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Three Part Question

In [adults with suspected acute coronary syndrome] does [soluble aspirin or chewed aspirin] lead to [faster inhibition of platelet aggregation]?

Clinical Scenario

You note that international guidelines recommend the use of chewable aspirin for patients with acute coronary syndromes (1). This conflicts with your personal experience of using soluble aspirin. You wonder if there is any evidence to suggest that chewable aspirin leads to faster inhibition of platelet function than soluble 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 (2). Two papers were relevant to the three part question (Table 1). A manual search of the references revealed a further paper but this looked at ASA levels rather than thromboxane or platelet aggregation (3). One further paper was found in using the Google search engine but this also looked at aspirin levels in the blood (4).

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Feldman et al 1995 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)	Prospective randomized controlled trial	Time (in minutes) to achieve 50% and 90% decrease in thromboxane B2 (TxB2) level (with the Standard Error of Mean)	Tablet: 50% decrease at 12.0 min (SEM +/- 2.3); 90% decrease at 25.7 min (SEM +/-4.6) Chewed: 50% decrease at 5.0 min (SEM +/- 0.6) (p = <0.05 vs dispersible aspirin); and 90% decrease at 13.6 min (SEM +/- 1.9) (p>0.05 vs dispersible aspirin) Dispersible: 50% decrease at 7.6 min (SEM +/- 1.2, p = 0.90 vs chewable aspirin); 90% decrease at 15.8 min (SEM +/- 1.8) (p = 0.34 compared to chewable aspirin	Small sample, no sample size calculation documented. Lack of observed differences could be due to small sample size. Patients had overnight fast, which is not representative of our population. No comment on whether laboratory personnel were blinded Measures platelet aggregation marker not platelet aggregation.
			Corresponding plasma aspirin levels at the time of achieving 50% and 90% TxB2 inhibition (ng/L)	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 triple crossover 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. Patients were fasted, unlike in the ED Possibly underpowered
			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 (5). Schwertner et al also note that there is no statistical difference between the soluble and chewable aspirin in platelet inhibition (6). 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

RB

Clinical Bottom Line

Both chewable and dispersible non enteric coated aspirin lead to faster inhibition of platelet function than swallowing an aspirin tablet. There is evidence to suggest that chewable aspirin may lead to speedier platelet inhibition, especially when one takes into consideration the time practicalities of dispersing the aspirin.

References

1. Amsterdam EA, Wenger NK, Brindis RG et al. 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 Dec 23;130(25):2354–94.
2. Sai Y, Kusaka A, Imanishi K, Matsumoto M 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.
3. Muir N, Nichols JD, Clifford JM, Stillings MR et al. The influence of dosage form on aspirin kinetics: implications for acute cardiovascular use. Curr Med Res Opin. 1997;13(10):547–53.
4. Sagar KA, Smyth M et al. A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography. J Pharm Biomed Anal. 1999 Nov;21(2):383–92.
5. 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.
6. 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.