Cardiovascular Drugs and Therapy最新文献

Purpose: Beta-blocker is a frequently used medication in cardiovascular diseases. However, long-term benefit of beta-blocker in patients with preserved left ventricular ejection function (LVEF) on major adverse cardiovascular events (MACEs) is uncertain.

Methods: The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) was a prospective study that enrolled Thai patients with high atherosclerotic risk including multiple atherosclerotic risk factors and established atherosclerotic cardiovascular diseases. Baseline demographic data, co-morbidities and medication were recorded. Patients were followed for 5 years. Patients with LVEF<50% were excluded. Primary outcome was the effect of beta-blocker on the occurrence of MACEs including all-cause death, non-fatal myocardial infarction and non-fatal stroke (3P-MACEs). Propensity score matching was used to control confounding factors.

Results: There was a total of 8513 patients in the pre-matched cohort, 4418 were taking beta-blocker and 4095 were not. After adjustment of confounders, beta-blocker was an independent predictor of 3P-MACEs (adjusted HR 1.29;95% CI 1.12-1.49;p<0.001). After propensity score matching, 4686 patients remained in the post-matched cohort. Propensity score analysis showed consistent results in which patient taking beta-blocker had higher risk of 3P-MACEs (adjusted HR 1.29;95% CI 1.10-1.53;p=0.002). Subgroup analysis in patients with coronary artery disease (CAD) indicated that taking beta-blocker did not increase the incidence of 3P-MACEs (adjusted HR 0.99;95% CI 0.76-1.29) while those without CAD did (adjusted HR 1.51; 95% CI, 1.22-1.86;p-interaction=0.015).

Conclusion: In patients with high atherosclerotic cardiovascular risk, taking beta-blockers had a higher risk of 3P-MACEs. Care should be taken when prescribing beta-blockers to patients without a clear indication.

Trial registration: TCTR20130520001 registered in Thai Clinical Trials Registry (TCTR) https://www.thaiclinicaltrials.org/ , date of registration 20 May 2013.

Polypharmacy is often necessary in complex, chronic, comorbid and cardiovascular patients and is a known risk factor for potential drug-drug interaction (DDI) that can cause adverse reactions (toxicity or therapeutic failure). Anti-thrombotic drugs (largely low-dose aspirin and a platelet P2Y12 receptor inhibitor) and statins are among the most co-administered drugs in cardiovascular patients. Ticagrelor is a selective antagonist of the platelet P2Y12-receptor, highly effective in inhibiting platelet aggregation and bio-transformed by the CYP3A4 and substrate of transporters, such as the breast cancer resistance protein (BCRP). Statins have different pharmacokinetic profiles; some undergo CYP3A4-mediated metabolism; rosuvastatin is primarily metabolized by the CYP2C9; and they have different affinities for drug transporters. Rhabdomyolysis is a very rare but severe adverse event, which is specific for statins which can be triggered by DDIs that increase statin's concentrations through blockade of their biotransformation and/or elimination. Large pharmacovigilance and small observational studies reported increased rhabdomyolysis in patients treated with some statins and ticagrelor but not aspirin, clopidogrel or prasugrel. Recent studies in vitro, pharmacokinetic trials and in silico drug modelling identified and validated the BCRP inhibition by ticagrelor, as a mechanism contributing to the DDI with statins, as 'victim' drugs, leading to increased rhabdomyolysis. While the clinical impact of this DDI deserves further investigation, a careful evaluation should be advised when ticagrelor is co-prescribed with some statins.

Purpose: Statin drugs are effective at reducing cardiovascular events, but adherence to statin therapy remains a problem for patients and their physicians. We review a paper estimating the economic costs of poor adherence to statin drugs.

Methods: The authors examined two large databases (Medicare and Market Scan databases) including 230,000 patients with hospitalization for myocardial infarction between 2018 and 2019 to determine how many patients were not adhering to guideline-recommended anti-hyperlipidemic medications. They have also calculated the potential consequences of patients who are not adhering to the recommended therapy.

Results: The authors estimate that if all patients were receiving guideline-directed medical therapy, then a 22% relative risk reduction would occur in the 3-year period following discharge from the initial cardiovascular event. These findings are consistent with prior reports. This editorial discusses rationale and strategies clinicians can use to improve patients' compliance with recommendations for lipid-lowering therapy.

Conclusion: The authors conclude that better compliance with guideline-directed lipid therapy after a cardiovascular event would lead to a large reduction in second events. Increased efforts by clinicians to improve adherence to statin therapy are warranted.

Purpose: While statins and antiplatelet therapies are largely prescribed together worldwide, limited information is available on the safety of their association regarding rhabdomyolysis occurrence. We aimed to assess the reporting of rhabdomyolysis in patients treated with a combination of statin and antiplatelet therapy, compared to statin alone.

Methods: We used the World Health Organization pharmacovigilance database (VigiBase®) to compare the rhabdomyolysis reporting between statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin) plus antiplatelet therapy (acetylsalicylic acid, clopidogrel, prasugrel and ticagrelor) groups versus statin alone groups, for each statin and antiplatelet therapy. Study setting was restricted to patients aged 45 or older, including reports up until 1^st September, 2021. We computed reporting Odds-Ratio (ROR) and their 95% confidence interval (CI) to quantify the disproportionality between groups, adjusted on age and sex.

