dihydropyridines and Coronary-Artery-Disease

Calcium antagonists are well accepted in the prevention of ischaemia in patients with chronic stable angina, unstable angina, variant angina, and silent ischaemia, and in the treatment of hypertension. Although all of these compounds increase myocardial oxygen supply by reducing coronary tone and decrease myocardial oxygen demand by reducing systolic pressure and myocardial contractility, the magnitude of these effects may differ from one agent to another. Some calcium antagonists, such as verapamil and diltiazem, reduce heart rate and attenuate heart rate increases in response to stress, while in contrast, dihydropyridine calcium antagonists such as nifedipine may cause reflex increases in heart rate. These differences may be of importance in light of epidemiologic evidence that lower heart rates are associated with a reduced long-term risk of cardiovascular mortality, and experimental data showing that a lower heart rate may protect against the development of atherosclerosis. Calcium antagonists also inhibit platelet aggregation and thrombus formation which may contribute to their anti-ischaemic effects. Clinical trial data suggest that calcium antagonists may stay the progression of atherosclerosis. Mechanisms underlying an anti-atherosclerotic effect may include attenuation of endothelial dysfunction, prevention of LDL, peroxidation, stimulation of LDL receptor activity, inhibition of superoxide radical generation, and inhibition of vascular smooth muscle cell growth. Heart-rate-controlling calcium antagonists, such as verapamil and diltiazem, may reduce reinfarction rates following acute myocardial infarction and thus may have a role in post-infarction patients who do not show evidence of heart failure. Their use in heart failure patients receiving an angiotension-converting enzyme inhibitor (ACE-I) is under investigation in several large trials. Because calcium antagonists have a mechanism of action different from ACE-I, the pairing of a heart-rate-controlling calcium antagonist with an ACE-I might be expected to offer additive cardioprotective and vascular protective effects.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Dihydropyridines; Drug Therapy, Combination; Endothelium, Vascular; Free Radicals; Heart Rate; Humans; Lipoproteins, LDL; Muscle, Smooth, Vascular; Myocardial Ischemia; Platelet Aggregation; Platelet Aggregation Inhibitors; Superoxides; Vasodilation

Topics: Aged; Amlodipine; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Dihydropyridines; Female; Humans; Hypertension; Male; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Preoperative Period; Prospective Studies; Ultrasonography, Interventional

A previous study reported that amlodipine retarded coronary plaque progression in patients with coronary artery disease. The goal of this multicenter study was to determine which calcium-channel blockers (CCBs) other than amlodipine attenuated the progression of plaque volume (PV) accessed by intravascular ultrasound (IVUS).. ALPS-J was a prospective, randomized open-label study conducted at 5 centers. Patients who had hypertension and were scheduled for coronary intervention were enrolled. Subjects were randomly assigned to receive 16 mg/day of azelnidipine or 5mg/day of amlodipine administered for 48 weeks. The primary endpoint was the percent change in coronary PV measured by IVUS. Between 2007 and 2009, 199 patients were enrolled; 115 had evaluable IVUS images at both baseline and after 48 weeks of treatment. Blood pressure significantly reduced to 128/68 mmHg at follow-up. The lipid profiles in the 2 groups were comparable (low-density lipoprotein cholesterol: 97 mg/dl). The %change in PV showed a significant regression of 4.67 and 4.85% in the azelnidipine and amlodipine groups, respectively. The upper limit of the 95% confidence interval of the mean difference in %change PV between the 2 groups (0.18%, 95% confidence interval 4.62 to 4.98%) did not exceed the pre-defined non-inferiority margin of 6.525%.. ALPS-J demonstrated that azelnidipine was not inferior to amlodipine for primary efficacy. In addition to standard medical therapy, dihydropyridine CCBs will retard PV progression in hypertensive patients.

Topics: Amlodipine; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Dihydropyridines; Humans; Hypertension; Lipids; Plaque, Atherosclerotic; Ultrasonography, Interventional

Many trials have shown that calcium channel blockers (CCBs) can reduce the cardiovascular (CV) events in patients with coronary artery disease (CAD). The mechanisms of this effect could be associated with plaque regression due to the anti-atherosclerotic properties of CCBs. The goal of this study is to determine the effects of CCB on volumetric quantitative changes of coronary plaques accessed by intravascular ultrasound (IVUS). To confirm this hypothesis, a multicenter randomized trial of CCBs treatment with azelnidipine or amlodipine will be conducted in hypertensive CAD patients undergoing elective percutaneous coronary intervention (PCI).. Patients who have hypertension and are scheduled for PCI will be enrolled. Subjects will be randomized to azelnidipine or amlodipine and observed for 48 weeks. The primary endpoint will be the percent change of coronary plaque volume. The secondary endpoint will include inflammatory markers, antioxidant activity, and incidence of composite cardiovascular events.. In this study, we will investigate the improvement of coronary plaque with IVUS by treatment with two dihydropyridine CCBs in hypertensive patients undergoing elective PCI. This result will lead to the discovery of more effective drug therapy for inhibition of coronary events.

Topics: Adult; Aged; Amlodipine; Azetidinecarboxylic Acid; Calcium Channel Blockers; Coronary Artery Disease; Dihydropyridines; Disease Progression; Double-Blind Method; Endpoint Determination; Female; Humans; Hypertension; Male; Middle Aged; Ultrasonography; Young Adult

To evaluate the effects of the calcium channel blocker lacidipine on vascular responses, such as endothelial function and carotid intima-media thickness (IMT), and on levels of high-sensitivity C-reactive protein (hs-CRP) in patients with coronary artery disease (CAD).. Endothelial function was assessed by measuring the flow-mediated vasodilation (FMD) of the brachial artery and IMT was measured in the common, bifurcating, and in the internal carotid artery by using high-resolution ultrasound. The study population consisted of 96 consecutive patients [mean age 60 years, male (n) = 70] who showed at least one coronary artery narrowed by more than 50% (coronary angiography). These patients were randomly assigned to lacidipine treatment (4 mg/day, n = 48) or to a placebo (n = 48). We measured FMD, IMT, and hs-CRP prior to and after 6 months of treatment and following coronary angiography in all patients.. Clinical and medical history revealed no significant differences between the groups. IMT of the common carotid artery was significantly diminished from 0.92 +/- 0.15 to 0.87 +/- 0.15 mm 6 months after treatment with lacidipine (p < 0.005). However, IMT of any region in the carotid artery did not show any significant changes in the placebo group. Endothelial function and hs-CRP levels were slightly improved (insignificant) in the lacidipine group. In the placebo group, there were no significant changes.. Lacidipine leads to a significant reduction of the common carotid artery IMT as well as to a decrease in markers of inflammation in patients with CAD during a relatively short period (6 months).

Topics: Blood Flow Velocity; Brachial Artery; C-Reactive Protein; Calcium Channel Blockers; Carotid Artery, Internal; Coronary Angiography; Coronary Artery Disease; Dihydropyridines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Tunica Intima; Ultrasonography, Doppler; Vasodilation

Topics: Amlodipine; Azetidinecarboxylic Acid; Coronary Artery Disease; Dihydropyridines; Humans; Hypertension

We experienced a case of vasospastic angina showing resolution of vasospasm in the acetylcholine provocation test corresponding to regression of coronary atherosclerotic plaque following treatment with a combination of benidipine and pravastatin.

Topics: Acetylcholine; Angina Pectoris; Angina Pectoris, Variant; Anticholesteremic Agents; Cholinergic Agents; Coronary Artery Disease; Coronary Vasospasm; Dihydropyridines; Humans; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Ultrasonography; Vasodilator Agents