Wei-Ting Chang1,2,3, Chien-Chou Su4, Yu-Ching Chang5, Ching-Lan Cheng4,6, Chih-Hsin Hsu7,8,9. 1. Department of Cardiology, Chi Mei Medical Center. 2. Department of Biotechnology, Southern Taiwan University of Science and Technology. 3. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University. 4. Department of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University. 5. Institute of Clinical Pharmacy and Pharmaceutical Sciences. 6. School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University. 7. Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan. 8. Department of Internal Medicine, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin. 9. Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
Background: Sildenafil, a phosphodiesterase-5 inhibitor, has been approved for the treatment of pulmonary hypertension (PH). It improves exercise capacity, symptoms and hemodynamics in patients with PH by lowering pulmonary pressures. Preclinical studies have indicated a possible protective effect of sildenafil on ischemia/reperfusion injury. Nevertheless, evidence showing the impact of sildenafil on ischemic disorders in patients with PH is lacking. Methods: Using the Taiwanese National Health Insurance Research Database and Cause of Death databases, we conducted a retrospective cohort study to investigate the hazard ratio (HR) with inverse probability of treatment weighting (IPTW) of sildenafil for the development of major adverse cardiovascular and cerebrovascular events (MACCEs), including new-onset acute myocardial infarction (AMI) and ischemic stroke in patients with PH. The follow-up period was 7 years. In addition, we performed sensitivity analysis by limiting the studied population to those who received right heart catheterization and excluding those with a history of coronary arterial disease. Results: After adjusting for age, sex and comorbidities, the patients receiving sildenafil had a significantly lower risk of subsequent AMI [adjusted HR with IPTW: 0.42; confidence interval (CI): 0.20-0.86] and a trend of less ischemic stroke (adjusted HR with IPTW: 0.72; CI: 0.51-1.02). Interestingly, among the sildenafil users, those who were older, had chronic kidney disease, and took cardiovascular medications showed the most significant reductions in the risk of MACCEs. The sensitivity analysis showed similar results. Conclusions: The use of sildenafil in patients with PH was associated with a lower risk of long-term MACCEs. More evidence is needed to validate our findings.
Background: Sildenafil, a phosphodiesterase-5 inhibitor, has been approved for the treatment of pulmonary hypertension (PH). It improves exercise capacity, symptoms and hemodynamics in patients with PH by lowering pulmonary pressures. Preclinical studies have indicated a possible protective effect of sildenafil on ischemia/reperfusion injury. Nevertheless, evidence showing the impact of sildenafil on ischemic disorders in patients with PH is lacking. Methods: Using the Taiwanese National Health Insurance Research Database and Cause of Death databases, we conducted a retrospective cohort study to investigate the hazard ratio (HR) with inverse probability of treatment weighting (IPTW) of sildenafil for the development of major adverse cardiovascular and cerebrovascular events (MACCEs), including new-onset acute myocardial infarction (AMI) and ischemic stroke in patients with PH. The follow-up period was 7 years. In addition, we performed sensitivity analysis by limiting the studied population to those who received right heart catheterization and excluding those with a history of coronary arterial disease. Results: After adjusting for age, sex and comorbidities, the patients receiving sildenafil had a significantly lower risk of subsequent AMI [adjusted HR with IPTW: 0.42; confidence interval (CI): 0.20-0.86] and a trend of less ischemic stroke (adjusted HR with IPTW: 0.72; CI: 0.51-1.02). Interestingly, among the sildenafil users, those who were older, had chronic kidney disease, and took cardiovascular medications showed the most significant reductions in the risk of MACCEs. The sensitivity analysis showed similar results. Conclusions: The use of sildenafil in patients with PH was associated with a lower risk of long-term MACCEs. More evidence is needed to validate our findings.
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