Diovan is indicated to reduce the risk of cardiovascular mortality.
Dosage & Administration of Diovan
Important Dosage and Preparation Information
Diovan tablets and oral suspension are not substitutable on a milligram-per-milligram basis. Do not combine two dosage forms to achieve the total dose. The systemic exposure to valsartan (AUC) is 60% higher with the suspension compared to tablets.
Use of the oral suspension is recommended: in pediatric patients aged 1 to 5 years in patients >5 years of age who cannot swallow tablets and in pediatric patients for whom the calculated dose (mg/kg) does not correspond to the available tablet strengths of Diovan. When switching between suspension and tablets, the dose of valsartan may need to be adjusted. Allow the suspension to stand for a minimum of 1 hour.
After the standing time, shake the suspension for a minimum of 1 additional minute. Add 80 mL of Ora-Sweet SF ® oral sweetening vehicle to the bottle and shake the suspension for at least 10 seconds to disperse the ingredients. The suspension is homogenous and can be stored for either up to 30 days at room temperature (below 30°C/86°F) or up to 75 days at refrigerated conditions (2°C to 8°C/35°F to 46°F) in the glass bottle with a child-resistant screw-cap closure.
Shake the bottle well (at least 10 seconds) prior to dispensing the suspension. Ora-Sweet SF ® and Ora-Plus ® are registered trademarks of Paddock Laboratories, Inc.
Adult Hypertension
The recommended starting dose of Diovan is 80 mg or 160 mg once daily when used as monotherapy in patients who are not volume-depleted. Patients requiring greater reductions may be started at the higher dose. Diovan may be used over a dose range of 80 mg to 320 mg daily, administered once a day.
The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks. If additional antihypertensive effect is required over the starting dose range, the dose may be increased to a maximum of 320 mg or a diuretic may be added. Addition of a diuretic has a greater effect than dose increases beyond 80 mg.
A higher starting dose of 2 mg/kg may be considered in selected cases when a greater reduction of blood pressure is needed. The dosage should be adjusted according to blood pressure response and tolerability, up to a maximum dose of 4 mg/kg once daily (maximum daily dose 160 mg). No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate < 30 mL/min/1.73 m 2.
Use of Diovan is not recommended in children less than 1 year of age.
Heart Failure
The recommended starting dose of Diovan is 40 mg twice daily. Uptitrate to 80 mg and 160 mg twice daily or to the highest dose tolerated by the patient. Consider reducing the dose of concomitant diuretics.
The maximum daily dose administered in clinical trials is 320 mg in divided doses.
Post-Myocardial Infarction Diovan may be initiated as early as 12 hours after a myocardial infarction. Patients may be uptitrated within 7 days to 40 mg twice daily, with subsequent titrations to a target maintenance dose of 160 mg twice daily, as tolerated by the patient. If symptomatic hypotension or renal dysfunction occurs, consider dosage reduction.
Diovan may be given with other standard post-myocardial infarction treatment, including thrombolytics, aspirin, beta-blockers, and statins.
Missed Dose If a dose of Diovan is missed, it should be administered as soon as possible, unless it is almost time for the next dose. The dose should not be doubled to make up for a missed dose.
| *As tolerated by patient | ||
| Indication | Starting Dose | Dose Range* |
| Hypertension Adults ( 2.2 ) | 80 mg to 160 mg once daily | 80 mg to 320 mg once daily |
| 1 to 16 years ( 2.3 ) | 1 mg/kg once daily Up to 40 mg daily | 1 mg/kg to 4 mg/kg once daily Up to 160 mg daily |
| Heart Failure ( 2.4 ) | 40 mg twice daily | 40 mg to 160 mg twice daily |
| Post-Myocardial Infarction ( 2.5 ) | 20 mg twice daily | 20 mg to 160 mg twice daily |
Side Effects of Diovan
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse reactions with Diovan was similar to placebo.
The overall frequency of adverse reactions was neither dose-related nor related to gender, age, race, or regimen. Discontinuation of therapy due to side effects was required in 2.3% of valsartan patients and 2.0% of placebo patients. The most common reasons for discontinuation of therapy with Diovan were headache and dizziness.
In trials in which valsartan was compared to an ACE inhibitor with or without placebo, the incidence of dry cough was significantly greater in the ACE-inhibitor group (7.9%) than in the groups who received valsartan (2.6%) or placebo (1.5%). In a 129-patient trial limited to patients who had had dry cough when they had previously received ACE inhibitors, the incidences of cough in patients who received valsartan, HCTZ, or lisinopril were 20%, 19%, and 69% respectively (p < 0.001). Dose-related orthostatic effects were seen in less than 1% of patients.
