Cardiovascular Journal of Africa: Vol 24 No 2 (March 2013)

CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 2, March 2013

AFRICA

in the PLATO results where ticagrelor

significantly reduced the combined

endpoints of cardiovascular death, myo-

cardial infarction and stroke.

‘Importantly, the overall risk reduc-

tion was not only driven by a myocar-

dial infarction rate reduction as was the

experience in the CURE study, but also

by a reduction in cardiovascular death

and all-cause mortality (Fig. 2). ‘While

the overall risk of experiencing an

event was higher in medically managed

patients who formed 36% of the total

PLATO cohort, ticagrelor treatment also

reduced the composite endpoints in this

important group of patients’, Dr Wheat-

croft noted.

Finally, in terms of today’s third cri-

teria of safety, the additional benefits

of ticagrelor did not come at the price

of increased bleeding, as there was no

significant difference in major bleed-

ing rates between the clopidogrel- and

ticagrelor-treated patients in the PLATO

study (Fig. 2). Non-coronary artery

bypass graft (CABG)-

related major bleeds were

more common in ticagre-

lor-treated patients, while

CABG-related

bleeding

rates were similar with

both agents.

While dyspnoea is an

important side effect, it

is typically mild, resulting

in a less than 1% discon-

tinuation rate in the PLATO

study. ‘In our own clinical

experience, this dyspnoea

is certainly mild and tran-

sient and, with appropriate

reassurance, patients can

continue with the medica-

tion’, Dr Wheatcroft con-

cluded.

clopidogrel requires a two-step bio-

transformation in the liver to its active

metabolite, thereby allowing genetic

polymorphisms to influence the reliability

of the antiplatelet response. Ticagrelor is

direct acting and its effect is independ-

ent of genetic polymorphisms, ensuring

a consistent inhibition of platelet activity.

Ticagrelor also produces a greater

inhibition of platelet aggregation than

clopidogrel. The more reliable platelet

inhibition with ticagrelor (180 mg load-

ing dose, then 90 mg bid) was seen

Dr Stephen

Wheatcroft

Fig. 2.

PLATO main endpoints.

New era in antiplatelet therapy

Is clopidogrel adequate in 2013?

There is a good evidence base . . .

that ticagrelor offers significant advantages

over clopidogrel

“

”

n reviewing oral anti-platelet therapy

for acute coronary syndromes today,

clinicians would most likely demand

that any acceptable therapy meet at least

three criteria and provide:

• rapid onset of action

• reproducible and reliable inhibition

of platelet activation

• acceptable risk of bleeding.

Adhering to today’s standard, Dr Ste-

phen Wheatcroft, consultant inter-

ventional cardiologist at the University

of Leeds noted that his Unit now uses

ticagrelor across the board for acute

coronary syndrome (ACS) patients, both

STEMI and NSTEMI patients. ‘There is no

doubt that clopidogrel is a good drug,

as shown in the CURE study. However,

there is also a good evidence base for

the new agents, prasugrel and tica-

grelor, and the latter offers significant

advantages over clopidogrel’, he noted.

In terms of today’s criteria, ticagre-

lor has a faster onset of action than the

other agents, as it is direct acting and

does not require

in vivo

biotransformation.

active metabolite is also

formed which contributes

in part to ticagrelor’s clini-

cal effect.

Reproducible and reli-

able platelet inhibition

is not a characteristic of

the clinical experience

with clopidogrel. ‘Low

responders are exposed to

a doubled risk of adverse

events compared to those

ACS patients who respond

well to clopidogrel’, Dr

Wheatcroft pointed out.

One of the reasons

for the heterogeneity of

platelet inhibition is that