On 2016 Aug 25, CREBP Journal Club commented:

After discussion in our journal club, we concluded that this is a high quality randomised controlled trial. The results show the intervention results in a statistically significant decrease in death from any cause and major cardiovascular events (myocardial infarction, acute coronary syndrome, stroke, heart failure), but at the risk of an increase in severe adverse events (principally hypotension, syncope, electrolyte abnormalities and kidney injury). For treatment benefit, 16 deaths or major cardiovascular events were prevented per 1000 patients treated for 3 ¼ years, whereas 23 patients per 1000 had a serious adverse event. We also had the following concerns about the trial:

a) The treatment benefit is possibly an overestimate due to the early stopping of the trial;

b) The standard treatment arm of the trial reduced blood pressure lowering medication dose if the patient went below the specified target.

c) Even in this selected and carefully monitored population less than half of the patients achieved the target blood pressure.

d) The more stringent measurement of blood pressure used in the trial are not used in routine clinical practice.

e) There was greater utilisation of blood pressure lowering medication in the intensive arm of the trial, and this could have led to the observed difference rather than the achievement of the blood pressure target.

Whether the interventions are beneficial for an individual patient appears to be dependent on the individual clinical circumstances and the preferences of the patient. We would strongly recommend the development of methods for improving shared decision making with patients on this topic before recommending this intervention be part of routine practice.

See CREBP Journal Club for more information.

On 2016 Apr 12, NephJC - Nephrology Journal Club commented:

This trial was discussed on Nov 10th and 11th 2015 in the open online nephrology journal club, #NephJC, on twitter. Introductory comments are available at the NephJC website. The discussion was quite dynamic, with more than 100 participants, including nephrologists, cardiologists, geriatricians, emergency medicine physicians, hypertension specialists, clinical pharmacists, fellows, residents and patients. The transcript of the entire tweetchat, along with a round up of the many commentaries that were published, is available on the NephJC website. Some of the highlights of the tweetchat were:

• The team of investigators should be commended for designing and conducting this trial, and the NIH institutes – NHLBI, NIDDK and the NIA for funding this important trial.

• Some of the crucial elements of the trial were the method of blood pressure measurement (5 minutes resting followed by three readings without patient-provider interaction), the specific medications used (often long acting and potent antihypertensive agents such as chlorthalidone, use of combinations) and the frequent evaluations to titrate therapy, all of which should be considered when applying these findings.

• Overall the results are quite robust across different subgroups, with an impressive NNT of 90 for mortality; at the same time, the NNH (number needed to harm) for acute kidney injury (56), syncope (167) and electrolyte disturbances (125) should also be considered when applying this in clinical practice, as also the important exclusion criteria (eg frail patients) for whom this data may not be applicable to. Subsequent studies, such as the effect on cognition, quality of life and ambulatory blood pressure data are also eagerly awaited.

Interested individuals can track and join in the conversation by following @NephJC on twitter, liking #NephJC on facebook, signing up for the mailing list, or visit the webpage at NephJC.com.

On 2016 Feb 09, Geriatric Medicine Journal Club commented:

This article was critically appraised at the January 2016 Geriatric Medicine Journal Club (follow #GeriMedJC on Twitter). The SPRINT Research Group conducted a study to address the question of what the optimal systolic blood pressure target ought to be in patients at high risk for cardiovascular outcomes. Over a quarter of the patients in the study were 75 years or older, making this study somewhat relevant to geriatricians. However, looking at the extensive exclusion criteria, certainly there were not too many frail folks there. Concerns raised included the following: 1) The increased risk of syncope raises some eyebrows, 2) There was a preference for the use of chlorthalidone in the treatment algorithm; one must exercise caution in using this drug in the elderly due to the risk of hypokalemia, 3) It’s too bad the trial was stopped early as we know that truncated randomized trials are usually associated with greater effect sizes than if not stopped early. It will be interesting to see how this trial may change practice guidelines and the outcomes on cognitive impairment is expected to be reported in a separate publication.

