Blood Pressure Goals

Motivation: 150?? Since medical school, we have been firmly taught that the upper limit of normal for systolic blood pressure is 140 mmHg.  Recently, the panel JNC8 ruled that for adults over 60, a reasonable systolic goal is less than 150 mmHg.  After having counseled countless times about the importance of blood pressure control, this increase sounded traitorous.  What is the data?  There have been two randomized trials addressing this issue over the past decade.  I will review here the one of the larger and latest one here.

Paper: Ogihara, T, Saruta, T, Raguki, H, et. al.  "Target Blood Pressure for Treatment of Isolated Systolic Hypertension in the Elderly" Hypertension (2010) 56: 196-202.

Methods: The study (VALISH) was a multicenter, prospective, randomized, open-label, blinded end point trial in Japanese adults between 70-85 years of age with isolated systolic hypertension (SBP > 160 mmHg with diastolic less than 90 mmHg).  Patients were randomly treated with valsartan (titrated first with addition of second agent if necessary) into two groups: (1) Systolic blood pressure < 140 mmHg (strict control) or (2) systolic blood pressure < 150 mm Hg (moderate control).  Patients were followed for minimum of two years.  Primary outcome was a composite of cardiovascular events (sudden death, stroke, MI,  death from cardiovascular cause, renal dysfunction).

Results:
Cohort: A total of 3260 patients were randomized.  There were 181 patients lost to follow-up (95% follow-up).  In total, 3079 patients were followed for average of 2.85 years.  Average age was 76.1 years with 62% women.  Baseline characteristics were mostly balanced between groups except there were more smokers in the strict control group vs. moderate control (21% vs. 17.4%; p = 0.01).  There was history of stroke in 6.5%, ischemic heart disease in 5%, heart failure in 1.7%, and diabetes mellitus in 13%.

Blood Pressure Control: At 36 months of follow-up, the blood pressure was 13.6./74.8 in strict control group and 142/76.5 in moderate control groups.  Heart rate did not differ significantly between the two groups.

Outcome: In the primary combined cardiovascular outcome, the overall rate did not differ between the groups in intention-to-treat analysis (10.6 events per 1000 patient years in strict control; 12 per 1000 patient years in moderate control group, p = 0.38).  There was no difference in any of the individual components of the composite outcome.  In subgroup analysis, there was not a statistical difference in patients with diabetes, dyslipidemia, and chronic kidney disease.

Adverse Effect: There was no difference in adverse effect between the two groups.

Discussion: After an average of 2.8 years of follow-up, there did not appear to be a difference in cardiovascular outcome by controlling blood pressure tighter in patients with isolated systolic hypertension.  While rather remarkable and against popular medical conception, I think that the lack of longitudinal data beyond 2.8 years is cautionary is depending on these blood pressure parameters too much.  This trial shows that systolic blood pressure control less than 150 mmHg versus 140 mm Hg may not make much of a difference in the short term, but what about in five to ten years?  We still do not know the answer.  Another problem with extending this dataset is that patients included in the cohort had low burden of disease (ischemic heart disease in only 5%).  For the patient with angina, the trial may not be powered enough to detect difference in this subgroup.    But then again, these arguments are probably my ingrained cognitive biases against change.  The bottom line, I think, is that we need more longitudinal data before having a blood pressure parameter in mid.

Stroke Recovery for How Long

Motivation: So, how long does it take to recover? Even after more than a year of treating patients with acute stroke, I am not sure how to answer this question.  I sometimes put it vaguely as "months."  But, really, after how many months do most post-stroke patients complete their recovery?

Paper: Jorgensen HS, Nakayama H, Raaschou HO, Vive-Larsen J, Stoier M, Olsen TS. "Outcome and time course of recovery in stroke: Part II: Time course of recovery. The copenhagen stroke study." Arch Phys Med Rehabil (1995); 76: 406-412.

Methods: All patients with acute stroke in Copenhagen, Denmark between September, 1991 to 1993 were followed from time of acute admission to end of rehabilitation to six months post-stroke.  Time course of recovery was plotted.

Results:
Cohort: The cohort of stroke survivors consisted of 947 patients (53% female) of mean age 73.3.  The strokes were 93% ischemic and 7% hemorrhagic.  The median time between symptom onset and admission was 16 hours.  After rehabilitation, 19% were placed in nursing homes while 81% were discharged home.

