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Advances in Therapy Jun 2021Combination antihypertensive therapy is required by most patients to achieve guideline-recommended blood pressure (BP) goals. This study assessed the effectiveness and... (Observational Study)
Observational Study
Effectiveness and Tolerability of the Single-Pill Combination of Bisoprolol and Perindopril in Patients with Arterial Hypertension and Stable Coronary Artery Disease in Daily Clinical Practice: The STYLE Study.
INTRODUCTION
Combination antihypertensive therapy is required by most patients to achieve guideline-recommended blood pressure (BP) goals. This study assessed the effectiveness and tolerability of bisoprolol/perindopril (Bis/Per) single-pill combination (SPC) in Russian patients with hypertension and coronary artery disease (CAD) treated in routine clinical practice.
METHODS
STYLE (NCT03730116) was an open-label, uncontrolled, prospective observational study conducted in patients who were already receiving Bis/Per SPC, switched to SPC from Bis or Per monotherapy, or switched from a free combination of Bis and Per. Primary endpoint criteria were assessed at 1 and 3 months and included change in mean office systolic/diastolic blood pressure (SBP/DBP), proportion achieving target BP (< 140/90 mmHg), and measures of antianginal effectiveness.
RESULTS
The full analysis set comprised 1892 subjects. Mean age was 61.9 ± 8.8 years, 53.2% were women, and mean durations of hypertension and CAD were 12.5 ± 7.9 and 7.2 ± 6.4 years, respectively. Mean SBP/DBP decreased by 22.3/11.0 mmHg and 31.5/15.9 mmHg at 1 and 3 months, respectively (P < 0.0001 vs baseline). Target BP was achieved by 49.2% and 86.7% of patients at 1 and 3 months, respectively. Reductions in mean number of angina attacks and nitrate consumption and improvements in heart rate were statistically significant. Treatment was well tolerated.
CONCLUSION
Treatment of patients with hypertension and CAD with Bis/Per SPC for 3 months was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by an improvement in angina symptoms. Treatment was well tolerated in a broad patient population representative of those seen in everyday clinical practice.
Topics: Aged; Antihypertensive Agents; Bisoprolol; Blood Pressure; Coronary Artery Disease; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Perindopril; Russia; Treatment Outcome
PubMed: 33991323
DOI: 10.1007/s12325-021-01754-2 -
MedComm Feb 2023In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results...
In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results demonstrated that bisoprolol improved the prognosis of chronic heart failure in comparison with carvedilol, and carvedilol exerted similar effects as metoprolol succinate and nebivolol and better effect than metoprolol tartrate (evidence levels: bisoprolol > carvedilol = metoprolol succinate = nebivolol > metoprolol tartrate; " > " means "prior to").
PubMed: 36628295
DOI: 10.1002/mco2.199 -
Journal of the American Heart... Feb 2019Background Many hospitalized patients with heart failure and reduced ejection fraction ( HF r EF ) have a slow heart rate at discharge, and the effect of β-blockers may...
Background Many hospitalized patients with heart failure and reduced ejection fraction ( HF r EF ) have a slow heart rate at discharge, and the effect of β-blockers may be reduced in those patients. We sought to examine the variable effect of β-blockers on clinical outcomes according to the discharge heart rate of hospitalized HF r EF patients. Methods and Results The KorAHF (Korean Acute Heart Failure) registry consecutively enrolled 5625 patients hospitalized for acute heart failure. In this analysis, we included patients with HF r EF (left ventricular ejection fraction ≤40%). Slow heart rate was defined as <70 beats per minute regardless of the use of β-blockers. The primary outcome was 1-year all-cause postdischarge death according to heart rate. Among 2932 patients with HF r EF , 840 (29%) had a slow heart rate and 56% received β-blockers at discharge. Patients with slow heart rates were older and had lower 1-year mortality than those with high heart rates ( P<0.001). A significant interaction between discharge heart rate and β-blocker use was observed ( P<0.001 for interaction). When stratified, only patients without a β-blocker prescription and with a high heart rate showed higher 1-year mortality. In a Cox-proportional hazards regression analysis, β-blocker prescription at discharge was associated with 24% reduced risk for 1-year mortality in patients with high heart rates (hazard ratio: 0.76; 95% CI, 0.61-0.95) but not in those with slow heart rates (hazard ratio: 1.02; 95% CI, 0.68-1.55). Conclusions Many patients with acute heart failure have slow discharge heart rates, and β-blockers may have a limited effect on HF r EF and slow discharge heart rate. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01389843.
