Side effects of using nitrates to treat angina

Nitrates are very effective antianginal and anti-ischaemic agents. Provision of a long nitrate-free interval or low plasma nitrate levels prior to the morning dose prevents the loss of clinical efficacy by preventing the development of tolerance. However, side effects during nitrate therapy are common. Headache is the most common side effect of nitrates; often dose-related and reported by up to 82% of patients in placebo-controlled trials. Nearly 10% of patients are unable to tolerate nitrates due to disabling headaches or dizziness. In others, headaches are mild-to-moderate in severity and either resolve or diminish in intensity with continued nitrate therapy. Nitrate-induced hypotension is common, but often asymptomatic. In rare instances, nitrate-induced hypotension is severe and accompanied by marked slowing of the heart rate and syncope. Use of nitrates in patients who experience syncope after administration of nitrates is contraindicated. Nitrates rarely cause coronary steal and myocardial ischaemia. Nitrate rebound may occur and patients may experience nocturnal anginal episodes during intermittent therapy with nitroglycerin patches. Administration of nitrates is contraindicated with concomitant use of phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction, as combination therapy may lead to profound hypotension and even death. There are disturbing observational reports in the literature that continuous, prolonged use of nitrates may lead to increased mortality and recurrent myocardial infarctions. Large, randomised, placebo-controlled studies are needed to confirm or refute these reports; until then, the use of nitrates to treat angina is here to stay.