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PubMed1997

Attenuation of cardiovascular responses to tracheal extubation: comparison of verapamil, lidocaine, and verapamil-lidocaine combination.

UNLABELLED: We recently showed that verapamil attenuated hemodynamic responses to tracheal extubation. The aim of the current study was to compare the efficacy of a combination of intravenous (I.V.) verapamil (0.1 mg/kg) and I.V. lidocaine (1 mg/kg) with that of each drug alone in suppressing the cardiovascular changes during tracheal extubation and emergence from anesthesia. One hundred adult patients (ASA physical status I) who were to undergo elective minor surgery were randomly assigned to one of four groups (n = 25 each): Group S = saline plus saline (control), Group V = verapamil 0.1 mg/kg I.V. plus saline, Group L = lidocaine 1 mg/kg I.V. plus saline, and Group V-L = verapamil 0.1 mg/kg I.V. plus lidocaine 1 mg/kg I.V. These medications were given 2 min before tracheal extubation. Anesthesia was maintained with 1.0%-2.0% sevoflurane and 60% nitrous oxide (N2O) in oxygen. Muscle relaxation was achieved with vecuronium, and a residual neuromuscular blockade was reversed with neostigmine 0.05 mg/kg (combined with atropine 0.02 mg/kg). Changes in heart rate (HR) and arterial blood pressure (AP) were measured during and after tracheal extubation. In the control group, the HR and systolic and diastolic AP increased significantly during tracheal extubation. Verapamil, lidocaine, and their combination attenuated the increases in these variables. The beneficial effect was the greatest with the combination of verapamil and lidocaine. These findings suggest that verapamil 0.1 mg/kg and lidocaine 1 mg/kg given I.V. concomitantly 2 min before tracheal extubation is a simple and more effective prophylaxis than verapamil or lidocaine alone for attenuating the cardiovascular changes associated with tracheal extubation. IMPLICATIONS: Tachycardia and hypertension associated with tracheal extubation, which may lead to myocardial ischemia, represent a potential risk for patients with coronary arterial disease. To seek effective pharmacological prophylaxis against these complications, we compared the attenuation of hemodynamic changes among verapamil, lidocaine, and a verapamil/lidocaine combination using ASA physical status I patients and found the combination to be effective.

Adult↗

PubMed1975

The pharmacodynamics of orally taken verapamil and verapamil retard as judged by their negative dromotropic effects.

The widely recognized, negative dromotropic effects of alpha-isopropyl-alpha-[N-methyl-N-homaveratryl)-gamma-aminopropyl]-3-4-dimethoxyphenylacetonitrile (verapamil, Isoptin) on arterio-venous (A-V) nodal conductions were studied using long-term atrial stimulation (AS) in 7 healthy volunteers whose mean age was 30 years. A control group consisting of three of the volunteers who underwent long-term atrial stimulation without medication was established. Since an isolated, well-known drug effect was studied over a long period of time, it was felt that this was an acceptable method for reaching valid pharmacodynamic conclusions. Atrial stimulation was carried out at hourly intervals up to 14-16 h and continued to the highest possible rate without the occurrence of 2nd degree A-V block before and following oral application of verapamil, 240 mg. The stimulus-Q (S-Q) prolongation at increased pace rates was compared to the control. Verapamil retard was tested in a similar course of investigation the following day. The results clearly demonstrated that both forms of verapamil are effective when taken orally. Verapamil acts 2 h after oral application. The peak effectiveness of the drug is found at 5 h and at this point A-V block can occur at low atrial stimulated rates. The effect of verapamil retard is obvious only after 6 h but is still apparent after 14 h and it remains constant with no peak in effectiveness. Characteristics of the resulting regressions allow to distinguish the effect of verapamil on A-V conduction from influences that might be mediated by the diurnal changes in tone of the autonomic nervous system only. The effect of verapamil after oral application is more pronounced with higher heart rates. The pharmacodnaymics of verapamil evaluated with regard to a single well-known pharmacological effect, have not necessarily to be identical with the pharmacokinetics and the bioavailability of the drug.

Adult↗

PubMed1990

The anaerobic metabolism of verapamil in rat cecal contents forms nor-verapamil and thiocyanate.

