Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of orally administered diltiazem combined with maximally tolerated doses of beta-blockers and nitrates were assessed in 12 patients, who during stress testing exhibited persistent effort angina and continued objective evidence for inducible myocardial ischemia. Patients performed multistage semisupine exercise on a bicycle ergometer during equilibrium-gated radionuclide angiography after consecutive 2 week treatment periods of placebo or diltiazem 90 mg qid (mean dose 340 mg/day) combined with maximally tolerated propranolol (mean dose 178 mg/day) and isosorbide dinitrate (mean dose 137 mg/day). All medications (including diltiazem or placebo) were administered four times daily for the duration of the study. Diltiazem or placebo was administered according to a double-blind design, with randomized cross-over at the end of each 2 week treatment period. The average number of angina attacks decreased during the double-blind cross-over phase of the trial (7 +/- 7 episodes/week at baseline vs 4 +/- 3 on placebo vs 2 +/- 2 on diltiazem; p = .08). Angina pectoris was abolished during peak exercise in eight of 12 patients on diltiazem (p less than .05 vs placebo). Diltiazem increased total exercise duration from 276 +/- 92 to 310 +/- 78 sec (p less than .005 vs baseline). Diltiazem likewise increased the time to onset of angina from 231 +/- 84 sec at baseline to 305 +/- 77 sec (p less than .005), as well as the time to the onset of 1 mm ischemic ST segment depression (p = .01). Diltiazem decreased heart rate at rest, during submaximal workload, and at peak exercise (p less than .05), and decreased systolic blood pressure at peak exercise only (p less than .05). A significant decline in rate-pressure product at submaximal and peak exercise was noted (p less than .05). At any given workload there was significantly less ST segment depression during submaximal (p = .05) and peak exercise (p less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study. 285 31

To assess the efficacy of long-term diltiazem therapy when added to beta blockers and nitrates, we prospectively studied patients with chronic exertional angina who were determined to have medically refractory angina pectoris which was too severe to enter placebo-controlled studies. The mean follow-up time was 24.6 months (8-47 months) and all patients were seen every 2-4 months. Angina frequency decreased from a prediltiazem frequency of 9.5 episodes per week (1-40 per week) to 3.3 attacks per week (0-21 per week) at 6 months and 3.3 attacks per week (0-40 per week) at the patients's last evaluation. Similar reductions in nitroglycerin consumption were reported. Five patients had an increase in angina frequency during the mean 24.6 months of follow-up, which necessitated coronary bypass surgery, 8, 10, 12, 19, and 23 months after study entry, respectively. Diltiazem daily dosage ranged from 120 to 480 mg/day, the mean daily dose was 298 mg/day. Twenty (65%) patients remained on beta-blocker therapy and 19 (61%) patients on nitrate therapy in an effort to achieve a completely pain-free state. New cardiovascular events were documented in 3 patients during the follow-up period, with one patient having an uncomplicated myocardial infarction at 6 months, one patient hospitalized for prolonged chest pain at 2 months, and one patient dying following cardioversion for unrelated atrial fibrillation at 14 months poststudy entry. Adverse effects were reported during 19 of the 354 patient visits, but no patient had to stop therapy because of these. Sinus bradycardia required reduction of beta-blocker dosage in three patients and prolonged PR interval was observed in two additional patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of diltiazem for medically refractory stable angina: long-term follow-up. 286 52

At present nitrates remain the initial treatment for relief or prevention of angina in patients with coronary artery disease. In cases where nitrates and beta blockers have been used and are ineffective for managing effort angina, calcium antagonists may be substituted or added to the beta-blocking treatment. When the predominant symptom is rest angina, and there is evidence suggesting coronary artery spasm, nitrates and a calcium antagonist can be effective therapy. In patients with heart block, bradyarrhythmias, heart failure, or hypertension nifedipine may be the drug of choice. In contrast verapamil merits choice when supraventricular tachycardia is present. Diltiazem appears intermediate between nifedipine and verapamil and may be particularly useful when hypotension or other side effects must be avoided.
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PMID:Calcium antagonists. 286 40

