1.
Renoprotective effect of diltiazem in hypertensive type 2 diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment.
Pérez-Maraver, M, Carrera, MJ, Micaló, T, Sahun, M, Vinzia, C, Soler, J, Montanya, E
Diabetes research and clinical practice. 2005;(1):13-9
Abstract
The aim of the study was to evaluate the effects of the non-dihydropyridine calcium antagonist (NDCA) diltiazem on the development of urinary albumin excretion (UAE) in type 2 hypertensive diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment. Thirty-six type 2 diabetic hypertensive patients with microalbuminuria persisting after at least 1 year of treatment with ACE inhibitors were randomized to receive captopril (n=22) or combined therapy with captopril and 120 mg diltiazem (n=14) for 2 years. Captopril dose was individualized according to blood pressure. Changes in UAE, blood pressure, and metabolic control were monitored to analyze the influence of the addition of diltiazem on progression of diabetic nephropathy. In patients treated with captopril and diltiazem, absolute UAE did not change during the study (baseline: 101 mg/24 h, range 39-298; 2 years after randomization: 74 mg/24 h, range 12-665). In contrast, UAE increased in patients treated with captopril monotherapy (baseline: 118 mg/24 h, range 32-282; 2 years after randomization: 164 mg/24 h, range 15-1161, p<0.05). In addition, fewer patients in the captopril/diltiazem group progressed to macroalbuminuria (eight patients in captopril group and one in captopril/diltiazem group, p<0.05). The beneficial effects of the addition of diltiazem were independent of blood pressure and metabolic control. We suggest that the combination of ACE inhibitors and NDCA should be considered in type 2 microalbuminuric patients at high risk for progression to established diabetic nephropathy.
2.
Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial.
Chaitman, BR, Pepine, CJ, Parker, JO, Skopal, J, Chumakova, G, Kuch, J, Wang, W, Skettino, SL, Wolff, AA, ,
JAMA. 2004;(3):309-16
Abstract
CONTEXT Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications. In a previous trial, antianginal monotherapy with ranolazine, a drug believed to partially inhibit fatty acid oxidation, increased treadmill exercise performance; however, its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina. OBJECTIVES To determine whether, at trough levels, ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of atenolol, amlodipine, or diltiazem and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia, effect on angina attacks and nitroglycerin use, and effect on long-term survival in an open-label observational study extension. DESIGN, SETTING, AND PATIENTS A randomized, 3-group parallel, double-blind, placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were randomly assigned to receive placebo or 1 of 2 doses of ranolazine. Patients treated at the 118 participating ambulatory outpatient settings in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial from July 1999 to August 2001 and followed up through October 31, 2002. INTERVENTION Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine. Treadmill exercise 12 hours (trough) and 4 hours (peak) after dosing was assessed after 2, 6 (trough only), and 12 weeks of treatment. MAIN OUTCOME MEASURES Change in exercise duration, time to onset of angina, time to onset of ischemia, nitroglycerin use, and number of angina attacks. RESULTS Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups (pooled) vs 91.7 seconds in the placebo group (P =.01). The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups, at peak more than at trough. The increases did not depend on changes in blood pressure, heart rate, or background antianginal therapy and persisted throughout 12 weeks. Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo (P<.02). Survival of 750 patients taking ranolazine during the CARISA trial or its associated long-term open-label study was 98.4% in the first year and 95.9% in the second year. CONCLUSION Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking standard doses of atenolol, amlodipine, or diltiazem, without evident adverse, long-term survival consequences over 1 to 2 years of therapy.
3.
Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial.
Lee, DS, Goodman, S, Dean, DM, Lenis, J, Ma, P, Gervais, PB, Langer, A, ,
American heart journal. 2002;(1):60-7
Abstract
BACKGROUND Mibefradil is a T-type calcium-channel antagonist and arterial vasodilator with negative chronotropic effects. It is not known if T-type calcium-channel blockade is superior to L-type calcium-channel blockade in patients with stable angina pectoris. METHODS A multicenter, randomized, double-blind trial was conducted in patients with documented coronary disease and stable angina to compare a 360 mg dose of diltiazem CD with 100 mg dose of mibefradil. The primary end point was change in time to symptom-limited exercise termination from baseline to 8 weeks. Secondary efficacy parameters included time to onset of persistent ST-segment depression, time to awareness of angina, and change in exercise duration from baseline to 2 and 4 weeks of treatment. RESULTS A total of 121 patients were randomized to mibefradil and 113 to diltiazem CD. At 8 weeks, the increase in exercise duration was 24.5 seconds greater in the mibefradil group (P =.017; 95% CI 4.4-44.7 seconds). At 8 weeks, time to development of > or =1 mm ST-segment depression was greater by 45.3 seconds (P =.0025; 95% CI 16.2-74.5) with mibefradil, but time to development of angina was not significantly different. CONCLUSION T-type calcium-channel antagonism with mibefradil improved treadmill exercise parameters compared with diltiazem in patients with chronic stable angina. Further investigation and development of antagonists of T-type calcium channels with fewer adverse drug interactions is warranted and may be promising in the management of ischemic heart disease.