Oral route of drug administration is the most practical and
cost-effective mode for preventing venous thrombo embolism, a major
complication following orthopedic surgery.
Venous Thrombo-embolism (VTE)
is a well-known
and a fairly common complication following general surgical procedures. The
common VTE events occurring in surgical procedures include Deep Vein Thrombosis
(DVT) and Pulmonary Embolism (PE).
The rate of
complications arising from VTE is notably higher amongst hospitalized patients
not receiving anti-coagulant therapy post-surgically. This rate is close to 10%
to 40% amongst medical or surgery patients while it is found to be around 40 to
60% amongst orthopedic surgery cases. Deep vein thrombosis
of lungs both can prove to be potentially fatal.
involved with VTE include the increased costs of diagnosing and treating
symptomatic VTE patients, the increased risk of recurrence of VTE including
post-thrombotic syndrome amongst those receiving in-hospital treatment and the
side-effects of the medications received as part of the prophylaxis.
While a prolonged
hospital stay adds to the cost of the treatment of the orthopedic surgery, VTE
often goes unnoticed in many cases. The Agency for Healthcare Research and
Quality, U.S., has recognized Pulmonary Embolism as the leading cause of
preventable hospital deaths.
The most common
risk factors of VTE include trauma, immobilization, hematoma and similar venous
compressions and a previous history of VTE.
pose a higher risk
of VTE especially in the first two months post-surgically and have been
observed to lead to higher number of hospital re-admissions amongst those
Prophylaxis for VTE
is thus necessary in most of the moderate to high-risk patients. This
prophylaxis prevents the incidence of DVT and PE significantly. But given the
fact that the risk and incidence of VTE continues post hospital stay, there
have been numerous researches to explore the potential of the Oral route of
administration of VTE prophylaxis.
The oral route of
VTE prophylaxis can prove to a more cost-effective and practical mode of
controlling the complications arising from VTE after general as well as
Many categories of
drugs are found to reduce the risk of VTE. These include LDUH (low-dose
unfractioned heparin), LMWH (low-molecular weight heparin), factor Xa
inhibitors, Vitamin K antagonists and direct thrombin inhibitors (DTI). Amongst
these, Warfarin (VKa antagonist), DTI dabigatran and FXa inhibitor rivaroxaban
can be delivered through the oral route.
L.Johnson from Louisiana and her co-researchers analyzed the efficacy of these
three agents in their recently published research in the US Pharmacist.
In their analysis
of 29 trials which made a comparison of VKa antagonist Warfarin with other
agents as part of the prophylaxis in orthopedic surgeries, it was found that
VKa Warfarin was significantly less effective than Low-molecular weight heparin
(LMWH) in the process of prevention of deep vein thrombosis.
The RECORD 1 trial
analyzed and made a comparison of the effectiveness of oral rivaroxaban 10mg
given once daily to the subcutaneous administration of enoxaparin 40mg once
daily. The comparison for the risk of DVT was evaluated amongst cases of
It was found
that rivaroxaban reduced the risk of development of complications of VTE in a
higher number of cases compared to enoxaparin.
The oral administration of rivaroxaban was
thus the preferred choice for VTE prophylaxis amongst Total Hip Arthroplasty
The RECORD2 trial
followed up and compared the outcomes of five weeks of rivaroxaban treatment
with two weeks of enoxaparin 40 mg. The researchers found a significantly
better outcome with rivaroxaban in terms of symptomatic VTE cases.
The RECORD3 and
RECORD4 trials compared these dosages amongst the cases of total knee
arthroplasty. It was noted that rivaroxaban was superior to enoxaparin in
prevention of any mortality, non-fatal PE or DVT for up to 17 days
post-surgically. However, no significant difference was found between the two
in terms of incidence of any major and symptomatic VTE and bleeding events.
compared the efficacy of dabigatran, an oral DTI with enoxaparin, in the cases
of total knee arthroplasty, total hip arthroplasty and knee replacement. The
researchers found no significant difference in the effectiveness of dabigatran
when compared to enoxaparin with a lower efficacy of the latter amongst knee
suggest a post discharge of VTE prophylaxis of at least 10 days and an
extended-duration prophylaxis for up to 35 days amongst the cases of hip
fracture and hip-replacement.
It was thus
concluded that oral anticoagulants specifically rivaroxaban and dabigatran
should be evaluated in future studies for their potential use and effectiveness
in oral VTE prophylaxis in Orthopedic Surgery
. This will lead to a significant reduction in the number of
complications and the mortality rate from VTE complications following
orthopedic surgical procedures.
: US Pharmacist2012