AIM: New study refutes FDA's contraindication for Plavix and PPIs
Heart patients who took proton-pump inhibitors (PPIs) along with clopidogrel were only half as likely to be hospitalized for upper digestive tract bleeding than those who used clopidogrel alone. In addition, the PPIs did not inhibit clopidogrel’s therapeutic effect, according to a study published in the March 16 issue of the Annals of Internal Medicine.
Although PPIs, such as omeprazole (Prilosec, Astrazeneca), were commonly prescribed with clopidogrel (Plavix) to reduce the risk of upper digestive tract bleeding, clinicians worried that this practice may decrease the antiplatelet drug's ability to prevent blood clots. Also, in November 2009, the FDA required a labeling change to Sanofi-Aventis and Bristol-Myers Squibb’s clopidogrel to indicate that it should not be used with Prilosec/Prilosec OTC and some other acid-reducing drugs. At the time, the agency said that “new data suggest that when patients take both Prilosec and Plavix, Plavix’s ability to block platelet aggregation may be reduced by about half.”
Until now, there has been limited research on the impact of PPIs on either the effectiveness of clopidogrel or on the ability of the PPIs to reduce digestive tract bleeding and which populations of patients may benefit the most from taking the drugs in combination, according to lead author Wayne A. Ray, PhD, and colleagues from Vanderbilt University Medical Center in Nashville, Tenn., and his colleagues.
However, COGENT, the first randomized, placebo-controlled trial to assess the interaction, presented at TCT.09, found that the combination of PPI and clopidogrel did not lead to adverse events.
Supporting the findings of COGENT, Ray and colleagues retrospectively analyzed data from nearly 21,000 patients hospitalized for MI, coronary artery revascularization or unstable angina pectoris (including 7,593 concurrent users of clopidogrel and PPIs) in the Tennessee Medicaid program between 1999 and 2005.
They found that concurrent use of a PPI and clopidogrel did not increase patients' risk of heart attack, sudden cardiac death, stroke or other cardiovascular problems. The same was true for patients who underwent PCI.
The adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50 percent lower than that in nonusers. For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 hospitalizations for gastroduodenal bleeding per 1,000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 for the entire cohort and 1.01 for the subgroup of patients who had PCI with stenting during the qualifying hospitalization.
Researchers noted that even though they did not find an elevated cardiovascular risk, they cannot rule it out and said that additional studies, including randomized clinical trials, will clarify how combining clopidogrel and PPIs affects heart and vascular health.
The primary sources of funding were the Agency for Healthcare Research and Quality and the National Heart, Lung and Blood Institute.
Although PPIs, such as omeprazole (Prilosec, Astrazeneca), were commonly prescribed with clopidogrel (Plavix) to reduce the risk of upper digestive tract bleeding, clinicians worried that this practice may decrease the antiplatelet drug's ability to prevent blood clots. Also, in November 2009, the FDA required a labeling change to Sanofi-Aventis and Bristol-Myers Squibb’s clopidogrel to indicate that it should not be used with Prilosec/Prilosec OTC and some other acid-reducing drugs. At the time, the agency said that “new data suggest that when patients take both Prilosec and Plavix, Plavix’s ability to block platelet aggregation may be reduced by about half.”
Until now, there has been limited research on the impact of PPIs on either the effectiveness of clopidogrel or on the ability of the PPIs to reduce digestive tract bleeding and which populations of patients may benefit the most from taking the drugs in combination, according to lead author Wayne A. Ray, PhD, and colleagues from Vanderbilt University Medical Center in Nashville, Tenn., and his colleagues.
However, COGENT, the first randomized, placebo-controlled trial to assess the interaction, presented at TCT.09, found that the combination of PPI and clopidogrel did not lead to adverse events.
Supporting the findings of COGENT, Ray and colleagues retrospectively analyzed data from nearly 21,000 patients hospitalized for MI, coronary artery revascularization or unstable angina pectoris (including 7,593 concurrent users of clopidogrel and PPIs) in the Tennessee Medicaid program between 1999 and 2005.
They found that concurrent use of a PPI and clopidogrel did not increase patients' risk of heart attack, sudden cardiac death, stroke or other cardiovascular problems. The same was true for patients who underwent PCI.
The adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50 percent lower than that in nonusers. For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 hospitalizations for gastroduodenal bleeding per 1,000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 for the entire cohort and 1.01 for the subgroup of patients who had PCI with stenting during the qualifying hospitalization.
Researchers noted that even though they did not find an elevated cardiovascular risk, they cannot rule it out and said that additional studies, including randomized clinical trials, will clarify how combining clopidogrel and PPIs affects heart and vascular health.
The primary sources of funding were the Agency for Healthcare Research and Quality and the National Heart, Lung and Blood Institute.