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(Circulation. 2003;107:e39.)
© 2003 American Heart Association, Inc.

Correspondence

Platelet Glycoprotein IIb/IIIa Inhibitors

H. Richard Hellstrom, MD

Anatomical Pathology, College of Medicine, Room 2106 Weiskotten Hall, SUNY Upstate Medical University, 750 East Adams St, Syracuse, NY 13210, hellstrr@mail.upstate.edu

To the Editor:

Platelet glycoprotein (GP) IIb/IIIa antagonists only prompt an overall 8.5% relative reduction in 30-day deaths or myocardial infarction in acute coronary syndromes (ACS),¹ and Quinn et al¹ suggested that this limited benefit may be due to factors such as antagonist-induced platelet activation. I suggest that limited benefits of GP IIb/IIIa inhibition are due basically to limited participation of platelets in ACS, although negative effects described by Quinn et al¹ are no doubt operative.

Cases of ACS with and without elevated troponin levels treated by GP IIb/IIIa inhibition provide evidence for a limited role of platelets in ACS. Inhibition in troponin-negative cases was ineffective² or slightly worsened ACS,³ but inhibition in troponin-positive patients yielded a reduction in deaths or infarction of 60% (average of 3 studies).³ Effects of GP IIb/IIIa inhibition probably define roughly the significant involvement of platelets in ACS, and the striking improvement of only troponin-positive cases provides evidence that platelets are involved significantly only in troponin-positive cases, which comprise about a third (30.9%) of cases of ACS.²

A study of abciximab supports significant platelet involvement only in troponin-positive cases.² The 6-month risk of death or nonfatal infarction in controls was 23.9% in troponin-positive and 7.9% in troponin-negative cases. Treatment with abciximab did not change the event rate in troponin-negative cases, but reduced the rate in troponin-positive cases to the level of troponin-negative cases.

As platelets are precursors of thromboses, the apparent absence of significant involvement of platelets in troponin-negative cases (about two thirds of ACS cases) raises questions about the validity of the plaque rupture/thromboses mechanism. In contrast, the spasm of resistance vessel (S-RV) concept can explain troponin findings.^4,5 The concept asserts that symptoms in ischemic heart disease are due to S-RV and, in the minority of cases with significant platelet activation, vasoconstrictive agents from platelets add to S-RV and worsen prognosis.

However, the concept asserts that the major source of S-RV in ACS is stenotic coronary artery disease that causes ischemic injury and consequent ischemia-induced S-RV; a vicious cycle of S-RV, more ischemia, and more ischemia-induced S-RV favors infarction. Plaque rupture, often preexisting, would tend to worsen ischemia and favor platelet activation in some cases. Thromboses are attributed to stasis caused by S-RV-induced no-reflow plus intimal irregularities.

-adrenergic blockade should be useful in treating ACS.⁵ The S-RV concept does give ischemia-induced S-RV the pivotal role in ACS, and ischemia-induced S-RV is reversed by -adrenergic blockade.⁵

References

1. Quinn MJ, Plow EJ, Topol EJ. Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword? Circulation. 2002; 106: 379–385.[Free Full Text]
   
2. Hamm CW, Heeschen C, Goldmann B, et al. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. N Engl J Med. 1999; 340: 1623–1629.[Abstract/Free Full Text]
   
3. Chew DP, Moliterno DJ. A critical appraisal of platelet glycoprotein IIb/IIIa inhibition. J Am Coll Cardiol. 2000; 36: 2028–2035.[Abstract/Free Full Text]
   
4. Hellstrom HR. Occlusions of epicardial arteries might not directly induce symptoms in ischemic heart disease. Med Hypotheses. 1999; 53: 533–542.[CrossRef][Medline] [Order article via Infotrieve]
   
5. Hellstrom HR. Can the premises of the spasm of resistance vessel concept permit improvement in the treatment and prevention of ischemic heart disease? Med Hypotheses. 2003; 60: 36–51.[CrossRef][Medline] [Order article via Infotrieve]
   

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