To determine if a sustained-release form of the calcium entry blocker diltiazem would be a satisfactory substitute for the combination of beta-adrenergic blocking agent and thiazide diuretic in the treatment of systemic hypertension and angina pectoris, 38 patients were studied in a 4-center trial. Blood pressure and heart rate were measured in the supine position, immediately after and 5 minutes after standing. Modified Bruce protocol treadmill tests were performed to determine the time to onset of 1 mm ST-segment depression, time to onset of chest pain and time to termination of exercise. Diltiazem monotherapy resulted in equivalent blood pressure control in 28 of 38 patients (74%). In the remaining patients, blood pressure control was achieved with resumption of the diuretic. Blood pressure with beta blocker plus diuretic compared with diltiazem were, in the supine position 137 +/- 22/82 +/- 7 (+/- 1 standard deviation) versus 139 +/- 22/82 +/- 8 mm Hg, immediately after standing 131 +/- 20/84 +/- 9 versus 133 +/- 21/82 +/- 10 mm Hg and after standing for 5 minutes 134 +/- 19/85 +/- 8 versus 137 +/- 18/85 +/- 9 mm Hg (difference not significant for each). The heart rate with diltiazem was higher supine (67 +/- 11 versus 60 +/- 11 beats/min), standing (73 +/- 13 versus 64 +/- 14 beats/min) and 5 minutes after standing (73 +/- 14 versus 63 +/- 14 beats/min, p less than 0.01 for each).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of sustained-release diltiazem as replacement therapy for beta blockers and diuretics for stable angina pectoris and coexisting essential hypertension: a multicenter trial. 289 Dec 91

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.
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PMID:Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects. 290 16

The safety and efficiency of the administration of diltiazem was evaluated in 10 patients with class II-III chronic stable angina. All the patients had ischemic heart disease documented by coronary angiography and/or an abnormal exercise test. A dose related improvement in both frequency of angina and exercise capacity were obtained by diltiazem administered in increased doses using a single blind protocol. The weekly frequency of angina was reduced from 7.5 +/- 9.8 with placebo to 3.8 +/- 5.5, 1.1 +/- (p less than 0.05) and 0.7 +/- 0.9 (p less than 0.01) with doses of 120, 240 and 360 mg/day respectively. The exercise duration on treadmill was significantly increased from 8.5 +/- 3.6 to 10.6 +/- 3.7 min (p less than 0.05) with the 360 mg/day dose. The mean exercise time required to develop 1 mm ST depression was 6.1 +/- 3 min on placebo and was significantly delayed to 9.0 +/- 3.8 min (p less than 0.05) with the 240 mg/day dose and to 10.7 +/- 4.0 min with 360 mg (p less than 0.01). In a double blind randomized crossover phase, the time to the onset of ischemia during exercise was increased from 8.5 +/- 3.8 min with placebo to 11.05 +/- 2.8 min with 360 mg/day of diltiazem (p less than 0.01). Diltiazem in doses ranging from 120 to 360 mg/day is an effective antianginal agent with no significant adverse effects.
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PMID:[Diltiazem in chronic stable angina]. 294 27

An analysis of 41 trials of angina of all varieties confirms that calcium antagonists are an important advance and are now established therapy for these syndromes. In effort angina, verapamil in a dose of 360-480 mg daily is better than propranolol in standard doses. Although nifedipine is highly effective against vasospastic angina, its use in threatened myocardial infarction or severe unstable angina is not supported by recent studies, unless combined with a beta-blocker. Diltiazem has recently been tested with apparent benefit in non-Q-wave myocardial infarction. Otherwise, these calcium antagonist agents all seem to have approximate equipotency in clinical ischemic syndromes including effort and vasospastic angina. Subjective side effects seem most troublesome in the case of nifedipine. All three calcium antagonists, especially nifedipine, have been successfully combined with beta-blocker therapy, yet occasional additive negative inotropic or chronotropic or dromotropic interactions may occur when verapamil or diltiazem is added to beta-blockade, and occasionally the direct negative inotropic potential of nifedipine may become evident. The choice between the calcium antagonists is determined not only by the clinical picture but also by the anticipated side effects in a given patient and by the overall cardiovascular status. In patients with supraventricular tachycardias or sinus tachycardia, verapamil or diltiazem is preferred, whereas in patients with a resting bradycardia or borderline heart failure nifedipine is likely to be chosen.
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PMID:Calcium channel antagonists. Part II: Use and comparative properties of the three prototypical calcium antagonists in ischemic heart disease, including recommendations based on an analysis of 41 trials. 315 77

