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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30

Nisoldipine coat-core is an extended-release once-daily formulation of a dihydropyridine calcium antagonist effective in the treatment of chronic stable angina pectoris. With immediate-release formulations of nisoldipine, plasma drug concentrations that produce therapeutic effects result rapidly, but are not sustained and do not maintain the effects throughout a 12-hour dosage interval. In contrast, with nisoldipine coat-core, a gradual increase in plasma nisoldipine concentrations occurs over 12 hours and therapeutic concentrations are then maintained for the duration of a 24-hour dosage interval. In dosages of 10 to 60 mg once daily, nisoldipine coat-core controls symptoms of angina and improves exercise-induced signs of ischaemia in patients with stable angina. Compared with placebo, daily nisoldipine coat-core doses of > or = 20 mg provide statistically significant increases in total exercise time and time to produce angina and a trend towards an increase in the time to produce 1 mm ST segment depression, in exercise tests conducted approximately 23 hours postdose. When administered in 20 and 40 mg daily doses, nisoldipine coat-core produces improvements in exercise test parameters that are similar to those seen with amlodipine 5 or 10 mg/day or regular-release or sustained-release (SR) diltiazem 240 mg/day. The frequency of daily angina attacks and consumption of short-acting nitrates are also reduced by nisoldipine to a similar extent to that observed with these other agents. After longer term (1 year) administration of 10 to 60 mg daily, improvements in exercise test parameters are maintained, with equivalent anti-ischaemic efficacy seen in patients receiving nisoldipine coat-core alone or with background nitrate or beta-blocker therapy. Adverse events associated with nisoldipine coat-core are typical of the dihydropyridine class of calcium antagonists, with peripheral oedema and headache being most common. Nisoldipine coat-core appears to be associated with fewer deaths than placebo, notably in the DEFIANT-II (Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy II) study, where only 1 death occurred with nisoldipine compared with 7 in the placebo group. Nisoldipine should not be taken during phenytoin therapy. In addition, grapefruit juice should be avoided during nisoldipine therapy and nisoldipine should not be taken concurrently with high-fat meals. Thus, the coat-core formulation of nisoldipine appears to have overcome the limitations of the shorter duration of action of immediate-release nisoldipine. Nisoldipine coat-core is well tolerated and once-daily administration produces a long duration of effective anti-ischaemic relief in patients with chronic stable angina pectoris.
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PMID:Nisoldipine coat-core. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of ischaemic heart disease. 912 71

Nisoldipine, a dihydropyridine calcium antagonist, has greater vascular selectivity than other calcium channel antagonists and does not depress the intact myocardium in vivo. It should be taken on an empty stomach. Both rapid-release and coat-core formulations are available for clinical use, but only the coat-core formulation extends antihypertensive, antiischemic, and antianginal effects throughout the dosing interval when given once daily. The coat-core formulation in daily doses of 10 to 40 mg does not cause the proischemic effects reported with the rapid-release formulation. When given as monotherapy, the coat-core formulation is highly effective in lowering blood pressure to a similar extent as other long-acting calcium channel blockers, diuretics, beta-blockers, or angiotensin-converting enzyme (ACE) inhibitors. The antihypertensive effects are potentiated when the coat-core formulation of nisoldipine is given in combination with lisinopril. In patients with stable angina pectoris nisoldipine coat-core increases exercise duration, reduces anginal frequency and myocardial ischemia, and is effective as monotherapy or in combination with a beta-blockers. In monotherapy the drug is as effective as other long-acting calcium channel blockers or a beta-blocker. The effects of nisoldipine coat-core in patients with heart failure are unclear at present.
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PMID:Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. 1172 Jun 35


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