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Preventing spasm of the radial artery conduit during coronary artery bypass grafting: Nicardipine versus verapamil.
Özdemir, HI, van Dijk, CHB, Özdemir, AB, van Straten, BHM, Haanschoten, M, Soliman-Hamad, MA
Journal of cardiac surgery. 2019;(12):1505-1510
Abstract
BACKGROUND AND AIM OF THE STUDY In vitro studies have shown a reduction in radial artery spasm with the use of calcium antagonists. The purpose of this study was to evaluate the efficacy of topical treatment of the radial artery conduit using either verapamil or nicardipine before the anastomoses. METHODS This prospective randomized study included 131 patients, who underwent coronary artery bypass grafting surgery with the use of the radial artery as a conduit. In 65 patients, the harvested radial artery was topically treated with verapamil and in 66 patients with nicardipine. After harvesting the radial artery, the direct flow through the conduit was measured in vitro before 5-minute incubation in nicardipine or verapamil and measured again after incubation. The flow before and after incubation was compared. Postincubation flow was also compared in the two groups. After performing the anastomosis, the flow through the radial artery was measured in vivo. RESULTS The mean flow after NaCl incubation was 19.93 ± 12.66 mL/min and after incubation in the Ca+ channel blocker 47.16 ± 14.58 mL/min (P < .001). No significant difference in postincubation free flow was found between verapamil (46.29 ± 15.43 mL/min) and nicardipine (48.01 ± 13.77 mL/min; P = .503). CONCLUSION Topical treatment with Ca+ channel blockers reduces radial artery spasm and significantly increases the free flow through the radial artery conduit. Nicardipine is a safe and effective alternative of verapamil in preventing spasm of radial artery conduit.
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Comparison of intralesional verapamil versus intralesional corticosteroids in treatment of keloids and hypertrophic scars: A randomized controlled trial.
Abedini, R, Sasani, P, Mahmoudi, HR, Nasimi, M, Teymourpour, A, Shadlou, Z
Burns : journal of the International Society for Burn Injuries. 2018;(6):1482-1488
Abstract
BACKGROUND Keloids and hypertrophic scars are due to overgrowth of dermal collagen following trauma to the skin that usually cause major physical, psychological and cosmetic problems. METHODS In this randomized controlled trial, with a paired design, 50 patients with 2 or more keloids were included. In the control group (50 lesions), intralesional triamcinolone acetonide (40mg/mL) was injected at three-week intervals for a total of 18weeks. In the other group (50 lesions), lesions were treated by verapamil (2.5mg/mL) with the same therapeutic sessions. Scar evaluation at each stage and at the end of 3months follow up was done by serial photographic records as well as by Vancouver Scar Scale (VSS). RESULTS Mean zero VSS scores were achieved with only triamcinolone in respect of scar height (week 15th) and pliability (week 15th). No therapeutic event (parameter=0) or significant improvement was seen in verapamil group. CONCLUSION Our results did not support verapamil's capability in treatment of keloid nor hypertrophic scars.
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Verapamil Use Is Associated With Reduction of Newly Diagnosed Diabetes Mellitus.
Yin, T, Kuo, SC, Chang, YY, Chen, YT, Wang, KK
The Journal of clinical endocrinology and metabolism. 2017;(7):2604-2610
Abstract
OBJECTIVE The mechanism of the beneficial effect of calcium-channel blockers (CCBs), especially verapamil, on the development of type 2 diabetes mellitus (T2DM) has been described. This study compared the incidence of T2DM in adults prescribed oral verapamil and propensity score-matched adults prescribed other oral CCBs. METHODS This retrospective population-based cohort study used Taiwan's National Health Insurance Research Database from 2000 to 2011. T2DM was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS During follow-up periods of 41,958 and 42,118 person-years, 269 of 4930 patients in the verapamil cohort and 340 of 4930 patients in the matched cohort, respectively, developed T2DM. The incidence rates were 6.41 and 8.07 per 1000 population per year among verapamil and other CCB users, respectively. The adjusted hazard ratio (HR) for T2DM associated with use of verapamil (vs. other CCBs) was 0.80 [95% confidence interval (CI), 0.68 to 0.94; P = 0.006]. After exclusion of patients followed for <180 days or <365 days (to avoid bias derived from delayed diagnosis), adjusted HRs remained significant [0.79 (95% CI, 0.67 to 0.93; P = 0.005) and 0.77 (95% CI, 0.65 to 0.91; P = 0.002), respectively]. Only the interaction term for age was significant (P = 0.009). Verapamil had a more prominent effect on patients aged older than 65 years (P < 0.001). CONCLUSIONS In patients with no known history of diabetes mellitus, oral verapamil use was associated with a decreased incidence of T2DM compared with other CCBs.
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Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids.
