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Current Therapeutic Research, Clinical... Feb 2010Amlodipine is a calcium channel blocker prescribed for the management of angina and hypertension. As a racemic mixture, amlodipine contains (R)- and (S)-amlodipine...
BACKGROUND
Amlodipine is a calcium channel blocker prescribed for the management of angina and hypertension. As a racemic mixture, amlodipine contains (R)- and (S)-amlodipine isomers, but only (S)-amlodipine as the active moiety possesses therapeutic activity. Based on pharmacologic research, it remains uncertain if (S)-amlodipine alone has similar efficacy and fewer associated adverse events (AEs) compared with the racemic mixtures.
OBJECTIVE
The aim of this systematic review and meta-analysis was to determine the effectiveness and tolerability of (S)-amlodipine compared with that of racemic amlodipine.
METHODS
A systematic literature search was performed using MEDLINE (1966-2009), EMBASE (1966-2009), the Cochrane Central Register of Controlled Trials (issue 3, 2009), the Chinese Biomedical Database (1978-2009), and the China National Knowledge Internet (1980-2009). All randomized controlled trials (RCTs) comparing (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in the treatment of hypertension were included in the review. The outcome measures to be collected were cardiovascular events, systolic blood pressure (SBP), diastolic BP (DBP), and AEs. Quality assessments of clinical trials were conducted using a modified Jadad Scale, with trials being rated as low quality (score 0-3) or high quality (score 4-7). Meta-analysis of the included studies was performed using RevMan software.
RESULTS
Of the 229 references identified, 214 were excluded after screening the titles, abstracts, or full texts. Fifteen RCTs were included, of which 13 were in Chinese and 2 in English. Based on the Jadad Scale score, 3 of the RCTs were classified as high quality (score 5 or 6) and the remaining 12 as low quality (score 1-3). None of the trials evaluated cardiovascular events beyond 40 weeks. Meta-analysis of the 15 trials indicated that (S)-amlodipine was not significantly different from racemic amlodipine in the effect on BP. When only high-quality studies were included, after 4 weeks' treatment, the weighted mean difference (WMD) of SBP and DBP decrease (1 study) was -2.84 (95% CI, -6.42 to 0.74) with (S)-amlodipine and -1.71 (95% CI, -3.48 to 0.06) with racemic amlodipine. After 8 weeks' treatment, the WMD of SBP and DBP decrease (2 studies) was -1.13 (95% CI, -5.29 to 3.03) and -1.34 (95% CI, -2.67 to -0.01), respectively. The risk difference (RD) for the number of patients who experienced AEs with (S)-amlodipine and racemic amlodipine was found to be -0.04 (95% CI, -0.06 to -0.02). When all the trials were included, (S)-amlodipine treatment was associated with significantly less edema than racemic amlodipine (RD, -0.02; 95% CI, -0.03 to 0.00); however, when only high-quality studies (2 studies) were included, no difference was found between the 2 groups (RD, 0.01; 95% CI, -0.02 to 0.03). One high-quality study found significant differences in increases in aspartate and alanine aminotransferase activities in the 2 groups (RD, 0.08; 95% CI, 0.01 to 0.05). No significant differences between the 2 groups were found in the incidence of headache (RD, 0.00; 95% CI, -0.02 to 0.01) or flushing (RD, -0.01; 95% CI, -0.02 to 0.00).
CONCLUSIONS
The majority of the clinical trials comparing (S)-amlodipine and racemic amlodipine treatment were low quality (12/15 [80%]). According to the limited evidence, there were no significant differences between (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in controlling BP. When all the trials were considered, (S)-amlodipine treatment was associated with significantly less edema than racemic amlodipine; however, when only high-quality trials were included, no significant difference was found. More long-term, high-quality RCTs with cardiovascular events as the primary outcome are needed to compare the safety and efficacy of (S)-amlodipine and racemic amlodipine.
PubMed: 24683248
DOI: 10.1016/j.curtheres.2010.02.005 -
Cancer Epidemiology Oct 2017Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association... (Meta-Analysis)
Meta-Analysis Review
Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I=0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I=35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712.
Topics: Breast Neoplasms; Calcium Channel Blockers; Female; Humans; Incidence
PubMed: 28866282
DOI: 10.1016/j.canep.2017.08.012 -
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 -
Cardiovascular & Hematological... Sep 2012The purpose of this study was to evaluate the efficacy and safety of Cilnidipine tablets to treat Chinese patients with mild to moderate essential hypertension, and to... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of cilnidipine on mild to moderate essential hypertension: a systematic review and meta-analysis of randomized controlled trials in Chinese patients.
