Low-Dose Aspirin for Primary Prevention of Cardiovascular Events Comparing East Asians With Westerners

Figure 1. Flow of Study Selection This flow represents how we selected the acceptable studies that were analyzed in this meta-analysis. Using the key words, the first selected 4,177 studies were listed and deleted by Excel software (Microsoft) when their title was duplicated. After that, roughly 3,009 studies were reviewed by authors for checking the inclusion/exclusion criteria. Finally, 11 studies were selected after a review of full text of 102 studies. RCT = randomized clinical trial.

Figure 2. Outcomes Between Aspirin and Placebo Across Westerners and East Asians The black, blue, and red squares indicate the cardiovascular (CV) outcome for overall, Western, and East Asian populations, respectively. The bold P values indicated the difference of CV outcomes between the Western and East Asian populations. A major adverse cardiovascular event (MACE) indicated CV death, myocardial infarction (MI), and stroke. The 2 studies (PPP [Primary Prevention Project] and POPADAD [Prevention of Progression of Arterial Disease and Diabetes]) did not suggest detailed information regarding ischemic or hemorrhagic stroke. GI = gastrointestinal; ICH = intracranial hemorrhage.

Figure 3. Forest Plots Regarding Efficacy of Aspirin Between Westerners and East Asians MACE indicated CV death, MI, and stroke. AAA = Aspirin for Asymptomatic Atherosclerosis; ARRIVE = Aspirin to Reduce Risk of Initial Vascular Events; ASCEND = A Study of Cardiovascular Events in Diabetes; ASPREE = Aspirin in Reducing Events in the Elderly; HOT = Hypertension Optimal Treatment; JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes; JPPP = Japanese Primary Prevention Project; WHS = Women’s Health Study; other abbreviations as in Figure 2.

Figure 4. Forest Plots Regarding Safety of Aspirin Between Westerners and East Asians Major bleeding indicated ICH and GI bleeding. Abbreviations as in Figures 2 and 3.

Figure 5. The Net RD and Net NNT The blue bar and negative value are the benefits of major adverse cardiovascular events (MACEs), which were 3.97 or 3.31 persons per 1,000 persons less occurred in the aspirin arm compared with the control arm. The orange bar and positive value are the harms of major bleeding, which were 4.66 or 11.35 persons per 1,000 persons more occurred in the aspirin arm. The green bar and value were net risk differences (RDs), which were calculated by benefit + harm values. The net number needed to treat (NNT) calculated by: 1 / (net RD).

Central Illustration. Aspirin for Primary Prevention: East Asian vs Western Population We searched randomized clinical trials (RCTs) for intervention with low-dose aspirin (≤100 mg once daily) in participants without symptomatic cardiovascular disease until December 31, 2021. Two RCTs included 17,003 East Asians, and 9 RCTs had 117,467 Western participants. Aspirin treatment showed a similar effect in reducing the rate of a major adverse cardiovascular event (MACE) (relative risk [RR] of East Asians: 0.87; 95% CI: 0.71-1.05; RR of Westerners: 0.90; 95% CI: 0.85-0.95) (Pinteraction = 0.721). In contrast, the risk of major bleeding during aspirin vs control was greater in the East Asian population (RR: 2.48; 95% CI: 1.86-3.30) compared with the Western population (RR: 1.45; 95% CI: 1.26-1.66) (Pinteraction = 0.001), which was driven by more frequent gastrointestinal (GI) bleeding (RR of East Asians: 3.29; 95% CI: 2.26-4.80 vs RR of Westerners: 1.56; 95% CI: 1.29-1.88) (Pinteraction < 0.001). The net relative differences (RDs) (RD of MACE plus RD of major bleeding) were 8.04 and 0.69 per 1,000 persons in East Asian and Western participants, indicating 124 and 1,449 of the net number needed to harm,…