Clopidogrel: a pharmacoeconomic review

Figures & data

Table 1. Summary of clopidogrel clinical effectiveness trials: design and end points.

Study	Population (n)	Design
CURE^5	UA and NSTEMI (12,562)	ASA vs. ASA and clopidogrel (75 mg) for average of 9 months
PCI-CURE^6	UA and NSTEMI with PCI (2,658)	ASA vs. ASA and clopidogrel pretreatment (300 mg) and long term (75 mg) for average of 8 months^*
CREDO^7	Patients undergoing elective PCI (2,116)	ASA vs. ASA and clopidogrel pretreatment (300 mg) and long term (75 mg) for average of 12 months^*
CLARITY-TIMI 28^8	STEMI treated with fibrinolytics (3,491)	ASA vs. ASA and clopidogrel 300-mg loading dose followed by 75 mg/day
CLARITY-PCI^9	STEMI treated with fibrinolytics then with PCI^† (1,863)	ASA vs. ASA and clopidogrel 300-mg loading dose followed by 75 mg/day until the time of angiography followed by long-term open-label use of clopidogrel in both groups after PCI
COMMIT^10	STEMI (50% fibrinolytic use, no PCI; 46,000)	ASA vs. ASA and clopidogrel 75 mg/day for up to 4 weeks
CAPRIE^11	Patients with recent ischaemic stroke, recent MI, or symptomatic peripheral arterial disease (19,185)	ASA vs. clopidogrel (follow-up for up to 3 years)
CHARISMA^12	High-risk patients without known cardiovascular disease or stable cardiovascular disease (15,603)	ASA vs. ASA and clopidogrel (followed for median of 28 months)

UA, unstable angina; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; MI, myocardial infarction; STEMI, ST elevation myocardial infarction, ASA: aspirin.

^* All patients received open-label thienopyridine for 28 days post-PCI.

^† Patients underwent angiography 48–192 hours after start of study. PCI was performed at the discretion of the investigators.

Table 2. Summary of clopidogrel clinical effectiveness trials: results.

		Results
Study	End point	Clopidegrol	ASA	RRR/OR	p
CURE^5	Cardiovascular death, nonfatal MI or stroke (mean 9 months)	9.3%	11.4%	0.20%	<0.0001
PCI-CURE^6	Cardiovascular death, MI or target vessel revascularisation at 30 days	4.5%	6.4%	0.30	<0.0001
	Cardiovascular death and MI (mean 8 months)	8.8%	12.6%	0.31	<0.002
	Cardiovascular death, nonfatal MI or stroke^* (mean 8 months)^34	9.6%	13.2%	0.27	(95% CI 0.10–0.41)
CREDO^7	Death, MI or stroke (12 months)	8.5%	11.5%	0.27	0.02
CLARITY-TIMI 28^8	Cardiovascular death, MI or occluded infarct-related artery (at time of angiography)^†	15%	21.7	0.36	<0.001
	Cardiovascular death, MI or recurrent ischaemia leading to urgent revascularisation (30 days)	11.6%	14.1%	0.20	0.03
CLARITY-PCI^9	Cardiovascular death, MI or stroke (30 days)	7.5%	12%	0.31	0.001
COMMIT^10	Death, reinfarction or stroke (at time of discharge)	9.2%	10.1%	0.09	0.002
	All-cause death (at time of discharge)	7.5%	8.1%	0.07	0.03
CAPRIE^11	First occurrence of ischaemic stroke, MI, or vascular death (up to 3 years)	5.32%/year	5.83%/ year	0.087	0.043
CHARISMA^12	Cardiovascular death, MI, or stroke (mean 28 months)	6.8%	7.3%	0.07	0.22

MI, myocardial infarction; ASA, aspirin; RRR, relative risk reduction; OR, odds reduction; CI, confidence interval.

^* Stroke was not part of the primary end point.

^† Patients underwent angiography 48–192 hours after start of study. PCI was performed at the discretion of the investigators.

Table 3. Within-trial analysis of cost effectiveness of clopidogrel based on the CURE trial.

