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1.
Beta blockers versus calcium channel blockers for provocation of vasospastic angina after drug-eluting stent implantation: a multicentre prospective randomised trial.
Sawano, M, Katsuki, T, Kitai, T, Tamita, K, Obunai, K, Ikegami, Y, Yamane, T, Ueda, I, Endo, A, Maekawa, Y, et al
Open heart. 2020;(2)
Abstract
BACKGROUND Drug-eluting stent-induced vasospastic angina (DES-VSA) has emerged as a novel complication in the modern era of percutaneous coronary intervention (PCI). Although beta blockers (BBs) are generally recommended for coronary heart disease, they may promote incidence of DES-VSA. This study aimed to compare the effects of calcium channel blockers (CCBs) perceived to be protective against DES-VSA and BBs on subsequent coronary events after second-generation drug-eluting stent implantation. METHODS In this multicentre prospective, randomised study, 52 patients with coronary artery disease who underwent PCI for a single-vessel lesion with everolimus-eluting stent placement were randomised into post-stenting BB (N=26) and CCB (N=26) groups and followed for 24 months to detect any major cardiovascular events (MACE). A positive result on acetylcholine provocation testing during diagnostic coronary angiography (CAG) at 9 months was the primary endpoint for equivalence. MACE included all-cause death, non-fatal myocardial infarction, unstable angina, cerebrovascular disease or coronary revascularisation for stable coronary artery disease after index PCI. RESULTS At 9 months, 42 patients (80.8%) underwent diagnostic coronary angiography and acetylcholine provocation testing. Among them, seven patients in each group were diagnosed with definite vasospasm (intention-to-treat analysis 26.9% vs 26.9%, risk difference 0 (-0.241, 0.241)). Meanwhile, the secondary endpoint, 24-month MACE, was higher in the CCB group (19.2%) than in the BB group (3.8%) (p=0.01). In detail, coronary revascularisation for stable coronary artery disease was the predominant endpoint that contributed to the greater proportion of MACE in the CCB group (CCB (19.2%) vs BB (3.8%), p=0.03). CONCLUSIONS The incidence of acetylcholine-induced coronary artery spasms did not differ between patients receiving BBs or CCBs at 9 months after PCI. However, a higher incidence of 2-year MACE was observed in the CCB group, suggesting the importance of BB administration. TRIAL REGISTRATION NUMBER This study was registered at the Japanese University Hospital Medical Information Network (UMIN) Clinical Trial Registry (The Prospective Randomized Trial for Optimizing Medical Therapy After Stenting: Calcium-Beta Trial; UMIN000008321, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009536).
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2.
A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions.
Werner, GS, Martin-Yuste, V, Hildick-Smith, D, Boudou, N, Sianos, G, Gelev, V, Rumoroso, JR, Erglis, A, Christiansen, EH, Escaned, J, et al
European heart journal. 2018;(26):2484-2493
Abstract
AIMS: The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO. METHOD AND RESULTS Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups. CONCLUSION Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone. TRIAL REGISTRATION NCT01760083.
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3.
Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation.
Ulimoen, SR, Enger, S, Pripp, AH, Abdelnoor, M, Arnesen, H, Gjesdal, K, Tveit, A
European heart journal. 2014;(8):517-24
Abstract
AIMS: Rate control of atrial fibrillation (AF) has become a main treatment modality, but we need more knowledge regarding the different drugs used for this purpose. In this study, we aimed to compare the effect of four common rate-reducing drugs on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent AF. METHODS AND RESULTS We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF and normal left ventricular function in a randomized, cross-over, investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered o.d. for 3 weeks. At baseline and on the last day of each treatment period, the patients underwent a maximal cardiopulmonary exercise test and blood samples were obtained at rest and at peak exercise. The exercise capacity (peak VO2) was significantly lower during treatment with metoprolol and carvedilol compared with baseline (no treatment) or treatment with diltiazem and verapamil (P < 0.001 for all). Compared with baseline, treatment with diltiazem and verapamil significantly reduced the NT-proBNP levels both at rest and at peak exercise, whereas treatment with metoprolol and carvedilol increased the levels (P < 0.05 for all). CONCLUSION Rate-reducing treatment with diltiazem or verapamil preserved exercise capacity and reduced levels of NT-proBNP compared with baseline, whereas treatment with metoprolol or carvedilol reduced the exercise capacity and increased levels of NT-proBNP.
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4.
N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF).