Topics: Adrenergic beta-Antagonists; Aged; Bisoprolol; Carvedilol; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Male; Metoprolol; Nebivolol; Patient Discharge; Prospective Studies; Republic of Korea; Stroke Volume; Survival Rate; Time Factors; Treatment Outcome
PubMed: 30755071
DOI: 10.1161/JAHA.118.011121 -
Clinical Pharmacokinetics May 2019Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug-drug interactions (DDIs). These DAAs are used for the treatment of... (Review)
Review
Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug-drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (β-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA.
Topics: Antiviral Agents; Cardiovascular Agents; Cardiovascular Diseases; Drug Interactions; Drug Therapy, Combination; Hepatitis C; Humans; Risk
PubMed: 30259390
DOI: 10.1007/s40262-018-0710-1 -
Farmacia Hospitalaria : Organo Oficial... Feb 2024Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is... (Review)
Review
INTRODUCTION
Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine.
MATERIALS AND METHODS
A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualizing dosing", "clinical routine", and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis.
RESULTS
49 articles were included for the final analysis following review by 2 investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found.
CONCLUSION
The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.
PubMed: 38341366
DOI: 10.1016/j.farma.2023.12.004 -
Pharmacogenomics and Personalized... 2022Bisoprolol is a widely used beta-blocker in patients with cardiovascular diseases. As with other beta-blockers, there is variability in response to bisoprolol, but the...
PURPOSE
Bisoprolol is a widely used beta-blocker in patients with cardiovascular diseases. As with other beta-blockers, there is variability in response to bisoprolol, but the underlying reasons for this have not been clearly elucidated. Our aim was to investigate genetic factors that affect bisoprolol pharmacokinetics (PK) and pharmacodynamics (PD), and potentially the clinical outcomes.
PATIENTS AND METHODS
Patients with non-ST elevation acute coronary syndrome were recruited prospectively on admission to hospital and followed up for up to 2 years. Patients from this cohort who were on treatment with bisoprolol, at any dose, had bisoprolol adherence data and a plasma sample, one month after discharge from index hospitalisation were included in the study. Individual bisoprolol clearance values were estimated using population pharmacokinetic modeling. Genome-wide association analysis after genotyping was undertaken using an Illumina HumanOmniExpressExome-8 v1.0 BeadChip array, while CYP2D6 copy number variations were determined by PCR techniques and phenotypes for CYP2D6 and CYP3A were inferred from the genotype. GWAS significant SNPs were analysed for heart rate response to bisoprolol in an independent cohort of hypertensive subjects.
RESULTS
Six hundred twenty-two patients on bisoprolol underwent both PK and genome wide analysis. The mean (IQR) of the estimated clearance in this population was 13.6 (10.0-18.0) L/h. Bisoprolol clearance was associated with rs11029955 (p=7.17×10) mapped to the region of coiled-coil domain containing 34 region (CCDC34) on chromosome 11, and with rs116702638 (p=2.54×10). Each copy of the minor allele of rs11029955 was associated with 2.2 L/h increase in clearance. In an independent cohort of hypertensive subjects, rs11029955 was associated with 24-hour heart rate response to 4-week treatment with bisoprolol (p= 9.3×10), but not with rs116702638.
CONCLUSION
A novel locus on the chromosomal region 11p14.1 was associated with bisoprolol clearance in a real-world cohort of patients and was validated in independent cohort with a pharmacodynamic association.
PubMed: 35356681
DOI: 10.2147/PGPM.S352719 -
Chonnam Medical Journal May 2021Following acute myocardial infarction (AMI), early use of beta-blockers (BBs) reduced the incidences of ventricular arrhythmia (VA) and death in the pre reperfusion era....
