Costas Thomopoulos1, Gianfranco Parati, Alberto Zanchetti. 1. aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece bDepartment of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano IRCCS, and Department of Medicine and Surgery, University of Milan Bicocca cScientific Direction, Istituto Auxologico Italiano IRCCS, and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy.
Abstract
BACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of hypertension, and cardiovascular and renal disease, and it has been recommended that management of hypertension should be more aggressive in presence than in absence of diabetes mellitus, but the matter is controversial at present. OBJECTIVES: Meta-analysing all available randomized controlled trials (RCTs) to compare the effects on cardiovascular and renal outcomes of blood pressure BP lowering to different systolic BP (SBP) and diastolic BP (DBP) levels or by different drug classes in patients with and without diabetes mellitus. METHODS: The database consisted of 72 BP-lowering RCTs (260 210 patients) and 50 head-to-head drug comparison RCTs (247 006). Among these two sets, RCTs or RCT subgroups separately reporting data from patients with and without diabetes mellitus were identified, and stratified by in-treatment achieved SBP and DBP, by drug class compared with placebo, and drug class compared with all other classes. Risk ratios and 95% confidence intervals, and absolute risk reductions of six fatal and non-fatal cardiovascular outcomes, all-cause death, and end-stage renal disease (ESRD) were calculated (random-effects model) separately for diabetes mellitus and no diabetes mellitus, and compared by interaction analysis. RESULTS: We identified 41 RCTs providing data on 61 772 patients with diabetes mellitus and 40 RCTs providing data on 191 353 patients without diabetes mellitus. For achieved SBP at least 140 mmHg, relative and absolute reductions of most cardiovascular outcomes were significantly greater in diabetes mellitus than no diabetes mellitus, whereas for achieved SBP below 130 mmHg, the difference disappeared or reversed (greater outcome reduction in no diabetes mellitus). Significant ESRD reduction was found only in diabetes mellitus, but it was greatest when achieved SBP was at least 140 mmHg, and no further effect was found at SBP below 140 mmHg. All antihypertensive drug classes reduced cardiovascular risk vs. placebo in diabetes mellitus and no diabetes mellitus, but angiotensin-converting enzyme inhibitors were the only class more effective in diabetes mellitus than in no diabetes mellitus. When compared to other classes, renin-angiotensin system blockers were equally effective in cardiovascular prevention in no diabetes mellitus, but moderately, though significantly, more effective in diabetes mellitus. CONCLUSION: BP-lowering treatment significantly and importantly reduces cardiovascular risk both in diabetes mellitus and no diabetes mellitus, but evidence for reduced ESRD risk is available only in diabetes. Contrary to past recommendations, in diabetes mellitus there is little or no further benefit in lowering SBP below 130 mmHg, whereas continuing benefit is seen in no diabetes mellitus also at SBP below 130 mmHg. Although all BP-lowering drugs can beneficially be prescribed in hypertensive patients with diabetes mellitus, the current recommendation to initiate or include a renin-angiotensin system blocker is supported by the evidence here presented.
BACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of hypertension, and cardiovascular and renal disease, and it has been recommended that management of hypertension should be more aggressive in presence than in absence of diabetes mellitus, but the matter is controversial at present. OBJECTIVES: Meta-analysing all available randomized controlled trials (RCTs) to compare the effects on cardiovascular and renal outcomes of blood pressure BP lowering to different systolic BP (SBP) and diastolic BP (DBP) levels or by different drug classes in patients with and without diabetes mellitus. METHODS: The database consisted of 72 BP-lowering RCTs (260 210 patients) and 50 head-to-head drug comparison RCTs (247 006). Among these two sets, RCTs or RCT subgroups separately reporting data from patients with and without diabetes mellitus were identified, and stratified by in-treatment achieved SBP and DBP, by drug class compared with placebo, and drug class compared with all other classes. Risk ratios and 95% confidence intervals, and absolute risk reductions of six fatal and non-fatal cardiovascular outcomes, all-cause death, and end-stage renal disease (ESRD) were calculated (random-effects model) separately for diabetes mellitus and no diabetes mellitus, and compared by interaction analysis. RESULTS: We identified 41 RCTs providing data on 61 772 patients with diabetes mellitus and 40 RCTs providing data on 191 353 patients without diabetes mellitus. For achieved SBP at least 140 mmHg, relative and absolute reductions of most cardiovascular outcomes were significantly greater in diabetes mellitus than no diabetes mellitus, whereas for achieved SBP below 130 mmHg, the difference disappeared or reversed (greater outcome reduction in no diabetes mellitus). Significant ESRD reduction was found only in diabetes mellitus, but it was greatest when achieved SBP was at least 140 mmHg, and no further effect was found at SBP below 140 mmHg. All antihypertensive drug classes reduced cardiovascular risk vs. placebo in diabetes mellitus and no diabetes mellitus, but angiotensin-converting enzyme inhibitors were the only class more effective in diabetes mellitus than in no diabetes mellitus. When compared to other classes, renin-angiotensin system blockers were equally effective in cardiovascular prevention in no diabetes mellitus, but moderately, though significantly, more effective in diabetes mellitus. CONCLUSION: BP-lowering treatment significantly and importantly reduces cardiovascular risk both in diabetes mellitus and no diabetes mellitus, but evidence for reduced ESRD risk is available only in diabetes. Contrary to past recommendations, in diabetes mellitus there is little or no further benefit in lowering SBP below 130 mmHg, whereas continuing benefit is seen in no diabetes mellitus also at SBP below 130 mmHg. Although all BP-lowering drugs can beneficially be prescribed in hypertensivepatients with diabetes mellitus, the current recommendation to initiate or include a renin-angiotensin system blocker is supported by the evidence here presented.
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