The anaerobic metabolism of verapamil was studied to determine the role the intestinal flora may have on the disposition of verapamil. Metabolites produced by the flora could be the source of adverse reactions reported only with the p.o. controlled release formulations but not with immediate release formulations. Verapamil was found to be metabolized to thiocyanate, nor-verapamil and several more polar metabolites that were detected by either a specific assay for cyanide and thiocyanate or a high-performance liquid chromatography (HPLC) assay, respectively. The rate of thiocyanate formation with an initial substrate concentration of 2 mM verapamil was found to be 0.008 +/- 0.004 microgram/hr/ml of 1:10 cecal suspension. The N-demethylated metabolite, nor-verapamil, was detected in the cecal suspensions but it also disappeared with time. The rate of verapamil disappearance was dependent on the concentration of bacteria in the incubation mixture; the rate being most rapid with the highest concentration of bacteria. Acetonitrile and butyronitrile were also found to be metabolized by the cecal flora. Cyanide as well as thiocyanate were produced from both organo-nitriles. These results suggest that the cyano group of verapamil, acetonitrile and butyronitrile were all cleaved to form cyanide and/or thiocyanate. With verapamil, cleavage of the cyano group would form new chemical entities that could be pharmacologically active and serve as a source of some of the adverse reactions or side-effects reported.

Acetonitriles↗

PubMed1993

Stereoselective verapamil disposition and dynamics in aging during racemic verapamil administration.

Stereoselective verapamil disposition and dynamics were evaluated after racemic verapamil administration of single i.v. doses, simulated steady-state intravenous infusions, chronic (1 week) administration of oral immediate-release tablets (120 mg three times daily) and chronic (1 week) administration of oral sustained-release tablets (240 mg once daily) to 15 young (mean +/- S.E.M. age 22 +/- 1 year) and 15 older (69 +/- 1 year) healthy male volunteers. After single i.v. doses S-verapamil clearance (young, 102 +/- 6 vs. older, 77 +/- 6 l/hr; P < .01) and R-verapamil clearance (young, 61 +/- 3 vs. older, 45 +/- 3 l/hr; P < .01) were similarly decreased. Electrocardiographic P-R prolongation using S-verapamil concentrations and an Emax model (young Emax, 69 +/- 8 vs. older, 42 +/- 6 msec; P < .05: young EC50, 15 +/- 1 vs. older, 23 +/- 3 ng/ml; P < .05) was greater in the young. Simulated steady-state i.v. S-verapamil clearance (young, 76 +/- 3 vs. older, 49 +/- 2 l/hr; P < .01) and R-verapamil clearance (young, 47 +/- 2 vs. older, 28 +/- 1 l/hr; P < .01) were similarly less in older subjects and this was unrelated to infusion rate. Qualitatively similar findings were observed during chronic oral (immediate release) treatment and chronic oral (sustained release) treatment. Plasma protein binding of S-verapamil was less in both groups (young, 8.5 +/- 0.4 and older, 8.0 +/- 0.5% unbound) than that of R-verapamil (young, 5.4 +/- 0.2 and older, 5.1 +/- 0.3% unbound) and not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2005

Pharmacokinetics of verapamil and its major metabolite, norverapamil from oral administration of verapamil in rabbits with hepatic failure induced by carbon tetrachloride.

The aim of this study was to investigate the pharmacokinetic changes of verapamil and its major metabolite, norverapamil, after oral administration of verapamil (10 mg/kg) in rabbits with slight, moderate and severe hepatic failure induced by carbon tetrachloride. The plasma verapamil concentrations in all groups of hepatic failure were significantly higher (p < 0.01) than the control. However, the plasma norverapamil concentrations in severe hepatic failure were significantly higher (p < 0.05) than the control. The peak concentrations (Cmax) and the areas under the plasma concentration-time curve (AUC) of verapamil in the rabbits were significantly (p<0.01) higher than the control. The absolute bioavailability (F(A.B)) and the relative bioavailability (F(R.B)) of verapamil in the rabbits with hepatic failure were significantly higher (13.6-22.2% and 150-244%, respectively) than the control (9.1% and 100%, respectively). Although the AUC and Cmax of its major metabolite, norverapamil, in slight, moderate hepatic failure were not significantly lower than the control, the metabolite-parent AUC ratio in all groups of hepatic failure was decreased significantly (p < 0.05, in slight group; p < 0.01, in moderate and severe group) than the control. This could be due to decrease in metabolism of verapamil in the liver because of suppressed hepatic function in the hepatic failure groups because verapamil is mainly metabolized in the liver. From our data, it would seem appropriate that in patients with liver disease, doses of verapamil should be decreased by degree of hepatic failure.

Administration, Oral↗

PubMed1987

Failure of episodic high-dose oral verapamil therapy to convert supraventricular tachycardia: a study of plasma verapamil levels and gastric motility.

