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Secondary Prevention Of Stroke
Secondary Prevention Of Stroke

3. Blood Pressure and Stroke Prevention

7th Edition – 2020 UPDATED

Recommendations

Note: These recommendations are applicable to transient ischemic attack, and stroke of ischemic and hemorrhagic origin unless otherwise stated, for secondary prevention.

3.0 Hypertension

Blood pressure should be assessed and managed in all persons with stroke or transient ischemic attack [Evidence Level A]. 

3.1 Blood Pressure Assessment
  1. All persons at risk of recurrent stroke should have their blood pressure measured routinely [Evidence Level A], no less than once annually and more frequently based on individual clinical circumstances [Evidence Level C]. 
  2. Proper standardized techniques should be followed for initial and subsequent blood pressure measurement including office, home, and community testing [Evidence Level B] as outlined by the Hypertension Canada Guidelines and Protocols for Blood Pressure Measurement.
  3. Patients found to have an automated office measured resting elevated blood pressure (systolic greater than 135 mm Hg and/or diastolic greater than 85 mm Hg) should undergo thorough assessment for the diagnosis of hypertension [Evidence Level C]. 
    1. During an office visit for assessment of hypertension consider taking the average of three blood pressure measurements conducted in accordance with the current Hypertension Canada Guidelines [Evidence Level C]. Refer to Hypertension Canada Algorithm for Diagnosis of Hypertension, including Home Blood Pressure Monitoring Targets.
  4. Patients with refractory hypertension should have comprehensive investigations for secondary causes of hypertension [Evidence Level B]. 
  5. Patients with hypertension or at risk for hypertension (in pre-hypertension state or other risk factors) should receive aggressive risk factor modification, lifestyle counselling and lifestyle modification interventions [Evidence Level B]. Refer to recommendations in Section 2 on Lifestyle Behaviour and Management for additional information, including sodium and diet management.
3.2 Blood pressure management
  1. Strong consideration should be given to the initiation of antihypertensive therapy after the acute phase of a stroke or transient ischemic attack [Evidence Level A].  
  2. For patients who have had an ischemic stroke or transient ischemic attack, blood pressure lowering treatment is recommended to achieve a target of consistently lower than 140/90 mm Hg [Evidence Level B]; this includes individuals with chronic kidney disease.  
  3. For patients who have had a small subcortical stroke (i.e., lacunar stroke), aggressive blood pressure lowering treatment is reasonable to achieve a systolic target of consistently lower than 130 mm Hg [Evidence Level B].
  4. In patients with intracerebral hemorrhage, blood pressure should be aggressively monitored, treated, and controlled [Evidence Level A] to sustain a target blood pressure consistently lower than 130/80 mm Hg [Evidence Level B].   Refer to Canadian Stroke Best Practice Recommendations: Management of Intracerebral Hemorrhage module.
  5. In patients with stroke and diabetes, blood pressure lowering treatment is recommended for the prevention of first or recurrent stroke to attain a target systolic blood pressure consistently lower than 130 mm Hg [Evidence Level C] and a target diastolic blood pressure consistently lower than 80 mm Hg [Evidence Level A]. 
  6. Randomized controlled trials have not defined the optimal time to initiate blood pressure lowering therapy after an acute stroke or transient ischemic attack. Blood pressure lowering treatment should be initiated or modified before discharge from hospital [Evidence Level B].  Refer to Hyperacute Module Recommendations Section 3.3 for blood pressure management during the acute phase of stroke (0 – 72 hours).
  7. Treatment with an ACE inhibitor and thiazide/thiazide-like diuretic combination is recommended [Evidence Level A].  Long-acting diuretics may be considered over short-acting [Evidence Level B]. *
  8. The use of an ACE inhibitor combined with an ARB is not recommended [Evidence Level B]. *
  9. Patients who are not started on antihypertensive therapy in acute care should have arrangements made for follow-up with primary care or stroke prevention service for ongoing evaluation and management [Evidence Level C].  Note: Blood pressure management is the responsibility of all healthcare team members, and initially stroke patients may require frequent monitoring (e.g., monthly) until they achieve target blood pressure levels and optimal therapy has been established. 
    Notes: * For recommendations on specific agents and sequence of agents in blood pressure management for the secondary prevention of ischemic stroke, refer to the current Hypertension Canada treatment guidelines.  

