G033: Risk of cardio-cerebrovascular accidents associated with nitrates and other cardiovascular drugs

• Published in: American journal of hypertension Vol. 13; no. S2; pp. 264A - 265A
• Main Authors: Boumendil, E.F., Mugnier, C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2000
• Subjects: Antianginals; calcium channel blockers; cardio-cerebrovascular accidents; nitrates; NO donors
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1016/S0895-7061(00)00994-8

There is uncertainty as to whether certain cardiovascular drugs increase the risks of cardio-cerebrovascular accidents. We have examined this question by determining whether common cardiovascular drugs in real situations of use are predictive of cardiovascular accidents. The study was conducted on a working population of men assembled as a cohort. Data were obtained from the company's health records, national death records, plus repeated individual questionnaires. Each questionnaire reported the current status of cardiovascular drug treatments and other traits at the start of each calendar year. Outcomes were non-fatal myocardial infarction, stroke and death related to cardio-cerebrovascular disease. Five 1-year follow-up studies were done, each linking the drug status of participants at the beginning of the period with the cardio-cerebrovascular events that occurred during the same year. Those who experienced an event were dropped from subsequent periods. The study included 11 390 men aged 42–52 years at the beginning of the study. A total of 100 men experienced at least one event. Cases were more likely to be on calcium antagonists (9%) than non cases (2.5%; P= 0.001), on beta-blockers (13% vs. 5.4%; P=.001), on angiotensin converting enzyme inhibitors (8% vs. 3.7%; P=.002), on nitrate or nitric oxide donors (9% vs. 0.6%; P=.001), on fibrates (15% vs. 7% P=.002), on HMG-COA reductase inhibitors (12% vs. 4.4%; P=.001). 15% of cases and 3% of non-cases were on 3 or more cardiovascular treatments (P=.0017). The ages of cases and non-cases were identical. Pooled logistic regression analyses taking in consideration for within-person correlation due to the pooling of the data accross intervals and restricted to subjects on cardiovascular drugs (n=4258, 41 cases), showed that subjects on nitrates or nitric oxide donors had 13-times more cardio-cerebrovascular accidents than subjects on other cardiovascular drugs [Odds Ratio (OD) 13.1; 95% confidence interval (CI) 6.07–28.20; P=.0000]; the excess risk remained large after adjustment for the number of cardiovascular treatments [OD 11.9; CI, 4.44–31.83); P=.0000]. With calcium antagonists the two fold excess risk observed [OD 2.1; CI, 0.99–4.39; P=.0521 was not maintained after adjustment for number of cardiovascular drug treatments [OD 1.5; CI, 0.60–3.77; P=.38]; results with other cardiovascular drugs were inconclusive. These results are for a prospective study with a follow-up of drug status that allowed us to take into consideration changes in treatment. The limitations for interpretation are the limited number of cases, the lack of information on the indications for the treatment, and on the severity of the medical status, although adjustment for the number of cardiovascular drug treatments takes into account the cardiovascular health status. Despite these limitations, our results signal that nitrates and the nitric oxide donors are the only cardiovascular drugs that are strongly predictive of cerebral-cardiovascular accidents at one year. This is in agreement with clinical, epidemiological and experimental findings indicate that nitrates do play a part in death and arterial ischemic diseases.