No relevant differences were identified between the adverse experience profile for pediatric patients and that previously reported for adult patients. Hyperkalemia was more frequently observed in pediatric patients aged 1 to 17 years with underlying chronic kidney disease (CKD). Cases of elevated ALT and/or AST have been reported in pediatric patients 1 to less than 6 years of age.
These events occurred in a study population which frequently had significant comorbidities; hence, a causal relationship to valsartan could not be established. The table shows adverse reactions in double-blind short-term heart failure trials, including the first 4 months of the Valsartan Heart Failure Trial, with an incidence of at least 2% that were more frequent in valsartan-treated patients than in placebo-treated patients. All patients received standard drug therapy for heart failure, frequently as multiple medications, which could include diuretics, digitalis, beta-blockers.
About 93% of patients received concomitant ACE inhibitors. of placebo patients for each of the following: elevations in creatinine and elevations in potassium. Other adverse reactions with an incidence greater than 1% and greater than placebo included headache, nausea, renal impairment, syncope, blurred vision, upper abdominal pain and vertigo. From the long-term data in the Valsartan Heart Failure Trial, there did not appear to be any significant adverse reactions not previously identified.
Post-Myocardial Infarction The table shows the percentage of patients discontinued in the valsartan and captopril-treated groups in the VALsartan In Acute myocardial iNfarcTion trial (VALIANT) with a rate of at least 0.5% in either of the treatment groups. Discontinuations due to renal dysfunction occurred in 1. Clinical Laboratory Test Findings Creatinine: In heart failure trials, greater than 50% increases in creatinine were observed in 3.9% of Diovan-treated patients compared to 0.9% of placebo-treated patients.
In post-myocardial infarction patients, doubling of serum creatinine was observed in 4.2% of valsartan-treated patients and 3.4% of captopril-treated patients. Neutropenia: Neutropenia was observed in 1.9% of patients treated with Diovan and 0.8% of patients treated with placebo. Blood Urea Nitrogen (BUN): In heart failure trials, greater than 50% increases in BUN were observed in 16.6% of Diovan-treated patients compared to 6.3% of placebo-treated patients.
Postmarketing Experience
The following additional adverse reactions have been reported in postmarketing use of Diovan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity: Angioedema has been reported.
Some of these patients previously experienced angioedema with other drugs, including ACE inhibitors. Diovan should not be re-administered to patients who have had angioedema. Digestive: Elevated liver enzymes and very rare reports of hepatitis Musculoskeletal: Rhabdomyolysis Renal: Impaired renal function, renal failure Dermatologic: Alopecia, bullous dermatitis Blood and Lymphatic: Thrombocytopenia Vascular: Vasculitis
| Valsartan (n = 3282) | Placebo (n = 2740) | |
|---|---|---|
| Dizziness | 17% | 9% |
| Hypotension | 7% | 2% |
| Diarrhea | 5% | 4% |
| Arthralgia | 3% | 2% |
| Fatigue | 3% | 2% |
| Back Pain | 3% | 2% |
| Dizziness, postural | 2% | 1% |
| Hyperkalemia | 2% | 1% |
| Hypotension, postural | 2% | 1% |
| Valsartan (n = 4885) | Captopril (n = 4879) | |
|---|---|---|
| Discontinuation for adverse reaction | 5.8% | 7.7% |
| Adverse reactions | ||
| Hypotension NOS | 1.4% | 0.8% |
| Cough | 0.6% | 2.5% |
| Blood creatinine increased | 0.6% | 0.4% |
| Rash NOS | 0.2% | 0.6% |
Warnings & Cautions for Diovan
Fetal Toxicity Diovan can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.
Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Diovan as soon as possible.
Hypotension
Excessive hypotension was rarely seen (0.1%) in patients with uncomplicated hypertension treated with Diovan alone. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of Diovan, or the treatment should start under close medical supervision.
Patients with heart failure or post-myocardial infarction patients given Diovan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients. In the VALsartan In Acute myocardial iNfarcTion trial (VALIANT), hypotension in post-myocardial infarction patients led to permanent discontinuation of therapy in 1.4% of valsartan-treated patients and 0.8% of captopril-treated patients.
If excessive hypotension occurs, place the patient in the supine position and, if necessary, give intravenous normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Impaired Renal Function Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on Diovan. Monitor renal function periodically in these patients.
Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Diovan.
Hyperkalemia
Some patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of Diovan may be required.
Drug Interactions with Diovan
Agents Increasing Serum Potassium
Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If co-medication is considered necessary, monitoring of serum potassium is advisable.
Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including valsartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving valsartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including valsartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.
Dual Blockade of the Renin-Angiotensin System (RAS)
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors.
Closely monitor blood pressure, renal function and electrolytes in patients on Diovan and other agents that affect the RAS. Do not coadminister aliskiren with Diovan in patients with diabetes. Avoid use of aliskiren with Diovan in patients with renal impairment (GFR < 60 mL/min).
Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use.
Pregnancy Safety for Diovan
Pregnancy Risk Summary Diovan can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
Published reports include cases of anhydramnios and oligohydramnios in pregnant women treated with valsartan (see Clinical Considerations). When pregnancy is detected, consider alternative drug treatment and discontinue Diovan as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage).
Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. In patients taking Diovan during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation.
Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to Diovan for hypotension, oliguria, and hyperkalemia.
In neonates with a history of in utero exposure to Diovan, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data No teratogenic effects were observed when valsartan was administered to pregnant mice and rats at oral doses of up to 600 mg/kg/day (9 and 18 times the maximum recommended human dose (MRHD) on a mg/m 2 basis) and to pregnant rabbits at oral doses of up to 10 mg/kg/day.
In rats, oral valsartan administered at maternally toxic doses (600 mg/kg/day) during organogenesis or late gestation and lactation, resulted in decreased fetal and pup weight, pup survival and delayed developmental milestones. In rabbits administered maternally toxic doses of 5 mg/kg/day and 10 mg/kg/day, fetotoxicity was observed.
Pediatric Use of Diovan
Pediatric Use The antihypertensive effects of Diovan have been evaluated in 5 clinical studies in pediatric patients from 1-16 years of age. The pharmacokinetics of Diovan have been evaluated in pediatric patients 1 to 16 years of age. The adverse experience profile of Diovan was similar to that described for adults.
In children and adolescents with hypertension where underlying renal abnormalities may be more common, renal function and serum potassium should be closely monitored as clinically indicated. Use of Diovan is not recommended in children less than 1 year of age. It is not known whether post-natal use of valsartan, before maturation of renal function is complete, has a long-term deleterious effect on the kidney.
No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate less than 30 mL/min/1.73 m 2.
Contraindications for Diovan
Do not use in patients with known hypersensitivity to any component. Do not coadminister aliskiren with Diovan in patients with diabetes. Known hypersensitivity to any component.
Overdosage Information for Diovan
Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse and shock have been reported.
If symptomatic hypotension should occur, institute supportive treatment. Diovan (valsartan) is not removed from the plasma by hemodialysis. Valsartan was without grossly observable adverse effects at single oral doses up to 2000 mg/kg in rats and up to 1000 mg/kg in marmosets, except for salivation and diarrhea in the rat and vomiting in the marmoset at the highest dose (60 and 31 times, respectively, the MRHD dose on a mg/m 2 basis) (Calculations assume an oral dose of 320 mg/day and a 60-kg patient).
Clinical Studies of Diovan
Heart Failure The Valsartan Heart Failure Trial (Val-HeFT) was a multinational, double-blind study in which 5010 patients with NYHA class II (62%) to IV (2%) heart failure and LVEF less than 40%, on baseline therapy chosen by their physicians, were randomized to placebo or valsartan (titrated from 40 mg twice daily to the highest tolerated dose or 160 mg twice daily) and followed for a mean of about 2 years. Although Val-HeFT’s primary goal was to examine the effect of valsartan when added to an ACE inhibitor, about 7% were not receiving an ACE inhibitor. Other background therapy included diuretics (86%), digoxin (67%), and beta-blockers (36%).
At the end of the trial, patients in the valsartan group had a blood pressure that was 4 mmHg systolic and 2 mmHg diastolic lower than the placebo group. There were two primary end points, both assessed as time to first event: all-cause mortality and heart failure morbidity, the latter defined as all-cause mortality, sudden death with resuscitation, hospitalization for heart failure, and the need for intravenous inotropic or vasodilatory drugs for at least 4 hours. These results are summarized in the following table.
Although the overall morbidity result favored valsartan, this result was largely driven by the 7% of patients not receiving an ACE inhibitor, as shown in the following table. The modest favorable trend in the group receiving an ACE inhibitor was largely driven by the patients receiving less than the recommended dose of ACE inhibitor. Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor.
Secondary end points in the subgroup not receiving ACE inhibitors were as follows. 0.42 In patients not receiving an ACE inhibitor, valsartan-treated patients had an increase in ejection fraction and reduction in left ventricular internal diastolic diameter (LVIDD). Effects were generally consistent across subgroups defined by age and gender for the population of patients not receiving an ACE inhibitor. The number of black patients was small and does not permit a meaningful assessment in this subset of patients.