The practicality of administering large oral doses of verapamil tablets to terminate supraventricular tachycardia (SVT) was investigated in 10 patients. A pilot study in four patients showed that unexpectedly low plasma levels (less than 40 ng/ml) were obtained 60 minutes after administering 160 mg or 240 mg of verapamil during SVT. Nuclear studies in the six other patients showed that fractional liquid gastric emptying times (T) were significantly prolonged in SVT compared to sinus rhythm (SR), p less than 0.05 from T 1/3 onward. Further verapamil absorption studies (200 to 360 mg) performed during SVT and SR in five of six patients showed that peak verapamil levels in four patients in SVT were 23% to 71% lower than in sinus rhythm, where they had peaked at greater than 250 ng/ml 60 minutes post verapamil ingestion, and areas under the plasma concentration time curves were 26% to 100% (mean 67%) less in SVT than in SR for all five patients. SVT was terminated by verapamil in one patient after 40 minutes and the rate of SVT was slowed after 90 minutes in two other patients. Thus plasma verapamil levels are considerably reduced during SVT as compared to SR, and changes in gastric emptying are likely a contributing cause. Since SVT was converted to sinus rhythm in only 1 of 10 patients within 1 hour, large oral doses of verapamil tablets appear unsatisfactory for the episodic treatment of SVT.

Administration, Oral↗

PubMed1990

Secondary prevention with verapamil after myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction.

The effect of verapamil on death and major events (i.e., death or reinfarction) after an acute myocardial infarction was studied in a double-blind, randomized, placebo-controlled, multicenter trial, the Danish Verapamil Infarction Trial II (DAVIT II). Eight hundred seventy-eight patients started treatment with verapamil 360 mg/day and 897 patients with placebo. Treatment continued for up to 18 months (mean 16 months). Ninety-five deaths and 146 major events occurred in the verapamil group and 119 deaths and 180 major events in the placebo group. Eighteen-month mortality rates were 11.1 and 13.8% (hazard ratio 0.80, 95% confidence limits 0.63 to 1.05, p = 0.108), and major event rates 18.0 and 21.6% (0.80, 0.64 to 0.99, p = 0.027) in the verapamil and placebo groups respectively. When combining the results of this trial with the results of the first Danish study on verapamil in myocardial infarction, the meta-analysis demonstrated that treatment with verapamil from the second week after an acute myocardial infarction resulted in a reduction of pooled odds ratios of 0.22 (95% confidence interval 0.01 to 0.37, p = 0.04) for death, 0.21 (0.05 to 0.35, p = 0.02) for major events, and 0.27 (0.06 to 0.43, p = 0.02) for first reinfarctions. It is concluded that long-term treatment with verapamil after an acute myocardial infarction is associated with a significant reduction in overall mortality as well as major event and reinfarction rates.

Cholesterol↗

PubMed1998

Effect of verapamil on heart rate variability after an acute myocardial infarction. Danish Verapamil Infarction Trial II.

Because decreased heart rate variability measured after an acute myocardial infarction (AMI) has been demonstrated to predict subsequent mortality and sudden death, and an efficacy analysis of the Danish Verapamil Infarction Trial II (DAVIT II) demonstrated that long-term postinfarction treatment with verapamil significantly reduced sudden death, the aim of the present substudy was to evaluate the effect of verapamil on heart-rate variability in the time and frequency domain, measured in two 5-minute segments during the day and night. Thirty-eight patients were examined by Holter monitoring, at 1 week, that is, before randomization, and at 1 month after infarction; 22 of the patients were examined 12-16 months after infarction as well. In both treatment groups (verapamil and placebo) no significant alteration of heart rate variability during the day-time was demonstrated from before to after 1 and 12-16 months of treatment. In accord with the known reduction of overall heart rate by verapamil, a significant increase of mean NN interval from before to after 1 (P = 0.0004) and 12-16 months (P = 0.004) of treatment was seen in the verapamil, but not in the placebo, group at night. Parameters generally interpreted as an index of parasympathetic modulation, that is, RMSSD, pNN50, and high-frequency power, increased significantly at 1 month (P = 0.04, P = 0.03, NS, respectively) and 12-16 months (P = 0.03, P = 0.04, P < 0.05) after AMI in the verapamil, but not in the placebo, group. In conclusion, the present study indicates that verapamil shifts the autonomic balance to a vagal preponderance or sympathetic attenuation in the postinfarction period.

