The Specialist Forum Volume 13 No 11 November 2013 | Page 78

HYPERTENSION

Patients with atrial fibrillation
According to Dr Beyer-Westendorf, numerous studies comparing the
efficacy of NOACs and warfarin in preventing ischaemic and haemorrhagic strokes in patients with atrial fibrillation (AF) found that the
NOACs were at least as effectice as or even more effective than warfarin. Again, all NOAC`s demonstrated lower bleeding rates and a dramatic risk reduction for intracranial bleedings, which is the most feared
bleeding complication seen with warfarin.However, he cautioned, that
patients seen in daily care are different from the selected patients
populations evaluated in clinical trials.

The real world setting
To compare the safety and efficacy of NOACs in a real world setting, Dr
Beyer-Westendorf and his team conducted a large local registry study.
More than 230 private practitioners as well as doctors based at various
hospitals in the region, enrolled patients. The team collected the data
and followed-up with patients on a quarterly basis. Routine questions
were asked and if any of the patients described any symptoms or
events of suspected thromboembolism, stroke, myocardial infarction,
bleeding, surgery or hospitalization, additional data was obtained from
their doctors as well as the hospital where they were treated.
Some 2200 patients participated in the study and of this number,
350 patients with AF were prescribed dabigatran, while 1200 were
treated using rivaroxaban. The team also included 500 patients with
acute or chronic deep vein thrombosis or pulmonary embolisms. For all
VTE and AF patients, event rates for cardiovascular or major bleeding
complications were much lower than 5%/100 patient years, indicating
the excellent risk-benefit relation of NOACs in daily care.

Overdosing
In 2011 the US Food and Drug Administration undertook a review of
serious drug-related injuries as a result of accidental patient overdosing or major bleeding events. Their review included 180 000 records of
serious drug-related injuries in 2011, including more than 30 000 fatal
complications. Not surprisingly, the drug with the highest number of
events in this evaluation was warfarin, said Dr Beyer-Westendorf, adding that a possible reason for this can be the fact that not all doctors
know what the correct dosages are and often base their decision on
a ‘gut feeling’ or ‘experience’. Furthermore, many drugs interact with
warfarin, patients need to have a stable diet and need to adhere to
frequent changes of drug dosage.
Dr Beyer-Westendorf and his team conducted another study looking at
patients using warfarin and who experienced hospitalisations for warfarinrelated bleeding complications. Their findings showed that the majority of
patients who experienced major bleeding events had AF and the average
age of these patients was 73 years. Most of these patients spent an average of 11 days in hospital. The team found that the mortality rate at 90 days
after hospitalisation was as high as 14%. Dr Beyer-Westendorf concluded
that warfarin related major bleeding complications are often related to
overdosing and have a huge impact on survival and quality of life,
In comparison, rivaroxaban dosing is far less complicated. Patients
usually take a single tablet daily containing 20 mg dose or, in case of
an increased risk of bleeding, a daily dose of 15 mg is recommended.
Only patients with acute DVT or PE ar atsrated on a more intense treatment, using 15 mg twice daily for the initial three weeks after diagnosis
of acute VTE. After 3 weeks, the dosage again is 20 mg once daily or
15 mg OD in cases of increased bleeding risks.
To illustrate the safety of rivaroxaban, Dr Beyer-Westendorf cited a

case in which a 26-year old male, took 30 tablets or 600mg at once to
commit suicide. He survived the attempt without any adverse events
or bleeding. “Obviously it is unlikely to die from a rivaroxaban overdose,
because although you ingest more, your body can’t absorb more than
50 to 60 mg of the drug (this is called the ‘ceiling effect’) and the rest is
excreted with the faeces.”
He conceded that - as with any other anticoagulant – patients using rivaroxaban will experience major bleeding events, but added that
this was not as a result of the drug, but rather as a result of a lesion,
an injury, a ruptured artery in the brain or a bleeding stomach ulcer. In
cases like these, it is extremely important to control both the intensity
and the cause of the bleeding.
In his registry, 900 reports of bleeding have been received. Some 62%
of the patients experienced minor bleeds. Another 33% were classified
as non-major, but clinically relevant events – meaning that the patient
experienced some kind of impairment or needed to see his doctor. Only
5% of the events were defined as major bleedings – meaning that only
25 patients experienced major events. Eighteen patients (72%) did not
require any kind of intensive treatment but could be stabilised and only
two out of the 25 patients died (8%) Therefore, even if bleedings occur
with NOACs in daily care, the outcome is good and management seems
to be simple in most cases, Dr. Beyer-westendorf concluded.

‘Feeding’ a drug to the patient
“We know that patients on warfarin need some kind of procedure or
surgery done at least three times a year. This is the average amount
of procedures for a patient taking warfarin. In these situations, most
patients have to undergo bridging therapy with low molecular heparin
for days or weeks,” said Dr Beyer-Westendorf .
Dr Beyer-Westendorf and his team analysed the outcomes of 450
procedures in his registry and evaluated the outcome for a period of
up to 30 days after the procedure. They found that 20% of the patients
underwent procedures without any interruption of the drug, while in
70% of the cases NOAC treatment was interrupted for longer than three
days before the procedure.
The majority of procedures performed included, for example superficial skin surgery (skin biopsy, molar removal), dental extractions or
colonoscopies. Major procedures included in the study were for fracture surgery, hip and knee replacement and brain surgery. An important finding of the registry was that in Germany, many doctors prescribe
heparin as a bridging drug to NOAC patients who have to undergo
surgical procedures despite the fact that experts discourage this.
“This doesn’t make sense, because with low molecular weight
heparin, you have peak levels at three hours, and you have a half-life of
around six to eight hours, when 50% of the drug is still in the patient. In
comparison, with the NOACs – given orally - you have peak levels after
three hours, and in most of them, the average half-life is around nine
hours. This means that after nine hours the patient still has 50% of the
drug in his/her system. Therefore, bridging NOAC with heparin doesn`t
make much sense: If I feel that if I can’t give them the NOAC before and
after the procedure, why do I give them heparin?”
To ensure the best possible outcome for your patient, anticoagulant
treatment with NOACs should be stopped one day before a procedure. This may be prolonged to two to three days, if patients undergo
a procedure with high risk of bleeding complications or in cases with
impaired renal function, when the drug will remain in the body for longer.. Heparin bridging should be discouraged, because it can induce
bleeding, concluded Dr Beyer-Westendorf.? CF

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November 2013 | Cardiology & Stroke Forum