Search Results (7)

Gender medicine has increasingly underscored the necessity of addressing sex-based differences in disease prevalence and management, particularly within cardiovascular conditions and drug intolerance. Women often present cardiovascular diseases distinctively from men, with a higher prevalence of non-obstructive coronary artery disease and varied ischemic manifestations, such as coronary microvascular dysfunction and epicardial or microvascular coronary spasm. This disparity is further exacerbated by elevated drug intolerance rates among women, influenced by hormonal, genetic, and psychosocial factors. The 2024 ESC guidelines for managing chronic coronary syndromes stress the need for personalized approaches to treat angina and ischemia with non-obstructive coronary artery disease (ANOCA/INOCA), recommending a combination of antianginal medications. Despite standard treatments, up to 40% of ANOCA/INOCA patients experience refractory angina, necessitating a multifaceted approach that often involves multiple antianginal drugs, which can increase the likelihood of drug intolerances. Future research should focus on including women in drug studies and addressing sex-specific differences, while healthcare providers must be equipped to manage gender-specific drug intolerances. Enhanced awareness, individualized treatment strategies, and gender-sensitive healthcare policies are crucial for improving outcomes and bridging the gender gap in cardiovascular medicine. Full article

Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine’s mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies. Full article

Pyrimidines play an important role in modern medical fields. They have a wide spectrum of biological activities such as antimicrobial, anticancer, anti-allergic, anti-leishmanial, antioxidant agents and others. Moreover, in recent years, 3,4-dihydropyrimidin-2(1H)ones have attracted researchers to synthesize them via Biginelli reaction and evaluate their antihypertensive activities as bioisosters of Nifedipine, which is a famous calcium channel blocker. Our new target compounds were prepared through one-pot reaction of thiourea 1, ethyl acetoacetate 2 and/or 1H-indole-2-carbaldehyde, 2-chloroquinoline-3-carbaldehyde, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, 3a–c in acid medium (HCl) yielding pyrimidines 4a–c, which in turn were hydrolyzed to carboxylic acid derivatives 5a–c which were chlorinated by SOCl₂ to give acyl chlorides 6a–c. Finally, the latter were reacted with some selected aromatic amines, namely, aniline, p-toluidine and p-nitroaniline, producing amides 7a–c, 8a–c, and 9a–c. The purity of the prepared compounds was examined via TLC monitoring, and structures were confirmed by different spectroscopic techniques such as IR, ¹HNMR, ¹³CNMR, and mass spectroscopy. The in vivo evaluation of the antihypertensive activity revealed that compounds 4c, 7a, 7c, 8c, 9b and 9c had comparable antihypertensive properties with Nifedipine. On the other hand, the in vitro calcium channel blocking activity was evaluated by IC₅₀ measurement and results revealed that compounds 4c, 7a, 7b, 7c, 8c, 9a, 9b, and 9c had comparable calcium channel blocking activity with the reference Nifedipine. Based on the aforementioned biological results, we selected compounds 8c and 9c to be docked onto Ryanodine and dihydropyridine receptors. Furthermore, we developed a structure–activity relationship. The designed compounds in this study show promising activity profiles in reducing blood pressure and as calcium channel blockers, and could be considered as new potential antihypertensive and/or antianginal agents. Full article

Angina is the main symptom of ischemic heart disease; mirroring a mismatch between oxygen supply and demand. Epicardial coronary stenoses are only responsible for nearly half of the patients presenting with angina; whereas in several cases; symptoms may underlie coronary vasomotor disorders; such as microvascular dysfunction or epicardial spasm. Various medications have been proven to improve the prognosis and quality of life; representing the treatment of choice in stable angina and leaving revascularization only in particular coronary anatomies or poorly controlled symptoms despite optimal medical therapy. Antianginal medications aim to reduce the oxygen supply-demand mismatch and are generally effective in improving symptoms; quality of life; effort tolerance and time to ischemia onset and may improve prognosis in selected populations. Since antianginal medications have different mechanisms of action and side effects; their use should be tailored according to patient history and potential drug-drug interactions. Angina with non-obstructed coronary arteries patients should be phenotyped with invasive assessment and treated accordingly. Patients with refractory angina represent a higher-risk population in which some therapeutic options are available to reduce symptoms and improve quality of life; but robust data from large randomized controlled trials are still lacking. Full article