Ahuja, RB, Chatterjee, P
Burns : journal of the International Society for Burn Injuries. 2014;(4):583-8
Abstract
There is not much level 1 evidence based literature to guide management of hypertrophic scars and keloids despite an array of therapeutic modalities at disposal. Intralesional (i/l) triamcinolone injections have remained a gold standard in non surgical management. Sporadic reports on use of i/l verapamil suggest its efficacy. Since verapamil has not found sufficient mention as an effective alternative modality, it was decided to undertake a randomized study which could also address some additional clinical parameters. A randomized, parallel group and observer blinded comparison with 40 patients (48 scars) was carried out to compare the effects of i/l triamcinolone (T) (22 scars) and verapamil injections (V) (26 scars). 1.5 ml was the maximum indicative volume decided in the study protocol for both the drugs (triamcinolone @40 mg/ml and verapamil @ 2.5 mg/ml). Patients included were aged between 15-60 years with scars ranging between 0.5-5 cm (but total area roughly <6 cm(2)), and scars under 2 years duration. Patients with keloidal diathesis were excluded. Injections were scheduled every three weeks until complete flattening of the scar or eight sessions, which ever came earlier. No concomitant therapies like massage, silicone gel or pressure garments were used. Scar evaluation at each stage was done by serial photographic records as well as by Vancouver Scar Scale (VSS). Comparative survival analysis between the two drugs was done using Kaplan Meier curves, and VSS scores were analyzed using Wilcoxon test and log rank test. Mean zero VSS scores were achieved with treatments in respect of scar height (T-12 weeks, V-21 weeks), vascularity (T-15 weeks, V-18 weeks) and pliability (T-15 weeks, V-21 weeks). The improvement in scar vascularity and pliability kept pace with decrease in scar height, in both the groups. There was not much difference in the rate of change of scar pigmentation with either drug but almost 60% patients in both the groups regained normal pigmentation. Our study adds to evidence of verapamil's capability in flattening the raised scars. With an extremely low cost and fewer adverse effects it deserves better positioning in the wide armamentarium against hypertrophic scars. It also offers several therapeutic possibilities to alternate with triamcinolone or be used simultaneously in larger (or multiple) scars.
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Comparison of transdermal electromotive administration of verapamil and dexamethasone versus intra-lesional injection for Peyronie's disease.
Mehrsai, AR, Namdari, F, Salavati, A, Dehghani, S, Allameh, F, Pourmand, G
Andrology. 2013;(1):129-32
Abstract
To compare the efficacy of transdermal electromotive administration and intra-lesional injection of verapamil plus dexamethasone for the treatment of Peyronie's disease. Patients with Peyronie's disease of less than 2-year duration were randomized into two groups of transdermal electromotive administration and intra-lesional injection of verapamil plus dexamethasone. During the 6-week therapy period, a single weekly dose of 10 mg verapamil and 4 mg dexamethasone solution was administered to 30 patients in each group either by transdermal electromotive method or via the conventional injection method by a syringe connected to a 25 G needle. Evaluations of plaque length, width, and volume, penile curvature, erectile dysfunction and penile deviations were carried out before and after 1 and 3 months of the interventions. Erectile pain was reduced in the electromotive group from a mean of 5.1-1.0 in scale of 10 and from 5.4 to 3.6 in the injection group (p = 0.006). Regarding plaque length, plaque width, penile curvature plaque volume and erectile dysfunction, the electromotive administration group showed better results which, however, were not statistically significant. (p > 0.05). Transdermal electromotive drug administration yielded comparable results as against current conventional intra-lesional injection technique and fared better in controlling erectile pain.
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Pharmacogenomic association of nonsynonymous SNPs in SIGLEC12, A1BG, and the selectin region and cardiovascular outcomes.
McDonough, CW, Gong, Y, Padmanabhan, S, Burkley, B, Langaee, TY, Melander, O, Pepine, CJ, Dominiczak, AF, Cooper-Dehoff, RM, Johnson, JA
Hypertension (Dallas, Tex. : 1979). 2013;(1):48-54
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Abstract
We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a β-blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)×treatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection.
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SF-6D utility index as measure of minimally important difference in health status change.
Gandhi, PK, Ried, LD, Bibbey, A, Huang, IC
Journal of the American Pharmacists Association : JAPhA. 2012;(1):34-42
Abstract
OBJECTIVES To combine anchor- and distribution-based approaches to identify minimally important differences (MIDs) for the short-form six-dimension utility index (SF-6D) and to identify variables associated with self-reported health status change. DESIGN Descriptive, exploratory, nonexperimental study. SETTING United States between April 1, 1999, and October 31, 1999. PATIENTS 2,317 participants of SADD-Sx (Study of Antihypertensive Drugs and Depressive Symptoms), aged 50 years or older and with hypertension and coronary artery disease. INTERVENTION Patients were randomized into a verapamil SR- or atenolol-led hypertensive treatment strategy and mailed baseline and 1-year surveys. MAIN OUTCOME MEASURE SF-6D utility scores for patients completing both surveys. RESULTS The pooled mean (±SD) MID change on the SF-6D of patients whose health status minimally changed was 0.035 ± 0.095. The anchor-based change scores had a median value of 0.036 (interquartile range -0.03 to 0.10). One-third and one-half of the SD of SF-6D change scores were 0.035 and 0.053, respectively. Whites were less likely to report minimally improved health status compared with nonwhites (odds ratio 0.59 [95% CI 0.40-0.88]). Change in SF-6D scores improved prediction of health status change. CONCLUSION We recommend using the MID range based on all patients combined (-0.03 to 0.10) to interpret SF-6D scores. These estimates can be used in conjunction with other measures of efficacy to determine meaningful changes. SF-6D demonstrates potential utility in predicting minimally important improvement or worsening among patients receiving different pharmacologic medications.
