Dataset Information

Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype.

ABSTRACT: Objective: To investigate the effect of telmisartan, rosuvastatin, or their combination on dementia and to understand the impact of apolipoprotein E (APOE) genotype on the effect of the medications in older patients with hypertension. Methods: This is a double-blind, randomized, and placebo-controlled trial using a 2 × 2 factorial design. Between April 2008 and November 2010, 1,244 hypertensive patients aged ?60 years without cognitive impairment were recruited from communities in six cities in Shandong area, China. Patients were randomized into telmisartan and rosuvastatin administration after a 2-week washout period. APOE genotype was identified at the baseline. Possible dementia was determined using the combination of the global cognitive function and Assessment of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Results: Over an average follow-up of 7 [interquartile range (IQR): 6.7-7.2] years, telmisartan and rosuvastatin significantly reduced the cognitive impairment progression and the incidence of dementia. There was a synergistic interaction between telmisartan and rosuvastatin to reduce the cognitive impairment and the incidence of dementia (P adjusted < 0.001). The cognitive impairment progression and the risk of dementia were higher in the hypertensive patients with APOE ?4 allele than in those without APOE ?4 allele. Rosuvastatin medication significantly alleviated the cognitive impairment progression and the risks of dementia in patients with APOE ?4 allele. Conclusion: The combination of telmisartan and rosuvastatin might be an effective prevention and/or treatment strategy for cognitive impairment and dementia, especially in hypertensive patients with the APOE ?4 allele. Clinical Trial Registration: www.ClinicalTrials.gov, ChiCTR.org.cn, identifier ChiCTR-IOR-17013557. Registered on April 12, 2017 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=23121.

SUBMITTER: Hu W

PROVIDER: S-EPMC7296075 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype.

Hu Wenjing W Li Ying Y Zhao Yingxin Y Dong Yuanli Y Cui Yi Y Sun Shangwen S Gong Gary G Zhang Hua H Chai Qiang Q Wang Juan J Liu Zhendong Z

Frontiers in aging neuroscience 20200609

Objective: To investigate the effect of telmisartan, rosuvastatin, or their combination on dementia and to understand the impact of apolipoprotein E (APOE) genotype on the effect of the medications in older patients with hypertension. Methods: This is a double-blind, randomized, and placebo-controlled trial using a 2 × 2 factorial design. Between April 2008 and November 2010, 1,244 hypertensive patients aged ≥60 years without cognitive impairment were recruited from c ...[more]

PMID: 32581766

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Project description:This multicenter, phase 4, Prospective Randomized Open, Blinded End-point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single-pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID-19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4-week single-group run-in period with telmisartan 40-80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between-group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between-group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between-group difference p = .078). Change of AIx had no significant difference (between-group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

Project description:PurposeHypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers.Patients and methodsAn open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration versus time curve over dosing interval (AUCτ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax,ss and AUCτ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions.ResultsThirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Cmax,ss and AUCτ,ss, were 0.9829 (0.8334-1.1590) and 1.0003 (0.9342-1.0710) for telmisartan; 0.9908 (0.9602-1.0223) and 1.0081 (0.9758-1.0413) for amlodipine; and 2.2762 (2.0113-2.5758) and 1.3261 (1.2385-1.4198) for rosuvastatin, respectively.ConclusionThe pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.

Dataset Information

Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype.

Publications

Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype.

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