Post-Myocardial Infarction The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) was a randomized, controlled, multinational, double-blind study in 14703 patients with acute myocardial infarction and either heart failure (signs, symptoms or radiological evidence) or left ventricular systolic dysfunction (ejection fraction ≤ 40% by radionuclide ventriculography or ≤ 35% by echocardiography or ventricular contrast angiography). Patients were randomized within 12 hours to 10 days after the onset of myocardial infarction symptoms to one of three treatment groups: valsartan (titrated from 20 mg or 40 mg twice daily to the highest tolerated dose up to a maximum of 160 mg twice daily), the ACE inhibitor, captopril (titrated from 6.25 mg three times daily to the highest tolerated dose up to a maximum of 50 mg three times daily), or the combination of valsartan plus captopril. In the combination group, the dose of valsartan was titrated from 20 mg twice daily to the highest tolerated dose up to a maximum of 80 mg twice daily; the dose of captopril was the same as for monotherapy.
The mean treatment duration was 2 years. The mean daily dose of Diovan in the monotherapy group was 217 mg. The primary endpoint was time to all-cause mortality.
Secondary endpoints included time to cardiovascular (CV) mortality, and time to the first event of cardiovascular mortality, reinfarction, or hospitalization for heart failure. The results are summarized in the following table. 0.955 There was no difference in overall mortality among the three treatment groups. There was thus no evidence that combining the ACE inhibitor captopril and the angiotensin II blocker valsartan was of value.
The data were assessed to see whether the effectiveness of valsartan could be demonstrated by showing in a non-inferiority analysis that it preserved a fraction of the effect of captopril, a drug with a demonstrated survival effect in this setting. A conservative estimate of the effect of captopril (based on a pooled analysis of 3 post-infarction studies of captopril and 2 other ACE inhibitors) was a 14% to 16% reduction in mortality compared to placebo. Valsartan would be considered effective if it preserved a meaningful fraction of that effect and unequivocally preserved some of that effect.
As shown in the table, the upper bound of the CI for the hazard ratio (valsartan/captopril) for overall or CV mortality is 1.09 to 1.11, a difference of about 9% to 11%, thus making it unlikely that valsartan has less than about half of the estimated effect of captopril and clearly demonstrating an effect of valsartan. The other secondary endpoints were consistent with this conclusion. Effects on Mortality Amongst Subgroups in VALIANT There were no clear differences in all-cause mortality based on age, gender, race, or baseline therapies, as shown in the figure above.
| Placebo | Valsartan | Hazard Ratio | Nominal | |
|---|---|---|---|---|
| (N = 2499) | (N = 2511) | (95% CI*) | p-value | |
| All-cause mortality | 484 | 495 | 1.02 | 0.8 |
| (19.4%) | (19.7%) | (0.90-1.15) | ||
| HF morbidity | 801 | 723 | 0.87 | 0.009 |
| (32.1%) | (28.8%) | (0.79-0.97) | ||
| CI = Confidence Interval | ||||
| Without ACE Inhibitor | With ACE Inhibitor | |||
|---|---|---|---|---|
| Placebo | Valsartan | Placebo | Valsartan | |
| (N = 181) | (N = 185) | (N = 2318) | (N = 2326) | |
| Events (%) | 77 (42.5%) | 46 (24.9%) | 724 (31.2%) | 677 (29.1%) |
| Hazard ratio (95% CI) | 0.51 (0.35, 0.73) | 0.92 (0.82, 1.02) | ||
| p-value | 0.0002 | 0.0965 | ||
| Placebo | Valsartan | Hazard Ratio | |
|---|---|---|---|
| (N = 181) | (N = 185) | (95% CI) | |
| Components of HF morbidity | |||
| All-cause mortality | 49 (27.1%) | 32 (17.3%) | 0.59 (0.37, 0.91) |
| Sudden death with resuscitation | 2 (1.1%) | 1 (0.5%) | 0.47 (0.04, 5.20) |
| CHF therapy | 1 (0.6%) | 0 (0.0%) | – |
| CHF hospitalization | 48 (26.5%) | 24 (13.0%) | 0.43 (0.27, 0.71) |
| Cardiovascular mortality | 40 (22.1%) | 29 (15.7%) | 0.65 (0.40, 1.05) |
| Non-fatal morbidity | 49 (27.1%) | 24 (13.0%) | 0.42 (0.26, 0.69) |
| Valsartan vs. Captopril (N = 4909) (N = 4909) | Valsartan + Captopril vs. Captopril (N = 4885) (N = 4909) | |||||
|---|---|---|---|---|---|---|
| No. of Deaths Valsartan/Captopril | Hazard Ratio CI | p-value | No. of Deaths Comb/Captopril | Hazard Ratio CI | p-value | |
| All-cause mortality | 979 (19.9%) /958 (19.5%) | 1.001 (0.902, 1.111) | 0.98 | 941 (19.3%) /958 (19.5%) | 0.984 (0.886, 1.093) | 0.73 |
| CV mortality | 827 (16.8%) /830 (16.9%) | 0.976 (0.875, 1.090) | ||||
| CV mortality, hospitalization for HF, and recurrent non-fatal MI | 1529 (31.1%) /1567 (31.9%) | 0.955 (0.881, 1.035) | ||||
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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