Following acute myocardial infarction (AMI), early use of beta-blockers (BBs) reduced the incidences of ventricular arrhythmia (VA) and death in the pre reperfusion era. However, some studies have reported a worsening of clinical outcomes and therefore, this study used a porcine model of AMI to evaluate the efficacy of bisoprolol on VAs and mortality. Twenty pigs were divided into two groups with one group using oral bisoprolol which was given for 3 hours before the experiment and then maintained for 7 days. A loop recorder was implanted, AMI was induced by balloon occlusion for 60 min, and then, reperfusion. One week later, the echocardiography and loop recorder data were analyzed in the surviving animals. Bisoprolol did not increase the heart rate (62.9±14.5 vs 79.0±20.3; p=0.048), lower the rate of premature ventricular contractions (PVC) (0.8±0.8 vs 11.0±12.8; p=0.021) or tend to lower recurrent VA (0.6±0.5 vs 1.1±1.1; p=0.131) during coronary artery occlusion. After reperfusion, bisoprolol did reduce VA in the early AMI period (0.1±0.3 vs 4.2±4.6; p=0.001) and it was not associated with the extent of myocardial recovery. In this porcine model, early oral bisoprolol might help reduce the incidences of PVC and recurrent VA and determine whether effects are more pronounced during the early AMI period. Our results suggest that bisoprolol might help reduce lethal VA and cardiac death following AMI in this reperfusion era.
PubMed: 34123741
DOI: 10.4068/cmj.2021.57.2.132 -
Temporal haemodynamic changes after bisoprolol treatment in patients with uncontrolled hypertension.Annals of Translational Medicine Jun 2021Anti-hypertensive drugs are widely used to control blood pressure, yet their effects on haemodynamics, especially in Chinese populations, and the potential for...
BACKGROUND
Anti-hypertensive drugs are widely used to control blood pressure, yet their effects on haemodynamics, especially in Chinese populations, and the potential for non-invasive methods to monitor these changes, are poorly understood. This study aimed to determine the early and late effects of bisoprolol treatment on blood pressure, cardiac output (CO), stroke volume (SV), heart rate (HR), systematic vascular resistance (SVR), and inotropy measured in Chinese patients with hypertension.
METHODS
Twelve Chinese subjects (median age: 55 years, interquartile range: 52-58 years; 33% male) with uncontrolled hypertension were recruited at the Prince of Wales Hospital in Hong Kong and haemodynamic measurements were assessed using a non-invasive Ultrasonic Cardiac Output Monitor (USCOM). Seven hourly measurements were taken before and after bisoprolol 2.5 mg on day 1 (T0 to T6), and in nine patients this was repeated six weeks later (TF0 to TF6). Any BP change of 5 mmHg was considered clinically significant and P<0.05 was considered statistically significant.
RESULTS
On day 1 (N=12), there was a significant drop in median CO [4.9 (4.7-5.6) 3.8 (3.3-4.7) L/m, P<0.0001] associated with a compensatory increase in SVR [1,698.1 (1,584.6-1,894.3) 2,222.6 (1,777.4-2,712.5) d·s·cm, P<0.0001] at T2. The median dBP {92 [87-95] 86 [79-89] mmHg, P=0.0002} and MAP {110 [104-114] 104 [101-109] mmHg, P=0.038} reduced significantly 6 hours after bisoprolol treatment. Except for HR, all other measured haemodynamics returned to baseline at T6. On week 6 (N=9), SVR was generally reduced, but major parallel swings in CO and SVR were still evident. All patients showed a trend to lower blood pressure, SVR, and inotropy (P<0.05), but HR, SV, and CO returned to baseline values after 6 weeks treatment (P>0.05).
CONCLUSIONS
The acute haemodynamic changes between 6 hours of the first dose and the dose after 6 weeks of bisoprolol treatment are similar. Long-term therapy can effectively reduce blood pressure by reducing SVR.
PubMed: 34350238
DOI: 10.21037/atm-21-1796 -
Cardiovascular Therapeutics 2022Cardiotoxicity is a well-recognized complication of chemotherapy with Anthracyclines. However, results from trials evaluating beta-blockers for prevention are... (Meta-Analysis)
Meta-Analysis
AIM
Cardiotoxicity is a well-recognized complication of chemotherapy with Anthracyclines. However, results from trials evaluating beta-blockers for prevention are controversial. Therefore, we performed a meta-analysis to find whether prophylactic administration of beta-blockers can help prevent Anthracyclines-induced cardiotoxicity.
