Antiplatelet therapy reduces atherothrombotic risk and has therefore become a cornerstone in the treatment of cardiovascular disease. Aspirin, adenosine diphosphate P2Y₁₂ receptor antagonists, glycoprotein IIb/IIIa inhibitors, and the thrombin receptor blocker vorapaxar are effective antiplatelet agents but significantly increase the risk of bleeding. Moreover, atherothrombotic events still impair the prognosis of many patients with cardiovascular disease despite established antiplatelet therapy. Over the last years, advances in the understanding of thrombus formation and hemostasis led to the discovery of various new receptors and signaling pathways of platelet activation. As a consequence, many new antiplatelet agents with high antithrombotic efficacy and supposedly only moderate effects on regular hemostasis have been developed and yielded promising results in preclinical and early clinical studies. Although their long journey from animal studies to randomized clinical trials and finally administration in daily clinical routine has just begun, some of the new agents may in the future become meaningful additions to the pharmacological armamentarium in cardiovascular disease.

Background Soluble P-selectin (sP-selectin), a biomarker of inflammatory pathologies including cardiovascular disease, is known to have pro-atherosclerotic effects such as the ability to increase leukocyte recruitment and modulate thrombotic response. We aimed to assess the impact of sP-selectin on long-term major adverse cardiovascular events (MACE) in patients after coronary stenting for coronary artery disease. Methods We analysed 733 patients of a single-centre registry undergoing percutaneous coronary intervention (PCI) between 2003 and 2006. Plasma samples were analysed for sP-selectin antigen concentration with an enzyme-linked immunoassay. The study population was categorized according to sP-selectin quartiles. Endpoint of the study was long-term MACE, a composite of all-cause death, myocardial infarction (MI) and stroke. Results Of the total patient cohort, 361 (49.2%) patients were admitted for stable coronary artery disease and 372 (50.8%) for acute coronary syndrome. Median age was 64 years and 70.7% were male. After a mean follow-up period of 9.7 years, MACE occurred in 344 (46.9%) patients. The primary endpoint components of all-cause death occurred in 211 (28.8%), MI in 88 (12.0%) and ischaemic stroke in 45 (6.1%) patients. After adjustment for confounders, patients in the 2nd, 3rd and 4th quartile were at higher risk for MACE compared with the 1st quartile (hazard ration [HR], 1.234 [0.899–1.695], p = 0.193; HR, 1.480 [1.085–2.019], p = 0.013; and HR, 1.571 [1.115–2.152], p = 0.004). sP-selectin as continuous variable model was significantly associated with MACE after adjustment (HR per 1 ng/mL increase of 1.009 [95% confidence interval, 1.002–1.017]; p = 0.016). Conclusion Elevated levels of sP-selectin were associated with increased risk for long-term MACE in patients undergoing PCI.

Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid versus placebo in patients with hyperlipidemia. A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As primary endpoint we analysed three-point major adverse cardiovascular events (MACE) consisting of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke. The analysis was carried out using the odds ratio as the outcome measure. Due to the expected heterogeneity across studies a random-effects model was fitted to the data. Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18,200 patients (9,765 on bempedoic acid, 8,435 on placebo). Bempedoic acid significantly reduced MACE compared to placebo (OR 0.84 [95% CI 0.76-0.96]; p<0.001; I²=0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; p=0.20, I²=0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; p=0.49; I²=18%). Bempedoic acid reduced non-fatal MI in patients with hyperlipidemia, whereas it had no significant effect on stroke and all-cause mortality.