Statins have an early antiplatelet effect in patients with acute myocardial infarction

Abstract

Statins confer an antiplatelet effect in hypercholesterolemic subjects and in stable coronary artery disease patients. We explored the antiplatelet effects of statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. Of 120 STEMI patients, 80 (67%) received statins while 40 (33%) did not. Ex vivo platelet reactivity was studied on admission and 72 hours later by conventional aggregometry and under flow conditions (Impact R). Measures of platelet reactivity under flow conditions included aggregate size and surface coverage, signifying platelet aggregation and adhesion respectively. The effect of statins on platelet function under flow conditions and platelet aggregation was studied in?vitro in platelets from 10 STEMI patients. Platelets from each patient were incubated in?vitro with lovastatin or PBS as a control. The effect of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was also studied. Patients treated with statins were compared with those who did not have significantly lower ADP-induced platelet aggregation on the 4th day (56 ± 18% vs. 64 ± 17%, p=0.02). Platelet deposition under flow conditions as measured by surface coverage was reduced from admission to 72 hours later among statin-treated patients (19 ± 28% reduction, p<0.01), but was unchanged in non-treated patients (for comparison p<0.01). The extent of platelet inhibition was unrelated to patient characteristics, including lipid profile and type of statin administered (lipophylic vs. hydrophilic). In the in vitro study platelet incubation with statin compared with PBS resulted in a lower aggregate-size (29 ± 9 μm(2) vs. 39 ± 15 μm(2), p<0.01), and lower surface coverage (8.5 ± 4% vs. 12 ± 4%, p<0.01). The effect of the statin on both parameters was significantly blunted by L-NMMA. Incubation with statin also resulted in a reduction in collagen-induced platelet aggregation (31 ± 20% vs. 54 ± 25%, p<0.01). We concluded that in acute myocardial infarction patients, statins have an early antiplatelet effect, in addition to that afforded by standard antiplatelet therapy.

Statins as Antithrombotic Drugs

“…In an experimental model of acute thrombosis induced in the carotid artery, Obi et al 30 demonstrated that intravenous infusion of lovastatin significantly reduced thrombosis by hampering platelet adhesion to the carotid lesion. Human studies confirmed these findings after 3 to 7 days of treatment with statins, 31,32 with the small inhibition of serum cholesterol that occurred after 3 days not fully supporting a direct antiplatelet effect by statins. To address this question, we measured several markers of platelet activation as early as 2 hours after administration of 40 mg of atorvastatin in hypercholesterolemic patients.…”

Platelets and their chemokines in atherosclerosis—clinical applications

“…The PRISM trial (Platelet Receptor Inhibition in Ischemic Syndrome Management) demonstrated a better outcome of ACS patients when they were on statins in the first month after the event, which is unlikely to be caused by remodeling processes of the plaque in such a short timeframe and are rather to be explained by reduced platelet activation and/or attenuated coagulation system. It was observed that statins have an early inhibitory effect on platelets of patients with AMI showing reduced aggregation after challenge with collagen and a markedly lower platelet surface adhesion in vitro (Matetzky et al, 2011). …”

Cardiovascular Devices and Platelet Interactions

“…Statin therapy has been associated with lower urinary thromboxane levels, 70 a marker of activated circulating platelets, and reduced ex vivo shear-induced platelet activation. 71 However, not all studies have found an effect of statins on platelet function. 72 …”