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International Journal of Hypertension 2019Hypertension (HTN) is the leading risk factor for cardiovascular mortality globally. The WHO estimates a 60% increase in Asian HTN patients between 2000 and 2025....
Systematic Review with Network Meta-Analysis: Comparative Efficacy and Safety of Combination Therapy with Angiotensin II Receptor Blockers and Amlodipine in Asian Hypertensive Patients.
BACKGROUND
Hypertension (HTN) is the leading risk factor for cardiovascular mortality globally. The WHO estimates a 60% increase in Asian HTN patients between 2000 and 2025. Numerous studies have compared safety and efficacy between antihypertensive classes, but in-class comparisons of angiotensin II receptor blockers (ARBs) in combination therapy (CT) (fixed-dose combination or dual combination) with a calcium channel blocker (CCB) are lacking in Asia.
OBJECTIVE
To compare the efficacy and safety of the various ARB-amlodipine CTs and amlodipine (AML) monotherapy for treatment of HTN in Asian population.
METHODS
A systematic literature review sourced Asian randomized controlled trials (RCTs) from PubMed and Cochrane Libraries to inform a network meta-analysis (NMA). We considered the ARB-AML CT. The primary efficacy and safety endpoints were short-term (8-12 weeks) treatment response and treatment-emergent adverse events (TEAEs), respectively. AML monotherapy was used as a comparator to allow for indirect treatment effect estimation in the absence of direct RCTs evidence comparing the different ARB-AML CTs.
RESULTS
The analysis included 1198 Asian HTN patients from seven studies involving six ARB-AML CTs: azilsartan (AZL), candesartan (CAN), fimasartan (FIM), losartan (LOS), olmesartan (OLM), and telmisartan (TEL). Compared to AML monotherapy, CT of AZL-AML had five times greater odds of prompting a treatment response (OR 5.2, 95% CI: 2.5, 11.2), while CAN-AML had 3.9 (95% CI: 2.5, 6.4), FIM-AML had 3.4 (95% CI: 1.4, 8.5), TEL-AML had 3.3 (95% CI: 1.6, 7.1), OLM-AML had 2.7 (95% CI: 1.6, 5.0), and LOS-AML had 2.0 (95% CI: 0.6, 7.3). All ARB-AML CTs had safety profiles comparable to AML monotherapy except TEL-AML, which had significantly lower odds of TEAEs (0.26 (95% CI: 0.087, 0.70)).
CONCLUSION
This study suggests that all ARB-AML CTs compared favorably to AML monotherapy regarding short-term treatment response in uncomplicated HTN patients of Asian origin. AZL-AML prompted the most favorable treatment response. Safety profiles among the ARB-AML CTs were largely comparable. Due to the limited study size and small number of trials (direct evidence), our findings should best be interpreted as an exploratory effort importance to inform future research direction.
PubMed: 31827918
DOI: 10.1155/2019/9516279 -
International Journal of Health Sciences 2019Uncontrolled hypertension is a main predisposing risk factor leading to chronic atrial fibrillation (AF). Although several treatment methods for patients with HTN and AF... (Review)
Review
OBJECTIVES
Uncontrolled hypertension is a main predisposing risk factor leading to chronic atrial fibrillation (AF). Although several treatment methods for patients with HTN and AF were developed in past decades, further investigations of their efficacies are needed. This systematic narrative review presents an overview of studies reporting treatment efficacies in patients with HTN and/or AF.
METHODS
A narrative-based systematic review was performed using EMBASE, Medline, PubMed, Google Scholar, and the Cochrane Library searching for relevant papers published between October 2008 and October 2018. Out of 4481 studies, only 15 studies could be included following the inclusion criteria.
RESULTS
Included studies reported treatment measures, measured outcomes, and efficacies in adult patients with HTN and AF with defined interventions and methodologies. Treatment methods with effective outcomes were administration of hydrochlorothiazide, losartan or atenolol, telmisartan or amlodipine, or general anti-hypertensive drugs. Treatment methods that showed the most effective outcomes (lowering AF recurrence and improving BP control) were those containing pulmonary vein (or antrum) isolation (PVI/PVAI) (6 studies) and/or in conjunction with renal denervation (RDN)(6 studies). Treatment methods showing the most effective outcomes were PVI/PVAI in conjunction with RDN.
CONCLUSION
The latest evidence shows that PVI (in conjunction with RDN in some instances) was more efficacious among patients suffering from HTN and/or AF.
PubMed: 31745397
DOI: No ID Found -
Reviews in Cardiovascular Medicine Jun 2019A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and... (Meta-Analysis)
Meta-Analysis
A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Chronotherapy; Humans; Hypertension; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31345001
DOI: 10.31083/j.rcm.2019.02.31814 -
International Journal of Environmental... Apr 2019Unlike chyloperitoneum associated with clinical conditions including cancer, cirrhosis, and traumatic surgery, calcium channel blocker (CCB)-associated chyloperitoneum...
