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Hypertension Research : Official... Jun 2024New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP... (Randomized Controlled Trial)
Randomized Controlled Trial
New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.
Topics: Humans; Female; Male; Hypertension; Middle Aged; Biphenyl Compounds; Antihypertensive Agents; Double-Blind Method; Benzimidazoles; Amlodipine; Tetrazoles; Blood Pressure; Aged; Treatment Outcome; Bisoprolol; Indapamide; Adult; Drug Therapy, Combination
PubMed: 38584159
DOI: 10.1038/s41440-024-01658-y -
European Heart Journal. Case Reports Apr 2024Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers...
BACKGROUND
Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis.
CASE SUMMARY
A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable.
DISCUSSION
Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear.
PubMed: 38576465
DOI: 10.1093/ehjcr/ytae161 -
The Journal of Veterinary Medical... May 2024An increase in systemic blood pressure causes bleeding and ischemia owing to peripheral vascular breakdown, leading to various forms of organ damage. The brain, eyes,...
An increase in systemic blood pressure causes bleeding and ischemia owing to peripheral vascular breakdown, leading to various forms of organ damage. The brain, eyes, kidneys, and cardiovascular system are known target organs for hypertension. To our knowledge, no reports in Japan describe, in detail, the types of antihypertensive drugs used to treat hypertension in cats or its underlying causes. Therefore, we aimed to investigate the use of antihypertensive drugs in domestic cats with hypertension in Japan, the causes of hypertension, and the vital prognosis of these patients. In the present survey, we found that amlodipine was used alone (60/80 cats) or concomitantly (20/80 cats) in all cat patients with hypertension in Japan. We also determined that blood pressure measurements were not yet routinely performed on cats at veterinary clinics in Japan. Furthermore, we have new information suggesting that amlodipine administration in cats with hypertension, which lowers systolic arterial pressure levels to within the normal range (<140 mmHg), may have a negative impact on their survival. Routine blood pressure measurements for cats during their regular health checkups can help identify hypertension, and proper interpretation of blood pressure readings can facilitate suitable treatment measures.
Topics: Animals; Amlodipine; Cats; Hypertension; Japan; Cat Diseases; Antihypertensive Agents; Male; Female; Blood Pressure
PubMed: 38569838
DOI: 10.1292/jvms.23-0444 -
Scientific Reports Mar 2024The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed...
The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.
Topics: Humans; Pharmacogenomic Variants; Phylogeny; Clinical Relevance; Polymorphism, Single Nucleotide; China; Nigeria; Gene Frequency; Genotype
PubMed: 38553524
DOI: 10.1038/s41598-024-58092-w -
Cureus Feb 2024Acute interstitial nephritis (AIN) is characterized by an inflammatory infiltrate of the interstitium of the kidney, typically causing a decline in kidney function....
Acute interstitial nephritis (AIN) is characterized by an inflammatory infiltrate of the interstitium of the kidney, typically causing a decline in kidney function. Drug-induced AIN (also called allergic AIN) is a type of AIN. Common drugs associated with AIN are antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs). A 59-year-old male with a history of recent laparoscopic robotic sleeve gastrectomy presented to the emergency department with five weeks of progressively worsening fatigue, nausea, and lightheadedness. Postoperatively, he was prescribed omeprazole 20 mg daily for gastric ulcer prophylaxis. His other home medications were amlodipine, atorvastatin, ursodiol, and budesonide-formoterol fumarate nebulizer. His physical examination was normal. Laboratory studies revealed elevated creatinine of 4.19 mg/dL from a baseline of 0.9 mg/dL two months ago and the presence of urine eosinophils. The etiology of this elevated creatinine was unclear, prompting CT-guided left renal biopsy. The biopsy showed diffuse interstitial inflammatory infiltration with numerous lymphocytes, a large number of neutrophils, and scattered eosinophils, consistent with the allergic type of AIN. Omeprazole was discontinued and the patient received a seven-day course of prednisone. Despite treatment, permanent renal damage occurred, and the patient's new baseline creatinine was 2.3 mg/dL. AIN caused by PPIs should be considered in the differential diagnosis of acute kidney injury (AKI). AIN can be difficult to diagnose, presenting with nonspecific symptoms, such as oliguria, malaise, nausea, and vomiting. An accurate and timely diagnosis can help prevent and treat worsening renal failure.