Maeder, MT, Rickenbacher, P, Rickli, H, Abbühl, H, Gutmann, M, Erne, P, Vuilliomenet, A, Peter, M, Pfisterer, M, Brunner-La Rocca, HP, et al
European journal of heart failure. 2013;(10):1148-56
Abstract
AIMS: To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF). METHODS AND RESULTS Patients with HFpEF (LVEF >45%; n = 123) and HF with reduced LVEF (HFrEF; LVEF ≤45%; n = 499) with age ≥60 years, NYHA class ≥ II, and elevated NT-proBNP (>400 ng/L or >800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA ≤II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P = 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n = 59) and NT-proBNP-guided (n = 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival. CONCLUSIONS Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF. Trial registration ISRCTN43596477.
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5.
Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation.
Ulimoen, SR, Enger, S, Carlson, J, Platonov, PG, Pripp, AH, Abdelnoor, M, Arnesen, H, Gjesdal, K, Tveit, A
The American journal of cardiology. 2013;(2):225-30
Abstract
Rate control of atrial fibrillation (AF) is a main treatment modality. However, data are scarce on the relative efficacy of calcium channel blockers and β blockers or between drugs within each class. The purpose of the present study was to compare the effect of 4 rate-reducing, once-daily drug regimens on the ventricular heart rate and arrhythmia-related symptoms in patients with permanent AF. We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF in an investigator-blind cross-over study. Diltiazem 360 mg/day, verapamil 240 mg/day, metoprolol 100 mg/day, and carvedilol 25 mg/day were administered for 3 weeks in a randomized sequence. The 24-hour heart rate was measured using Holter monitoring, and arrhythmia-related symptoms were assessed using the Symptom Checklist questionnaire before randomization and on the last day of each treatment period. The 24-hour mean heart rate was 96 ± 12 beats/min at baseline (no treatment), 75 ± 10 beats/min with diltiazem, 81 ± 11 beats/min with verapamil, 82 ± 11 beats/min with metoprolol, and 84 ± 11 beats/min with carvedilol. All drugs reduced the heart rate compared to baseline (p <0.001 for all). The 24-hour heart rate was significantly lower with diltiazem than with any other drug tested (p <0.001 for all). Compared to baseline, diltiazem significantly reduced both the frequency (p <0.001) and the severity (p = 0.005) of symptoms. In contrast, verapamil reduced symptom frequency only (p = 0.012). In conclusion, diltiazem 360 mg/day was the most effective drug regimen for reducing the heart rate in patients with permanent AF. Arrhythmia-related symptoms were reduced by treatment with the calcium channel blockers diltiazem and verapamil, but not by the β blockers.
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6.
Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review.
Brewster, LM, Seedat, YK
BMC medicine. 2013;:141
Abstract
BACKGROUND Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. METHODS Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. RESULTS We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. CONCLUSION Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs.
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7.
Beyond medication prescription as performance measures: optimal secondary prevention medication dosing after acute myocardial infarction.
Arnold, SV, Spertus, JA, Masoudi, FA, Daugherty, SL, Maddox, TM, Li, Y, Dodson, JA, Chan, PS
Journal of the American College of Cardiology. 2013;(19):1791-801
Abstract
OBJECTIVES The aim of this study was to examine the prescribing patterns of medications quantified by the performance measures for acute myocardial infarction (AMI). BACKGROUND Current performance measures for AMI are designed to improve quality by quantifying the use of evidence-based treatments. However, these measures only assess medication prescription. Whether patients receive optimal dosing of secondary prevention medications at the time of and after discharge after AMI is unknown. METHODS We assessed treatment doses of beta-blockers, statins, and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) at discharge and 12 months after AMI among 6,748 patients from 31 hospitals enrolled in 2 U.S. registries (2003 to 2008). Prescribed doses were categorized as none, low (<50% target [defined from seminal clinical trials]), moderate (50% to 74% target), or goal (≥ 75% target). Patients with contraindications were excluded from analyses for that medication. RESULTS Most eligible patients (>87%) were prescribed some dose of each medication at discharge, although only 1 in 3 patients were prescribed these medications at goal doses. Of patients not discharged on goal doses, up-titration during follow-up occurred infrequently (approximately 25% of patients for each medication). At 12 months, goal doses of beta-blockers, statins, and ACEI/ARBs were achieved in only 12%, 26%, and 32% of eligible patients, respectively. After multivariable adjustment, prescription of goal dose at discharge was strongly associated with being at goal dose at follow-up: beta-blockers, adjusted odds ratio (OR): 6.08 (95% confidence interval [CI]: 3.70 to 10.01); statins, adjusted OR: 8.22 (95% CI: 6.20 to 10.90); ACEI/ARBs, adjusted OR: 5.80 (95% CI: 2.56 to 13.16); p < 0.001 for each. CONCLUSIONS Although nearly all patients after an AMI are discharged on appropriate secondary prevention medications, dose increases occur infrequently, and most patients are prescribed doses below those with proven efficacy in clinical trials. Integration of dose intensity into performance measures might help improve the use of optimal medical therapy after AMI.
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8.