 

 
Section 3 Clinical Considerations

  1. (New for 2020)  For patients with a non-revascularized critical intracranial or extracranial arterial stenosis who are experiencing neurological symptoms attributed to hemodynamic (low flow) cerebral or retinal ischemia (e.g. orthostatic TIAs), it is reasonable to aim for higher than usual blood pressure targets (i.e. permissive hypertension), and avoidance of hypotension, for prevention of hemodynamic stroke; if such patients are asymptomatic, then usual blood pressure targets should be followed in the post-acute phase of stroke.
Rationale +-

Elevated blood pressure is the single most important risk factor for stroke. One in five adult Canadians has blood pressure in the range of 130–139/85–89 mm Hg (labeled by some investigators as “pre-hypertension”), and up to 60 percent of them will develop hypertension within four years. Among persons aged 55 and older with normal blood pressure, 90 percent will develop hypertension if they live to an average age. All adults require ongoing assessment of blood pressure throughout their lives. Each 1 mm Hg increase in blood pressure increases the risk of poor late-life cognitive function by approximately one percent. Epidemiologic studies have shown a graded increase in the risk of stroke as blood pressure increases.

Numerous population-based studies have found that elevated blood pressure is a significant risk factor for first and recurrent stroke; hypertension is estimated to account for about 60 percent of the population-attributable risk for cerebrovascular disease. The InterStroke study reported an odds ratio of 2.64 for patients with hypertension experiencing a stroke. Several trials have shown a 28 percent risk reduction in recurrent stroke in patients treated with blood pressure lowering medication. Among persons with a previous stroke the risk of recurrent stroke was reduced significantly with intensive antihypertensive therapy, with an NNT of 67. (Kitagawa et al. 2019)

The optimal target for blood pressure in people who have had a stroke and people at risk of stroke has not been formally defined through randomized controlled trials. The current treatment recommendation is to attain a blood pressure of consistently lower than 140/90 mm Hg for people who have had a cerebrovascular event. Epidemiologic data have shown that those with a response to treatment attaining blood pressure levels well below 140 systolic and 90 diastolic have better outcomes yet these treatment trials have not yet clearly defined how far blood pressure should be lowered. 

People who have experienced a stroke have reported lack of awareness or attention to blood pressure readings prior to their stroke.  They emphasize that education on blood pressure management is an essential part of care, yet they also reflect that the magnitude of impact of elevated blood pressure on secondary stroke risk was not made clear to them. Stroke teams and other care providers have opportunities to improve awareness and management of blood pressure and equip people who have experienced a stroke with the knowledge, measurement, and tracking/recording tools they need to mitigate future risk.

 

 
System Implications +-
  1. Coordinated hypertension awareness programs at the provincial and community levels that involve community groups, primary care providers (physicians, nurse practitioners and pharmacists) and other relevant partners.
  2. Stroke prevention, including routine blood pressure monitoring, offered by primary care providers in the community as part of comprehensive patient management.
  3. Increased availability and access to education programs about hypertension diagnosis and management for adults and children for healthcare providers across the continuum of care.
  4. Increased support for home blood pressure monitors (e.g., programs or tax credits) for patients and families on home monitoring of blood pressure and blood pressure self-management programs.
  5. Universal and equitable access to cost-effective medicines for all people in Canada, regardless of geography, age, or ability to pay. 
Performance Measures +-
  1. Proportion of persons at risk for stroke who had their blood pressure measured at their last healthcare encounter; and within the last 12 months.
  2. Proportion of the population who have diagnosed elevated blood pressure (hypertension).
  3. Proportion of the population who are aware of hypertension and the risks of high blood pressure.
  4. Percentage of the population with known hypertension who are on blood pressure lowering therapy.
  5. Proportion of the population with hypertension who are being treated and have achieved control of their blood pressure within defined targets (as per Canadian Hypertension Education Program guidelines) though lifestyle changes and/or medication.
  6. Proportion of stroke and transient ischemic attack patients who have received a prescription for blood pressure lowering agents on discharge from acute care.
  7. Proportion of stroke and transient ischemic attack patients who have received a prescription for blood pressure lowering agents after assessment in a secondary prevention clinic.

