Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis.

AIMS: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) prevent the progression of diabetic nephropathy (DN). Studies suggest that combination renin-angiotensin-aldosterone system (RAAS)-inhibiting therapy provides additive benefit in DN. However, these studies are small in size. We performed a meta-analysis of studies investigating combination therapy for DN. METHODS: Studies were identified through a search of medline, embase, cinahl and the Cochrane Database. All trials involving combined ACEI and ARB for slowing progression of DN were included. The primary end point was 24-h urinary protein excretion. Blood pressure, serum potassium and glomerular filtration rate (GFR) were secondary end points. RESULTS: In the 10 included trials, 156 patients received ACEI + ARB and 159 received ACEI only. Most studies were 8-12 weeks in duration. Proteinuria was reduced with ACEI + ARB (P = 0.01). This was associated with significant statistical heterogeneity (P = 0.005). ACEI + ARB was associated with a reduction in GFR [3.87 ml/min (7.32-0.42); P = 0.03] and a trend towards an increase in serum creatinine (6.86 micromol/l 95% CI -0.76-13.73; P = 0.09). Potassium was increased by 0.2 (0.08-0.32) mmol/l (P < 0.01) with ACEI + ARB. Systolic and diastolic blood pressure were reduced by 5.2 (2.1-8.4) mmHg (P < 0.01) and 5.3 (2.2-8.4) mmHg (P < 0.01), respectively. CONCLUSIONS: This meta-analysis suggests that ACEI + ARB reduces 24-h proteinuria to a greater extent than ACEI alone. This benefit is associated with small effects on GFR, serum creatinine, potassium and blood pressure. These results should be interpreted cautiously as most of the included studies were of short duration and the few long-term studies (12 months) have not demonstrated benefit.

Calcium-channel antagonists and nitrates in coronary artery bypass patients receiving radial artery grafts.

OBJECTIVE: To review the literature assessing the role of vasodilators for the prevention of vasospasm leading to graft failure in patients receiving the radial artery (RA) as a conduit in coronary artery bypass grafting (CABG). DATA SOURCE: A MEDLINE search (January 1966-May 2000) was performed using calcium-channel antagonists, nitrates, radial artery, and coronary artery bypass as key words. English-language articles were identified, and the references of these articles were used to further identify pertinent articles. DATA SYNTHESIS: RAs can be used as conduits in CABG. It has been suggested that failure of these grafts may be due to vasospasm, leading to occlusion observed angiographically. Calcium-channel antagonists and nitrates have been proposed as a means of preventing vasospasm and subsequent graft failure. CONCLUSIONS: Currently published data on the use of calcium-channel antagonist or nitrate therapy as prophylaxis against vasospasm in patients receiving RA grafts are inconclusive. Systematic evaluations of currently available pharmacologic agents are needed to guide clinical practice in this area.

Dofetilide: a class III-specific antiarrhythmic agent.

OBJECTIVE: To review published reports on the pharmacology and clinical use of dofetilide in the management of cardiac dysrhythmias. DATA SOURCES: A MEDLINE search (January 1966-June 1999) was performed using dofetilide and UK-68,798 as key words. English-language articles were identified, and the references of these articles were used to further identify pertinent articles. STUDY SELECTION: All acquired studies and reviews discussing the pharmacology, pharmacokinetics, chemistry, and clinical efficacy of dofetilide were reviewed. DATA EXTRACTION: Articles were selected based on quality of review of the pharmacology and clinical use of dofetilide. Given the paucity of data on the clinical pharmacology and use of dofetilide, most articles obtained were used, including abstracts when full reports were not available. DATA SYNTHESIS: Dofetilide is a relatively specific class III antiarrhythmic agent. It increases action potential duration and effective refractory period without impacting conduction velocity. These actions of dofetilide are explained by its ability to inhibit the rapid component of the delayed, outward-rectifying potassium current, thus blocking the efflux of potassium during repolarization. Introductory investigations suggest that dofetilide may be of use in treating and preventing atrial dysrhythmias such as atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Dofetilide may also have a role in preventing ventricular tachycardia from occurring. Some data also suggest that dofetilide may improve the morbidity of heart failure patients. Currently, the most troublesome adverse effect of dofetilide is its propensity to induce ventricular proarrhythmias, especially torsade de pointes. CONCLUSIONS: Based on the data currently available, dofetilide should have a role in the pharmacotherapy of cardiac dysrhythmias, especially those of atrial origin. More data on its efficacy and tolerability are needed, however, to fully delineate dofetilide's role amid currently available antiarrhythmic agents.