Table 1.
Primary prevention in diabetes
| Study | Patients | Primary efficacy endpoint | Median follow-up | Predicted vs. observed incidence and expected benefit | Absolute and relative benefit | Absolute and relative harm | Comments |
|---|---|---|---|---|---|---|---|
| ATT meta-analysis (2009)42 | 95 000 patients from six primary prevention trials which included 4% of DM patients (n = 3818) | Stroke, MI, and CV death | NA | NA |
Overall population: Aspirin: 0.51% Control: 0.57% HR 0.88 (0.82–0.94) DM subgroup: Aspirin: 1.63% Control: 1.87% HR 0.88 (0.67–1.15) |
GI/extracranial bleed Overall population: Aspirin: 0.10% Control: 0.07% HR 1.54 (1.30–1.82) DM subgroup: Aspirin: 0.23%/year Control: 0.21%/year HR 1.10 (0.52–2.34) |
NNT/NNH ratio: 0.83 No difference in fatal bleeding |
| JPAD (2008)43 | 2539 T2DM patients without a history of atherosclerotic disease | Sudden death; death from coronary, cerebrovascular, and aortic causes; non-fatal acute MI; UA; exertional angina; non-fatal ischaemic and haemorrhagic stroke; TIA; or non-fatal aortic and PVD | 4.4 years |
Predicted: 5.2%/year vs. Observed: 1.7%/year Expected benefit: 30% RRR |
Aspirin: 5.4% Placebo: 6.7% HR 0.80 (0.58–1.10) |
Any GI bleeding: Aspirin: n = 12 Placebo: n = 4 |
Observed primary endpoint rate ∼1/3 of predicted. Expected benefit likely unrealistic based on previous data (trial largely underpowered). |
| POPADAD (2008)44 | 1276 adults aged ≥40 years with T1DM or T2DM and ABI ≤0.99 (asymptomatic) | Death from CAD or stroke, non-fatal MI or stroke, or amputation for critical limb ischaemia; and death from CAD or stroke | 6.7 years |
Predicted: 28%/year vs. observed: 2.9%/year Expected benefit: 25% RRR |
Aspirin: 18.2% Placebo: 18.3% HR 0.98 (0.76–1.26) |
Any GI bleeding: Aspirin: 4.4% Placebo: 4.9% HR 0.90 (0.53–1.52) |
Observed events were approx. 1/10 of predicted. The expected benefit was likely unrealistic based on previous data (trial was largely underpowered). |
| ASCEND (2018)45 | 15 480 Patients aged ≥40 years with DM and no evident CV disease | Non-fatal MI, non-fatal stroke (excluding confirmed ICH), TIA, or death from any vascular cause (excluding confirmed ICH) | 7.4 years |
Predicted: 1.2–1.3%/year vs. Observed: 1.3%/year Expected benefit: 15% RRR |
Aspirin: 8.5% Placebo: 9.6% HR 0.88 (0.79–0.97) |
BARC 2, 3, and 5 bleeding: Aspirin: 4.1% Placebo 3.2% HR 1.29 (1.09–1.52) ICH: Aspirin: 0.7% Placebo: 0.6% HR 1.22 (0.82–1.81) Fatal bleeding: Aspirin: 0.2% Placebo: 0.2% HR 1.18 (0.61–2.30) |
Consistency between predicted and observed incidence event rate NNT/NNH: 0.81 |
| THEMIS (2019)47 |
19 220 patients with DM, ≥50 years, stable CAD with no previous MI or stroke Randomized to ticagrelor or placebo on a background of aspirin therapy |
Stroke, MI, and CV death | 3.3 years |
Predicted benefit: 16% RRR Predicted: 2.5%/year vs. Observed: 2.5%/year |
Ticagrelor: 7.7% Placebo: 8.5% HR 0.90 (0.81–0.99) |
TIMI major bleeding: Ticagrelor: 2.2% Placebo: 1.0% HR 2.32 (1.82–2.94) BARC 3–5 bleeding: Ticagrelor: 3.7% Placebo: 1.7% HR 2.36 (1.96–2.84) ICH: Ticagrelor: 0.7% Placebo: 0.5% HR 1.71 (1.18–2.48) |
High rate of ticagrelor discontinuation: Placebo 25% vs. Ticagrelor: 35% HR 1.50 (1.42–1.58) Predicted benefit higher than observed. NNT/NNH: 1.48 (TIMI-major defined bleeding) |
|
Meta-analysis Seidu et al. (2019)50 |
34 227 participants with DM, individual patient data from 2306 participants | Stroke, MI, and CV death | 5 years | NA |
Aspirin: 8.6% Control: 9.6% HR 0.89 (0.83–0.95) |
Major bleeding: Aspirin: 4% Control: 3.5% HR 1.30 (0.92–1.82) |
Summary of primary prevention studies.
Significant differences are reported in bold.
ABI, ankle-brachial index; BARC, Bleeding Academic Research Consortium; CAD, coronary artery disease; CV, cardiovascular; DM, diabetes mellitus; GI, gastrointestinal; HR, hazard ratio; ICH, intracranial haemorrhage; MI, myocardial infarction; NA, not applicable; NNH, number needed to harm; NNT, number needed to treat; PVD, peripheral vascular disease; RRR, relative risk reduction; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; TIA, transient ischaemic attack; TIMI, Thrombolysis in Myocardial Infarction; UA, unstable angina.