METHODS
We assessed randomized trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal left ventricular ejection fraction (LVEF) receiving Anthracyclines. The primary outcome was EF reduction. The secondary outcome was the development of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD), defined as a decrease in the LVEF of >10% to a value of <53%.
RESULTS
We included 17 trials comprising 1291 patients (671 patients in the intervention arm and 620 in the control arm). Carvedilol was administered in eight studies, and others used bisoprolol, metoprolol, or nebivolol. Compared with baseline, LVEF reduced in both intervention and control groups after chemotherapy (MD = -1.93%, 95% CI: -2.94, -0.92, = 0.001, I = 72.1% vs. MD = -4.78%, 95% CI: -6.51, -3.04, = 0.001, = 91.6%, respectively). LVEF was less reduced among the beta-blocker receivers (MD = 3.44%, 95% CI: 1.41-5.46, = 0.001, I = 94.0%). Among the eight studies reporting the incidence of CTRCD, 45 out of 370 participants in the intervention arm and 54 out of 341 in the control arm were reported to experience this complication (RR = 0.76; 95% CI: 0.53,1.09; = 24.4%; = 0.235).
CONCLUSION
Treatment with beta-blockers prevents dilatation of the left ventricle, development of diastolic dysfunction, and reduction of LVEF. However, these hemodynamic effects do not translate into a significant reduction in CTRCD incidence and prevention of hospitalization for heart failure or cardiac death.
Topics: Humans; Stroke Volume; Cardiotoxicity; Anthracyclines; Ventricular Function, Left; Randomized Controlled Trials as Topic; Adrenergic beta-Antagonists; Antibiotics, Antineoplastic; Heart Diseases; Primary Prevention
PubMed: 36687509
DOI: 10.1155/2022/8367444 -
Advances in Therapy Jan 2022The combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable... (Observational Study)
Observational Study
Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCE II, PROTECT I, and PROTECT III Observational Studies.
INTRODUCTION
The combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable coronary artery disease and/or elevated heart rate. This post hoc analysis of three observational studies provides effectiveness and safety data on treatment with perindopril on top of bisoprolol-based therapy, in routine clinical practice.
METHODS
Data were analyzed from three open-label, prospective, multicenter, observational studies of Canadian patients with mild-to-moderate hypertension, which shared the same inclusion and exclusion criteria, treatment duration, and primary outcome. This post hoc analysis focused on the subpopulation of patients treated with perindopril on top of bisoprolol-based therapy. All patients were followed for 16 weeks and underwent baseline, week 4, and week 16 visits. Primary outcomes were mean changes in blood pressure (BP) and proportion of patients achieving BP control (< 140/90 mmHg) in the full analysis set (FAS).
RESULTS
A total of 845 patients (mean age 68.3 ± 11.3 years, mean baseline BP 151.5/86.0 mmHg) were analyzed in the FAS. After 16 weeks, mean SBP/DBP decreased by - 20.4/- 9.8 mmHg with statistically significant reductions observed at all visits in all three studies allowing 78% of patients to achieve the BP treatment goal. No statistically significant changes in heart rate were observed and no serious adverse events reported. The most frequent doses of bisoprolol and perindopril were 5 + 4 mg (34.9%), followed by 5 + 8 mg (16.9%), and 2.5 + 4 mg (12.5%).
CONCLUSION
The addition of perindopril on top of bisoprolol-based therapy in patients with mild-to-moderate hypertension was associated with significant reductions in BP compared with baseline and with achievement of BP targets in the majority of patients. The results suggest this strategy is safe and effective for use in routine clinical practice.
Topics: Aged; Antihypertensive Agents; Bisoprolol; Blood Pressure; Canada; Drug Combinations; Humans; Hypertension; Middle Aged; Perindopril; Prospective Studies; Treatment Outcome
PubMed: 34755324
DOI: 10.1007/s12325-021-01958-6