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Identifying iatrogenic depression using confirmatory factor analysis of the Center for Epidemiologic Studies Depression Scale in patients prescribed a verapamil-sustained-release-led or atenolol-led hypertension treatment strategy.
Wilson, DL, Ried, LD
Research in social & administrative pharmacy : RSAP. 2012;(4):309-20
Abstract
BACKGROUND β-blockers and calcium channel blockers are highly effective medications indicated for treatment and prevention of hypertension. However, the literature regarding the potential depressive effects of β-blockers and calcium channel blockers is equivocal regarding whether one or both are associated with depression. OBJECTIVES To determine whether self-reported depressive symptoms of older persons with hypertension and coronary artery disease and who were randomly assigned to a verapamil-sustained-release-led (Ve-led) or atenolol-led (At-led) hypertension treatment strategy were similar using confirmatory factor analytical models of the Center for Epidemiologic Studies Depression Scale (CES-D). METHODS This study used a mail survey of patients enrolled in a substudy of an international randomized controlled clinical trial. Complete data on the CES-D after 1 year of treatment were obtained from 1019 study subjects. Multiple group confirmatory factor analysis (CFA) procedures were used to test for differences in the fit of the data to the initial 4-factor CES-D model among patients assigned to the 2 treatment groups after 12 months of therapy. A test of configural invariance was conducted by sequentially constraining various matrices to be equal across groups. The convergent validity of the model was tested by examining the standard errors of the lambda-X parameter estimates of the configural model. The factor loadings for like items were investigated across the 2 groups using a test of strong factorial invariance. Finally, the 2 treatment groups were compared on the 4 factors to detect differences in the model's parameters. RESULTS Overall, the data fit the CFA models across the 2 treatment groups based on the 4-factor model. However, 3 items differed slightly, including appetite, depressed, and crying. The data suggested significant differences across groups on the positive affect, interpersonal relations, and somatic and retarded activity latent variables. CONCLUSIONS The domains indicating less happiness and more depressive symptoms were most likely to be unfavorably impacted by the At-led treatment strategy. Given a choice between these equally effective high blood pressure treatment strategies, it may be prudent to use the Ve-led strategy. This is especially true if the risk of the occurrence of a mood-related side effect of the β-blocker outweighs its other benefits in comparison.
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[Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars].
Xu, SJ, Teng, JY, Xie, J, Shen, MQ, Chen, DM
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery. 2009;(1):37-40
Abstract
OBJECTIVE To investigate the effects of intralesional steroid, interferon alpha-2b or verapamil injection on proliferation, apoptosis and TGF-beta1 expression in keloid and hypertrophic scar in vivo. METHODS 6 patients with keloids and 6 patients with hypertrophic scar were treated with intralesional injection of triamcinolone acetonide (40 mg/ml) or IFN alpha-2b (15 x 10(5) U/ml) or verapamil (2.5 mg/ml). Samples were collected on the 7th day after intralesional injection. Samples of untreated keloid and hypertrophic scar and normal skin were used as control. Expression of PCNA and TGF-beta1 was detected in situ by immunohistochemical staining, and apoptosis was detected in situ by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL). RESULTS 1) Triamcinolone acetonide could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, as well as inducing apoptosis. 2) IFN alpha-2b could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, but not inducing apoptosis; 3) Verapamil could also prohibit proliferative scars through inhibiting proliferation and TGF-beta1 expression in fibroblasts, as well as inducing apoptosis. While the effect of inducing apoptosis was stronger than that of triamcinolone acetonide, the effect of inhibiting TGF-beta1 expression was weaker than those of triamcinolone acetonide and IFN alpha-2b. CONCLUSIONS Although intraleional injection of steroid, interferon alpha-2b or verapamil were all effective in the treatment of keloid and hypertrophic scar, their mechanisms are not similar.
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INVEST revisited: review of findings from the International Verapamil SR-Trandolapril Study.
Cooper-DeHoff, RM, Handberg, EM, Mancia, G, Zhou, Q, Champion, A, Legler, UF, Pepine, CJ
Expert review of cardiovascular therapy. 2009;(11):1329-40
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Abstract
The International Verapamil SR-Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a beta-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.