Purpose

1
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial

• Purpose
• To compare the angiotensin-converting enzyme
  (ACE) inhibitor ramipril, the angiotensin
  receptor blocker (ARB) telmisartan, and their
  combination in patients with cardiovascular
  disease or diabetes mellitus but without heart
  failure.
• Reference
• ONTARGET Investigators, Yusuf S, Teo KK, Pogue
  J, et al. Telmisartan, ramipril, or both in
  patients at high risk for vascular events. N Engl
  J Med 200835815471559.

2
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial-
TRIAL DESIGN -

• Design
• Single-blind run-in, followed by double-blind,
  randomized, multicenter, multinational trial.
• Patients
• Run-in 29,019 patients aged 55 years old with
  at least one of the following coronary artery
  disease (CAD), peripheral artery disease,
  cerebrovascular disease, and diabetes mellitus.
• Exclusion criteria included heart
  failure.Randomization phase 25,260 patients.
• Follow-up and primary endpoint
• Follow-up visits at 6 weeks, 6 months, and every
  6 months until a median of 56 months. The primary
  endpoint was a composite outcome of
  cardiovascular death, myocardial infarction (MI),
  stroke, or hospitalization for congestive heart
  failure.

3
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial
- TRIAL DESIGN continued -

• Treatment
• Run-in ramipril 2.5 mg once daily for 3 days,
  followed by telmisartan 40 mg plus ramipril 2.5
  mg once daily for 7 days, followed by telmisartan
  40 mg plus ramipril 5 mg for 1118
  days.RandomizationFirst 2 weeks telmisartan
  80 mg once daily, ramipril 5 mg once daily, or
  combined drug therapy.After 2 weeks ramipril
  dose increased to 10 mg/day.

4
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial
- TRIAL DESIGN continued -

Baseline characteristics
Combination Therapyn8502
Telmisartan(n8542)?
Ramipril(n8576)
Mean age (years)?
66.4
66.5
66.4
Female sex ()?
26.3
26.5
27.2
European ethnicity ()?
72.7
73.2
73.1
Blood pressure (mmHg)?
141.9/82.1
141.7/82.1
141.8/82.1
Current smoker ()?
12.9
12.4
12.4
Clinical history ()?
74.4
CAD
74.5
74.7
MI
49.3
49.3
48.3
Diabetes
38.0
37.9
36.7
Yusuf et al. N Eng J Med 200835815471559.
5
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial
- RESULTS -

• At a median of 56 months, the primary outcome had
  occurred in 16.5 with ramipril, 16.7 with
  telmisartan, and 16.3 with combination-therapy
  (relative risk RR, 1.01 for telmisartan vs.
  ramipril p0.83, 0.99 for combination therapy
  vs. ramipril p0.38)?.
• Over the study period, patients in the
  telmisartan and combination therapy groups had
  slightly lower blood pressure than those in the
  ramipril group (average reductions, 0.9/0.6 mm Hg
  and 2.4/1.4 mm Hg, respectively)?.
• There were no significant differences in
  secondary outcomes apart from rates of renal
  impairment (10.2 with ramipril, 10.6 with
  telmisartan, and 13.5 with combination-therapy
  RR, 1.04 for telmisartan vs. ramipril
  (non-significant), 1.33 for combination therapy
  vs. ramipril plt0.001)?.

6
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial
- RESULTS continued -

• There were significant differences in the
  specific reasons for discontinuation between
  ramipril and telmisartan
• Hypotensive symptoms (1.7 with ramipril, 2.7
  with telmisartan RR, 1.54 plt0.001)?
• Cough (?4.2 with ramipril, 1.1 with
  telmisartan RR, 0.26 plt0.001)?
• Angioedema (0.3 with ramipril, 0.1 with
  telmisartan RR, 0.4 p0.01)?
• There were also differences in the specific
  reasons for discontinuation between the
  combination therapy and ramipril groups, with
  combination therapy causing significantly greater
  rates of hypotensive symptoms, syncope and
  diarrhea, at relative risks of 2.75 (plt0.001),
  1.95 (p0.03) and 3.28 (plt0.001), respectively.

7
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial
- RESULTS continued -

Kaplan-Meier curves for the composite primary
endpoint
The p value is for comparison with the
non-inferiority margin
No. at risk Telmisartan Ramipril Telmisartan plus
ramipril
Yusuf et al. N Eng J Med 200835815471559.
8
ONTARGET ONgoing Telmisartan Alone and in
combination with Ramipril Global Endpoint Trial
- SUMMARY -

• In patients with vascular disease or high-risk
  diabetes but without heart failure
• Telmisartan is equally as effective as ramipril
  (non-inferior and non-superior)?
• In comparison with ramipril, telmisartan causes a
  reduced risk of cough and angioedema, and an
  increased risk of hypotensive symptoms
• The choice between telmisartan and ramipril will
  depend on patient and physician preferences, and
  susceptibility to specific adverse effects
• Combination therapy offers no advantage and an
  increased risk of harm at full doses in
  comparison with ramipril alone