Results: Among the 11,431,708 reports of adverse reactions, we extracted 9,489 cases of rhabdomyolysis in patients treated with statins, of whom 2,464 (26%) were also treated with antiplatelet therapy. The reporting of rhabdomyolysis was increased when ticagrelor was associated with atorvastatin (ROR 1.30 [1.02-1.65]) or rosuvastatin (ROR 1.90 [1.42-2.54]) compared to the respective statin alone but did not change when aspirin, clopidogrel or prasugrel were considered.

Conclusion: Rhabdomyolysis reporting was increased when ticagrelor -but not other antiplatelet agents- was notified with the most prescribed statins in practice. This finding needs to be considered by physicians especially in high-risk patients.

Purpose: Novel, effective, and safe preventive therapy targets for AF are still needed. Circulating proteins with causal genetic evidence are promising candidates. We aimed to systematically screen circulating proteins for AF drug targets and determine their safety and efficacy using genetic methods.

Methods: The protein quantitative trait loci (pQTL) of up to 1949 circulating proteins were retrieved from nine large genome-proteome-wide association studies. Two-sample Mendelian Randomization (MR) and colocalization analyses were used to estimate the causal effects of proteins on the risk of AF. Furthermore, phenome-wide MR was conducted to depict side effects and the drug-target databases were searched for drug validation and repurposing.

Results: Systematic MR screen identified 30 proteins as promising AF drug targets. Genetically predicted 12 proteins increased AF risk (TES, CFL2, MTHFD1, RAB1A, DUSP13, SRL, ANXA4, NEO1, FKBP7, SPON1, LPA, MANBA); 18 proteins decreased AF risk (PMVK, UBE2F, SYT11, CHMP3, PFKM, FBP1, TNFSF12, CTSZ, QSOX2, ALAD, EFEMP1, FLRT2, LRIG1, OLA1, SH3BGRL3, IL6R, B3GNT8, FCGR2A). DUSP13 and TNFSF12 possess strong colocalization evidence. For the proteins that were identified, extended phe-MR analysis was conducted to assess their side-effect profiles, while drug-target databases provided information on their approved or investigated indications.

Conclusion: We identified 30 circulating proteins as potential preventive targets for AF.

Purpose: Radial artery occlusion (RAO) is an unresolved complication after transradial artery (TRA) puncture. The aim of this observational study was to assess the feasibility and safety of retrograde recanalization of RAO through distal transradial access (dTRA).

Methods: From June 2021 to March 2022, 28 consecutive patients with successful puncture and intubation through the dTRA in the anatomical snuffbox and RAO confirmed by angiography were enrolled.

Results: Among the 28 patients, 27 (96.4%) patients with RAO were successfully retrogradely recanalized through the dTRA and successfully underwent coronary angiography or coronary intervention. After the procedure, only 1 (3.7%) patient developed a forearm hematoma, and there were no other bleeding complications or nerve disorders.

Conclusions: DTRA is a safe and feasible approach for retrograded recanalization of RAO, with a high procedure success rate and few complications.

Purpose: Polycystic ovarian syndrome (PCOS) has been associated with cardiovascular risks and comorbid pathologies, particularly cardiorenal disorder. Short-chain fatty acids (SCFAs), especially butyrate, are essential fatty acids that regulate metabolic health and ameliorate granulosa inflammation in PCOS. However, the effect of butyrate on cardiorenal damage associated with PCOS is unknown. This study investigated the impact of SCFA and butyrate on cardiorenal abnormalities in PCOS rat model and the probable involvement of paraoxonase-1 (PON-1).

Methods: Eight-week-old female Wistar rats were allotted into three groups, n = 5, namely control (CTL), PCOS (LEZ), and LEZ + BUT. Induction of PCOS with letrozole (1 mg/kg) lasted for 21 days, while treatment with butyrate (200 mg/kg) commenced after the induction and lasted for 6 weeks uninterruptedly.

Results: PCOS rats showed hyperandrogenism, multiple ovarian cysts, disrupted metabolic indices (fasting insulin and homeostatic model of insulin resistance), and increased (p < 0.05) plasma troponin T, urea, and creatinine, as well as increased cardiac/renal stroma cell-derived factor-1/caspase-6, malondialdehyde/nuclear factor-kappaB, transforming growth factor-β1, and renal ϒ-glutamyl transferase, while a significant decrease (p < 0.05) in systemic nitric oxide/endothelial nitric oxide synthase and cardiac/renal hypoxia-inducible factor-1α and nuclear factor erythroid 2-related factor 2, which were accompanied with a decreased level of PON-1. These systemic and cardiorenal derangements were reversed by butyrate administration.

Conclusions: The results demonstrate the therapeutic benefits of SCFAs, butyrate, against cardiorenometabolic disorder in a model of PCOS. This beneficial effect is accompanied by an elevated level of PON-1. The present data possibly provides a preclinical relevance for the management of cardiorenal syndrome in PCOS.