PubMed: 38550437
DOI: 10.7759/cureus.55035 -
Clinical and Translational Science Apr 2024This study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population-based, matched, cohort study included users of... (Observational Study)
Observational Study
This study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population-based, matched, cohort study included users of originator amlodipine using claims data during 2018-2020 from a health system in Tianjin, China, in which usage of generic amlodipine was promoted by a drug procurement policy, the national volume-based procurement. Non-switchers refer to those remained on originator after the policy, while pure-switchers were those who switched to and continued using generic amlodipine, and back-switchers were those switched to generic amlodipine but then back to the originator. Propensity score matching generates comparable non-switchers and pure-switchers pairs, and non-switchers and back-switchers pairs. The primary outcome was major adverse cardiovascular events (MACEs), defined as all-cause mortality, stroke, and myocardial infarction during follow-up (April 1, 2019 to December 30, 2020). Secondary outcomes included heart failure, atrial fibrillation, and adherence to amlodipine. The hazard ratio (HR) for each clinical outcome was assessed through Cox proportional hazard regression. In total, 5943 non-switchers, 2949 pure-switchers, and 3061 back-switchers were included (mean age: 62.9 years; 55.5% men). For the matched pairs, pure-switchers (N = 2180) presented no additional risks of clinical outcomes compared to non-switchers (N = 4360) (e.g., MACEs: 2.86 vs. 2.95 events per 100 person-years; HR = 0.97 [95%CI: 0.70-1.33]). Back-switchers (N = 1998) also presented no additional risk compared to non-switchers (N = 3996) for most outcomes except for stroke (HR = 1.55 [95%CI: 1.03-2.34]). Pure-switchers and back-switchers all had better amlodipine adherence than non-switchers. Generic substitution of amlodipine is not associated with increased risk of cardiovascular events or all-cause mortality, but improves medicine adherence.
Topics: Male; Humans; Middle Aged; Female; Cohort Studies; Retrospective Studies; Drug Substitution; Stroke; Atrial Fibrillation
PubMed: 38545866
DOI: 10.1111/cts.13779 -
Pathogens (Basel, Switzerland) Feb 2024A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general...
A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general condition and moderately enlarged mandibular and popliteal lymph nodes. The initial blood work showed severe azotemia and hypoalbuminemia. In the urinalysis, marked proteinuria with a urine protein/creatinine ratio (UPC) of 4.69 was found. Further workup showed a high leishmania antibody titer. The dog was diagnosed with leishmaniosis and glomerulonephritis. Initial treatment consisted of intravenous fluid therapy, allopurinol, miltefosine, amlodipine, clopidogrel, and a diet with a low purine content. Creatinine temporarily decreased but increased again after three days. For further supportive treatment, intermittent hemodialysis in combination with hemoperfusion with the cytosorb adsorber was performed. A total blood volume of 17.7 L was processed within three hours. Thereafter, immunoadsorption (IA) was performed with the COM.TEC and ADAsorb platforms and a LIGASORB adsorber to eliminate circulating immunocomplexes. Treatment time for IA was two hours with a blood flow of 50 mL/min. A total plasma volume of 2.4 L was processed. Over the following days, creatinine declined, and the patient improved significantly. UPC decreased to 1.74 on day 17 after IA. The patient was discharged after two and a half weeks. Two years after the initial event, the patient is still in excellent condition, with creatinine, UPC, and albumin levels in the reference range. Therefore, IA might be an additional therapeutic option for dogs with leishmaniosis-induced glomerulonephritis and subsequent severe azotemia to improve immunocomplex-mediated glomerulonephritis.
PubMed: 38535536
DOI: 10.3390/pathogens13030193 -
Global Heart 2024Hypertension treatment coverage is low in India. A stepwise simple treatment protocol is one of the strategies to improve hypertension treatment in primary care. We...
BACKGROUND
Hypertension treatment coverage is low in India. A stepwise simple treatment protocol is one of the strategies to improve hypertension treatment in primary care. We estimated the effectiveness of various protocol steps to achieve blood pressure (BP) control in public sector health facilities in Punjab and Maharashtra, India, where the India Hypertension Control Initiative (IHCI) was implemented.
