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Three Part Question

In [adults with suspected acute coronary syndrome] is [soluble aspirin or chewed aspirin faster] at [inhibiting platelet aggregation]?

Clinical Scenario

One Friday night you decide to leaf through the 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes. You note that the guidelines recommend chewable aspirin yet the majority of departments you have worked in use soluble aspirin. You wonder if there is any evidence to back the use of chewable aspirin?

Search Strategy

We searched the following databases using the Ovid interface: EBM Reviews - Cochrane Database of Systematic Reviews 2005 to November 2014, EBM Reviews - ACP Journal Club 1991 to December 2014, EBM Reviews - Database of Abstracts of Reviews of Effects 4th Quarter 2014, Ovid MEDLINE(R) 1946 to January Week 2 2014, Embase 1974 to 2014 Week 02

[exp thromboxane/ or exp thromboxane A2/ or exp thrombocyte aggregation/ or exp Thromboxanes/ or exp Blood Platelets/ or *Platelet Aggregation/de] AND [Platelet Aggregation Inhibitors/pharmacokinetics or Thromboxane B2/blood or exp thromboxane/ or exp thromboxane A2/ or exp thromboxanes/ or exp thrombocyte aggregation/ or Platelet Aggregation Inhibitors/pharmacokinetic] AND [[dispersible or soluble AND [aspirin]] or [chew or chewable AND [aspirin]].

Search Outcome

Fifteen papers were found after removal of duplicates. One paper was discarded as it only compared swallowing a tablet of aspirin versus chewing a tablet[Sai]. Two papers were relevant to the three part question [See Table]. A manual search of the references revealed a further paper but this looked at ASA levels rather than thromboxane or platelet aggregation[Muir]. One further paper was found in using the Google search engine but this also looked at aspirin levels in the blood[Sagar].

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Feldman 1999 USA	12 fasting volunteers ingested 325 mg of buffered aspirin, either by chewing a tablet for 30 seconds before swallowing it with 4 ounces of water, swallowing a whole tablet with 4 ounces of water, or drinking 4 ounces of dispersible aspirin. Age range 21 – 64 (mean age 39)	PRCT	Thromboxane B2 level decrease in minutes (with the Standard Error of Mean)	Tablet:50% decrease in TxB2 12.0 (SEM +/- 2.3) and 90% decrease in TxB2 25.7 (SEM +/-4.6) Chewed: 5.0 (SEM +/- 0.6) (p = <0.05 vs dispersible aspirin) and 13.6 (SEM +/- 1.9) (p not less than 0.05 vs dispersible aspirin) Dispersible: 7.6 (SEM +/- 1.2) (p = 0.90 vs chewable aspirin) When there is a 50% TxB2 decrease (ng/ml) and 15.8 (SEM +/- 1.8) (p = 0.34 compared to chewable aspirin) When there is a 90 % TxB2 decrease (ng/ml)	Small sample, no sample size calculation documented. Large p values for dispersible aspirin. P values may be due to small sample size. Patients had overnight fast not representative of our population. No comment on whether lab staff were blinded could this have an effect or not as using radioimmunoassay. Measures platelet aggregation marker not platelet aggregation.
			Corresponding plasma levels at the same time	Tablet: 1143 (SEM +/-136) and 3311 (SEM +/- 259) Chewed: 999 (SEM +/- 88) and 3407 (SEM +/- 244) Dispersible: 982 (SEM +/- 135) and 3491 (SEM +/- 364)
Schwertner et al 2006 USA	Dispersible aspirin 325 mg, chewed aspirin, 324 mg, and whole compressed non-enteric coated aspirin, 324 mg. Twenty-four healthy volunteers, 18—39 years of age mean 33.5 . All subjects crossed over to the other two formulations with at least 2 weeks between ingestions.	Prospective single-blinded triplecrossover study	Time taken for platelet inhibition in 2.5 minutes	Solid aspirin: Number of patients with platelet inhibition 4. Cumulative percent 16.6 Chewable: Number of patients with platelet inhibition 0. Cumulative percent 0 Dispersible aspirin: Number of patients with platelet inhibition 0. Cumulative percent 0	Mean age of 18-39, not representative of population. Empty stomachs not realistic. Possible underpowered large p value and doesn’t define what the moderate difference the sample size was designed to demonstrate
			Time taken for platelet inhibition in 5 minutes	Solid aspirin: Number of patients with platelet inhibition 5. Cumulative percent 37.5 Chewable: Number of patients with platelet inhibition 9. Cumulative percent 37.5 Dispersible aspirin: Number of patients with platelet inhibition 3. Cumulative percent 12.5
			Time taken for platelet inhibition in 7.5 minutes	Solid aspirin: Number of patients with platelet inhibition 5. Cumulative percent 58.3 Chewable: Number of patients with platelet inhibition 9. Cumulative percent 75 Dispersible aspirin: Number of patients with platelet inhibition 7. Cumulative percent 41.7
			Time taken for platelet inhibition in 10 minutes	Solid aspirin: Number of patients with platelet inhibition 6. Cumulative percent 83.3 Chewable: Number of patients with platelet inhibition 4.Cumulative percent 91.7 Dispersible aspirin: Number of patients with platelet inhibition 2. Cumulative percent 50
			Time taken for platelet inhibition in 15 minutes	Solid aspirin: Number of patients with platelet inhibition 3.Cumulative percent 95.8 Chewable: Number of patients with platelet inhibition 1.Cumulative percent 95.8 Dispersible aspirin: Number of patients with platelet inhibition 7. Cumulative percent 79.2
			Time taken for platelet inhibition in 20 minutes	Solid aspirin: Number of patients with platelet inhibition 0.Cumulative percent 95.8 Chewable: Number of patients with platelet inhibition 1. Cumulative percent 100 Dispersible aspirin: Number of patients with platelet inhibition 0. Cumulative percent 79.2
			Time taken for platelet inhibition in 25 minutes	Solid aspirin: Number of patients with platelet inhibition 1. Cumulative percent 100 Chewable: Number of patients with platelet inhibition 0. Cumulative percent 100 Dispersible aspirin: Number of patients with platelet inhibition 5. Cumulative percent 100

