No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified. Limitations: Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing. Conclusion: Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.

/pdf/systematic-review-comparative-effectiveness-of-angiotensin-1eesn1f56t.pdf

Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension.

Uric acid (UA) is the final product of purine catabolism in man, and it is excreted mainly by the kidneys when renal function is not impaired. Consequently, serum (S) UA increases as a function of purine intake, and it varies inversely to uricosuria. The latter variable diminishes in response to low-sodium intakes and vice versa. Insofar as the diet is not usually controlled in studies in which the response of SUA to drugs is evaluated, most reports are to be considered cautiously. Common diuretics elevate SUA in healthy subjects, hypertensives and patients with heart failure, apparently by elevating net UA reabsorption in the nephronal proximal tubule. This drug action, which becomes noticeable shortly after the institution of treatment and remains throughout it, starts at low doses (e.g., 12.5 mg hydrochlorothiazide or 1.25 mg bendrofluazide once daily in subjects with uncomplicated hypertension) and increases in dose-dependent fashion. Beta-blockers tend to elevate SUA. The angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril and ramipril have been found to increase uricosuria mildly, likely by lowering the net reabsorption of UA in the proximal tubule. These three drugs and lisinopril can blunt the rise in SUA provoked by diuretics in hypertensives if used at sufficiently high doses relative to the dose of the diuretic. The angiotensin II antagonist losartan augments uricosuria mildly and thereby decreases SUA. The cardiovascular implications of the response of SUA to drugs remain speculative. Uric acid can scavenge various reactive oxygen species and thus reduce oxidative stress, which seems to contribute to the development and/or progress of various cardiovascular conditions, including hypertension, atherosclerosis and heart failure. Consequently, it may be theorised that the elevations in SUA induced by diuretics might contribute to the established favourable action of these agents on cardiovascular prognosis. Conversely, diuretic-induced increases in SUA are to be considered detrimental according to an old hypothesis that maintains that SUA is a cardiovascular risk factor; this construct is largely based upon the results of selected epidemiological undertakings. The cardiovascular implications of the effects of drugs on SUA, if any, should be elucidated through purposive research.

Cardiovascular Drugs and Serum Uric Acid

Hypertension is a major health problem worldwide, yet remains under-diagnosed and under-treated. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) are highly effective at reducing blood pressure (BP), exhibit renoprotective properties and have placebo-like tolerability. However, it is unclear whether there are clinical differences in efficacy and tolerability between the available ARBs. A review of published, randomized, comparative clinical trials suggests that differences in BP-lowering efficacy and 24-hour BP control may exist between ARBs, although it appears that there is no evidence for important differences in tolerability between ARBs. Few studies have assessed attainment rates for important combined systolic BP (SBP)/diastolic BP (DBP) goals recommended in treatment guidelines. Likewise, few studies have directly compared more than two agents or ARB/hydrochlorothiazide fixed-dose combinations, and most ARBs have not been compared across their full recommended dosage ranges. Overall, there is insufficient weight of evidence to allow definitive conclusions to be drawn regarding the comparative efficacy of the available ARBs. However, newer ARBs (e.g. olmesartan medoxomil and telmisartan) appear to be more effective than older ARBs (e.g. losartan and valsartan) in reducing DBP and/or SBP in some trials. In addition, olmesartan medoxomil treatment regimens resulted in high BP control rates in several trials, but head-to-head trials with other ARBs are required to put these control rates into perspective, especially for SBP control with various agents. The purpose of this review is to present published data from ARB efficacy trials for a comparison of various efficacy parameters among the agents within this drug class.

Comparison of Angiotensin II Type 1 Receptor Antagonists in the Treatment of Essential Hypertension

OBJECTIVES
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.

Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information

Objectives A 2007 comparative effectiveness review (CER) evaluated the long-term benefits and harms of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin II receptor blockers/antagonists (ARBs) for treating essential hypertension in adults. Since then, significant additional research has been published comparing these agents, and direct renin inhibitors (DRIs) have been introduced to the market. We sought to update 2007 CER on ACEIs versus ARBs and expand this to include comparisons with DRIs. Data Sources We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, a list of systematic reviews underway in the Cochrane Hypertension Review Group, and selected gray literature sources. Review Methods We included studies that directly compared ACEIs, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of followup; and reported at least one outcome of interest. Two investigators reviewed each article, and a standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence. When appropriate, quantitative meta-analysis was performed. Results We included 97 studies (36 new since 2007) directly comparing ACEIs versus ARBs and 3 studies directly comparing DRIs to ACEIs or ARBs. The strength of evidence remains high for equivalence between ACEIs and ARBs for blood pressure lowering and use of a single antihypertensive agent, and for superiority of ARBs over ACEIs for short-term adverse events (primarily due to cough). The new evidence did not strengthen our conclusions regarding long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, or differences in key patient subgroups: the strength of evidence for these outcomes remained low to moderate. For DRIs, we were not able to reach definitive conclusions for any of the outcomes of interest. Few studies involved a representative sample treated in a typical clinical setting over a long duration; treatment protocols had marked heterogeneity; and significant amounts of data about important outcomes and patient subgroups were missing. Conclusion Evidence does not support a meaningful difference between ACEIs and ARBs for any outcome except short-term adverse events. Few, if any, of the questions that were not answered in the 2007 CER have been addressed by the 39 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly.

Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update

The efficacy and tolerability of losartan 100 mg/hydrochlorothiazide (HCTZ) 25 mg and enalapril 10 mg/HCTZ 25 mg were compared in a double-blind, randomized trial in hypertensive patients inadequately controlled and experiencing side effects on prior therapy. Patients with moderate or severe hypertension, currently treated with at least two single-agent drugs (excluding angiotensin-converting enzyme inhibitors), with a sitting diastolic blood pressure (DBP) above 90 mm Hg, and at least one undesirable drug-related symptom were randomized to once-daily treatment with one of the combinations for 12 weeks. Losartan/HCTZ lowered sitting DBP from the prior therapy baseline by 13.7 mm Hg and sitting systolic blood pressure 19.3 mm Hg; similar reductions occurred with enalapril/HCTZ. Trough sitting DBP was reduced to normal levels (< 90 mm Hg) in 63% of patients switched to the losartan combination and in 58% of those treated with the enalapril combination. Each combination was associated with improved tolerability compared with prior therapy, although fewer patients reported each of 24 undesirable symptoms after 12 weeks of losartan/HCTZ. The improvement from prior therapy in the occurrence of cough was significantly greater with losartan/HCTZ (P = .005). Enalapril/HCTZ, but not losartan/HCTZ, increased serum uric acid levels at week 12. In conclusion, the combination of losartan 100 mg/HCTZ 25 mg offers a beneficial therapeutic option for patients with a history of moderate to severe hypertension whose blood pressure is not adequately controlled or who exhibit side effects while on two or more single-agent antihypertensive drugs. In this population, the switch from prior antihypertensive therapies to once daily losartan 100 mg/HCTZ 25 mg improves blood pressure control and reduces side effects.

Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies.

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Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies.