Calcium Antagonists In Patients Research Articles

Feasibility evaluation of long-term use of beta-blockers and calcium antagonists in patients with Brugada syndrome.

Beta-blockers (BBs) and calcium antagonists (CAs) are reported to aggravate ST-segment elevation in some patients with Brugada syndrome (BrS). The feasibility of their long-term use in BrS still remains unknown. We investigated the safety of long-term use of BB and CA in BrS patients. Of the 360 consecutive BrS patients, 29 [5: a history of ventricular fibrillation (VF), 17: syncope, 7: asymptomatic] took BB and/or CA (BB: 22, CA: 8) for more than 1 year for the treatment of co-morbidities such as atrial tachyarrhythmia, vasospastic angina, and neurally mediated syncope. The electrocardiographic changes and clinical outcome after the treatment were evaluated. Eleven patients showed type 1 electrocardiogram (ECG) at baseline. BBs and CAs were used within normal dosage range in all patients. After starting a BB and/or CA, type 1 ECG was still observed in 9 patients. There were no significant differences in the ECG parameters such as the amplitude of J-point, QRS duration, and corrected QT intervals before and after starting BB and/or CA. During follow-up of 89 ± 65 months after initiation of the drugs, 1 patient experienced a VF recurrence without significant changes of ECG parameters 2 years after BB therapy was started. Long-term intake of BB or CA within normal dosage range was not associated with the aggravation of ECG parameters and clinical outcome in patients with BrS. The use of BBs and CAs is acceptable under careful observation.

Indicators of central pressure and rigidity during the long-term therapy of calcium antagonists in patients with metabolic syndrome and hypertension

Indicators of central pressure and rigidity during the long-term therapy of calcium antagonists in patients with metabolic syndrome and hypertension

Calcium antagonists for acute ischemic stroke

The sudden loss of blood supply in ischemic stroke is associated with the increase of calcium ions within neurons. Inhibiting this increase could protect neurons and hence might reduce neurological impairment, disability and handicap after stroke. To determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. To investigate the influence of different drugs, dosages, routes of administration, time intervals after stroke and trial design on the risk of a primary outcome. We searched the Cochrane Stroke Group Trials Register (January 2012), MEDLINE (1950 to December 2011), EMBASE (1980 to December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011 issue 4) and four Chinese databases (December 2011): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese scientific periodical database of VIP information and Wanfang Data. We also contacted trialists and researchers. All truly randomized trials comparing a calcium antagonist with control in patients with acute ischemic stroke. Two authors assessed all trials and extracted the data. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. Analyses were, if possible, intention-to-treat. We included 34 trials including 7731 patients. There was no effect of calcium antagonists on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13), or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17). Comparisons of different doses of nimodipine suggested that the highest doses were associated with poorer outcome. No evidence is available using calcium antagonists in patients with acute ischemic stroke is effective.

Long-Acting Calcium Antagonists in Patients with Coronary Artery Disease: A Meta-Analysis

Background The use of calcium channel blockers (CCBs) in patients with coronary artery disease remains controversial, with reports of increased risk of myocardial infarction and all-cause mortality. Short-acting CCBs have an unfavorable hemodynamic profile. The role of long-acting CCBs in patients with coronary artery disease is unknown. Methods MEDLINE/CENTRAL/EMBASE database were searched from 1966 to August 2008 for randomized controlled trials of long-acting CCBs in patients with coronary artery disease with follow-up for at least 1 year. We extracted from the studies the baseline characteristics and 6 outcomes: all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, angina pectoris, and heart failure. Results Of the 100 randomized controlled trials of CCBs in patients with coronary artery disease, 15 studies evaluating 47,694 patients fulfilled our inclusion criteria. When compared with the comparison group (including placebo), CCBs were not associated with an increased risk of all-cause mortality (relative risk [RR] 0.99; 95% confidence interval [CI], 0.94-1.05), cardiovascular mortality (RR 1.03; 95% CI, 0.95-1.11), nonfatal myocardial infarction (RR 0.96; 95% CI, 0.87-1.06), or heart failure (RR 0.86; 95% CI, 0.71-1.05), and with a 21% reduction in the risk of stroke (95% CI, 0.70-0.89) and 18% reduction in the risk of angina pectoris (95% CI, 0.72-0.94). When compared with placebo, CCBs resulted in a 28% reduction in the risk of heart failure (95% CI, 0.73-0.92). The results were similar for both dihydropyridines and nondihydropyridine CCBs. Conclusions In patients with coronary artery disease, long-acting CCBs (either dihydropyridines or nondihydropyridines), were associated with a reduction in the risk of stroke, angina pectoris, and heart failure, with similar outcomes for other cardiovascular events as the comparison group.

The role of calcium antagonists in patients with chronic renal failure

The objective of antihypertensive treatment in patients with chronic renal failure, many of whom have elevated blood pressure levels, is to reduce cardiovascular events and to slow down the progression of kidney function impairment. Calcium antagonists have been shown to be effective and safe antihypertensive drugs in patients from different age groups, including children. On the basis of numerous studies, one may conclude that the main benefit of antihypertensive therapy is because of the blood pressure lowering effect per se and that calcium antagonists do not differ from other antihypertensive drugs in the ability to prevent cardiovascular complications of hypertension. In particular, calcium antagonists are not inferior to other groups of antihypertensive agents in the prevention of coronary artery disease. There is, however, now evidence from controlled clinical trials that drugs interfering with the renin-angiotensin system are more beneficial than other antihypertensive agents in patients with chronic renal failure. Thus, several studies have demonstrated that ACE-inhibitors and, in patients with type-2 diabetic nephropathy, AT 1-antagonists are superior to other classes of antihypertensive drugs, including calcium antagonists, in delaying the progression of renal insufficiency. Therefore, in hypertensive patients with chronic renal failure antihypertensive treatment should be initiated with a drug that inhibits the renin-angiotensin system.

Myocardial Metabolism: A new target for the treatment of heart disease?

Introduction: Ranolazine, a drug believed to partially inhibit the oxidation of long-chain fatty acids, has previously been shown to increase treadmill exercise performance in patients with ischemic heart disease. The drug’s long-term efficacy and safety have not been studied in a more realistic setting—that is, in combination with β-blockers or calcium antagonists in patients with chronic, severe angina.

Calcium antagonists in patients with type 2 diabetes and hypertension.

Hypertension is twice as common in patients with diabetes compared to those without diabetes. It accounts for up to 75% of cardiovascular disease risk leading to the substantial increase in morbidity and mortality. Control of blood pressure in people with diabetes has been shown in randomized controlled trials to decrease cardiovascular risk and improve outcome especially in preventing stroke. A target blood pressure goal of <130/80 mm Hg is currently recommended for patients with diabetes. However, less than 1/3 of these patients achieve such a goal. This is in part due to the inherent difficulty in controlling blood pressure in these patients where hypertension is usually associated with increased salt sensitivity, volume expansion and isolated systolic hypertension. Therefore, patients with diabetes usually require multiple medications for optimal blood pressure control. Calcium channel antagonists have been shown in large clinical trials to be both safe and effective in controlling blood pressure in diabetic patients and will continue to play a major role in the management of hypertension in this population, particularly in the combination therapy that these patients usually require.

Nifedipine upregulates manganese superoxide dismutase expression in vascular smooth muscle cells via endothelial cell-dependent pathways.

Calcium antagonists normalize endothelial dysfunction and improve the clinical outcome in patients with hypertension. However, the mechanism underlying these beneficial effects remains to be elucidated. Here, we show that the calcium antagonist nifedipine upregulates the expression of manganese superoxide dismutase (Mn SOD), an endogenous antioxidant enzyme, in vascular smooth muscle cells (VSMC) via cellular interactions between VSMC and endothelial cells (EC). Nifedipine induced upregulation of Mn SOD activity and expression in VSMC when cocultured with EC but not when cultured individually. NG-Monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, inhibited the upregulation of Mn SOD expression induced by nifedipine. Additionally, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine, a NO donor, reversed this inhibition by L-NMMA, indicating that NO may be involved in the mechanism underlying the nifedipine-induced upregulation of Mn SOD in VSMC. Preincubation of VSMC with Mn SOD antisense oligodeoxyribonucleotides (ODN) blocked the suppressive effects of nifedipine on DNA synthesis in VSMC cocultured with EC, whereas sense ODN had no effect. We conclude that the calcium antagonist nifedipine induces upregulation of Mn SOD expression in VSMC via NO derived from EC. This finding may provide some insight into the mechanism underlying the beneficial effects of calcium antagonists in patients with hypertension.

The use of calcium antagonists in the treatment of hypertensive persons with kidney disease.

The treatment of hypertension is proven to reduce cardiovascular and renal risk. Combination drug therapy is becoming recognized as a necessity in most patients with hypertension and kidney disease. Allegations about the safe use of calcium antagonists in patients with kidney disease have led to questions and confusion about their use in this common condition. This article reviews the cardiovascular and renal safety of the long-acting calcium antagonists from studies comparing calcium antagonists with placebo and with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients with kidney disease and hypertension. Patients with proteinuria and kidney disease should have their blood pressure brought as close to target (< 130/80 mm Hg) as possible for cardiovascular and renal protection. Lowering blood pressure in this setting will require an average of three antihypertensive agents. In patients with hypertension and proteinuria, angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be part of the regimen, and calcium antagonists are safe and effective in this condition when used with them in combination.

Effect of lipid-lowering agents, angiotensin-converting enzyme inhibitors, and calcium antagonists on coronary disease risk

Dyslipidemia is a causative, yet modifiable risk factors for the development of adverse outcomes secondary to coronary artery disease. Recent trials have focused on the level of low-density lipoprotein cholesterol (LDL-C) necessary to achieve maximum reduction in clinical events. Data also exist demonstrating that intensive lowering of LDL-C in patients with unstable angina reduces the incidence of adverse clinical events. The statins appear to be fundamental therapy in patients with established coronary disease as well as a mainstay for those with early evidence of atherosclerosis. The angiotensin-converting enzyme (ACE) inhibitors have demonstrated a reduction in ischemic events in patients with heart failure. Recent trials of ACE inhibitors in patients with vascular disease who do not have the traditional indications for ACE inhibition have shown a reversal of endothelial dysfunction and a reduction in adverse clinical endpoints. A role for the use of calcium antagonists in patients with atherosclerosis is less well established, despite the evidence of excellent results in patients with symptomatic coronary disease. A recent clinical trial, using a third-generation dihydropyridine calcium antagonist with novel mechanisms, found promising results with regard to its effects on atherosclerosis

Calcium antagonists as an add-on therapy for drug-resistant epilepsy.

As up to 30% of patients with epilepsy do not have their seizures controlled with current treatments, there have been continuous attempts to find new antiepileptic drugs based on increasing knowledge of cellular and molecular biology involved in the genesis of epilepsy and seizures. Calcium has been established to play a major role in seizure occurrence, thus, calcium antagonists that can alter the effects of calcium on brain cells have been investigated for effect on epileptic seizures. To evaluate the effects of calcium antagonists on seizures, side effects, quality of life and cognition, when used as an add-on therapy for patients with drug-resistant epilepsy. We searched MEDLINE from 1966 to 2000 and the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2001). Randomized placebo-controlled add-on trials of any calcium antagonists in patients with drug-resistant epilepsy. Two reviewers independently selected trials for inclusion and extracted data. Outcomes were: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. For crossover trials, the first treatment period was treated as a parallel trial. Analyses were by intention to treat. Due to problems acquiring the data needed from crossover trials, overall results from these trials were summarised in tables. Eleven trials were included. One parallel and seven crossover trials of flunarizine, two crossover trials of nimodipine and one crossover trial of nifedipine. For flunarizine, the odds ratio (OR) (95% Confidence Intervals (CIs)I) for a 50% or greater reduction in seizure frequency for the parallel trial was 1.64 (0.55, 4.94) indicating a non-significant advantage for flunarizine. We were unable to acquire data for this outcome from the seven crossover trials. The overall OR (95% CI) for treatment withdrawal for flunarizine was 5.83 (2.06, 16.45) indicating patients were significantly more likely to have flunarizine withdrawn than placebo. No side effects were statistically associated with flunarizine. For nifedipine we were unable to acquire the data we required from the two crossover trials for our specified outcomes. For the outcomes reported in the trials, nifedipine had no significant effect in seizures frequency. For nimodipine, we only had data from the first treatment period from one of the two crossover trials (17 subjects). The ORs (95% CIs) for a 50% or greater reduction in seizure frequency was 11.34 (1.00, 128.03) and for treatment withdrawal was 2.46 (0.22, 27.75). Flunarizine may have a weak effect on seizure frequency, but had a significant withdrawal rate probably due to side effects, and should not be recommended for use as an add-on treatment. Similarly, there is no convincing evidence to support the use of nifedipine or nimodipine as add-on treatments for epilepsy.

Cardiovascular Adverse Drug Reaction Associated with Combined β-Adrenergic and Calcium Entry-Blocking Agents

Numerous studies have shown a beneficial effect of combination therapy with beta-blockers and calcium antagonists in patients with anginal syndrome and/or hypertension. However, because both agents exert a negative chronotropic effect, their combined use may cause bradyarrhythmias with resultant symptoms of cerebral, coronary, and systemic hypoperfusion. We describe our clinical experience with patients who had cardiovascular adverse drug reactions (CVADRs) with combination therapy. This prospective study included 26 patients who had CVADRs among 2,574 admissions during a 2-year period. The study group included 14 men and 12 women with a median age of 73 years. Various combinations of calcium antagonists and beta-blockers were associated with the CVADRs. The most frequent pharmacologic combination was diltiazem plus propranolol. The CVADRs were the cause for hospital admission in 10 patients, an associated cause in nine patients, and developed during hospitalization in seven patients. Cardiac bradyarrhythmias were found in 22 patients. These rhythm abnormalities resolved within 24 h after discontinuation of the offending drugs. Temporary transvenous pacemaker insertion was necessary in only one patient with complete atrioventricular block. Twenty-two patients recovered, two patients died of pump failure not associated with CVADRs, and in two patients, the CVADRs contributed to the patients' death. CVADRs are not uncommon in elderly patients with ischemic heart disease and/or hypertension treated with the concomitant use of calcium antagonist and beta-adrenergic blocking drugs. Use of calcium antagonist plus beta-blocker may unpredictably cause serious hemodynamic events, marked suppression of sinus node activity, and prolongation of atrioventricular conduction in some patients. Enhanced therapeutic monitoring may be warranted when calcium antagonists are combined with beta-blockers.

Are angiotensin-converting enzyme inhibitors the best treatment for hypertension in type 2 diabetes?

The influence of hypertension on the clinical course and complications of type 2 diabetes is well established. With a special focus on angiotensin-converting enzyme inhibitors, this paper will review recently published results of prospective studies addressing two important aspects: the degree of blood pressure control, and the choice of antihypertensive regimen, in the prevention of complications in hypertensive type 2 diabetic patients. None of the recent studies have shown worse outcomes in patients treated with angiotensin-converting enzyme inhibitor-based regimens compared with alternative treatments. Some studies have suggested that angiotensin-converting enzyme inhibitor-based antihypertensive regimens may be superior to alternative treatments in reducing the risk of micro- and macrovascular complications, whereas other studies found similar effects for beta-blockers or calcium antagonists. Several trials showed beneficial effects of angiotensin-converting enzyme inhibitors over calcium antagonists, and have raised concerns about the use of dihydropyridine calcium antagonists in these patients. However, it remains to be determined whether there should be more reserved use of calcium antagonists in such patients, in the light of more major trials showing the safety and efficacy of calcium antagonists in preventing cardiovascular and renal endpoints. The degree of reduction of blood pressure rather than the choice of a particular drug may be the most important factor. Studies focusing on renal endpoints suggest that angiotensin-converting enzyme inhibitors have a better antiproteinuric effect than other agents, but this phenomenon is not always reflected by a more beneficial effect of angiotensin-converting enzyme inhibitors on the decline in glomerular filtration rate. In many ways, the question of whether angiotensin-converting enzyme inhibitors are the best class of agent in these patients is academic. Angiotensin-converting enzyme inhibitors are sufficiently safe, and, according to recent evidence, equally or more effective than other classes of agents. Tight blood pressure control is usually achievable only with a combination of agents. On the basis of available evidence, it appears that angiotensin-converting enzyme inhibitors, together with a low-dose cardioselective beta-blocker and a diuretic, should be used in most hypertensive type 2 diabetes patients, with calcium antagonists serving as reserve drugs in case of insufficient blood pressure control.

Calcium antagonists for acute ischemic stroke.

The sudden loss of blood supply in ischemic stroke is associated with increased levels of calcium ions within neurones. Inhibiting this increase could protect neurones and is thought to reduce neurological impairment, disability and handicap after stroke. The aim of this review is to determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. The influence of different drugs, dosages, routes of administration, time intervals after stroke and trial design on the risk of poor outcome was investigated. Relevant trials were identified in the Specialised Register of Controlled Trials (last searched: March 1999). All truly randomised trials comparing a calcium antagonist with control in patients with acute ischaemic stroke were included. Two authors assessed all trials and extracted the data. Poor outcome, defined as death or dependency in activities of daily living, was used as the main outcome. Analyses were, if possible, "intention-to-treat". 46 trials were identified of which 28 were included (7521 patients). No effect of calcium antagonists on poor outcome at the end of follow-up (OR 1.07, 95% CI 0.97/1.18), or on death at end of follow-up (OR 1.10, 95% CI 0.98/1.24) was found. Intravenous administration (i.v.) of calcium antagonists was associated with an increase in the number of patients with poor outcome compared to oral administration (indirect comparisons). Comparisons of different doses of nimodipine suggested that the highest doses were associated with poorer outcome. Administration within 12 hours of onset was associated with an increase in the proportion of patients with poor outcome, but this effect was largely due to the poor results associated with i.v. administration. A subgroup analysis on nimodipine (oral, 120 mg/day) started within 12 hours of stroke onset, did not show a beneficial effect. No evidence is available to justify the use of calcium antagonists in patients with acute ischaemic stroke.