Did you miss the #GeriMedJC tweetchat? Check out the transcript in our Archives section: http://gerimedjc.utorontoeit.com/index.php/2015/12/01/missed-gerimedjc-all-archived-here/

On 2015 Nov 17, Johan van Schalkwyk commented:

SPRINT strikes me as a work of pure genius. Conceive the following scenario: Take a carefully selected mixture of high-risk patients with a variety of blood pressures and risk factors, making sure that the low threshold for selection into the study is below the current sytolic blood pressure 'standard' of 140 mmHg. Apply two protocols, one that will aggressively reduce blood pressure in the intermediate term, another that's far more conservative. It's not beyond the bounds of possibility that a group of smart statisticians using current simulation methods and access to large hypertension databases might even predict the intermediate-term outcomes with a fair degree of confidence.

The fact that this trial is exactly what every manufacturer of anti-hypertensives needs at this point, that it was stopped very early, and that it seems to contradict the prior evidence that has informed treatment guidelines to date should make us pause and think. Particularly as the results from a highly selected group, treated for a few years, may well be extrapolated to lifetime treatment of many or even most people with a systolic blood pressure of over 130 mmHg. Let's see how this is marketed.

You may well choose to ignore the fact that one of the principal authors has received "personal fees" and/or grants from Bayer, Boeringer Ingelheim, GSK, Merck, AstraZeneca, Novartis, Arbor, Amgen, Medtronic and Forest. Your choice. Everyone has to make a living.

Of greater concern might be the near tripling of the rate of acute kidney injury or acute renal failure in the intensive-treatment group, as these conditions are not cheap to manage. We might also be a bit puzzled that almost half of the "extra deaths" in the standard therapy group were NOT from cardiovascular causes. How on earth does this work?

But anyone who understands a bit about MCMC methods should be in awe of the way this study was put together.

On 2015 Nov 14, Arnaud Chiolero MD PhD commented:

This study will probably change practice. Nevertheless, the absolute CVD risk reduction remains to be considered when these blood pressure levels are targeted.

On 2015 Nov 14, Arnaud Chiolero MD PhD commented:

This study will probably change practice. Nevertheless, the absolute CVD risk reduction remains to be considered when these blood pressure levels are targeted.

On 2015 Nov 17, Johan van Schalkwyk commented:

SPRINT strikes me as a work of pure genius. Conceive the following scenario: Take a carefully selected mixture of high-risk patients with a variety of blood pressures and risk factors, making sure that the low threshold for selection into the study is below the current sytolic blood pressure 'standard' of 140 mmHg. Apply two protocols, one that will aggressively reduce blood pressure in the intermediate term, another that's far more conservative. It's not beyond the bounds of possibility that a group of smart statisticians using current simulation methods and access to large hypertension databases might even predict the intermediate-term outcomes with a fair degree of confidence.

The fact that this trial is exactly what every manufacturer of anti-hypertensives needs at this point, that it was stopped very early, and that it seems to contradict the prior evidence that has informed treatment guidelines to date should make us pause and think. Particularly as the results from a highly selected group, treated for a few years, may well be extrapolated to lifetime treatment of many or even most people with a systolic blood pressure of over 130 mmHg. Let's see how this is marketed.

You may well choose to ignore the fact that one of the principal authors has received "personal fees" and/or grants from Bayer, Boeringer Ingelheim, GSK, Merck, AstraZeneca, Novartis, Arbor, Amgen, Medtronic and Forest. Your choice. Everyone has to make a living.

Of greater concern might be the near tripling of the rate of acute kidney injury or acute renal failure in the intensive-treatment group, as these conditions are not cheap to manage. We might also be a bit puzzled that almost half of the "extra deaths" in the standard therapy group were NOT from cardiovascular causes. How on earth does this work?

But anyone who understands a bit about MCMC methods should be in awe of the way this study was put together.

