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Long-term nitrate use may be deleterious in ischemic heart disease: A study using the databases from two large-scale
Y Nakamura1, A J Moss, M W Brown
1First Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. nakamura@belle.shiga-med.ac.jp
Insights
Long-acting nitrate use in chronic coronary disease patients was linked to increased mortality risk. This finding raises concerns about the safety of these commonly used medications in secondary prevention.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Secondary coronary prevention trials often overlook common therapies.
- Long-term nitrate use has not been extensively studied in large clinical trials.
Purpose of the Study:
- To investigate the association between long-acting nitrates and patient outcomes during the chronic phase of coronary disease.
Main Methods:
- Analysis of prospective data from 1042 patients in the Multicenter Study of Myocardial Ischemia (MSMI) and 1779 patients in the Multicenter Diltiazem Post Infarction Trial (MDPIT).
- Cox proportional hazards analyses and propensity score methods were employed to assess mortality risk.
Main Results:
- Long-acting nitrates were significantly associated with increased mortality risk in patients post-acute coronary event (MSMI: HR 3.78, P=.011; MDPIT: HR 1.61, P=.019).
- Propensity score analyses confirmed an elevated cardiac death risk with nitrate use across subgroups.
Conclusions:
- Findings raise concerns regarding potential adverse effects of long-acting nitrates in chronic coronary heart disease management.
- Further research is warranted to evaluate the safety profile of long-term nitrate therapy.
Background:
Secondary coronary prevention studies have generally focused on specific medications, often to the exclusion of commonly used therapies. To date, long-term nitrate use has not been investigated in large-scale clinical trials.
Methods And Results:
We examined the relation between long-acting nitrates given during the chronic phase of the disease and the outcome. We analyzed data prospectively acquired in a large, observational study involving 1042 patients enrolled for the Multicenter Study of Myocardial Ischemia (MSMI) in North America, Israel, and Japan as well as 1779 patients enrolled for the Multicenter Diltiazem Post Infarction Trial (MDPIT). The Cox analyses with all the variables retained revealed that nitrates were associated with a significantly increased mortality risk (MSMI: hazard ratio 3.78, P =.011; MDPIT: hazard ratio 1.61, P =.019) in patients who had recovered from an acute coronary event. The analyses with the propensity score method on the MSMI and the MSMI databases also showed that the risk for cardiac death with use of nitrates was increased in most of the 5 subclasses according to the score.
Conclusion:
These analyses raise concern about the potential adverse effects of long-acting nitrate therapy in chronic coronary disease.