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- Goodman, Shaun G., et al.
(författare)
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Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor : Outcomes With Clopidogrel and Ticagrelor
- 2012
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 125:8, s. 978-986
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Tidskriftsartikel (refereegranskat)abstract
- Background-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n = 6539) compared with those not on a PPI (n = 12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.
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| 2. |
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| 3. |
- Kilhamn, Jan, 1961
(författare)
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B- and T- cell responses in colectomized and healthy individuals after mucosal vaccination
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aims were to study the induction of intestinal and systemic B- and T-cell immune responses in patients colectomized due to ulcerative colitis and in healthy volunteers after mucosal administration of enteric vaccines. An inactivated B-subunit whole-cell (B-WC) cholera vaccine and a live attenuated Salmonella enterica serovar Typhi Ty21a vaccine were used as model immunogens.Ileostomy fluid was shown to be a suitable specimen for determination of IgA antibodies in the intestine after mucosal vaccination. Two oral doses of B-WC vaccine induced significant IgA antibody responses in ileostomy fluids against cholera toxin in 14 of 15 colectomized patients and against whole bacteria in 9 cases. Increased IgA antitoxin levels were found in ileostomy fluids as late as 2 years after vaccination. The antibody responses in serum after oral B-WC vaccination were somewhat lower in colectomized patients than in healthy volunteers. When the B-WC vaccine was administered into the ileal pouch of colectomized patients, strong cholera toxin B subunit-specific IgA antibody-secreting cell (ASC) responses were found in the duodenum of 5 of 5 patients, whereas weaker and less frequent responses were seen in the ileal pouch and in peripheral blood. These findings clearly show that it is possible to induce B-cell responses within the "entire" small intestine without the presence of antigen at the effector site.No enhancement of the B-cell immune responses was noted when the B-WC vaccine was administered on intestinal mucosa with a mild lymphocytic infiltration, i.e. into the ileal pouch of colectomized patients, or when the vaccine was given together with a mucolytic substance, acetylcysteine, orally to healthy volunteers.Three oral doses of Ty21a vaccine induced significant anti-Salmonella IgA antibody titer increases in ileostomy fluids from 6 of 9 colectomized patients. Both the frequencies and magnitudes of the IgA as well as IgG antibody responses in serum were lower in the colectomized patients than in healthy volunteers. The vaccination failed to induce proliferative T-cell responses in peripheral blood in all the 6 colectomized patients, and increases in gamma interferon (IFN-g) production were only found among CD8+ cells from 3 patients. In contrast, a proliferative response and/or increased IFN-g production were observed for CD4+ cells in 5 of 10 healthy volunteers and for CD8+ cells in 8 individuals.In conclusion, both the B-WC and Ty21a vaccines induced strong intestinal B-cell responses in colectomized patients, whereas the B- and T-cell responses in the circulation were weaker than in healthy volunteers. The impaired responsiveness, in particular among the T cells, may be of relevance for the future use of live vaccine strains which predominantly colonize the colon, e.g. attenuated Salmonella or Salmonella vector vaccines. Our observations should be considered when planning immunizations for colectomized patients traveling to areas endemic for cholera or typhoid fever.
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| 4. |
- Steg, Philippe Gabriel, et al.
(författare)
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Ticagrelor Versus Clopidogrel in Patients With ST-Elevation Acute Coronary Syndromes Intended for Reperfusion With Primary Percutaneous Coronary Intervention A Platelet Inhibition and Patient Outcomes (PLATO) Trial Subgroup Analysis
- 2010
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 122:21, s. 2131-2141
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Tidskriftsartikel (refereegranskat)abstract
- Background-Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result-Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR, 1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76). Conclusion-In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial.
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