Aged↗

PubMed1994

The prognostic significance of post-infarction angina pectoris and the effect of verapamil on the incidence of angina pectoris and prognosis. The Danish Study Group on Verapamil in Myocardial Infarction.

The prognostic significance of angina pectoris and the effect of intervention with verapamil on the incidence of angina pectoris were studied in patients recovering from myocardial infarction and included in the Danish Verapamil Infarction Trial II. During the second week after admission patients were doubly-blindly randomized to treatment with verapamil 360 mg.day-1 or placebo. Treatment was continued for up to 18 months. At discharge angina pectoris was reported in 11% of 869 patients randomized to verapamil and in 12% of 888 randomized to placebo (ns). One month after discharge a significant increase in the prevalance of angina pectoris was reported in both the verapamil (33%) (P < 0.001) and the placebo groups (39%) (P < 0.001). The one month prevalence of angina pectoris (P = 0.03) and the 18 months overall incidence of angina pectoris (P = 0.002) were both significantly lower in the verapamil group compared with placebo. Stable angina pectoris during the first month of follow-up was a significant predictor of major events (i.e. death or reinfarction) (hazard ratio = 1.45; 95% confidence limits: 1.10, 1.89). As verapamil significantly reduced the incidence of angina pectoris during daily activities, and thereby the number of patients at high risk, the beneficial effect of verapamil in reducing major events in patients recovering from myocardial infarction is likely to be due to abolishing myocardial ischaemia.

Adult↗

PubMed1992

[Verapamil therapy improves the prognosis after acute myocardial infarction. A review over the Danish studies of verapamil therapy during and after acute myocardial infarction].

The effect of verapamil therapy in a dosage of 120 thrice daily on the mortality and re-infarction from the time of admission and for the subsequent six months was investigated in a double-blind, randomized, placebo-controlled, multicentre investigation (The Danish Verapamil Infarction Trial (DAVIT I)). Seven hundred and seventeen patients were treated with verapamil and 719 with placebo. The mortalities after six months were 12.8% in the verapamil group and 13.9% in the placebo group (NS) and re-infarction occurred in 7.0% and 8.3%, respectively (NS). The effect of verapamil on the mortality and major events, i.e. death or the first re-infarction from the second week after an acute myocardial infarction was investigated in a double-blind, randomized, placebo-controlled, multicentre investigation (DAVIT II) in which 878 patients commenced treatment with verapamil in a dosage of 360 mg daily and 897 patients received a placebo. This treatment was continued for up to 18 months, on an average for 16 months. Ninety-five patients died and 146 major events were registered in the verapamil group while 119 died and 180 major events occurred in the placebo group. The 18 months mortality rates were 11.1 and 13.8% (hazard ratio 0.80, 95% confidence limits 0.63-1.05, p = 0.11) and the major event rates were 18.0 and 21.6% (0.80, 0.64-0.99, p = 0.03) in the verapamil and placebo groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Denmark↗

PubMed1986

The Danish studies on verapamil in acute myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction.

A double-blind study comparing verapamil with placebo was conducted in 16 Danish departments of internal medicine with coronary care units (CCU). All patients below 75 years of age admitted to the CCU with a suspicion of acute myocardial infarction (AMI) were evaluated. Of 7415 patients, 3917 were excluded on admission because of heart failure, heart block, other severely disabling diseases, or treatment with beta-adrenoceptor blockers or calcium antagonists. Treatment was started in 3498 patients with 0.1 mg kg-1 verapamil i.v. and 120 mg orally on admission followed by 120 mg three times daily, or matched placebo. Treatment was continued for 6 months for patients verified to have had an AMI according to all three WHO criteria. Treatment was stopped in patients for whom the diagnosis of AMI was ruled out. Of 1436 patients with AMI, 717 were treated with verapamil and 719 with placebo. After 6 months, 92 patients (12.8%) in the verapamil group and 100 patients (13.9%) in the placebo group were dead (NS). Fifty patients (7%) in the verapamil group and 60 patients (8.3%) in the placebo group had reinfarctions (NS). After 12 months, 109 patients (15.2%) in the verapamil group and 118 patients (16.4%) in the placebo group were dead (NS). It is concluded that verapamil treatment used in the early phase of an AMI does not improve survival. Based on the experience from the first study we are at present performing a further secondary prevention study with verapamil to a modified design.

Aged↗

PubMed1998

Congestive heart failure and ischaemic heart disease treated with trandolapril and verapamil. DAVIT Study Group. Danish Verapamil Infarction Trial.