β-blockers had similar clinical outcomes and were better tolerated than calcium antagonists in patients with stable angina

β-blockers had similar clinical outcomes and were better tolerated than calcium antagonists in patients with stable angina

Renal failure in the recipients of nonrenal solid organ transplants.

The increased success and availability of transplantation of solid organs other than kidneys has resulted in a large number of patients at risk for the usual medical complications of long-term immunosuppressive therapy. Acute and chronic renal failure play a critical role in the success of these

Gender differences and practice implications of risk factors for frequent hospitalization for heart failure in an urban center serving predominantly African-American patients

To identify the clinical correlates of recurrent heart failure hospitalization in a large urban hospital serving predominately African-American patients, and to provide further insight into modifiable risks for heart failure readmissions, a retrospective period prevalence review of the records of all adult patients admitted with a primary diagnosis of heart failure (International Classification of Diseases-9 code 428.0) between January and December 1995 was performed.The main outcome was the number of heart failure hospitalizations over 12 months. Twelve hundred patients were identified. Mean age was 64 ± 16 years, 94% were black, 57% were women, and 40% were ≥65 years old. Ninety-eight percent had a history of systemic hypertension and 55% had uncontrolled hypertension. Other comorbidities were left ventricular (LV) hypertrophy (64%), coronary artery disease (52%), and tobacco abuse (28%). Sixty-five percent of patients were on angiotensin-converting enzyme (ACE) inhibitors, 51% on calcium antagonists, and 8% on β blockers. Most patients had suboptimal dosing of ACE inhibitors and there was inappropriate use of calcium antagonists in 56% of patients with moderate or severe systolic dysfunction. Diabetes mellitus and echocardiographic wall motion abnormality were independently associated with frequent admissions for women but not for men. Medication-related increase in heart failure hospitalization was seen for calcium antagonists in patients with severe LV dysfunction (odds ratio 2.24, 95% confidence intervals 1.0 to 5.03; p <0.03). Uncontrolled hypertension, underdosing of ACE inhibitors, and overuse of calcium antagonists in patients with significant LV dysfunction are potential targets for intervention.

Improved short-term blood pressure control by treatment with calcium antagonists in patients with mild to moderate hypertension.

Improved short-term blood pressure control by treatment with calcium antagonists in patients with mild to moderate hypertension.

Effect of amlodipine on mode of death among patients with advanced heart failure in the praise trial

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.

Reversal of abnormal coronary vasomotion by calcium antagonists in patients with hypercholesterolemia.

It has been shown that exercise-induced coronary vasodilation of angiographically normal coronary vessels is reduced in hypercholesterolemic patients. The purpose of this study was to evaluate the effect of calcium channel blockers on coronary vasomotion of angiographically smooth coronary arteries in hypercholesterolemic patients. A total of 57 patients were included in the present analysis. Vasomotion of angiographically normal coronary arteries was evaluated in 37 control subjects (group 1) without and 20 patients (group 2) with calcium blocker administration before physical exercise. Both groups were subdivided into subgroup A (normal cholesterol values: < or = 5.5 mmol/L or 212 mg%) and subgroup B (elevated cholesterol values: >5.5 mmol/L or 212 mg%). Coronary luminal area at rest and during exercise was assessed by biplane quantitative coronary angiography. The normal vessels showed a significant increase in coronary luminal area during exercise in subgroup A (n=13) with normal cholesterol values (31%; P<.05) but not in subgroup B (n=24; 13%; P=NS). In contrast, all patients in group 2 showed similar vasodilation during exercise, namely, 22% (P<.05) in subgroups A (n=8) and B (n=12) (P<.05). Independent of the actual cholesterol level, the stenotic lesions showed coronary vasoconstriction during exercise in group 1 but vasodilation in group 2 after pretreatment with calcium antagonists. Coronary vasomotor response to exercise is inversely related to actual serum cholesterol level in angiographically normal vessels. Administration of calcium antagonists normalizes exercise-induced vasodilation and thus eliminates cholesterol-induced abnormal vasomotion, probably by a direct effect on the smooth muscles of the vasculature.