EMERGING EVIDENCE THAT MAKES A BIG DIFFERENCE

Efficacy

HOT Trial was conducted to:
  • Assess the association between major cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death) and the target blood pressures 90 mm Hg, 85 mm Hg, and 80 mm Hg during antihypertensive treatment to assess the association between major cardiovascular events and the diastolic blood pressure achieved during treatment.1
Study Design:1
  • 18790 patients, from 26 countries, aged 50–80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mmHg and 115 mmHg (mean 105 mmHg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure 90 mmHg, 6264 to 85 mmHg, and 6262 to 80 mmHg.
  • Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid, and 9391 patients were assigned placebo.
Conclusion:1
  • Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of fatal bleeds, but non-fatal major bleeds were twice as common.

ASCEND Trial

The use of low-dose aspirin led to a lower risk of serious vascular events than placebo, p=0.01.

ASCEND Trial
  • Was conducted to assess the efficacy and safety of enteric-coated aspirin at a dose of 100 mg daily, as compared with placebo, in persons who had diabetes without manifest cardiovascular disease at trial entry. 2
Study Design:2
  • A total of 15,480 participants underwent randomization. During a mean follow-up of 7.4 years.
  • Adults were assigned randomly, who had diabetes but no evident cardiovascular disease to receive aspirin at a dose of 100 mg daily or matching placebo.
  • The primary efficacy outcome was the first serious vascular event (i.e. myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial hemorrhage).
Conclusion:2
  • Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major bleeding events.
  • The absolute benefits were largely counterbalanced by the bleeding hazard.
ATTC metanalysis
  • Long term low dose aspirin reduces the major coronary events in secondary prevention.3
Study Design:3
  • Meta-analysis of serious vascular events (myocardial infarction, stroke, or vascular death)
  • And major bleeds in six primary prevention trials (95 000 individuals at low average risk, 660 000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17 000 individuals at high average risk, 43 000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control, was undertaken.
  • Intention-to-treat analyses of first events during the scheduled treatment period were reported.
Conclusion:3
  • In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress.
  • In the absence of a high bleeding risk, aspirin is likely to be beneficial in individuals <70 years of age with a CAC ≥ 100, and they have an absolute net benefit with its use.4
  • Aspirin (75–100 mg/day) for primary prevention may be considered in patients with diabetes at very high/high risk in the absence of clear contraindications.5
  • 11% Relative risk reduction in ASCVD event using aspirin for the prevention of CVD in individuals without a history of CVD.6

In a Multi-Ethnic Study of Atherosclerosis

Aspirin use for 1ry prevention of CHD had favorable risk/benefit estimates in patients with CAC ≥100 and CAC ≥ 400.6
The red horizontal lines represent the NNH threshold for each ASCVD risk stratum.

CPS for allocation of aspirin in primary prevention8

Study Design

In a sample of >11 000 US adults- who were not taking aspirin and were free of high‐risk bleeding features-NNT5 to prevent 1 ASCVD event with aspirin was approximately 50% to 70% lower among individuals with prevalent or moderate carotid plaque (CPS ≥2) versus absent carotid plaque (NNT5 = ≈150–212 versus 448).

Conclusion

As reflected in recent guidelines, the approach to using aspirin as primary prevention therapy is continuously evolving and requires personalization; therefore, there is an urgent need to identify the patients who are most and least likely to derive net benefit from daily aspirin therapy.

ASCVD: Atherosclerotic cardiovascular disease; CVD: Cardiovascular disease; MI: myocardial infarction; CAC: coronary artery calcium scoring; NNH: number needed to harm; CPS: carotid plaque score; NNT: number needed to treat.

References

  1. Hansson L, Zanchetti A, Carruthers S et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. The Lancet. 1998;351(9118):1755-1762.
  2. Louise B, Marion M, Karl W et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. New England Journal of Medicine. 2018;379(16):1529-1539.
  3. Baigent C, Blackwell L, Collins R et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. The Lancet. 2009;373(9678):1849-1860.
  4. Verghese D, Manubolu S, Budoff MJ. Contemporary use of coronary artery calcium for the allocation of aspirin in light of the 2022 USPSTF guideline recommendations. Am J Prev Cardiol. 2022;12:100427.
  5. Volpe M, Gallo G, Modena MG, Ferri C, Desideri G, Tocci G; Members of the Board of the Italian Society of Cardiovascular Prevention. Updated Recommendations on Cardiovascular Prevention in 2022: An Executive Document of the Italian Society of Cardiovascular Prevention. High Blood Press Cardiovasc Prev. 2022;29(2):91-102.
  6. Cainzos-Achirica M, Miedema MD, McEvoy JW, et al. Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis). Circulation. 2020;141(19):1541-1553.
  7. Dammann H, Burkhardt F, Wolf N. Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions. Alimentary Pharmacology & Therapeutics. 1999;13(8):1109-1114.
  8. Dzaye O, et al. Carotid Ultrasound‐Based Plaque Score for the Allocation of Aspirin for the Primary Prevention of Cardiovascular Disease Events: The Multi‐Ethnic Study of Atherosclerosis and the Atherosclerosis Risk in Communities Study. Journal of the American Heart Association. 2024:e034718.