CLINICAL TRIALS WITH VERAPAMIL AND TRANDOLAPRIL: In the Danish Verapamil Infarction Trial II, verapamil improved survival in patients without heart failure but had no effect in patients with heart failure who were receiving diuretic treatment. In the Acute Infarction Ramipril Efficacy study ramipril improved survival in patients receiving diuretic treatment but had no effect in patients not receiving diuretics. COMBINATION WITH THERAPY WITH VERAPAMIL AND TRANDOLAPRIL: By combining verapamil with trandolapril we hypothesized that we could obtain an improvement in left ventricular function and prevent cardiac events. In an open study of 14 patients with angina pectoris and left ventricular ejection fraction below 40%, treatment with trandolapril-verapamil significantly improved left ventricular function. In a double-blind randomized study of 100 postinfarct patients with congestive heart failure the cardiac event rate was significantly lower in verapamil-trandolapril-treated than in the trandolapril-treated patients. These results indicate that the combined treatment with verapamil and trandolapril might be beneficial in patients with ischaemic heart disease and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

The relationship of dose to the antihypertensive response of verapamil-sustained release in patients with mild to moderate essential hypertension. The Verapamil-SR Study Group.

The dose-response relationship of verapamil-SR was studied in 221 hypertensive patients. This double-blind, parallel-group, placebo-controlled study compared placebo to 60 mg, 120 mg, 240 mg and 480 mg daily of verapamil-SR. After 6 weeks of therapy, peak diastolic blood pressure was similar in the placebo group and the verapamil-SR 60 mg group, 93.0 and 92.0 mmHg, respectively. The 120 mg, 240 mg and 480 mg verapamil-SR groups produced significantly lower diastolic blood pressure, 89.8, 85.3 and 83.7 mmHg (P less than 0.01), respectively. At trough, placebo and verapamil-SR 60 mg groups and 120 mg groups had diastolic blood pressures of 96.6, 97.0 and 97.1 mmHg, respectively. Diastolic blood pressure with the 240 mg dose (92.4 mmHg) was significantly lower than with the 120 mg dose (P less than 0.01). The 480 mg dose resulted in a diastolic blood pressure of 88.6 mmHg, which was significantly lower than the 240 mg dose (P less than 0.01). The responder rate with 240 mg at peak was 82%. The trough to peak ratio was 0.58. Plasma concentrations were highly correlated with dose (r greater than 0.8; P less than 0.01); but not with diastolic blood pressure (r greater than 0.4; P less than 0.01). Headache and constipation, although not significantly different from placebo, were the most commonly reported adverse reactions in the verapamil-SR groups, 6.3% (placebo--6.7%) and 5.1% (placebo--4.4%), respectively. Graded doses of verapamil-SR produced a dose-response curve in hypertensive patients with a greater than 80% responder rate at the 240 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed1986

Ionization and surface properties of verapamil and several verapamil analogues.

We have investigated the ionization and surface properties of verapamil (5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3, 4-dimethoxyphenyl)-2-isopropylvaleronitrile, 1) and several verapamil analogues since these properties appear to be involved in the biologic activities of these compounds. Our results show that verapamil and its analogues are surface-active and bind to amphiphilic surfaces. The affinity toward, as well as the capacity of, an amphiphilic surface for verapamil and its ionizable analogues is pH dependent, with the surface having both higher affinity and capacity for the neutral form of the molecules. Thus, verapamil exists as protonated and neutral forms, both of which are free in solution and adsorbed to the interface, and the ionization of verapamil at an interface changes with respect to its ionization in solution. From analyses of the pH dependency of surface binding and of solution and interfacial ionizations, we determined the values of the four equilibrium constants. These equilibrium constants permit correlative studies between the pH-dependent abundance of each species and biologic activity. We discuss preliminary studies which indicate that the negative inotropic effect of verapamil is mediated by the membrane-bound neutral form of the drug.

Absorption↗

PubMed2004

Evaluation of the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention: the randomized, double-blind, placebo-controlled, multicenter Verapamil Slow-Release for Prevention of Cardiovascular Events After Angioplasty (VESPA) Trial.

OBJECTIVES: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI). BACKGROUND: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers. METHODS: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography. RESULTS: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014). CONCLUSIONS: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.

Administration, Oral↗

PubMed1998

The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness.