Measurement Notes

  • Performance measures 1 through 3: data may be available through the Canadian Hypertension Education Program database, the Canadian Community Health Survey, and other provincial and local health surveys and patient self-reports.
  • Performance measures 4: data may be available through audit of primary care provider’s charts. Prescription information may also be available through provincial drug plan databases, although these may have limitations with respect to the age of those covered by the plans, and there is variation across provinces and territories.
  • Performance measures 7: prescriptions for blood pressure lowering agents may be given during the inpatient stay or during a secondary prevention assessment and follow- up. When tracking these performance rates, it is important to record the setting where this therapy is initiated. Data sources may include patient/medical order sheets, physicians’ or nurses’ notes, discharge summaries or copies of prescriptions given to patients.
  • Prescriptions given to a patient do not imply compliance.
  • Algorithms to identify incidence and prevalence of hypertension from administrative databases have been validated in Canada and should be used for consistency in measurement when possible.104
Implementation Resources and Knowledge Transfer Tools +-

Health Care Provider Information

Patient Information

Summary of the Evidence +-

Blood Pressure and Stroke Prevention Evidence Tables and Reference List

Stroke Risk and Hypertension

Hypertension is widely regarded as the most important modifiable risk factor for stroke. Results from phases 1 and 2 of the INTERSTROKE study (O’Donnell et al. 2010, O’Donnell et al. 2016), indicated that among the five risk factors that accounted for more than 80% of the risk for stroke, hypertension was found to be most significant. The others included current smoking, abdominal obesity, diet, and physical activity. In phase 1 of the study, a self-reported history of hypertension or measured blood pressure ≥160/90 mm Hg was associated with an increased risk of all stroke (OR=2.98, 99% CI 2.72-3.28), but was highest for hemorrhagic stroke (OR=9.18, 99% CI 6.80-12.39). The same risk pattern was reported in phase 2 of the study, which used a self-reported history of hypertension or measured blood pressure ≥140/90 mm Hg to define hypertension (O’Donnell et al. 2016). The risk of hemorrhagic stroke was significantly increased (OR=4.09, 99% CI 3.51-4.77). In another case-control study, Du et al. (2000) reported the risk of stroke was significantly higher among subjects who were hypertensive (OR=2.45, 95% CI 1.62 to 3.71, p< 0.001) and the risk of stroke increased with additional risk factors including smoking and diabetes. The authors suggested that at least three-quarters of strokes in hypertensive patients are preventable given appropriate treatment. The authors further emphasized that strokes are caused not by a single risk factor, but by the interaction of multiple risk factors, with some having a stronger independent relationship with stroke than others.  A meta-analysis (Lewington et al. 2002) that included the results of one million adults from 61 prospective studies found that an increase of 20 mm Hg in systolic and 10 mm Hg in diastolic blood pressure led to a two-fold increase in stroke mortality in persons aged 40 – 69 years, without any evidence of a threshold down to at least 115/75 mm Hg for all vascular deaths. Age-specific associations were found to be similar for men and women, and for cerebral hemorrhage and cerebral ischemia.   Data from 1.25 million people without a history of cardiovascular disease, included in the CALIBER database were used to estimate lifetime risks and years of life lost to cardiovascular disease (Rapsomanki et al. 2014). During a median follow-up of 5.2 years, for each 20/10 mm Hg increase, the risks of transient ischemic attack, ischemic stroke and ICH increased across age cohorts (30-59, 60-79 and ≥80 years), with the highest risks noted in the youngest patients. The lifetime risk of ischemic stroke (from index age of 30 years) in persons with hypertension, defined as ≥140/90 mm Hg, was 7.6% (95% CI 7.3%-7.8%) compared with 6.5% (95% CI 6.2%-6.9%) for persons without hypertension. The years of life lost to ischemic stroke for those with hypertension was approximately a half a year.

