Valsartan versus lisinopril or extended-release metoprolol in preventing cardiovascular and renal events in patients with hypertension
The objective of this study was to compare cardiovascular and renal events in patients with hypertension receiving the angiotensin II-receptor blocker valsartan versus those receiving the angiotensin-converting-enzyme lisinopril or the beta-blocker metoprolol succinate in an extended-release formulation.
A retrospective study was conducted using a health insurance claims database spanning the period from January 1997 through December 2003 and representing approximately 40 million members enrolled in over 70 health plans across the United States. Study subjects included all persons in the database with two or more outpatient prescriptions for valsartan, lisinopril, or extended-release metoprolol and two or more prior claims with a diagnosis of hypertension. Those with a history of major cardiovascular or renal events (diagnosis of myocardial infarction, stroke, heart failure, ventricular arrhythmias, or cardiac arrest; coronary revascularization procedure; diagnosis of renal failure; or dialysis or kidney transplantation) or using other antihypertensive medications except diuretics during the 12 months before treatment with valsartan, lisinopril, or extended-release metoprolol were excluded. Risks of major cardiovascular or renal event during follow-up were analyzed using Cox proportional hazards regression.
A total of 29,357 antihypertensive patients were identified who initiated therapy with valsartan (n = 6,645), lisinopril (n = 17,320), or extended-release metoprolol (n = 5,392). In multivariate analyses, therapy with valsartan was associated with a significantly lower risk of a major cardiovascular or renal event versus extended-release metoprolol (heart rate [HR], 0.70; 95% confidence interval [CI], 0.56-0.87; p = 0.0015). Patients receiving valsartan had a nominally lower risk of a major cardiovascular or renal event than those receiving lisinopril, although this difference was not statistically significant (HR, 0.89; 95% CI, 0.74-1.07; p = 0.1987).
Results of this observational study suggest that the use of valsartan may reduce the risk of major cardiovascular and renal events compared with extended-release metoprolol.
Available from: Giorgio Gentile
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ABSTRACT: To compare the effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, stroke, cardiovascular mortality and total mortality.
We conducted a meta-analysis of randomized comparative trials between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. Inclusion criteria were publication in peer-reviewed journals indexed in Medline, randomized comparison of angiotensin II receptor blockers vs. angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers + angiotensin-converting enzyme inhibitors vs. angiotensin-converting enzyme inhibitors, report of major complications including myocardial infarction, stroke, cardiovascular mortality or all-cause mortality; average follow-up of at least 1 year in at least 200 patients.
Six trials fulfilled the inclusion criteria, for a total of 49 924 patients. In the pooled estimate, there were no significant differences between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction (odds ratio 1.01; 95% confidence interval 0.95-1.07; P = 0.75), cardiovascular mortality (odds ratio 1.03; 95% confidence interval 0.98-1.08; P = 0.23) and total mortality (odds ratio 1.03; 95% confidence interval 0.97-1.10; P = 0.20). This was the case also when the analysis involved only the comparison between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Overall, the risk of stroke was slightly lower with angiotensin II receptor blockers than angiotensin-converting enzyme inhibitors (odds ratio 0.92; 95% confidence interval 0.85-0.99; P = 0.037), the direct angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers comparison showing a nonsignificant trend in a similar direction. Statistical heterogeneity among trials was not significant, with a low to null inconsistency statistic, for stroke (P = 0.67), myocardial infarction (P = 0.86), cardiovascular mortality (P = 0.14) and total mortality (P = 0.12).
This overview suggests that angiotensin II receptor blockers are as effective as angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, cardiovascular mortality and total mortality. Angiotensin II receptor blockers may be slightly more protective than angiotensin-converting enzyme inhibitors on the risk of stroke.
Available from: Remy Coeytaux
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ABSTRACT: A 2007 systematic review compared angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in patients with hypertension. Direct renin inhibitors (DRIs) have since been introduced, and significant new research has been published. We sought to update and expand the 2007 review.
We searched MEDLINE and EMBASE (through December 2010) and selected other sources for relevant English-language trials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies that directly compared ACE inhibitors, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of follow-up; and reported at least one outcome of interest. Ninety-seven (97) studies (36 new since 2007) directly comparing ACE inhibitors versus ARBs and three studies directly comparing DRIs to ACE inhibitor inhibitors or ARBs were included.
A standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence.
In spite of substantial new evidence, none of the conclusions from the 2007 review changed. The level of evidence remains high for equivalence between ACE inhibitors and ARBs for blood pressure lowering and use as single antihypertensive agents, as well as for superiority of ARBs for short-term adverse events (primarily cough). However, the new evidence was insufficient on long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, and differences in key patient subgroups.
Included studies were limited by follow-up duration, protocol heterogeneity, and infrequent reporting on patient subgroups. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Evidence does not support a meaningful difference between ACE inhibitors and ARBs for any outcome except medication side effects. Few, if any, of the questions that were not answered in the 2007 report have been addressed by the 36 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly.
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