BACKGROUND: It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). DESIGN AND METHODS: In 498 hypertensive patients in eight Italian centres, randomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standardized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatment. The maximum intima-media thicknesses of the far walls of common, bifurcation and internal carotid arteries were measured bilaterally, and the following indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum thickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initial mean over the six sites (baseline + 3 months) as a covariate (mm/year per mm). The patients were also classified into three strata according to their baseline single maximum thickness: those with normal carotid arteries (single maximum ( 1 mm), those with thickened carotid arteries (single maximum > 1 and < or = 1.5 mm and those with carotid plaques (single maximum > 1.5 mm). RESULTS: Among the 456 patients with satisfactory baseline ultrasound readings, 33% were classified with normal carotid arteries, 27% with thickened carotid arteries and 40% with plaques. In the intention-to-treat population (377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the mean thickness at the six sites measured was rather small (0.015 mm/year), but significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P < 0.01). Although rates of change in the carotid intima-media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone, when changes in the mean thickness of six sites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versus chlorthalidone -0.037 mm/year per mm, P < 0.02). The blood pressure-lowering effect of the two randomized treatments was similar. Taking fatal and nonfatal, major and minor cardiovascular events together, there were 19 events in the verapamil group and 35 in the chlorthalidone group, with a significantly (P < 0.01) greater incidence in patients with plaques, and among patients with plaques in those who were randomized to chlorthalidone (P < 0.05). CONCLUSIONS: In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions. Changes in the carotid intima-media thickness were small in both groups, and the differences between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events (better intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaques may have clinical and prognostic relevance.

Adult↗

PubMed1993

Postinfarct treatment with verapamil. Effect of verapamil in patients with hypertension.

In the Danish Verapamil Infarction Trial II (DAVIT II), treatment with verapamil 360 mg/day improved reinfarction-free survival compared with administration of placebo. Verapamil appears to effectively prevent reinfarction and sudden death, i.e. sudden events (hazard ratio 0.78 compared with placebo, 95% confidence limits 0.62 to 0.99). In a retrospective analysis of data from DAVIT II, verapamil treatment in patients with systemic hypertension prevented reinfarction significantly better than placebo (15 of 149 verapamil recipients compared with 27 of 152 placebo recipients reinfarcted, p = 0.04). Similarly, first cardiovascular events, i.e. first reinfarction, first stroke or death, were prevented more effectively by verapamil treatment than by administration of placebo (29 verapamil recipients vs 42 placebo recipients had first cardiovascular events, p = 0.07).

Cerebrovascular Disorders↗

PubMed2000

Early administration of verapamil after thrombolysis in acute anterior myocardial infarction. Effect on left ventricular remodeling and clinical outcome. VAMI Study Group. Verapamil Acute Myocardial Infarction.

BACKGROUND: The administration of verapamil during the reperfusion phase of acute myocardial infarction can reduce the extent and severity of microvessel damage and limit myocardial dysfunction. We aimed at investigating the effect of early verapamil administration on left ventricular remodeling and the clinical evolution after myocardial infarction. METHODS: Eighty-eight patients with first acute anterior myocardial infarction thrombolysed < 4 hours from symptom onset were enrolled in a multicenter, randomized, double-blind, controlled study of verapamil administration (5 mg i.v. + 2 microg/kg/min over 24 hours). Echocardiographic end-diastolic (EDV) and end-systolic (ESV) left ventricular volumes were assessed by biplane Simpson's rule. RESULTS: At 90 days, EDV in the verapamil and placebo groups was respectively 88.9 +/- 27.8 and 95.8 +/- 30.7 ml (p = 0.11), ESV was 52.6 +/- 22.7 and 57.7 +/- 25.4 ml (p = 0.18). There was no change over time in the verapamil group (day 3 vs day 90: EDV 85.0 +/- 17.7 vs 88.9 +/- 27.8 ml, p = NS; ESV 48.7 +/- 14.1 vs 52.6 +/- 22.7 ml, p = NS) while left ventricular volume increased in the placebo group (day 3 vs day 90: EDV 87.6 +/- 21.1 vs 95.8 +/- 30.7 ml, p = 0.03; ESV 52.0 +/- 16.9 vs 57.7 +/- 25.4 ml, p = 0.08). NYHA functional classes were differently distributed at 30 and 90 days (chi2 = 0.009 and 0.07), with a lower prevalence of classes II and III in the verapamil group (p = 0.03). CONCLUSIONS: The early intravenous administration of verapamil in thrombolysed patients can reduce left ventricular remodeling and NYHA functional class after acute anterior myocardial infarction.

Calcium Channel Blockers↗