The Unfiltered Truth: Anticoagulation Alone is Highly Effective, even in Patients with High-risk Pulmonary Embolism

The Prévention du Risque d’Embolie Pulmonaire par Interruption Cave 2 (PREPIC2) study was designed to determine whether patients with acute, high-risk PE might fare better if, instead of anticoagulation alone, they received both anticoagulation and a retrievable IVCF. To be included in this randomized, open-label trial conducted from August 2006 to January 2013, patients had to have acute, symptomatic PE associated with lower-limb vein thrombosis, plus at least one criterion for severity (Table 1). Anticoagulation was mandatory for six months in both groups, and for the patients randomized to IVCF deployment, the filter had to be removed within three months of insertion. Slightly more than half of the enrolled patients were older than 75 years, and approximately two-thirds had some evidence of right ventricular dysfunction or myocardial injury. Only about 9 percent of enrolled patients had iliocaval thrombosis. The primary outcome was symptomatic pulmonary embolism (including fatal PE) three months after enrollment. Safety outcomes included the three- and six-month rates of both major bleeding as well as all-cause mortality. Filter complications such as thrombosis, migration, and penetration of the vena cava wall were recorded. Although PREPIC2 was an open-label trial for the patients and treating clinicians, the adjudicators of outcomes were blinded to treatment assignment.

Of the 200 patients randomly assigned to IVCF placement, the filter was successfully deployed in 193 and was retrieved within three months in 153 of the 164 patients in whom retrieval was attempted. After three months, six (3.0%) of the patients who received a filter had experienced recurrent PE; all six recurrences were fatal. Throughout the same follow-up period, three patients (1.5%) from the control group were diagnosed with recurrent PE; two of these three recurrences were fatal. The relative risk estimate for the primary endpoint in patients with filter (vs. no filter)was 2.00 (95% CI, 0.51-7.89; p = 0.50). Results were similar at six months. Thrombosis of the IVCF occurred in three individuals, and the relative risk of the primary outcome did not change when recalculated using an “as treated” analysis. For the key secondary and safety outcomes, the two treatment groups were similar, including deep vein thrombosis, major bleeding, and all-cause death. The most common cause of death in both arms was cancer. The most common filter-related complications are listed in Table 2.

Although hematologists are often not involved in the very first clinical decisions for patients with acute, high-risk PE, the report by Dr. Patrick Mismetti and colleagues provides very important information about the optimal management of such patients. Much like previously published trials of systemic thrombolysis in this population, PREPIC2 highlights the effectiveness of simple, well-managed anticoagulation in patients with pulmonary embolism. Indeed, in this group of nearly 200 PE patients with at least one high-risk feature (two-thirds of whom had evidence of right ventricular dysfunction), treatment with standard anticoagulation alone prevented recurrences in all but 1.5 percent of individuals. PREPIC2 reminds us that anticoagulation is the mainstay of treatment for patients with high risk PE and, unless anticoagulation is contraindicated, IVCF placement has no definite benefit, and may additionally expose patients to important complications.