METHODS
We analyzed the records of people enrolled for hypertension treatment and follow-up under IHCI between January 2018 and December 2021 in public sector primary and secondary care facilities across 23 districts from two states. Each state followed a different treatment protocol. We calculated the proportion with controlled BP at each step of the protocol. We also estimated the mean decline in BP pre- and post-treatment.
RESULTS
Of 281,209 patients initiated on amlodipine 5 mg, 159,292 continued on protocol drugs and came for a follow-up visit during the first quarter of 2022. Of 33,450 individuals who came for the follow-up in Punjab and 125,842 in Maharashtra, 70% and 76% had controlled BP, respectively, at the first step with amlodipine 5 mg. In Punjab, at the second step with amlodipine 10 mg, the cumulative BP control increased to 75%. A similar 5% (76%-81%) increase was seen in the second step after adding telmisartan 40 mg in Maharashtra. Overall, the mean (SD) systolic blood pressure (SBP) decreased by 16 mmHg from 148 (15) mmHg at the baseline in Punjab. In Maharashtra, the decline in the mean (SD) SBP was about 15 mmHg from the 144 (18) mmHg baseline.
CONCLUSION
Simple drug- and dose-specific protocols helped achieve a high control rate among patients retained in care under program conditions. We recommend treatment protocols starting with a single low-cost drug and escalating with the same or another antihypertensive drug depending on the cost and availability.
Topics: Humans; Blood Pressure; India; Hypertension; Antihypertensive Agents; Amlodipine; Clinical Protocols; Treatment Outcome
PubMed: 38524909
DOI: 10.5334/gh.1305 -
Ochsner Journal 2024Carotid webs are nonatherosclerotic fibrous bands that may alter hemodynamic flow and increase the risk of platelet aggregation, leading to thromboembolism in young,...
Carotid webs are nonatherosclerotic fibrous bands that may alter hemodynamic flow and increase the risk of platelet aggregation, leading to thromboembolism in young, otherwise healthy individuals. Although rare, carotid webs are important causes of thromboembolic strokes and are often overlooked in the routine workup for a stroke. Treating physicians and radiologists must recognize and properly manage patients who present with carotid webs to prevent recurrent thromboembolism. A healthy 30-year-old female presented with slurred speech and unilateral left upper and lower extremity numbness. Imaging modalities showed an acute infarction of the right middle cerebral artery and bilateral carotid webs. The patient was managed operatively with a right carotid endarterectomy and discharged on day 3 of admission on a regimen of ticagrelor, amlodipine, and aspirin. The patient was asymptomatic at 1-year follow-up. Our case highlights the clinical relevance of considering carotid web as a potential etiology for ischemic stroke in young, otherwise healthy patients and emphasizes the importance of timely diagnosis and appropriate management to prevent recurrent cerebrovascular events.
PubMed: 38510226
DOI: 10.31486/toj.23.0082 -
International Journal of Pharmaceutics Apr 2024Surface powder sticking in pharmaceutical mixing vessels poses a risk to the uniformity and quality of drug formulations. This study explores methods for evaluating the...
Surface powder sticking in pharmaceutical mixing vessels poses a risk to the uniformity and quality of drug formulations. This study explores methods for evaluating the amount of pharmaceutical powder mixtures adhering to the metallic surfaces. Binary powder blends consisting of amlodipine and microcrystalline cellulose (MCC) were used to investigate the effect of the mixing order on the adherence to the vessel wall. Elevated API concentrations were measured on the wall and within the dislodged material from the surface, regardless of the mixing order of the components. UV imaging was used to determine the particle size and the distribution of the API on the metallic surface. The results were compared to chemical maps obtained by Raman chemical imaging. The combination of UV and VIS imaging enabled the rapid acquisition of chemical maps, covering a substantially large area representative of the analysed sample. UV imaging was also applied in tablet inspection to detect tablets that fail to meet the content uniformity criteria. The results present powder adherence as a possible source of poor content uniformity, highlighting the need for 100% inspection of pharmaceutical products to ensure product quality and safety.
Topics: Powders; Drug Compounding; Tablets; Diagnostic Imaging; Particle Size
PubMed: 38493839
DOI: 10.1016/j.ijpharm.2024.124010