Recovery: When assessed by the Scandinavian Stroke Scale (0-58 points, higher indicating milder deficits), best neurological recovery was reached in 80% by 4.5 weeks (95% CI: 4 to 5 weeks) and in 95% by 11 weeks (95% CI: 10.1 to 11.9 weeks) from stroke onset.  Best ADL function (measured by Barthel Index) was reached in 80% by 6 weeks (95% CI: 5.3 to 6.7 weeks) and in 95% by 12.5 weeks (95% CI: 11.6 to 13.4).

Initial Severe Functional Deficits: Severity of functional deficits were judged by the Barthel Index (scale of 0 to 100 with very severe disability in 0-20 and no disability with score of 100).  In those with very severe initial disability (index of 0-20), best ADL function was reached in 80% of patients within 11 weeks (95% CI: 10-12) and in 95% within 17 weeks (95% CI: 15-19).

Initially Mild Disability: In those with mild disability (Barthel Index 75-95), best ADL function was reached in 80% of patients within 2.5 weeks (95% CI: 2-3) in 95% of patients within 5 weeks (95% CI: 4-6).  

Discussion: In this remarkable study with 100% follow-up of all stroke patients in Copenhagen over two years, the overall message is that 95% will regain their best ADL function in about three months.  The rate of recovery is slower in those with more severe disability and more rapid in those with mild disability.  However, even in those with very severe initial functional deficits, best ADL function was reached in 17 months.  For general counseling purposes, an appropriate summary statement might be that mild strokes take about a month to regain best function while severe strokes take about four to five months to regain best function.  While this study is well done, some cautionary aspects are that (1) acute stroke therapy has changed since  the study, and (2) physical therapy has changed since the early 1990s.  How these aspects change the natural history of stroke disorders is unclear.  Also note that this study also talks about the rate of recovery and not the extent of recovery.

Time to Defibrillation and Survival - How soon?

Motivation: Last year, a man walked into my clinic, shook my hand, and said that he had survived a v-fib cardiac arrest.  My heart skipped a beat.  He told me that he had been unconscious for more than ten minutes.  I did not know whether to believe him.  What is the relation between survival and time to defibrillation in out of hospital cardiac arrest?

Paper: De Maio, V.J., Stiell, I.G., Wells, G.A. et al. "Optimal Defibrillation Response Intervals for Maximum Out-of-Hospital Cardiac Arrest Survival Rates"  Ann Emerg Med. (2003) 42: 242-250.

Methods: Prospective cohort study of the Ontario Prehospital Advanced Life Supports (OPALS) study, in which 21 Ontario study communities received a basic life support level of care with defibrillation by EMS.  The study assessed the relation of survival to defibrillation response time by EMS between 1991-1997.

Results:

Cohort: There were a total of 9,273 out of hospital cardiac arrests.  The mean age of 68.3 with 67.7% male sex.  The initial rhythm was ventricular fibrillation in 38.5%, asystole in 42.3%, and pulseless electrical activity in 19.1%.  There was return of spontaneous circulation in 10.4%.  Of the total 9,273 patients with cardiac arrest, 392 were discharged alive from hospital (4.2%).

Defibrillation: Of the 9,273 cardiac arrests, 4,059 received defibrillation (43.8%).  The median time to defibrillation was 6 minutes.  The 90th percentile for defibrillation response was 9.3%.

Survival:  When survival to hospital discharge is related to response time to defibrillation:

• Response time less than 4 minute: 7.6% survival.
• Response time between 4-6 minutes: 4.0% survival
• Response time between 6-8 minutes: 2.8% survival
• Response time greater than 8 minutes: 1.6% survival

When survival is modeled continuously to time to defibrillation, the predicted survival is (90th percentile prediction):

• Defibrillation time 1 min: 28.1% survival
• Defibrillation time 2 mins: 23.1% survival
• Defibrillation time 3 mins: 18.8% survival
• Defibrillation time 4 mins: 15.1% survival
• Defibrillation time 5 mins: 12.0% survival
• Defibrillation time 6 mins: 9.5% survival
• Defibrillation time 7 mins: 7.5% survival
• Defibrillation time 8 mins: 5.9% survival

Discussion: I think that the overall lesson is that surviving an out of hospital cardiac arrest is hard!  Even with good response time between 4-6 minutes, there is only a 4% survival.  While defibrillation definitely appears to increase survival (by almost four fold when comparing response time less than 4 minutes to greater than 8 minutes), the really steep drop in survival comes at the very beginning of the cardiac arrest (for example, almost 20% drop in predicted survival from two minutes to three minutes).  This study, however, has some flaws in accounting for the benefit of defibrillation.  Most notably, there were more defibrillations performed than there were ventricular fibrillations.  Consequently, some PEA and asystole arrests were also defibrillated without a clear indication.  Including these in the accounting probably dilutes the effect of defibrillation.