The Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Risk of Developing Venous Thromboembolism in Patients with Atherosclerotic Disease.

Arterial and venous thrombosis may share common pathophysiology involving the activation of platelets and inflammatory mediators. A growing body of evidence suggests prothrombotic effect of renin angiotensin system (RAS) including vascular inflammation and platelet activation. We hypothesized that the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), therefore, plays a role in protecting against venous thromboembolism (VTE) in patients with history of atherosclerosis. Whether ACEIs and ARBs actually prevents VTE has never been studied in a clinical setting.

We conducted a retrospective study, reviewing 596 consecutive patients admitted to Albert Einstein Medical Center (AEMC), Philadelphia with a diagnosis of either myocardial infarction or ischemic stroke during September 2007 to January 2009. Patients were followed up to maximum of 30 months. Patients who had been treated with anticoagulation therapy before or after the first visit at AEMC were excluded. The occurrence of VTE during the follow up period, risk factors for VTE on admission, and use of ACEIs and ARBs during the follow up period were recorded.

The mean age of the entire study population was 68.1 years. 52.0% of the patients were female and 76.5% were African American. The overall incidence of VTE was 13.4% (n=80); and 68.8% (n= 410) were on RAS inhibitors [either ACEIs only (n=348, 58.4%) or ARBs only (n=89, 14.9%) or both (n=27, 4.5%)]. Among patients on RAS inhibitors, 11.0 % (45/410) developed a VTE, compared with 18.8% (35/186) in the nonuser group [OR (Odd ratio), 0.53; 95% CI (confidence interval), 0.33 – 0.86; P=0.01]. Even after controlling for factors related to VTE (smoking, history of cancer, and immobilization, hormone use) and diabetes, the use of RAS inhibitors was still associated with lower risk of developing VTE [OR, 0.55; 95% CI, 0.34 – 0.90; P=0.02]. Although statitistically not significant due to small sample size, the OR of VTE for ACEI only users were 0.66 [CI, 0.37-1.16, p=0.15], whereas the OR for ARB only users was 0.75 [CI, 0.30-1.85, p=0.53]. Interestingly, Among patients using both ACEI and ARB, no one developed VTE (0/27), compared with 10.9% (38/348) in ACEI only users and 7.9% (7/89) in ARB only users.

The use of RAS inhibitors appears to be associated with a reduction in the risk of VTE. This possible antithrombotic effect of antagonizing RAS warrants further prospective clinical investigation.

No relevant conflicts of interest to declare.