Selective COX-2 inhibitors have significantly reduced gastrointestinal side effects, and their use has been on the rise since their clinical introduction in the 1990s. However, with the discovery of cardiovascular events such as hypertension, coronary artery disease and myocardial infarction in some patients after the use of COX-2 inhibitors since 2002, there were concerns. 2004 adenomatous polyp prevention clinical trial showed a 2-fold increase in myocardial infarction and stroke events associated with the administration of Merck’s vanillo (rofecoxib), which forced Merck to discontinue vanillo on September 30, 2004. Merck had to discontinue Vanlord on September 30, 2004, resulting in significant losses for Merck. Large clinical trials have shown that cardiovascular adverse events with selective COX-2 inhibitors are related to daily dose and duration of therapy. High-dose, long-course use of selective COX-2 inhibitors significantly increased the incidence of cardiovascular adverse events. It is now believed that both conventional cyclooxygenase inhibitors and selective COX-2 inhibitors increase cardiovascular and cerebrovascular adverse events (e.g., thrombotic events, hypertension, MI, CHF, and severe coronary artery disease), and that increased cardiovascular and cerebrovascular adverse events are a class effect of cyclooxygenase inhibitors. Among cyclooxygenase inhibitors, naproxen may have the lowest risk of causing cardiovascular events. The more COX-1 inhibition, the fewer cardiovascular and cerebrovascular adverse events, but the more upper GI adverse events; the more COX-2 inhibition, the fewer upper GI adverse events, but the more cardiovascular and cerebrovascular adverse events. Selective COX-2 inhibitors inhibit prostaglandins but not thromboxane, thus leading to an imbalance between pro- and antithrombotic effects and procoagulation. By reducing the production of PGI2, which has a dilating effect, selective COX-2 inhibitors tip the balance toward pro-thrombotic and may increase the incidence of thrombotic events in the cardiovascular system. The use of cyclooxygenase inhibitors can cause symptoms such as heart failure in some patients, especially in those with a history of cardiovascular disease and impaired left ventricular function. In people with cardiovascular risk factors such as ischemic heart disease or stroke, hypertension, hyperlipidemia, diabetes mellitus or peripheral arterial disease, the use of NSAIDs should avoid selective COX-2 inhibitors, even if the combination of selective COX-2 inhibitors and aspirin does not reduce the incidence of cardiovascular adverse events, and naproxen may be one of the better options. Caution should be exercised when using ibuprofen as it can diminish the antiplatelet effect of aspirin. Caution should be exercised in the choice of drug therapy for patients with cardiovascular disease predisposing factors. Cyclooxygenase inhibitors can sometimes increase blood pressure in people with normal blood pressure, and they can also antagonize many hypertensive drugs, making it more difficult to control blood pressure, especially in elderly people who buy their own painkillers over the counter. The antihypertensive effect of almost all hypertensive drugs including diuretics (e.g., dihydrocortisone), beta-blockers (e.g., betalactam), alpha-blockers (e.g., cortisol, Doxaben), and vasotransformation enzyme inhibitors (e.g., captopril) is affected by cyclooxygenase inhibitors. The effects of cyclooxygenase inhibitors are not identical and are perhaps related to the type and dose of the drug. The severity of the effects of non-selective cyclooxygenase inhibitors is ranked as follows: Piroxicam > anti-inflammatory pain > ibuprofen > diclofenac > naproxen > flurbiprofen > sulindac. In patients undergoing antihypertensive therapy, sulindac is the most appropriate anti-inflammatory agent because, unlike other cyclooxygenase inhibitors, it has few corresponding effects with antihypertensive drugs. There is no evidence that celecoxib is associated with the development of hypertension. Rofecoxib significantly increases the risk of developing hypertension, and in patients with chronic kidney disease, liver disease, and congestive heart failure, the risk of developing hypertension is twice as high in patients taking rofecoxib as in those taking celecoxib. The increase in blood pressure caused by the combination of cyclooxygenase inhibitors with vascular converting enzyme inhibitors is the most pronounced of all antihypertensive drugs, e.g., anti-inflammatory pain reduces the antihypertensive effect of enalapril by 45%, and special care should be taken when cyclooxygenase inhibitors are used in hypertensive patients taking vascular converting enzyme inhibitors. It is safe to use cyclooxygenase inhibitors in combination with calcium blockers.