The causal relationship between antihypertensive drugs and depression: a Mendelian randomization study of drug targets.

Background: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets. Method: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression. Results: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk. Conclusion: The study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.

Dabigatran versus aspirin for stroke prevention after cryptogenic stroke with patent foramen ovale: A prospective study.

BACKGROUND: Medical treatment for stroke prevention in cryptogenic stroke (CS) patients with patent foramen ovale (PFO) remains inconclusive. We compared the efficacy and safety of dabigatran with aspirin on stroke prevention for patients with recent CS and PFO. METHODS: In this prospective cohort study, we randomly assigned patients with PFO who had a cryptogenic stroke, in a 1:1 ratio, to dabigatran or aspirin group. Patients were followed for 2 years and the primary efficacy outcome was the recurrence of stroke or systemic embolism. The primary safety outcome was occurrence of bleeding complications. RESULTS: A total of 375 patients were enrolled in the study, 188 assigned to the dabigatran group and 187 to the aspirin group. During the 2-year follow-up, the primary efficacy outcomes occurred in 4 patients in the dabigatran group (annualized rate, 2.0%) and 11 patients in the aspirin group (annualized rate, 5.1%) (hazard ratio, 0.74; 95% confidence interval, 0.51-0.98; P = 0.049). TIA/acute ischemic stroke occurred in 3 patients in the dabigatran group and 8 patients in the aspirin group (hazard ratio, 0.72; 95% confidence interval, 0.52-0.95; P = 0.039). Bleeding complications occurred in 8 patients in the dabigatran group (annualized rate, 3.9%) and in 7 patients in the aspirin group (annualized rate, 3.5%) (hazard ratio, 1.24; 95% confidence interval, 1.01-1.52; P = 0.886). CONCLUSION: For cryptogenic stroke with PFO, dabigatran was superior to aspirin for stroke prevention. There is no increased risk of bleeding complication with dabigatran.

Early and long-term outcomes of argatroban use in patients with acute noncardioembolic stroke.

BACKGROUND: Argatroban in acute noncardioembolic stroke ineligible for intravenous thrombolysis (IVT) or endovascular treatment (EVT) remains unclear. This study aimed to evaluate whether argatroban improved early and long-term outcomes compared with antiplatelet treatment. METHODS: This retrospective observational study, using the prospective stroke database from our hospital, included all consecutive patients who hospitalized from January 1, 2017 to December 31, 2019, with a diagnosis of acute non-cardioembolic stroke within 48 hours of stroke onset but not receiving IVT and EVT. Patients were divided into 2 groups: the argatroban group and the control group without argatroban. Outcome assessment with early neurological deterioration (END), National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), bleeding complications, and mortality were compared between the 2 groups in all cases and different stroke subtypes. An ordinal logistic regression analysis evaluated the association between argatroban use and mRS score at 90 days. RESULTS: Of 1325 patients were enrolled, 519 patients in the argatroban group and 806 in the control. Baseline characteristics, hospital bleeding complications, and 90-day mortality were similar for the 2 groups. The argatroban group showed lower END, larger improvement of 7-day NIHSS score and higher percentage of a 90-day mRS score of 02. Similar results were found in subgroup analysis with large-artery atherosclerosis, anterior circulation infarction, and moderate stroke. Also, argatroban use was significantly associated with an excellent long-term stroke outcome (mRS ≤ 2). CONCLUSION: The current study suggested that argatroban was safe and effective for improving short and long-term outcomes in noncardioembolic stroke patients.