Stroke or TIA: perindopril and indapamide reduced stroke and major vascular events.

Clinical bottom line (level 1b)

  1. Patients with a previous stroke or TIA who took perindopril and indapamide if tolerated compared with placebo were less likely to have a stroke (NNT = 27 at 4 years) , a major vascular event (NNT = 21 at 4 years) , or be admitted to hospital (NNT = 32 at 4 years) .
  2. Patients on perindopril with indapamide were more likely to withdraw due to hypotension (NNH = 87 at 4 years) .
  3. There was no difference in mortality between the two groups.
  4. Patients who took both perindopril and indapamide compared with placebo were less likely to have a stroke (NNT = 17 at 4 years) or a major vascular event (NNT = 13 at 4 years) .
  5. There was no difference in stroke or major vascular events for patients who took perindopril alone.
PROGRESS collaborative group : Lancet 2001; 358 : 1033-1041
Expires October 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 172 hospitals, Asia, Australasia, Europe

6105 patients (aged mean 64, 70% male) with a history of stroke (evidence of an acute disturbance of focal neurological function lasting more than 24 hours thought to be due to intracerebral haemorrhage (11%) or ischaemia (71%)) or transient ischaemic attack (22%) (as above but lasting less than 24 hours and thought due to arterioembolic disease or thrombotic vascular disease) within previous 5 years

Excluded if
  • within 2 weeks of vascular event or still unstable
  • unable to tolerate run-in period
  • definite indication or contraindication for ACE inhibitor

Control Group: (n = 3054, 3054 analysed): placebo
Experimental Group: (n = 3051, 3051 analysed): perindopril 4 mg daily and indapamide 2.5 mg daily if no specific indication for or contraindication to a diuretic
All patients had 4-week run-in period on perindopril (2 mg daily for 2 weeks, followed by 4 mg daily for 2 weeks). All patients received antiplatelet therapy and additional antihypertensive medication if necessary.
99.9% followed for 3.9 years
Outcome notes:
  • major vascular event : non-fatal stroke, non-fatal myocardial infarction, or death from any vascular cause

The evidence

Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
stroke 3.8 years 420
(13.8%)		 307
(10.1%)		 27%
(16% to 36%)		 3.69%
(2.07% to 5.31%)		 27
(19 to 48)
major vascular event 3.8 years 604
(19.8%)		 458
(15.0%)		 24%
(15% to 32%)		 4.77%
(2.87% to 6.66%)		 21
(15 to 35)
hospital admission 3.8 years 1349
(44.2%)		 1252
(41.0%)		 7%
(2% to 12%)		 3.14%
(0.66% to 5.62%)		 32
(18 to 150)
withdrawal due to hypotension 3.8 years 29
(0.95%)		 64
(2.10%)		 -120%
(-43% to -240%)		 -1.15%
(-1.76% to -0.534%)		 -87
(-190 to -57)
death 3.8 years 319
(10.5%)		 306
(10.0%)		 4%
(-11% to 17%)		 0.42%
(-1.10% to 1.94%)		 240
(NNT = 90 to infinity;
NNH = 52 to infinity)

a priori sub-group analysis: dual therapy v. placebo
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
stroke 3.8 years 255
(14.4%)		 150
(8.47%)		 41%
(29% to 51%)		 5.90%
(3.81% to 7.99%)		 17
(13 to 26)
major vascular events 3.8 years 367
(20.7%)		 231
(13.1%)		 37%
(27% to 46%)		 7.64%
(5.18% to 10.1%)		 13
(10 to 19)

a priori subgroup analysis: single therapy v. placebo
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
stroke 3.8 years 165
(12.9%)		 157
(12.3%)		 5%
(-17% to 22%)		 0.63%
(-1.93% to 3.20%)		 160
(NNT = 52 to infinity;
NNH = 31 to infinity)
major vascular event 3.8 years 237
(18.5%)		 227
(17.7%)		 4%
(-13% to 19%)		 0.80%
(-2.19% to 3.78%)		 130
(NNT = 46 to infinity;
NNH = 26 to infinity)

Comments

  1. Patients were stratified by physician's intention to give single or dual therapy, sex, age, entry blood pressure, qualifying event and study centre.
  2. 58% of patients took perindopril and indapamide.
  3. Blood pressure was reduced by a mean of 9/4 mmHg - 12/5 mmHg for patients with dual therapy, compared with 5/3 mmHg for patients on single therapy.
  4. Both patients with hypertension and no hypertension on enrollment received benefit - and to a similar degree.

Citation

  1. PROGRESS collaborative group , : Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358 : 1033-1041
Search Terms: hand-search
Contributor: Chris Ball and Clare Wotton, October 2001
Reviewer:

Clinical Question.
Patient previous stroke or TIA
Intervention or Exposure perindopril +/- indapamide
Comparison placebo
Outcome stroke, death, myocardial infarction