Comparison of rate versus rhythm control in patients with atrial fibrillation and a pacemaker.
Badheka, AO, Marzouka, GR, Rathod, AD, Patel, NJ, Myerburg, RJ, Mitrani, RD
The American journal of cardiology. 2013;(12):1759-63
Abstract
The effect of rate versus rhythm control in patients with atrial fibrillation who have undergone previous pacemaker (PM) implantation is unknown. We evaluated the mortality in patients with atrial fibrillation and a PM randomized to rate or rhythm control treatment strategies. The Atrial Fibrillation Follow-up Investigation of Rhythm Management data set was stratified by the presence (n = 250) or absence (n = 3,810) of a PM at randomization into the rate or rhythm control arm. Kaplan-Meier curves were used for univariate analysis, and proportional hazards were used for multivariate analysis. The subjects with a PM (n = 250) were older (73 vs 69 years, p <0.01) and had a greater prevalence of coronary artery disease (53% vs 37%, p <0.01) and congestive heart failure (33% vs 23%, p <0.01). All-cause mortality was significantly greater in the PM patients who were randomized to the rhythm control arm (n = 128) than in the patients enrolled in the rate control arm with or without a PM (n = 2,027, p <0.01) and those in the rhythm control arm without a PM (n = 1,905, p <0.01). Multivariate analysis revealed that predictors of all-cause mortality included PM patients randomized to the rhythm control arm (hazard ratio 2.59, 95% confidence interval 1.46 to 4.58, p <0.01) and the presence of congestive heart failure (hazard ratio 2.42, 95% confidence interval 1.40 to 4.16, p <0.01). In conclusion, all-cause mortality was greater among patients with atrial fibrillation with a PM, who were randomized to the rhythm control arm of the Atrial Fibrillation Follow-up Investigation of Rhythm Management study compared with all other patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management study. The rhythm control strategy in patients with a PM was an independent predictor of mortality.
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9.
The impact of carvedilol and metoprolol on serum lipid concentrations and symptoms in patients with hyperthyroidism.
Ozbilen, S, Eren, MA, Turan, MN, Sabuncu, T
Endocrine research. 2012;(3):117-23
Abstract
BACKGROUND Hyperthyroidism is associated with unpleasant symptoms and hypertension due to increased adrenergic tone. Therefore, beta-blockers are often used in hyperthyroid patients. While some beta-blockers (such as propronolol and metoprolol) may have unwanted effects on lipid profile, carvedilol, a new alpha- and beta-blocker, has been suggested to have some metabolic advantages with respect to lipid profiles in hypertensive patients. However, this has not been shown in hyperthyroid patients. OBJECTIVE We aimed to compare the effects of two beta-blockers (metoprolol and carvedilol) on the lipid profiles of hyperthyroid patients with hypertension. METHODS Thirty patients with hyperthyroidism and hypertension were randomly assigned to receive either carvedilol (n = 15) or metoprolol (n = 15). Thyroid-stimulating hormone (TSH), free T3, free T4, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and total cholesterol levels were measured before and following 3 months of treatment. RESULTS Systolic and diastolic blood pressure, heart rate, TSH, and free T4 improved significantly in both treatment groups. There were no statistically significant changes in the lipid parameters in either of the two treatment groups; however, triglyceride levels slightly decreased with carvedilol treatment. There were also no differences between the two groups in terms of the typical symptoms of hyperthyroidism. CONCLUSION Carvedilol might be a preferred agent to treat hyperthyroid patients who have hypertension and dyslipidemia. This is likely due to the possible beneficial effect of carvedilol on lipid parameters, especially on triglyceride levels.
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10.
Anti-adrenergic medications and edema development after intracerebral hemorrhage.
Sansing, LH, Messe, SR, Cucchiara, BL, Lyden, PD, Kasner, SE
Neurocritical care. 2011;(3):395-400
Abstract
BACKGROUND Use of antihypertensive medications is common after intracerebral hemorrhage (ICH). Medications that block adrenergic activation (e.g., beta-blockers and the alpha(2)-agonist, clonidine) may reduce the inflammatory response and therefore have secondary benefit after ICH. METHODS The patients with acute ICH enrolled in the placebo arm of the CHANT trial were included. Univariate and multivariate analyses were undertaken for factors associated with blood pressure medication use, edema at 72 h, and clinical outcome at 90 days. RESULTS Of the 303 patients, 87.8% received some antihypertensive treatment during the first 72 h of hospitalization. Edema volume on neuroimaging at 72 h was independently associated with clinical outcome. Use of anti-adrenergic medications was associated with less edema after controlling for hemorrhage volume and blood pressure. CONCLUSIONS Antihypertensive medications that antagonize the sympathetic nervous system may reduce perihematomal edema after ICH.