Comment(s)

There is evidence that chewable aspirin leads to a statistically different 50% decrease in thromboxane B2 levels compared to soluble aspirin. When it gets to a 90% decrease (the clinically significant level required for platelet inhibition) there is no statistical difference. Schwertner et al also note that there is no statistical difference between the soluble and chewable aspirin in platelet inhibition. One needs to bear in mind that these studies may be underpowered. Both studies already pre-dispersed their aspirin in water, this is not representative of the clinical setting and would add several minutes delay to the anti-platelet activities of the dispersible aspirin.

Editor Comment

KvDW

Clinical Bottom Line

Both chewable and dispersible non enteric coated aspirin are far superior to swallowing an aspirin tablet There is evidence that suggests that chewable aspirin may lead to speedier platelet inhibition especially when one takes into consideration the time practicalities of dispersing the aspirin.

References

1. Muir N, Nichols JD, Clifford JM et al. The influence of dosage form on aspirin kinetics: implications for acute cardiovascular use. Med Res Opin. 1997;13(10):547-53.
2. Feldman M, Cryer B. Aspirin absorption rates and platelet inhibition times with 325-mg buffered aspirin tablets (chewed or swallowed intact) and with buffered aspirin solution. Am J Cardiol. 1999 Aug 15;84(4):404-9.
3. Sagar KA, Smyth MR. A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography. J Pharm Biomed Anal. 1999 Nov;21(2):383-92.
4. Schwertner HA, McGlasson D, Christopher M et al. Effects of different aspirin formulations on platelet aggregation times and on plasma salicylate concentrations. Thromb Res. 2006;118(4):529-34.
5. Sai Y, Kusaka A, Imanishi K et al. A randomized, quadruple crossover single-blind study on immediate action of chewed and unchewed low-dose acetylsalicylic acid tablets in healthy volunteers. J Pharm Sci. 2011 Sep;100(9):3884-91.
6. Amsterdam EA, Wenger NK, Brindis RG et al. ACC/AHA Task Force Members. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014 23;130(25):2354-94.