Study	Country	Incremental cost/CV event avoided
Lamy et al^20	Canada	CAD$7,973 (€5,754)^*
	France	€16,186
	Sweden	SEK127,951 (€13,980)^*
	UK	£10,366 (€14,978)^*
	US	US$22,484 (€15,929)^*
Annemans et al^21	Belgium	€18,149
	Italy	€18,348
	The Netherlands	€4,790
	Spain	€19,484
	Switzerland	€15,652
Lindgren et al^22	Denmark	€14,447
	Finland	€24,700
	Norway	€13,391
	Sweden	€15,652
Pietrasik et al^23	Poland	€23,076
Belousov et al^24	Russia	US$27,000 (€–19,139)^*

CV, cardiovascular; CAD, Canadian dollar; SEK, Sweden Kroner.

^* Converted from the published currency to Euro at the rate on the 9^th October 2007.

Table 4. Long-term cost effectiveness of clopidogrel based on the CURE trial: US analysis²⁵.

	Cost	Life years	ICER	% <50,000/life years gained
Framingham
Medicare	$639	0.0699	$9,144	92.8%
MEDSTAT	$535	0.0699	$7,654	93.4%
Blend	$541	0.0699	$7,742	93.4%
Saskatchewan
Medicare	$637	0.0682	$9,343	97.0%
MEDSTAT	$534	0.0682	$7,833	97.6%
Blend	$540	0.0682	$7,921	97.5%

ICER, incremental cost-effectiveness ratio.

Table 5. Long-term cost effectiveness of clopidogrel plus aspirin vs. aspirin based on the CURE trial: European analyses.

Study	Country	Net direct cost	Net total cost	Cost/life year gained (direct)	Cost per life year gained (total)
Lindgren et al^26	Sweden	€160	–€54	€1,365	Dominant
Lindgren et al^22	Denmark	€64	–€145	€549	Dominant
	Finland	€510	€296	€5,048	€2,935
	Norway	€137	–€82	€1,171	Dominant
	Sweden	€160	–€54	€1,365	Dominant
Schwartz et al^27	Austria				€4,146
Badia et al^28	Spain	€953		€8,132
Bruggenjurgen et al^29	Germany			€3,113
Van Hour et al^30	The Netherlands	–€17		Dominant

Table 6. Incremental cost per patient and per event avoided with clopidogrel plus aspirin vs. aspirin alone based on PCI-CURE trial31–33.

Country	Net cost	Incremental cost/event avoided
Austria	€385	€11,000
Belgium	€346	€9,851
Italy	€279	€7,931
Spain	€390	€11,065
Switzerland	€166	€4,732
The Netherlands	–€62	Cost saving
France	€323	€9,229
Sweden	SEK3,062 (€335)^*	SEK87, 486 (€9,558)^*
US	US$420 (€298)^*	US$12,000 (€8,503)^*
Canada	CAD$215 (€155)^*	CAD$6,143 (€4,432)^*
UK	£180 (€260)^*	£5,143 (€7,431)^*

CAD, Canadian dollar; SEK, Sweden Kroner.

^* Value between parentheses is cost per event converted to Euro at the rate on the 9th October 2007.

Table 7. Reported long-term cost-effectiveness ratios for cardiovascular interventions.

Intervention	Cost-effectiveness ratio per life year gained
Smoking cessation post-MI^46	US$220
Lisinopril post-MI^47	US$2,080
Perindopril in stable CAD^48	US19,816^*
Beta-blocker post-MI^49	US$4,500
Statin (simvastatin and pravastatin)50,^51	US$5,400–US$3,200
Clopidogrel for PCI: CREDO^36	US$2,929–US$4,353
Clopidogrel for PCI in ACS: PCI-CURE^34	US$2,856–US$4,775
Clopidogrel for ACS: CURE^25	US$7,654–US$9,144
Tirofiban for early invasive ACS^52	US$12,739
Eptifibatide for ACS^53	US$16,491
Alteplase versus streptokinase^54	US$32,678

ACS, acute coronary syndrome; MI, myocardial infarction; PCI, percutaneous coronary intervention.

^* Per quality-adjusted life year.