Unlike chyloperitoneum associated with clinical conditions including cancer, cirrhosis, and traumatic surgery, calcium channel blocker (CCB)-associated chyloperitoneum is rarely discussed in comprehensive studies on chyloperitoneum. We aimed to investigate the prevalence and characteristics of CCB-associated chyloperitoneum in peritoneal dialysis (PD) patients. The MEDLINE, Embase, CENTRAL, CiNii, and RISS databases were systematically searched for clinical studies on CCB-associated chyloperitoneum in PD patients published up to 31 July 2018. A total of 17 studies (four cohort studies, one case series, and 12 case reports) were selected. Eight CCBs, namely amlodipine, benidipine, diltiazem, lercanidipine, manidipine, nifedipine, nisoldipine, and verapamil, were reported to be associated with chyloperitoneum; manidipine and lercanidipine were the most frequently reported. The average prevalence of chyloperitoneum for lercanidipine was 25.97% in three cohort studies, two of which had a moderate or high risk of bias. Most of the studies revealed chyloperitoneum development within 4 days of initiation of CCB therapy and chyloperitoneum disappearance within 24 h of CCB withdrawal. The results of this study emphasise on the need for awareness among healthcare professionals regarding CCB-associated chyloperitoneum in PD patients. Further studies elucidating the causality and clinical implication of CCB-associated chyloperitoneum are needed.
Topics: Calcium Channel Blockers; Chylous Ascites; Humans; Peritoneal Dialysis; Risk Factors
PubMed: 31013922
DOI: 10.3390/ijerph16081333 -
European Heart Journal Jan 2019Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy...
Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy with drugs classified as being first line (beta blockers, calcium channel blockers, short acting nitrates) or second line (long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine). Second line drugs are indicated for patients who have contraindications to first line agents, do not tolerate them or remain symptomatic. Evidence that one drug is superior to another has been questioned. Between January and March 2018, we performed a systematic review of articles written in English over the past 50 years English-written articles in Medline and Embase following preferred reporting items and the Cochrane collaboration approach. We included double blind randomized studies comparing parallel groups on treatment of angina in patients with stable coronary artery disease, with a sample size of, at least, 100 patients (50 patients per group), with a minimum follow-up of 1 week and an outcome measured on exercise testing, duration of exercise being the preferred outcome. Thirteen studies fulfilled our criteria. Nine studies involved between 100 and 300 patients, (2818 in total) and a further four enrolled greater than 300 patients. Evidence of equivalence was demonstrated for the use of beta-blockers (atenolol), calcium antagonists (amlodipine, nifedipine), and channel inhibitor (ivabradine) in three of these studies. Taken all together, in none of the studies was there evidence that one drug was superior to another in the treatment of angina or to prolong total exercise duration. There is a paucity of data comparing the efficacy of anti-anginal agents. The little available evidence shows that no anti-anginal drug is superior to another and equivalence has been shown only for three classes of drugs. Guidelines draw conclusions not from evidence but from clinical beliefs.
Topics: Adrenergic beta-Antagonists; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Humans; Nitrates; Randomized Controlled Trials as Topic
PubMed: 30165445
DOI: 10.1093/eurheartj/ehy504 -
The Cochrane Database of Systematic... Jul 2018Beta thalassaemia is a common inherited blood disorder. The need for frequent blood transfusions in this condition poses a difficult problem to healthcare systems. The... (Review)
Review
BACKGROUND
Beta thalassaemia is a common inherited blood disorder. The need for frequent blood transfusions in this condition poses a difficult problem to healthcare systems. The most common cause of morbidity and mortality is cardiac dysfunction from iron overload. The use of iron chelation therapy has reduced the severity of systemic iron overload but specific, non-toxic treatment is required for removal of iron from the myocardium.
OBJECTIVES
To assess the effects of calcium channel blockers combined with standard iron chelation therapy in people with transfusion-dependent beta thalassaemia on the amount of iron deposited in the myocardium, on parameters of heart function, and on the incidence of severe heart failure or arrhythmias and related morbidity and mortality.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials databases, and the reference lists of relevant articles and reviews.Date of last search: 24 February 2018.
SELECTION CRITERIA
We included randomised controlled trials of calcium channel blockers combined with standard chelation therapy compared with standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia.
DATA COLLECTION AND ANALYSIS
Two authors independently applied the inclusion criteria for the selection of trials. Two authors assessed the risk of bias of trials and extracted data and a third author verified these assessments. The authors used the GRADE system to assess the quality of the evidence.