Twenty-three patients with essential hypertension and diabetes mellitus type II were treated with the calcium antagonist diltiazem (120 to 180 mg twice daily). The mean dose was 307 mg/day. The study was a double-blind, placebo-controlled, crossover design. All measurements were performed 12 to 14 hours after drug intake. Blood pressure, heart rate and forearm blood flow were measured noninvasively. Platelet function was studied by measuring adenosine diphosphate-induced platelet aggregation and the platelet specific proteins, beta thromboglobulin and platelet factor 4. Thromboxane B2 formation in serum and the plasma concentration of diltiazem and its metabolites N-demethyldiltiazem, deacetyldiltiazem and N-demethyldeacetyldiltiazem were measured both during placebo and diltiazem treatment. Diabetic control was evaluated by following HbA1C, fasting blood glucose and urinary glucose. Diltiazem reduced both systolic and diastolic (supine and standing) blood pressure significantly. Forearm blood flow was significantly increased by 32%, p less than 0.05. Supine heart rate decreased significantly, while no such change was seen in the standing position. No significant changes were observed in platelet function during diltiazem treatment. There was no relation between the observed blood pressure reduction and the plasma concentration of diltiazem or its metabolites. A positive correlation between the change in heart rate and the metabolite N-demethyldeacetyldiltiazem was observed (r = 0.647, p = 0.005). Three patients were excluded during diltiazem treatment (skin exanthema, headache and atrial fibrillation) and 1 during placebo treatment (angina pectoris). No negative effect on diabetes control was observed. Thus, diltiazem could be used for treatment of hypertension in diabetic patients.
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PMID:Diltiazem in hypertensive patients with type II diabetes mellitus. 317 28

Calcium antagonists have proved effective in stable angina, unstable angina and vasospastic angina. However, despite a strong theoretical rationale for their use and promising experimental data, these agents have not reduced infarct size in acute myocardial infarction (AMI) in the large clinical trials performed to date. Their role as adjunctive therapy in combination with reperfusion needs to be examined. Diltiazem has been demonstrated to reduce angina and reinfarction in the 2-week period after AMI in patients receiving multidrug therapy. Results of the single large trial of a calcium antagonist (verapamil) for secondary prevention after AMI were negative; however, several well-designed studies are currently ongoing.
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PMID:Calcium antagonists in acute myocardial infarction. 327 63

The efficacy and safety of oral nifedipine and diltiazem were compared in 20 patients with stable angina pectoris with use of a placebo run-in, randomized, double-blind titration to maximal effect crossover protocol. The effects of treatment withdrawal were also analyzed. All patients received placebo for 2 weeks and were then randomly assigned to receive either diltiazem or nifedipine. A 2 week drug titration phase in which patients received either diltiazem (180 to 360 mg/day) or nifedipine (30 to 120 mg/day) in three divided doses was followed by a 1 week maintenance phase. Patients then received placebo for 1 to 2 weeks, followed by crossover to the other treatment regimen and a second placebo washout period of 1 week. Patients (n = 13) who remained symptomatic on both diltiazem and nifedipine during the monotherapy periods entered a 3 week combination treatment phase, followed by a final 1 week placebo washout period. Frequency of angina, nitroglycerin consumption, exercise tolerance (Naughton protocol), and frequency of daily episodes of ST segment deviations on the electrocardiogram (1 mm of ST segment depression persisting for at least 1 min with and without chest pain) on an ambulatory electrocardiographic monitor were assessed during the baseline placebo, active monotherapy, placebo withdrawal, and combination treatment phases. Plasma drug levels were also measured. Compared with initial placebo values, the frequency of angina and the amount of nitroglycerin treatment were reduced by both diltiazem (p less than .001) and nifedipine (p less than .02). Diltiazem was more effective than nifedipine in reducing angina (p less than .02). Exercise duration increased with both drugs (p less than .0001). Diltiazem was significantly better than nifedipine in reducing the episodes of ST segment depression on the ambulatory monitor (p less than .01). Diltiazem reduced the resting heart rate (p less than .01); both drugs reduced the resting blood pressure and rate-pressure product. Overall, combination therapy was more effective in patients who did not maximally respond to diltiazem or nifedipine alone with respect to anginal and exercise variables and in reducing blood pressure at rest and during exercise. Plasma drug levels could not predict an individual patient's treatment response. Diltiazem may increase nifedipine drug levels when the drugs are combined. Fewer side effects were observed with diltiazem than nifedipine; the most side effects were seen with combination treatment. There were no apparent withdrawal effects observed with either treatment regimen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diltiazem, nifedipine, and their combination in patients with stable angina pectoris: effects on angina, exercise tolerance, and the ambulatory electrocardiographic ST segment. 328 Jan 58


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