Pharmacological Treatment of Hypertension Reduces Stroke Risk

Among persons who sustained an acute stroke, antihypertensive treatment, initiated within 48 hours of the event was shown to significantly reduce the risk of recurrent stroke at >12 months, compared with placebo or no treatment (RR=0.81, 95% CI 0.70-0.93). The effect was most pronounced for persons with baseline SBP>140 mm Hg. ACE inhibitors and diuretics were found to be the most effective antihypertensive agents (Zonneveld et al. 2018). The risks of recurrent stroke, disabling or fatal stroke and cardiovascular death were all significantly reduced following antihypertensive treatment compared with placebo in a systematic review including 14 RCTs (Katsanos et al. 2017). In meta-regression analysis, increasingly lower SBP was linearly associated with significant reductions in recurrent stroke, MI, death from any cause and cardiovascular death. Several meta-analyses included trials with persons both with and without previous stroke. Intensive blood pressure treatment was shown to decrease the risk of recurrent stroke compared with less intensive treatment by 22% (HR=0·78, 95% CI 0·67–0·90, p=0·001), after a mean duration of follow-up of 3.8 years (Xie et al. 2016, n=19 trials). Bangalore et al. (2017) included trials comparing different goal systolic blood pressure (SBP) targets (<150, <140, <130 and <120 mm Hg) against a reference standard of <160 mm Hg. The risk of stroke was decreased in a comparison of target SBP <120 vs. <160 mm Hg, the reference standard (RR=0.54, 95% CI 0.29-1.00), but there were no significant reductions in risk for any of the other pairings (<150 vs. <160 mm Hg; <140 vs. <160 mm Hg; <130 vs. <160 mm Hg). Looking from a different perspective, compared with a target SBP of <120 mm Hg, the risk of stroke was significantly increased with SBP <140 mm Hg (RR=1.72, 95% CI 1.42-2.58), <150 mm Hg (RR=1.97, 95% CI 1.26-3.08) and <160 mm Hg (RR=3.27, 95% CI 1.78-6.00). The authors suggested that SBP targets of <120 and <130 mm Hg were best for stroke prevention. Ettehad et al. (2016) included the results of 123 RCTs examining persons with and without previous stroke or transient ischemic attack. The risk of major cardiovascular events was reduced significantly for each 10 mm Hg reduction in SBP (RR= 0·80, 95% CI 0·77–0·83), including stroke (RR=0·73, 95% CI 0·68–0·77), with the magnitude of risk reduction proportional to the blood pressure reduction achieved. The risk of stroke was reduced significantly per each 10 mm Hg decrease in SBP with antihypertensive treatment in persons with and without existing cardiovascular disease (RR=0·74, 95% CI 0.67-0.81 and RR=0·75, 95% CI 0.63-0.89, respectively). The most effective antihypertensive agents for the reduction in stroke risk were angiotensin receptor blockers and calcium channel blockers. Beta-blockers were inferior to other classes of antihypertensives. The risk of stroke was reduced with antihypertensive treatment across different 10 mm Hg strata of baseline SBP ≥130. Lee et al. (2012) included the results of 11 RCTs representing data from 42,572 participants (794 with previous stroke) who were at high risk for cardiovascular disease and compared treatment of tight blood pressure control (SBP <130 mm Hg) with usual control (SBP 130 to 139 mm Hg) on subsequent stroke risk.  Tight SBP target was associated with reduced risks of future stroke, and major vascular events, and major coronary events, but was not associated with a significantly lower risk of death. Among patients with diabetes, those without a history of CVD, and younger than 65 years experienced the greatest stroke risk reduction. 