The purpose of this study was to evaluate the efficacy and safety of Cilnidipine tablets to treat Chinese patients with mild to moderate essential hypertension, and to examine the ability of Cilnidipine to lower blood pressure without eliciting unfavorable side effects. Medical databases and review articles were screened for randomized controlled trials that reported the effects of and adverse reactions to Cilnidipine and Amlodipine in treating Chinese patients with mild to moderate essential hypertension. The quality of the included studies was critically evaluated. A total of 547 articles were found, from which 11 articles met the inclusion criteria. The heterogeneity test, the efficacy analysis (Q statistic = 4.62, p = 0.91, I(2) = 0%) and safety analysis (Q statistic = 3.73, p = 0.93, I(2) = 0%) showed that Cilnidipine was equally effective and safe compared to Amlodipine. The funnel-plot displayed a symmetrical figure, indicating there was no publication bias, and all articles included described high quality trials. In conclusion, Cilnidipine is a useful agent to treat mild to moderate essential hypertension in China.
Topics: Calcium Channel Blockers; China; Dihydropyridines; Humans; Hypertension; Randomized Controlled Trials as Topic
PubMed: 22746347
DOI: 10.2174/187152912801823165 -
International Journal of Clinical... Aug 2013Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis; however, their potential to affect zinc is less well known. The primary... (Review)
Review
BACKGROUND
Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis; however, their potential to affect zinc is less well known. The primary aim was to explore whether antihypertensive medicines have the potential to affect zinc status.
METHODS
A review of electronic databases was undertaken. Full-length English language articles describing clinical trials involving antihypertensive medicines and reporting on zinc measurements were reviewed.
RESULTS
Eight eligible studies were identified which involved the use of ACE inhibitors, thiazide diuretics, beta blockers, or ARB drugs of which five included a control group Studies used urinary zinc excretion, plasma zinc levels or erythrocyte zinc as key measures of zinc status. Studies reported increased urinary zinc losses for captopril (from 50 mg/day), enalapril (20 mg/day), losartan (50 mg/day), losartan (50 mg/day) together with hydrochlorothiazide (12.5 mg/day), captopril (75 mg/day) together with frusemide (40 mg/day) and stand-alone hydrochlorothiazide (25 mg/day). Serum levels of zinc decreased with captopril (50-150 mg/day), verapamil (240 mg/day), atenolol (50-150 mg/day) and the combination of losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day), eryrthrocyte levels decreased with use of valsartan (80 mg/day) and in some studies for captopril, but not for metoprolol (100 mg/day), atenolol (50-150 mg/day), verapamil (240 mg/day), doxazosin (4 mg/day) or amlodipine 10 mg/day). Major limitations were that most studies were small and did not report on dietary zinc intake.
CONCLUSION
The available evidence suggests that use of ACE inhibitors and angiotensin 2 receptor antagonists or thiazide diuretics have the potential to reduce zinc levels in hypertensive patients. Additional research using larger participant numbers and accounting for dietary zinc intakes are required.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Food-Drug Interactions; Humans; Hypertension; Risk Factors; Sodium Chloride Symporter Inhibitors; Trace Elements; Zinc
PubMed: 23279674
DOI: 10.1111/ijcp.12040 -
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 -
Journal of Clinical Hypertension... Mar 2013Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple... (Meta-Analysis)
Meta-Analysis Review
Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Treatment Outcome
PubMed: 23458592
DOI: 10.1111/jch.12040 -
Clinical Toxicology (Philadelphia, Pa.) May 2021Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can...
BACKGROUND
Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning.
METHODS
We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods.
RESULTS
A total of 83 publications (6 and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR.
CONCLUSIONS
Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.
Topics: Adult; Aged; Aged, 80 and over; Calcium Channel Blockers; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Pharmaceutical Preparations; Poisoning; Practice Guidelines as Topic; Renal Dialysis
PubMed: 33555964
DOI: 10.1080/15563650.2020.1870123 -
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 -
Journal of the American Society of... Apr 2015A systematic review identified 86 outcome-based clinical trials involving perindopril, amlodipine, or other antihypertensive drugs. In fixed-effects meta-analyses of 11... (Meta-Analysis)
Meta-Analysis Review
A systematic review identified 86 outcome-based clinical trials involving perindopril, amlodipine, or other antihypertensive drugs. In fixed-effects meta-analyses of 11 clinical trials (90,208 subjects), amlodipine was associated with a significant 24% increase in heart failure, but a significant decrease in death, cardiovascular death, stroke, coronary heart disease, and first major cardiovascular adverse event. In five clinical trials (52,565 subjects), perindopril was associated with a significant reduction in all six cardiovascular endpoints. Network and Bayesian meta-analyses suggested that (with the exception of amlodipine and heart failure), each agent was at least as effective as an initial diuretic to prevent these events. Short-term trials have demonstrated that the combination of perindopril and amlodipine is safe and effective, with statistically greater lowering of blood pressure than either agent alone and a potential synergistic effect on pedal edema. The single-pill combination of perindopril and amlodipine may be a useful addition to the antihypertensive armamentarium.
Topics: Amlodipine; Antihypertensive Agents; Cardiovascular Diseases; Clinical Trials as Topic; Drug Combinations; Humans; Perindopril
PubMed: 25817217
DOI: 10.1016/j.jash.2014.12.012