Ischemic heart disease is a significant public health problem with high mortality and morbidity. Extensive scientific investigations from basic sciences to clinics revealed multilevel alterations from metabolic imbalance, altered electrophysiology, and defective Ca²⁺/Na⁺ homeostasis leading to lethal arrhythmias. Despite the recent identification of numerous molecular targets with potential therapeutic interest, a pragmatic observation on the current pharmacological R&D output confirms the lack of new therapeutic offers to patients. By contrast, from recent trials, molecules initially developed for other fields of application have shown cardiovascular benefits, as illustrated with some anti-diabetic agents, regardless of the presence or absence of diabetes, emphasizing the clear advantage of “old” drug repositioning. Ranolazine is approved as an antianginal agent and has a favorable overall safety profile. This drug, developed initially as a metabolic modulator, was also identified as an inhibitor of the cardiac late Na⁺ current, although it also blocks other ionic currents, including the hERG/Ikr K⁺ current. The latter actions have been involved in this drug’s antiarrhythmic effects, both on supraventricular and ventricular arrhythmias (VA). However, despite initial enthusiasm and promising development in the cardiovascular field, ranolazine is only authorized as a second-line treatment in patients with chronic angina pectoris, notwithstanding its antiarrhythmic properties. A plausible reason for this is the apparent difficulty in linking the clinical benefits to the multiple molecular actions of this drug. Here, we review ranolazine’s experimental and clinical knowledge on cardiac metabolism and arrhythmias. We also highlight advances in understanding novel effects on neurons, the vascular system, skeletal muscles, blood sugar control, and cancer, which may open the way to reposition this “old” drug alone or in combination with other medications. Full article

Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increases in MedDiet adherence were linearly associated with a decreased initiation of glucose-lowering (HR: 0.76 [0.71–0.80]), antihypertensive (HR: 0.79 [0.75–0.82]), statin (HR: 0.82 [0.78–0.85]), fibrate (HR: 0.78 [0.68–0.89]), antiplatelet (HR: 0.79 [0.75–0.83]), vitamin K antagonist (HR: 0.83 [0.74; 0.93]), antianginal (HR: 0.84 [0.74–0.96]), and cardiac glycoside therapy (HR: 0.69 [0.56–0.84]). LTPA was non-linearly related to a delayed initiation of glucose-lowering, antihypertensive, statin, fibrate, antiplatelet, antianginal, and cardiac glycoside therapy (minimum risk: 180–360 metabolic equivalents of task-min/day). Both combined were synergistically associated with a decreased onset of glucose-lowering drugs (p-interaction = 0.04), antihypertensive drugs (p-interaction < 0.001), vitamin K antagonists (p-interaction = 0.04), and cardiac glycosides (p-interaction = 0.01). Summarizing, sustained adherence to a MedDiet and LTPA were associated with lower risk of initiating cardiovascular-related medications. Full article

An association between trimetazidine (TMZ), an anti-anginal drug, and parkinsonism has been reported in a number of studies. However, evidence from studies with long-term follow-up and better validity is lacking. We investigated the risk of TMZ-associated parkinsonism, specifically the incidence rate, cumulative dose–response relationship, and combined effects with other parkinsonism-inducing medications. This propensity score-matched retrospective cohort study was conducted using 14-year health insurance claims data in South Korea. The risk of parkinsonism was evaluated using multivariate Cox proportional hazard regression analysis, adjusted for comorbidities and concurrent medications. A total of 9712 TMZ users and 29,116 matched non-TMZ users were included. TMZ users had a significantly higher incidence rate of parkinsonism than non-TMZ users (9.34 vs. 6.71 per 1000 person-years; p < 0.0001). TMZ use significantly increased the risk of parkinsonism (adjusted hazard ratio = 1.38; 95% confidence interval = 1.26–1.51). Increased risks were observed with accumulated doses of TMZ, as well as concurrent use of other parkinsonism-inducing medications. The findings indicate that TMZ use significantly increases the risk of parkinsonism in the South Korean population. Closer monitoring should be considered for TMZ users, especially for those who are older, using TMZ at high cumulative doses and other parkinsonism-inducing medications. Full article