On 2016 Feb 09, Geriatric Medicine Journal Club commented:

This article was critically appraised at the January 2016 Geriatric Medicine Journal Club (follow #GeriMedJC on Twitter). The SPRINT Research Group conducted a study to address the question of what the optimal systolic blood pressure target ought to be in patients at high risk for cardiovascular outcomes. Over a quarter of the patients in the study were 75 years or older, making this study somewhat relevant to geriatricians. However, looking at the extensive exclusion criteria, certainly there were not too many frail folks there. Concerns raised included the following: 1) The increased risk of syncope raises some eyebrows, 2) There was a preference for the use of chlorthalidone in the treatment algorithm; one must exercise caution in using this drug in the elderly due to the risk of hypokalemia, 3) It’s too bad the trial was stopped early as we know that truncated randomized trials are usually associated with greater effect sizes than if not stopped early. It will be interesting to see how this trial may change practice guidelines and the outcomes on cognitive impairment is expected to be reported in a separate publication.

Did you miss the #GeriMedJC tweetchat? Check out the transcript in our Archives section: http://gerimedjc.utorontoeit.com/index.php/2015/12/01/missed-gerimedjc-all-archived-here/

On 2016 Apr 12, NephJC - Nephrology Journal Club commented:

This trial was discussed on Nov 10th and 11th 2015 in the open online nephrology journal club, #NephJC, on twitter. Introductory comments are available at the NephJC website. The discussion was quite dynamic, with more than 100 participants, including nephrologists, cardiologists, geriatricians, emergency medicine physicians, hypertension specialists, clinical pharmacists, fellows, residents and patients. The transcript of the entire tweetchat, along with a round up of the many commentaries that were published, is available on the NephJC website. Some of the highlights of the tweetchat were:

• The team of investigators should be commended for designing and conducting this trial, and the NIH institutes – NHLBI, NIDDK and the NIA for funding this important trial.

• Some of the crucial elements of the trial were the method of blood pressure measurement (5 minutes resting followed by three readings without patient-provider interaction), the specific medications used (often long acting and potent antihypertensive agents such as chlorthalidone, use of combinations) and the frequent evaluations to titrate therapy, all of which should be considered when applying these findings.

• Overall the results are quite robust across different subgroups, with an impressive NNT of 90 for mortality; at the same time, the NNH (number needed to harm) for acute kidney injury (56), syncope (167) and electrolyte disturbances (125) should also be considered when applying this in clinical practice, as also the important exclusion criteria (eg frail patients) for whom this data may not be applicable to. Subsequent studies, such as the effect on cognition, quality of life and ambulatory blood pressure data are also eagerly awaited.

Interested individuals can track and join in the conversation by following @NephJC on twitter, liking #NephJC on facebook, signing up for the mailing list, or visit the webpage at NephJC.com.

On 2016 Aug 25, CREBP Journal Club commented:

After discussion in our journal club, we concluded that this is a high quality randomised controlled trial. The results show the intervention results in a statistically significant decrease in death from any cause and major cardiovascular events (myocardial infarction, acute coronary syndrome, stroke, heart failure), but at the risk of an increase in severe adverse events (principally hypotension, syncope, electrolyte abnormalities and kidney injury). For treatment benefit, 16 deaths or major cardiovascular events were prevented per 1000 patients treated for 3 ¼ years, whereas 23 patients per 1000 had a serious adverse event. We also had the following concerns about the trial:

a) The treatment benefit is possibly an overestimate due to the early stopping of the trial;

b) The standard treatment arm of the trial reduced blood pressure lowering medication dose if the patient went below the specified target.

c) Even in this selected and carefully monitored population less than half of the patients achieved the target blood pressure.

d) The more stringent measurement of blood pressure used in the trial are not used in routine clinical practice.

e) There was greater utilisation of blood pressure lowering medication in the intensive arm of the trial, and this could have led to the observed difference rather than the achievement of the blood pressure target.

Whether the interventions are beneficial for an individual patient appears to be dependent on the individual clinical circumstances and the preferences of the patient. We would strongly recommend the development of methods for improving shared decision making with patients on this topic before recommending this intervention be part of routine practice.

See CREBP Journal Club for more information.