A recent clinical trial (RESPECT) compared standard blood pressure treatment, with a target of <140/90mm Hg, with intensive treatment target of <120/80 mm Hg, among 1,280 patients with a stroke sustained within the previous 30 days to 3 years with a baseline SBP of 130 to 180 mm Hg or DBP of 80 to 110 mm Hg. Unfortunately, the trial was stopped prematurely, before planned recruitment of 2,000 participants (Kitagawa et al. 2019). After a mean duration of follow-up of 3.8 years, there were 52 strokes (2.26% per year) in the standard group and 39 (1.65% per year) in the intensive group.  The risk of recurrent stroke was not reduced significantly with intensive BP treatment (HR=0.73, 95% CI 0.49-1.11, p=0.15). The Secondary Prevention of Small Subcortical Strokes (SPS3 Trial) examined the effectiveness of medical management to reduce recurrent stroke in persons with a lacunar stroke, sustained within the previous 180 days. Lowering systolic blood pressure (SBP) to a target of < 130 mm Hg resulted in a non-significant reduction on all stroke, disabling stroke, myocardial infarction and vascular death compared with target SBP levels of 130-149 mm Hg (Benavente et al. 2013). 

Lower blood pressure targets (<130/80 mm Hg) have been recommended for persons with diabetes for the prevention of first or recurrent stroke. A Cochrane review (Arguedas et al. 2013) included the results from 5 RCTs comparing ‘lower’ blood pressure targets (any target <130/85mm Hg) with ’standard’ targets (<140-160/90-100 mm Hg). Participants were adults with type 2 diabetes and elevated blood pressure, or already receiving treatment for elevated blood pressure. In the single included trial, which aimed at reductions in systolic blood pressure (ACCORD 2010) intensive BP control was not associated with reductions in total mortality (RR= 1.05, 95% CI 0.84-1.30) but was associated with reduction in the risk of stroke (RR=0.58, 95% CI 0.39 to 0.88, p= 0.009); however, serious adverse events, attributed to therapy occurred more often in patients in the intensive group (3.3% vs. 1.3%, p<0.001). In the 4 trials aimed at reductions in diastolic blood pressure, intensive BP control was not associated with reductions in total mortality (RR= 0.73, 95% CI 0.53-1.01, p=0.054) or stroke (RR= 0.67, 95% CI 0.42-1.05, p=0.077). In the UKPDS (Turner et al. 1988), the risk of fatal and nonfatal stroke (combined) was reduced by 44% (HR= RR=0.56, 95% CI 0.35-0.89, p=0.013) among patients in the tight BP control (mean BP achieved 144/82 mm Hg) compared with less aggressive control (mean BP achieved 154/87 mm Hg).

Sex and Gender Considerations

The evidence is conflicting regarding the increased risk of ischemic stroke associated with hypertension according to sex. There was no indication to suggest a sex difference in the relationship between systolic blood pressure (SBP) and the risk of stroke in a large meta-analysis including 124 studies (Peters et al. 2013) or from the CALIBER study including over 1.25 million persons (Rapsomaniki et al. 2014). In one of the REGARDS publications (Madsen et al. 2019), which included data from 26,461 participants, the risk of stroke was increased significantly more per each 10 mm Hg increase in SBP in women (HR=1.15, 95% CI, 1.10–1.20 vs. HR=1.08, 95% CI, 1.03–1.14, p for interaction=0.09). 

Control of hypertension was found to be significantly higher among women <60 years compared with men (56.3% vs. 50.6%); but was lower among women aged ≥60 years (50.8% for women vs. 54.6% for men, p<0.05) (Yoon et al. 2015). Although not statistically significant, intensive blood pressure lowering was found to reduce the risk of major cardiovascular events, including stroke, more in men compared with women in a sub analysis of the SPRINT trial (HR=0.84, 95% CI 0.61–1.13 vs. HR=0.73, 95% CI 0.59–0.89, p value for interaction=0.45) (Foy et al. 2018).


Stroke Resources
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