Combination Therapy with Dipyridamole and Clopidogrel for Secondary Stroke Prevention in Aspirin-Intolerant Patients After Myocardial Infarction: Results of a Nationwide Case-Control Study

Fig. 1. Identification process of the study cohort. AMI acute myocardial infarction, ICD International Classification of Diseases, MI myocardial infarction, CVA cerebrovascular accident

Fig. 2. Kaplan–Meier survival curves with first AMI and previous stroke in overall, sex-specific, and age-specific subanalyses (a–e). Overall, the 12-year survival rate was not different between patients in the two groups after first AMI [log-rank p = 0.6247] (a). In the sex subgroup analysis, the long-term outcomes of the clopidogrel group did not differ from those of the clopidogrel–dipyridamole group among the male [log-rank p = 0.7431] (b) or female subgroups [log-rank p = 0.6788] (c). In the age subgroup analysis, there was no survival difference between the two groups, regardless of whether patients were older [log-rank p = 0.6833] (d) or younger [log-rank p = 0.5630] (e). AMI acute myocardial infarction

Fig. 3. Kaplan–Meier survival curves after first AMI in the DM, AMI type, and PCI subgroups of patients (a–f). There were no statistical differences between the two therapeutic strategies in patients with [log-rank p = 0.3436] (a) or without [log-rank p = 0.7833] DM (b). No superiority of any therapy in subgroups of different types of myocardial infarction was observed, regardless of AMI type [log-rank p = 0.4066] (c), and log-rank p = 0.9812 (d). There were similar effects of the two strategies in patients who did [log-rank p = 0.8185] (e) or did not [log-rank p = 0.8838] undergo PCI therapy (f). AMI acute myocardial infarction, DM diabetes mellitus, PCI percutaneous coronary intervention, STEMI ST elevation myocardial infarction, NSTEMI non-ST elevation myocardial infarction

Fig. 4. Event-free survival curves of patients with first AMI and previous stroke (a–d). There was no difference in stroke-free survival [log-rank p = 0.6842] (b) between the two groups of patients after AMI. Clopidogrel plus dipyridamole did not lead to worse intracerebral hemorrhage-free survival [log-rank p = 0.6191] (c) or gastrointestinal bleeding-free survival [log-rank p = 0.9539] (d). Furthermore, the combination with dipyridamole did not improve recurrent myocardial infarction-free survival [log-rank p = 0.8344] (a). AMI acute myocardial infarction

Fig. 5. Forest plot of hazard ratios in patients with first AMI and previous stroke. Dipyridamole showed no benefit in any subgroup analysis regardless of sex, age (younger or older than 75 years), comorbidities (HTN, dyslipidemia, DM, PVD, ESRD, COPD), PCI, or medications (ACEIs or ARBs, statins, β-blockers, heparin, or LMWH). ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, COPD chronic obstructive pulmonary disease, DM diabetes mellitus, ESRD end-stage renal disease, LMWH low-molecular-weight heparin, PVD peripheral vascular disease, HTN hypertension, PCI percutaneous coronary intervention, HR hazard ratio, CI confidence interval, AMI acute myocardial infarction