MAIN RESULTS
Two randomised controlled trials (n = 74) were included in the review; there were 35 participants in the amlodipine arms and 39 in the control arms. The mean age of participants was 24.4 years with a standard deviation of 8.5 years. There was comparable participation from both genders. Overall, the risk of bias in included trials was low. The quality of the evidence ranged across outcomes from low to high, but the evidence for most outcomes was judged to be low quality.Cardiac iron assessment, as measured by heart T2*, did not significantly improve in the amlodipine groups compared to the control groups at six or 12 months (low-quality evidence). However, myocardial iron concentration decreased significantly in the amlodipine groups compared to the control groups at both six months, mean difference -0.23 mg/g (95% confidence interval -0.07 to -0.39), and 12 months, mean difference -0.25 mg/g (95% confidence interval -0.44 to -0.05) (low-quality evidence). There were no significant differences between treatment and control groups in serum ferritin (low-quality evidence), liver T2* (low-quality evidence), liver iron content (low-quality evidence) and left ventricular ejection fraction (low-quality evidence). There were no serious adverse events reported in either trial; however, one trial (n = 59) reported mild adverse events, with no statistically significant difference between groups (low-quality evidence).
AUTHORS' CONCLUSIONS
The available evidence does not clearly suggest that the use of calcium channel blockers is associated with a reduction in myocardial iron in people with transfusion-dependent beta thalassaemia, although a potential for this was seen. There is a need for more long-term, multicentre trials to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should be designed to compare commonly used iron chelation drugs with the addition of calcium channel blockers to investigate the potential interplay of these treatments. In addition, the role of baseline myocardial iron content in affecting the response to calcium channel blockers should be investigated. An analysis of the cost-effectiveness of the treatment is also required.
Topics: Adolescent; Adult; Amlodipine; Blood Transfusion; Calcium Channel Blockers; Cardiomyopathies; Chelation Therapy; Child; Combined Modality Therapy; Female; Ferritins; Humans; Iron; Iron Overload; Liver; Myocardium; Randomized Controlled Trials as Topic; Time Factors; Transfusion Reaction; Young Adult; beta-Thalassemia
PubMed: 29998494
DOI: 10.1002/14651858.CD011626.pub2 -
Journal of Clinical and Experimental... Jun 2018Amlodipine, a dihydropyridine calcium channel blocker (CCB) is commonly prescribed for cardiovascular conditions. Its administration may produce an uncommon adverse oral... (Review)
Review
BACKGROUND
Amlodipine, a dihydropyridine calcium channel blocker (CCB) is commonly prescribed for cardiovascular conditions. Its administration may produce an uncommon adverse oral manifestation, the gingival overgrowth (GO). Lately, there has been an increase in the rate of GO in patients on amlodipine therapy. The current systematic review was undertaken to evaluate the evidence on plausible risk factors involved in amlodipine induced gingival overgrowth (AIGO).
MATERIAL AND METHODS
Literature search was conducted in the databases like Pubmed (Medline), Scopus and Google Scholar to include the original research articles related to etio-pathogenesis of AIGO.
RESULTS
About 270 documents were identified through primary search, of which 13 original research articles were included. Most common risk factor for AIGO was administration of amlodipine in subjects with poor plaque control. However, high dosage of drug, duration of therapy and inherent genetic susceptibility were recognized as other plausible risk factors.
CONCLUSIONS
It was concluded that AIGO is no longer a rare phenomenon. It is therefore imperative for the physician to identify and inform patients, about the risk factors associated with the overgrowth at the initiation of therapy. This would prevent the development of GO's and improve the patient's quality of life. Amlodipine, calcium channel blockers, gingival overgrowth, hypertension.
PubMed: 29930781
DOI: 10.4317/jced.54715 -
Frontiers in Neuroscience 2018Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.
PubMed: 29670504
DOI: 10.3389/fnins.2018.00203 -
Lancet (London, England) Mar 2017Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs.
METHODS
We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis.
FINDINGS
Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen.
INTERPRETATION
The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability.
FUNDING
National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.
Topics: Female; Humans; Male; Middle Aged; Administration, Oral; Amlodipine; Antihypertensive Agents; Atenolol; Biphenyl Compounds; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Combinations; Hydrochlorothiazide; Hypertension; Irbesartan; Medication Adherence; Tetrazoles; Treatment Outcome
PubMed: 28190578
DOI: 10.1016/S0140-6736(17)30260-X -
Medicine Jul 2016The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients' characteristics associated with... (Meta-Analysis)
Meta-Analysis Review
Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement.
BACKGROUND
The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients' characteristics associated with best performance of the drugs will improve management of hypertensive patients.
OBJECTIVE
To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease.
DATA SOURCES
MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers.
STUDY ELIGIBILITY CRITERIA
Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data.
STUDY APPRAISAL AND SYNTHESIS METHODS
Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework.
MAIN OUTCOME(S) AND MEASURE(S)
Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination.
RESULTS
Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases.Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats.
LIMITATIONS
Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses.
CONCLUSIONS AND IMPLICATIONS
Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised.
Topics: Antihypertensive Agents; Black People; Drug Therapy, Combination; Humans; Hypertension; Obesity; Randomized Controlled Trials as Topic; Sex Factors
PubMed: 27472680
DOI: 10.1097/MD.0000000000004071